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The answer to this question is probably very straightforward, but I have actually had some difficulty finding an explicit answer online.
To what extent does the oscillatory pattern of arterial blood pressure (over small increments in time) mirror the oscillatory pattern of heart beat. For simplicity, imagine my heart beat signal is a binary signal where 0 means blood is not being ejected and 1 means blood is being ejected into circulation.
Said differently, if I detect a transient (where the interval of time is less than one second) increase in arterial pressure (e.g. a local peak), can I always accurately map that event to the "causal" contraction of the ventricles during blood ejection?
Similarly, can I use an arterial blood pressure time series to accurately recreate the binary signal of the heart beat? (Though, perhaps there will be a slight time shift due to the propagation speed of a pressure wave).
To provide another silly example: if my arterial pressure time series has 60 peaks (and corresponding "separating troughs"), can I confidently assert that the heart beat 60 times?
Healthcare knowledge of relationship between time series electrocardiogram and cigarette smoking using clinical records
In the few studies of clinical experience available, cigarette smoking may be associated with ischemic heart disease and acute coronary events, which can be reflected in the electrocardiogram (ECG). However, there is no formal proof of a significant relationship between cigarette smoking and electrocardiogram results. In this study, we therefore investigate and prove the relationship between electrocardiogram and smoking using unsupervised neural network techniques.
In this research, a combination of two techniques of pattern recognition feature extraction and clustering neural networks, is specifically investigated during the diagnostic classification of cigarette smoking based on different electrocardiogram feature extraction methods, such as the reduced binary pattern (RBP) and Wavelet features. In this diagnostic system, several neural network models have been obtained from the different training subsets by clustering analysis. Unsupervised neural network of clustering cigarette smoking was then implemented based on the self-organizing map (SOM) with the best performance.
Two ECG datasets were investigated and analysed in this prospective study. One is the public PTB diagnostic ECG databset with 290 samples (age 17–87, mean 57.2 209 men and 81 women 73 smoking and 133 non-smoking). The other ECG database is from Taichung Veterans General Hospital (TVGH) and includes 480 samples (240 smoking, and 240 non-smoking). The diagnostic accuracy regarding smoking and non-smoking in the PTB dataset reaches 80.58% based on the RBP feature, and 75.63% in the second dataset based on Wavelet feature.
The electrocardiogram diagnostic system performs satisfactorily in the cigarette smoking habit analysis task, and demonstrates that cigarette smoking is significantly associated with the electrocardiogram.
Materials and methods
Grass shrimp, Palaemonetes pugio, were purchased from Gulf Specimen Marine Laboratories, Inc. (Panacea, FL, USA), and maintained in 20 L aquaria in aerated seawater (30–32 ppt at 20°C). Animals were maintained in laboratory conditions for two weeks prior to experimental use and were fed marine flakes (Tetra) three times a week. Experimental animals were separated from the general population and fasted two days prior to use.
Pressure–volume loop of the left ventricle for a single cardiac cycle[adapted from Berne and Levy (Berne and Levy, 1986)].
Pressure–volume loop of the left ventricle for a single cardiac cycle[adapted from Berne and Levy (Berne and Levy, 1986)].
Grass shrimp were attached to the flattened end of a wooden applicator stick at the lateral cephalothorax with cyanoacrylate glue. The animal was held in place and positioned within the experimental chamber with a micromanipulator (World Precision Instruments, Sarasota, FL, USA). The video camera was placed over the chamber so that video images of the heart could be captured through the transparent exoskeleton [see methods from Harper and Reiber (Harper and Reiber,1999)]. The transparent exoskeleton allows for the measurements of area and pressure in vivo.
Seawater (30±2 ppt) within a flow-through experimental chamber was maintained at 20°C and the partial pressure of oxygen(PO2) in the water was maintained at normoxic levels by bubbling room air into the flow-through chamber. All animals were placed in the experimental chamber in normoxic water(PO2=20.5 kPa) and acclimated for 1 h. Thereafter a minimum of three recordings of pressure and volume were made for each animal.
Dorsal view of the heart through the carapace. (A) Outline of heart in systole defines the minimal area. (B) Outline of heart in diastole defines the maximal area. The area between the maximal and minimal area defines the ROI used in automated area analysis.
Dorsal view of the heart through the carapace. (A) Outline of heart in systole defines the minimal area. (B) Outline of heart in diastole defines the maximal area. The area between the maximal and minimal area defines the ROI used in automated area analysis.
Intraventricular pressure was measured using a servo-null pressure system(model 900A World Precision Instruments) and an analog–digital (AD)board (DAQPad 6020-50E National Instruments, Austin, TX, USA) at a rate of 600 Hz. A glass micropipette with a 2–5 μm diameter tip was filled with 3 mol l –1 NaCl and positioned in the ventricle with the use of a micromanipulator (World Precision Instruments). The micropipette tip was inserted through the soft dorsal arthrodial membrane at the junction of the thorax and abdomen to minimize disturbance to the animal, and then slowly advanced into the ventricle. The servo-null system measures the resistance of the 3 mol l –1 NaCl-filled pipette tip and prevents changes in resistance by generating an opposing pressure to the pressure present at the tip. Intraventricular pressure was calculated after correcting for the`zero-pressure' or calibration pressure, recorded when the tip was placed in the experimental chamber at a level adjacent to the heart.
Video image processing
Video images were acquired in vivo through the transparent exoskeleton at a rate of 60 Hz using a stereo-microscope (Leica MZ12.5 McBain Instruments, Chatsworth, CA, USA) equipped with a video camera (World Precision Instruments), frame-grabber board (LG-3 Scion, Frederick, MD, USA)and programmed frame-grabbing software (Scion Image Scion). Each video image was analyzed using custom-programmed image analysis software (LabViewNational Instruments) commonly used in the study of chick embryos(Tobita and Keller, 2000). First, maximum and minimum ventricular borders were traced from recorded sequences to determine ventricular cross-sectional area. The number of pixels and individual pixel values in the area contained between the maximum and minimum borders was stored in memory as a region of interest (ROI)(Fig. 3). Assuming that movement of the ventricular border would be associated with changes in the pixel values within the image of the heart, changes in ventricular area from the minimum area during the cardiac cycle were identified automatically by detecting the pixels that changed value in the ROI for sequential video fields. Total ventricular cross-sectional area in each video field was then calculated as the sum of the changes in area within the ROI defined by the maximum (Fig. 3B) and minimum(Fig. 3A) ventricular areas. The pressure signal (600 Hz) and video images (60 Hz) were acquired simultaneously for 4 s by an output trigger to the AD board and the frame-capturing board. Using a custom computer program (K. Tobita using LabView National Instruments) the pressure waveform was interpolated with the image data to yield a series of x, y coordinates required for the PA loop.
Area was converted to volume in a method used in previous studies(Harper and Reiber, 1999 Guadagnoli and Reiber, 2005). The use of dimensional analysis, with the heart modeled as a trapezoid
Heart rate (fH), maximum pressure(Pmax), minimum pressure (Pmin),change in pressure (ΔP), maximum area(Amax), minimum area (Amin) and change in area (ΔA) were determined by independently analyzing the pressure and video output from LabView (National Instruments) using a customized computer program, MATLAB (The Mathworks, Inc., Natwick, MA, USA). Area was converted to volume to obtain end-diastolic volume (EDV),end-systolic volume (ESV) and stroke volume (Vs). After interpolation of the PV data to generate multiple loops in LabView, the data were analyzed using MATLAB to obtain a mean PV loop as well as the area enclosed by the loop. The area of the PV loop is an estimate of stroke work(SW). The PV loop does not account for heart rate therefore, the product of area and fH yields an estimate of minute cardiac work(CW). However, either a PV or PA loop can be used to elucidate the phases of the cardiac cycle and cardiac dynamics in general. All values are means± s.e.m. (N=12).
The dynamics of the respiratory and cardiovascular systems were studied by continuously slowing respiration from 0.46 to 0.05 Hz. The time-frequency distribution and global spectral analysis were used to assess the R-R interval (R-R) and the systolic and diastolic blood pressure fluctuations in 16 healthy subjects. During rest, the nonrespiratory-to-respiratory frequency ratios were not affected by occasional slow breathing, whereas the low- (0.01–0.15 Hz) to high- (0.15–0.3 Hz) frequency indexes for blood pressure were increased (P < 0.05). The respiratory fluctuations in R-R and the systolic and diastolic pressures were paced over the 0.46- to 0.05-Hz range. As respiration slowed to 0.07–0.09 Hz, the frequency content of the respiration and cardiovascular variables increased sharply and nonlinearly to a maximum that exceeded values at higher frequencies (P < 0.001). The nonrespiratory frequency content remained stable in the 0.01- to 0.05-Hz range and did not significantly differ from that at rest. In contrast, the nonstable 0.05- to 0.1-Hz component was suppressed. A slow 0.012- to 0.017-Hz rhythm modulated respiration and hemodynamic fluctuations at both respiratory and nonrespiratory frequencies. The study indicated that respiration input should be considered in the interpretation of global spectra. Furthermore the time-frequency distributions demonstrated that a close nonlinear coupling exists between the respiratory and cardiovascular systems.
HRV is More than the Autonomic Nerve System: Some Physiological Systems with Influence on HRV
Autonomic Nerve System
The autonomic nervous system (ANS) is an important part in the control of different physiological systems, e.g., the heart, smooth muscles, endocrine, and exocrine glands. It has an afferent (sensory) and efferent parts and is distinct from the somatic nervous system in several ways. The main function of ANS is homeostasis, largely regulated by autonomic reflexes, (almost) not under voluntary control. Sensory information is frequently transmitted through afferent vegetative nerve fibers to homeostatic control centers, processed and specific reactions are sent through efferent vegetative fibers. The ANS has as mentioned specific transmitter substances—mostly acetylcholine (ACh) and norepinephrine (NE)𠅌orresponding receptors and can be divided into preganglionic and postganglionic fibers. The central control of the vegetative nerve system has been identified in several subdivisions of the hypothalamus, but several other brain regions including the association areas of the limbic cortex, the amygdala, and the prefrontal cortex are also connected to these hypothalamus nuclei.
The hypothalamus itself controls two more systems in addition to the ANS, the endocrine system and an ill-defined neural system involved in motivation (19) and social behavior ((20, 21)). The ANS has three major divisions: sympathetic (SNS), parasympathetic (PNS), and enteral (the latter is often underestimated). In a traditional view, the sympathetic and the parasympathetic systems are opposed to each other. In this view, the SNS is responsible for stress reactions and the PNS for relaxing. All visceral reflexes are processed by local circuits in the spinal cord and brainstem (22). The sympathetic system’s phasic activity is triggered by (positive and negative) stress and increases cardiac energy demand by increasing heart frequency and contractility through binding of NE to adrenoreceptors on cardiomyocytes (23). The parasympathetic system’s more tonic activity maintains homeostatic heart frequencies and contractility without exhausting, triggered by the release of ACh binding directly to muscarinic receptors on cardiomyocytes and also on nicotinic receptors on postsynaptic neurons (24, 25). The PNS reacts faster on external and internal changes, within 1 s, whereas the SNS reacts after ϥ s (26). The role of the ANS in the regulation of heart function is important, but much more influences exist, which makes it to a complex system with several likewise complex subsystems. The following interactions with other systems are only examples.
The sinoatrial node is, of course, the origin for the pace of the heart. It can, however, itself be considered as a system of weakly coupled oscillators with self-organizing properties, synchronized by a mechanism of mutual entrainment or phase locking (27).
Already on the intracellular level, cell organelles behave as weakly coupled oscillators. A combined experimental and simulation study showed with the help of two photon laser scanning microscope an oscillating network behavior of cardiac mitochondria, distinctly different from random behavior in the form of an inverse power law typical for fractal behavior. They might play a role as an intracellular timekeeper and have a long-time memory function of the oscillations, suggested by a calculated fractal dimension close to 1.0 (28). This kind of network behavior is of particular importance when HRV is interpreted within a complexity theory paradigm (8), as discussed below.
Cardiac neurons are localized both in the heart as intrinsic neurons and intrathoracically. They form a local distributive network, controlled by brainstem and spinal cord neurons and processing both central and local information to control the heart (29). Major intrinsic cardiac ganglionated plexus have sensory neurons responding to metabolic changes within particular heart regions (30). Such sensory inputs might be responsible for the generally stochastic behavior displayed by many atrial and ventricular neurons (31). In the same way as intracellular organelles, intrathoracic neurons have long-time memory properties based on cardiovascular events during the last subsequent cardiac cycles and influence efferent neuronal inputs (29). Because of this, perturbations can have effects over the next few cardiac cycles already based on the coupling of intrathoracic neurons. Because of multiple feedback circles complex behavior is already existent on this level. Typical for a complex system, its behavior is robust even when some subpopulations are compromised (32, 33).
One of the leading causes of sinus arrhythmia is probably central coupling of respiratory drive to cardiac vagal motor neurons (34). Medullary respiratory neurons provide efferent signals to medullary sympathetic premotor neurons (36).
The term RSA is used to describe the fluctuation of heart rate during the respiratory cycle. It is highly dependent on the vagal tone in the heart and is observable at a frequency band of 0.15𠄰.4 Hz. Usually, RSA is interpreted to mirror the vagal activity (37), involving several interaction levels. Beyond others, the fluctuations of blood pressure due to changes in intrathoracic pressure during the respiratory cycle have been discussed as one of the most important mechanisms of RSA (38). The baroreflex𠅊 rapid feedback loop where elevated blood pressure results in decreased heart rate and decreased blood pressure decreases baroreflex activation—has been associated with RSA, but some evidence indicates that the baroreflex is mostly involved in upright, but not in supine position (where HRV frequently is obtained) (37, 39, 40). An alternative explanation is based on the notion that neural networks generating the respiratory drive have also influence on oscillatory patterns in the vagal and sympathetic outflows, as already proposed several decades ago (41).
A classical interaction between the respiratory and cardiac system occurs in congestive heart failure, present in more than 50% of the patients (44). The pathophysiology of Cheyne–Stokes respiration is based on the combination of low cardiac output, pulmonary congestion, and high sympathetic activation. Both congested lungs and sympathetic hyperactivity lead to hyperventilation causing a decrease in arterial CO2 to a level below the apneic threshold. The hyperventilation pattern consecutively becomes periodic because the diminished arterial CO2 reaches the brainstem delayed due to the low cardiac output. When first the low partial pressure of CO2 is detected, respiration drive is stopped until CO2 increases. This again is detected late, which results in hyperventilation until CO2 is again on a low level and a new cycle begins (45). The increased sympathetic drive is in particular caused by increased CO2 partial pressure in the blood (46). The significance of Cheyne–Stokes respiration might be a mechanism to improve the efficacy of pulmonary gas exchange by phase-locking heart beats with phasic hyperpnea within the respiration cycle length (47). Cheyne–Stokes respiration again affects both sinus rhythm and AF. The latter does usually not react to normal ventilation, possibly due to changes of the atrioventricular nodal refractory period (48, 49).
In difference to other pathological conditions, endocrinological diseases can be associated with increased HRV parameters. Subjects with increased sodium excretion associated with an increased number of CYP11B2-344T alleles showed a higher LF/HF ratio, but not subjects with the AT1R 1166C allele. Increased sodium excretion correlates with expanded plasma volume which might explain the effect on the parasympathetic tone (50). Cortisol concentration is negatively correlated with HRV (51). Estrogen increases the parasympathetic parameters and progesterone sympathetic parameters of HRV (52, 53). Oxytocin application increase (rather moderate) HF and detrended fluctuation scaling exponent (54).
Infection, injury, or trauma causes an inflammatory reaction in the body which aims to restore homeostasis. The inflammatory response of the host is based on a complex combination of different immune mechanisms contributing to the neutralization of the invading pathogens, the restoration of injured tissues and to wound healing (55). The first steps of inflammatory reactions involve the release of pro-inflammatory mediators, especially, interleukin (IL)-1 and tumor necrosis factor (TNF), but also adhesion molecules, vasoactive mediators, and reactive oxygen species. This first release of pro-inflammatory cytokines is initiated by activated macrophages and is considered as crucial to trigger local inflammatory response (56).
Excessive production of cytokines, such as TNF, IL-1, and high mobility group B1, however, is causing more damage than invading pathogenes, like in the case of sepsis where immune reactions cause tissue injury, hypotension, diffuse coagulation, and in a high proportion of patients, death (57). Therefore, the inflammatory response needs to be balanced which is based on the nearly simultaneous release of anti-inflammatory factors like the cytokines IL-10 and IL-4, soluble TNF receptors, and transforming growth factor (TGF-beta). Using the terms pro- and anti-inflammatory is, however, rather simplistic, but widely used in the discussion of the complex cytokine network. If the local inflammation increases, TNF, and IL-1 β starts to circulate in the blood and other body fluids. This has major consequences for the CNS because these molecules are also signal molecules for the activation of brain-derived neuroendocrine immunomodulatory responses. Another superordinate control instance of the immune reaction is based on neuroendocrine pathways, as the well-known hypothalamic–pituitaryrenal axis, but, usually underestimated, the sympathetic division of the ANS (SNS) (58, 59). The CNS is also able to control inflammation and contributes to the other anti-inflammatory balancing mechanisms (55).
The cross talk between the immune system and the brain relies, therefore, not only on classical humoral pathways but also substantially on recently discovered neural pathways. Vagus nerve afferent sensory fibers play a vital role in the communication between body and brain when inflammation is occurring. Immunogenic stimuli stimulate vagal afferents both directly by cytokines released from dendritic cells, macrophages, and other vagal-associated immune cells, and indirectly through the chemoreceptive vagal ganglion cells (55).
Acetylcholine plays a major role as neurotransmitter and neuromodulator in the CNS. ACh is an important transmitter substance in ganglion synapses of sympathetic and parasympathetic neurons and is the main neurotransmitter in the postganglionic parasympathetic efferent neurons. Two types of receptors have a high affinity to ACh: muscarinic (metabotropic) and nicotinic (ionotropic). However, like other mediator substances as opioids, ACh is also involved in immune responses. RNA for muscarinic and nicotinic receptors has been detected in mixed populations of lymphocytes and other cytokine-producing cells (60, 61).
A majority of the cells are also capable of producing ACh (62). ACh has an anti-inflammatory effect, beyond others because ACh decreases TNF production via a posttranscriptional mechanism. ACh blocks also the release of other endotoxin-inducible pro-inflammatory cytokines, such as IL-1b, IL-6, and IL-18, by same mechanisms it does, however, not suppress the anti-inflammatory cytokine IL-10 (63, 64). In several experimental models of sepsis, myocardial ischemia and pancreatitis, all characterized by an excessive immune reaction, vagus stimulation was sufficient to block cytokine activity (65). The vegetative system may, therefore, play a major role in the immune defense (68). This works in both ways: changed activity of the vagal system modulates the inflammatory response by increasing the release of transmitter substances in the synaptic space like noradrenaline or ACh. On the other hand, inflammatory influences can also enhance or block vagal activity. Pro-inflammatory cytokines activate vagal afferent signaling which again activates efferent vagal signaling directly through the nucleus of the solitary tract (NTS) or indirect through NTS neurons activation of vagal efferents in the dorsal motor nucleus. The vagal system can be considered as an inflammatory control circuit for the inflammatory status in the periphery (69). If this system in animals is destroyed, they are more sensitive to endotoxemic shock (55). The area postrema, a region in the brain stimulated by increased blood concentrations of IL-1 beta can also activate the cholinergic anti-inflammatory pathway (70).
Sepsis is a life-threatening condition, usually caused by invasive bacteria. Success in treatment depends on early identification and treatment with appropriate antibiotics (71). Sepsis is traditionally diagnosed with the help of the clinical picture and blood samples of immunologic parameters (72). HRV changes are sometimes the earliest measurements before the first clinical effects of sepsis are observed (73, 74). This might be based on the close interaction between the PNS and the immune system, as described. HRV parameters change under inflammatory conditions. Soluble TNF-α receptors and IL-6 correlate (negatively) with time-domain HRV variables (SDNN, SDANN) (75), also endothelin 1 blood concentration is negative correlated with TP and ULF (78). Although TNF-α might not be associated with HRV variables, a clear relation between IL-6 and decreased HRV has been demonstrated (79). The liver releases CRP as a response to increased IL-1 and Il-6 concentrations, decreased HRV parameters are associated with increased CRP (80). In both newly diagnosed and chronic diabetic patients, increased IL-6 is correlated with decreased time domain (SDNN) and frequency-domain parameters (84). In a long-time cohort study with a follow-up of 15 years, linear HRV parameters and DFA was associated with inflammatory parameters at baseline. VLF, LF, TP, and SDNN was negatively correlated with CRP, Il-6, and WBC, DFA had and an inverse association with Il-6 and CRP, and HRT slope to WBC and Il-6 (85).
In conclusion, inflammatory parameters, such as IL-6, CRP, and TNF-alpha, correlate negatively with different HRV parameters. This is not only observed in classical “parasympathetic” parameters like rMSSD or HF but also for more general or “sympathetic” parameters like SDNN, SDANN, TP, VLF, and LF (86). The immune system is a still underestimated physiological and pathophysiological cause of HRV dynamics.
Insulin is a major player in metabolic function. In the heart, two different insulin signaling pathways have been identified: the phosphatidylinositol-3-OH kinase pathway, predominant in metabolic tissues and the growth-factor-like pathway (mediated by mitogen-activated protein kinase). Insulin resistance in the heart inhibits the metabolic pathway and stimulates the growth factor-like pathway (87, 88). This leads to decreased glucose uptake with possible consequences for cardiac cell metabolism (88, 89) and is a rather complex process also involving coagulation factors and the immune system (88). Already isolated obesity is associated with increased release of cytokines and other inflammatory markers like the intercellular adhesion molecule-1 (90). The islets with insulin-producing beta cells in the pancreas are innervated by both sympathetic and parasympathetic neurons, making possible a direct control by the CNS. This might also indicate that central nervous circuits have a major role in the functional adaptation to changes in insulin sensitivity. When the ventromedial hypothalamus is lesioned in experiments, increased vagal activity is observed and insulin is released, which can be blocked by vagotomy (91). The PNS effect on the beta cells is mediated by ACh and its effect on the M2 muscarinic receptor. Activation of the SNS through the 㬒-adrenergic receptor is associated with decreased insulin release, stimulation of β-adrenergic receptors enhance insulin output (92, 93).
There are several factors which can affect HRV in acute and chronic metabolic changes. The direct involvement of the vegetative nerve system can be attenuated in more chronic conditions, when the diabetic autonomous neuropathy, which necessarily occurs after a certain length of illness (94). HRV is an established tool in the diagnoses of diabetic neuropathy. During its sub-clinical phase, HRV can help in detecting cardiac autonomic neuropathy before the disease is symptomatic (95). Interestingly, reduced HRV in diabetes might be related to increased glycemic variability (96). Theoretically, this could be explained with the help of the concept of coupled oscillators—when the HRV-system as one oscillator fluctuates less, the coupling decreases which again allow the glycemic system to fluctuate independently with less control.
The LF parameter of HRV has been used to predict hypoglycemia (97), this might be even work in patients with advanced diabetic neuropathy (98). Parameters like SDNN and rMSSD are reduced when glucose and insulin are elevated (99). Regarding lipid metabolism, change of diet has been associated with HRV changes (100), but reports are conflicting regarding possible correlations between lipid concentrations in blood and HRV (101, 102).
Events of Cardiac Cycle: 5 Main Events | Cardiovascular System | Biology
Cardiac cycle is the term referring to all of the events that occurs from the beginning of one heartbeat to the beginning of the next. The frequency of the cardiac cycle is the heart rate. The time taken to complete one cardiac cycle is 0.8 sec and is called cardiac cycle time.
Some events of cardiac cycle are as follows:
Event # 1. Mechanical Changes:
Atrial systole initiates the cycle, because of presence of pacemaker SA node and is followed by atrial diastole. At the end of diastole, the atrial systole returns, and the cycle goes on.
II. Ventricular Events:
a. Ventricular Systole (0.3s):
i. Isovolumetric contraction phase
b. Ventricular Diastole (0.5s):
ii. Isovolumetric relaxation
At the end of atrial systole, ventricular systole (0.3s) starts. This is followed by ventricular diastole (0.5s). At the end of diastole, the ventricular systole repeats, and the cycle goes on like this.
Cardiac cycle begins with the atrial systole. During this period, the atria contract and expel their contents into the ventricles. The LA being away from the SA node, contract a little after the RA. But practically their contractions are simultaneous.
After atrial systole, comes atrial diastole. During this period, the atria relax and receive blood from the great veins. RA from vena cavae, and LA from pulmonary veins.
Ventricular systole commences at the end of atrial systole. This is because the impulse originating in the SA node after passing through the atria, will travel down the junctional tissues and enter the ventricles resulting in contraction. Systoles of atria and ventricles will never overlap.
At the end of ventricular systole, the first heart sound occurs. It is caused by sudden closure of AV valves due to sharp rise in intraventricular pressure. The semilunar valves open a little later, because, until the intraventricular pressure goes above that in the aorta and pulmonary artery, SL valves will not open.
Thus, at the beginning of ventricular systole, there is a brief period during which both the valves are closed and the ventricles are contracting as closed cavities. No blood passes out and hence, no shortening of the muscle will occur. This period is called isovolumetric contraction phase (0.05s).
At the end of this period, SL valves open and ejection phase starts (0.25s). During this phase, blood is expelled from the ventricles, from LV to systemic aorta and from RV to pulmonary artery. In the first part of this period (0.11s), the outflow is very rapid. Hence, this is known as rapid ejection phase. In the last part, (0.14s) the rate of outflow slows down. Hence, this is called reduced ejection phase. Here, the ventricular systole ends and the diastole start.
As soon as the ventricles relax, the intraventricular pressure starts falling. The blood column in the aorta and pulmonary trunk try to roll back towards ventricles, but are stopped by the sharp closure of SL valves. This produces the second heart sound. The second sound occurs at the end of ventricular systole. But this statement is not exact, because, till the falling of intraventricular pressure goes below the intra- aortic pressure, the SL valves will not close.
Consequently, there will be short interval between the onset of diastole and the closure of SL valves. This is called protodiastolic phase (0.04s).
Although the SL valves have closed, yet the AV valves are still not open. Because the falling intra­ventricular pressure takes a little time to go below that of atria, so that the AV valves may open. So, there will be a brief interval during which both the valves remain closed and ventricles are relaxing as closed cavities. Since no blood enters the ventricles there will be no lengthening of cardiac muscle fibers. This phase is called as isovolumetric relaxation phase (0.05s).
At the end of isometric relaxation phase, the AV valves open. Blood rushes into the ventricles and ventricular filling begins. The first part of this phase is known as the first rapid filling phase (0.11s). Because, as soon as the AV valves open, blood accumulating so long in the atria rushes into the ventricles.
The steep fall of the intraventricular pressure during the isometric relaxation phase, makes the inflow all the more intense. Although the duration is less, yet the largest part of ventricular filling takes place during it. The rapid rush of blood produces a third heart sound.
In the next phase, the rate of filling slows down. The ventricles are already full to a large extent and ventricular pressure slowly rises. Consequently, the rate of inflow from the atria will be gradually slower. This phase is called diastasis or slow filling phase (0.16s). Although this is the longest phase of ventricular diastole, the amount of filling during this phase is minimum.
Then comes the last phase of ventricular diastole which corresponds to atrial systole. Due to atrial contraction, blood rushes into the ventricles rapidly and this is called second rapid filling phase (0.1s). The rapid rush of blood produces a fourth heart sound. Here the ventricular diastole ends. Again the ventricular systole starts and the cycle repeats.
Period when all chambers are at rest and filling. 70% of ventricular filling occurs during this period. The AV valves are open, the semilunar valves are closed.
Pushes the last 30% of blood into the ventricle.
Event # 2. Pressure Changes:
I. Atrial Pressure Changes:
During atrial systole, atrial pressure rises (‘a’ wave). During atrial diastole, since the AV valves bulge into the atrial cavity in isometric contraction period of ventricle, intra-atrial pressure rises (‘c’ wave).
Then pressure falls during rapid ejection period of ventricles due to three reasons:
a. Atrial relaxation continues
b. As the ventricular muscle shortens, the AV ring is pulled down, so that atrial cavity enlarges
c. Due to reduction of ventricular volume, mediastinal pressure falls. Owing to this negative pressure, the thin walled atria dilate and atrial pressure falls.
In the later part of ventricular systole, intra-atrial pressure slowly rises (‘v’ wave) due to accumulation of blood in the atria as a result of venous filling, and AV valves remaining closed. This rise slowly continues until AV valves open.
During isovolumetric relaxation phase, AV ring rises up and is an additional cause for pressure rising.
As soon as the AV valves open, atrial blood rushes into the ventricles, so that intra-atrial pressure decreases. This fall continues till about middle of ventricular diastole.
As the ventricles fill up during diastasis, intra-atrial pressure slowly rises. After this atrial pressure comes down again.
II. Ventricular Pressure Changes:
a. During Ventricular Systole:
i. In the Isometric Contraction Phase:
Intraventricular pressure rises.
ii. In the Rapid Ejection Phase:
For a short period, force of contraction is more than the rate of outflow intraventricular pressure rises. Then, gradually equalize: horizontal plateau at the summit.
iii. In the Reduced Ejection Phase:
Force of contraction is less than the rate of outflow ― intraventricular pressure decreases.
b. During Ventricular Diastole:
i. In the Protodiastolic Phase:
Intraventricular pressure decreases.
ii. In the Isovolumetric Relaxation Phase:
Ventricles are relaxing as closed cavities—intraventricular pressure decreases.
iii. In the First Rapid Filling Phase:
Rate of relaxation is more than filling intraventricular pressure decreases slowly to some extent.
Ventricles are no more relaxing, blood accumulates in it intraventricular pressure rises slowly.
v. In Second Rapid Filling Phase:
Intraventricular pressure rises.
III. Aortic Pressure Changes:
During isovolumetric contraction phase of ventricles, a slight rise of aortic pressure is due to bulging of SL valves into the aorta.
With the opening of SL valves, blood enters the aorta and aortic pressure smoothly rises and falls running parallel to intraventricular pressure.
The fall of aortic pressure in reduced ejection phase is due to two causes:
a. Ventricle is contracting less forcibly than before, so that a comparatively less amount blood is entering the aorta now.
b. More blood is running out into the periphery than is entering the aorta from the ventricles.
With the onset of diastole, ventricular pressure sharply falls causing a backward flow of the aortic blood towards ventricles. Owing to this, aortic pressure drops causing the ‘incisura’. The blood column is reflected back by the sudden closure of SL valves, thus causing a sharp rise in the aortic pressure. The aortic pressure then slowly falls due to continuous passage of blood to periphery. The fall continues till ventricles contract again.
Event # 3. Volume Changes:
Ventricular Volume Changes:
The volume changes of ventricles are to some extent the reverse of its pressure changes.
i. During atrial systole, ventricular volume rises due to rapid filling. This rise is maintained during isovolumetric contraction phase of ventricles, because no blood is going out.
ii. During ejection phase, ventricular volume smoothly and continuously falls up to the end of systole.
iii. In isovolumetric relaxation phase, volume remains same, because no blood is entering.
iv. During first rapid filling phase, volume rises.
v. During diastasis, ventricular volume very slowly increases.
The stroke volume is the volume of blood, in milliliters (ml), pumped out of the heart with each beat, 70 ml/beat.
The output per minute is also called as minute volume. End-diastolic volume (EDV) is the amount of blood in the ventricle at the end of diastole. Normal value is about 120 ml.
Ejection fraction (EF) is the portion of end diastolic volume that is pumped out during one systole. EF = SV/EDV = 70/120 × 100 = 60%
End-systolic volume (EDV) is the amount of blood in the ventricle at the end of systole. Normal value is about 50 ml.
Ventricular Pressure-Volume Relationship:
Left ventricular pressure-volume (PV) loops are derived from pressure and volume information found in the cardiac cycle diagram (see left panel of Fig. 6.13). To generate a PV loop for the left ventricle, the left ventricular pressure (LVP) is plotted against left ventricular (LV) volume at multiple time points during a complete cardiac cycle. When this is done, a PV loop is generated (right panel of Fig. 6.13).
To illustrate the pressure-volume relationship for a single cardiac cycle.
The cycle can be divided into four basic phases:
i. Ventricular filling (phase A, diastole)
ii. Isovolumetric contraction (phase B)
iv. Isovolumetric relaxation (phase D).
Point 1 on the PV loop is the pressure and volume at the end of ventricular filling (diastole), and therefore, represents the end-diastolic pressure and end-diastolic volume (EDV) for the ventricle. As the ventricle begins to contract isovolumetrically (phase B), the LVP increases but the LV volume remains the same, therefore, resulting in a vertical line (all valves are closed). Once LVP exceeds aortic diastolic pressure, the aortic valve opens (point 2) and ejection (phase C) begins.
During this phase the LV volume decreases as LVP increases to a peak value (peak systolic pressure) and then decreases as the ventricle begins to relax. When the aortic valve closes (point 3), ejection ceases and the ventricle relaxes isovolumetrically that is, the LVP falls but the LV volume remains unchanged, therefore the line is vertical (all valves are closed). The LV volume at this time is the end-systolic (i.e. residual) volume (ESV).
When the LVP falls below left atrial pressure, the mitral valve opens (point 4) and the ventricle begins to fill. Initially, the LVP continues to fall as the ventricle fills because the ventricle is still relaxing. However, once the ventricle is fully relaxed, the LVP gradually increases as the LV volume increases. The width of the loop represents the difference between EDV and ESV, which is by definition the stroke volume (SV). The area within the loop is the ventricular stroke work.
The filling phase moves along the end-diastolic pressure-volume relationship (EDPVR), or passive filling curve for the ventricle. The slope of the EDPVR is the reciprocal of ventricular compliance. The maximal pressure that can be developed by the ventricle at any given left ventricular volume is defined by the end-systolic pressure-volume relationship (ESPVR), which represents the inotropic state of the ventricle.
The pressure-volume loop, therefore, cannot cross over the ESPVR, because that relationship defines the maximal pressure that can be generated under a given inotropic state. The end-diastolic and end-systolic pressure-volume relationships are analogous to the passive and total tension curves used to analyze muscle function.
Event # 4. Electrical Changes:
ECG stands for electrocardiogram and represents the electrophysiology of the heart. Cardiac electrophysiology is the science of the mechanisms, functions, and performance of the electrical activities of specific regions of the heart. The ECG is the recording of the heart’s electrical activity as a graph. The graph can show the heart’s rate and rhythm, it can detect enlargement of the heart, decreased blood flow, or the presence of current or past heart attacks.
i. The P is the atrial depolarization.
ii. QRS is the ventricular depolarization, as well as atrial repolarization.
iii. T is the ventricular repolarization.
During ventricular systole, all the diameters of the heart are reduced, and the base of the heart is pulled down towards the apex. On account of the spiral arrangement of the cardiac muscle fibers, the apex of the heart is rotated anteriorly and to the right, bringing most of the left ventricle to the front.
Due to this movement, as well as the hardening of the ventricular wall during contraction, there is a forward thrust of the apical region against the chest wall. This causes an impulse which is visible and palpable on the chest wall during each contraction and is called the apical impulse. This is felt on the left 5th intercostal space, 1/2 an inch internal to the midclavicular line. Pal­pation of the apical impulse gives useful clinical information.
Event # 5. Phonocardiogram:
In healthy adults, there are two normal heart sounds often described as a lub and a dub (ordup), that occur in sequence with each heart-beat. These are the first heart sound (SI) and second heart sound (S2). In addi­tion to these normal sounds, other sounds may be present including gallop rhythms S3, S4 and heart murmurs.
In cardiac auscultation, an examiner uses a stethoscope to listen for these sounds, which provide important information about the condition of the heart.
The aortic area, pulmonary area, tricuspid area and mitral area are areas on the surface of the chest where the heart is auscultated.
S1 is a soft, low pitched sound of long duration 0.1- 0. 17. and frequency of 25-45 Hz. Best heard at the apex.
1. Sudden closure of AV valves
2. Vibrations set up by the turbulence of blood due to accelerations and decelerations caused by ventricular contractions
3. Vibrations set up in the ventricular muscle fibers as it begins contracting.
S1 is normally slightly split (
0.04 sec) because mitral valve closure precedes tricuspid valve closure, however, this very short time interval cannot normally be heard with a stethoscope so only a single sound is perceived. It coincides with the spike of the QRS complex of the ECG and just precedes the C wave of the atrial pressure curve.
S2 is shorter, sharper and of slightly higher pitch, best heard at the base, having duration of 0.1-0.14s and a frequency of 50 Hz.
1. Sudden closure of SL valves
2. Vibrations set up in the blood columns and in the walls of aorta and pulmonary artery.
S2 is physiologically split because aortic valve closure normally precedes pulmonary valve closure. This splitting is not of fixed duration. S2 splitting changes depending on respiration, body posture and certain pathological conditions. It coincides with the upstroke of the V wave of atrial pressure curve and the end of T wave of ECG.
S3 is low pitched, and duration of 0.1s occurs in first rapid filling phase, and may represent tensing of the chordae tendinae and the atrioventricular ring, which is the connective tissue supporting the AV valve leaflets. This sound is normal in children, but when heard in adults it is often associated with ventricular dilation.
Is normally not heard, but only seen in phonocardiogram recording. It has a low frequency of 20 Hz and is caused by vibration of the ventricular wall during atrial contraction. This sound is usually associated with a stiffened ventricle (low ventricular compliance), and therefore is heard in patients with ventricular hypertrophy, myocardial ischemia, or in older adults.
Heart murmurs are generated by turbulent flow of blood, which may occur inside or outside the heart. Murmurs may be physiological (benign) or pathological (abnormal).
Physiologic murmurs also called functional murmurs can occur in the absence of valvular pathology. Very high flow velocities in the aorta can lead to turbulent flow which will result in murmurs during the ejection phase of the cardiac cycle. Examples of this include high cardiac outputs in trained athletes and high output states during anemia. Another example is pregnancy where the increase in cardiac output especially when coupled with anemia can result in physiologic ejection murmurs.
Abnormal murmurs can be caused by stenosis restricting the opening of a heart valve, resulting in turbulence as blood flows through it. Abnormal murmurs may also occur with valvular insufficiency (or regurgitation), which allows backflow of blood when the incompetent valve closes with only partial effectiveness. Different murmurs are audible in different parts of the cardiac cycle, depending on the cause of the murmur.
Recent basic researches on molecular and genetic mechanism of diastolic dysfunction resulted in a newer therapeutic approach, such as gene therapy, in this specific disease entity. In mammalian hearts, aging is associated with impaired cardiac relaxation.77),78) Senescent myocytes are characterized by prolonged relaxation, diminished contraction velocity, a decrease in β-adrenergic response, and increased myocardial stiffness.79) This impairment in diastolic function contributes to the increased incidence of congestive heart failure in the elderly.80) A number of cellular and molecular mechanisms may contribute to the age-related defects. The abnormalities in cardiac relaxation have been attributed to a defect in SERCA2 activity.81-83) Schmidt et al.84) evaluated cardiac function in senescent rat using catheter-based adenoviral gene transfer to achieve global myocardial transduction of SERCA2. They found that overexpression of SERCA2 normalized both the maximal rate of decline of LV systolic pressure and the LV time constant of isovolumic relaxation. These data demonstrate the feasibility of achieving important functional cardiac effects through in vivo somatic gene transfer in a rodent model of senescence and it also demonstrated that the overexpression of SERCA2 through adenoviral gene transfer in senescent rat hearts improves diastolic function and restores contractile reserve. Thus, targeting SERCA2 may be an important strategy to improve diastolic function in the aging myocardium.
Recently, it has been shown that the decay phase of the calcium transient is accelerated by parvalbumin expression at the level of the isolated adult cardiac myocytes in vitro.85) Parvalbumin is a soluble, small-molecular weight intracellular calcium-binding protein that is highly expressed in ultrafast contracting/relaxing striated muscle fibers, but is not naturally expressed in the heart.86) Parvalbumin functions as a delayed calcium sink in fast muscle based on the relative affinities of its two calcium/magnesium binding sites.87),88) Parvalbumin is therefore ideally designed to speed the rate of decline in intracellular calcium, with additional advantages of this occurring via a non--ATP-dependent process. Although parvalbumin is not naturally expressed in the heart, Szatkowski et al.89) have shown that parvalbumin gene transfer to the heart in vivo produces levels of parvalbumin characteristic of fast skeletal muscles, causes a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhances relaxation performance in an animal model of slowed cardiac muscle relaxation. They suggested that parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism.
Russo, M. A., Santarelli, D. M. & O’Rourke, D. The physiological effects of slow breathing in the healthy human. Breathe 13, 298–309 (2012).
Brown, R. P. & Gerbarg, P. L. Sudarshan Kriya yogic breathing in the treatment of stress, anxiety, and depression: part I-neurophysiologic model. J. Altern. Complement. Med. 11, 189–201 (2005).
Jerath, R., Edry, J. W., Barnes, V. A. & Jerath, V. Physiology of long pranayamic breathing: neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system. Med. Hypotheses 67, 566–71 (2006).
Bernardi, L., Gabutti, A., Porta, C. & Spicuzza, L. Slow breathing reduces chemoreflex response to hypoxia and hypercapnia, and increases baroreflex sensitivity. J. Hypertens. 19, 2221–9 (2001).
Joseph, C. N. et al. Slow breathing improves arterial baroreflex sensitivity and decreases blood pressure in essential hypertension. Hypertension 46, 714–8 (2005).
Fonoberova, M. et al. A computational physiology approach to personalized treatment models: the beneficial effects of slow breathing on the human cardiovascular system. Am. J. Physiol. Heart. Circ. Physiol. 307, H1073–91 (2014).
Froeliger, B., Garland, E. L. & McClernon, F. J. Yoga meditation practitioners exhibit greater gray matter volume and fewer reported cognitive failures: results of a preliminary voxel-based morphometric analysis. Evid. Based Complement. Alternat. Med. 2012, 821307 (2012).
Radaelli, A. et al. Effects of slow, controlled breathing on baroreceptor control of heart rate and blood pressure in healthy men. J. Hypertens. 22, 1361–70 (2004).
Dick, T. E., Mims, J. R., Hsieh, Y. H., Morris, K. F. & Wehrwein, E. A. Increased cardio-respiratory coupling evoked by slow deep breathing can persist in normal humans. Respir. Physiol. Neurobiol. 204, 99–111 (2014).
Chang, Q., Liu, R. & Shen, Z. Effects of slow breathing rate on blood pressure and heart rate variabilities. Int. J. Cardiol. 169, e6–8 (2013).
Bateman, G. A., Levi, C. R., Schofield, P., Wang, Y. & Lovett, E. C. The venous manifestations of pulse wave encephalopathy: windkessel dysfunction in normal aging and senile dementia. Neuroradiology 50, 491–7 (2008).
Gruszecki, M. et al. Subarachnoid space width oscillations as a potential marker of cerebrospinal fluid pulsatility. Adv. Exp. Med. Biol. 1070, 37–47 (2018).
Kelly, E. J. & Yamada, S. Cerebrospinal Fluid Flow Studies and Recent Advancements. Semin. Ultrasound. CT. MR. 37, 92–9 (2016).
Plucinski, J., Frydrychowski, A. F., Kaczmarek, J. & Juzwa, W. Theoretical foundations for noninvasive measurement of variations in the width of the subarachnoid space. J. Biomed. Opt. 5, 291–9 (2000).
Frydrychowski, A. F., Guminski, W., Rojewski, M., Kaczmarek, J. & Juzwa, W. Technical foundations for noninvasive assessment of changes in the width of the subarachnoid space with near-infrared transillumination-backscattering sounding (NIR-TBSS). IEEE Trans. Biomed. Eng. 49, 887–904 (2002).
Pluciński, J. & Frydrychowski, A. F. New aspects in assessment of changes in width of subarachnoid space with near-infrared transillumination/backscattering sounding, part 1: Monte Carlo numerical modeling. J. Biomed. Opt. 12, 044015 (2007).
Frydrychowski, A. F. & Plucinski, J. New aspects in assessment of changes in width of subarachnoid space with near-infrared transillumination-backscattering sounding, part 2: clinical verification in the patient. J. Biomed. Opt. 12, 044016 (2007).
Frydrychowski, A. F. et al. Use of Near Infrared Transillumination / Back Scattering Sounding (NIR-T/BSS) to assess effects of elevated intracranial pressure on width of subarachnoid space and cerebrovascular pulsation in animals. Acta Neurobiol. Exp. 71, 313–21 (2011).
Frydrychowski, A. F., Szarmach, A., Czaplewski, B. & Winklewski, P. J. Subarachnoid space: new tricks by an old dog. PLoS One 7, e37529 (2012).
Kalicka, R. et al. Modelling of subarachnoid space width changes in apnoea resulting as a function of blood flow parameters. Microvasc. Res. 113, 16–21 (2017).
Winklewski, P. J. et al. Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects. PLoS One 10, e0135751 (2015).
Gruszecki, M. et al. Human subarachnoid space width oscillations in the resting state. Sci. Rep. 8, 3057 (2018).
Gruszecki, M. et al. Coupling of Blood Pressure and Subarachnoid Space Oscillations at Cardiac Frequency Evoked by Handgrip and Cold Tests: A Bispectral Analysis. Adv. Exp. Med. Biol. https://doi.org/10.1007/5584_2018_283 (2018).
Wszedybyl-Winklewska, M. et al. Central sympathetic nervous system reinforcement in obstructive sleep apnoea. Sleep Med. Rev. 39, 143–154 (2018).
Stefanovska, A., Bračič, M. & Kvernmo, H. D. Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique. IEEE Trans. Bio. Med. Eng. 46, 1230–1239 (1999).
Bernjak, A., Stefanovska, A., McClintock, P. V. E., Owen-Lynch, P. J. & Clarkson, P. B. M. Coherence between fluctuations in blood flow and oxygen saturation. Fluct. Noise Lett. 11, 1–12 (2012).
Palatini, P. et al. Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension. Vasc. Health Risk. Manag. 7, 725–39 (2011).
Bruno, R. M. et al. Carotid and aortic stiffness in essential hypertension and their relation with target organ damage: the CATOD study. J. Hypertens. 35, 310–318 (2017).
Guntheroth, W. G. & Morgan, B. C. Effect of respiration on venous return and stroke volume in cardiac tamponade. Circ. Res. 20, 381–390 (1967).
Schrijen, F., Ehrlich, W. & Permutt, S. Cardiovascular changes in conscious dogs during spontaneous deep breaths. Pflugers Archiv. 355, 205–215 (1975).
Robotham, J. L., Rabson, J., Permutt, S. & Bromberger-Barnea, B. Left ventricular hemodynamics during respiration. J. Appl. Physiol. 47, 1295–1303 (1979).
Cheyne, W. S., Gelinas, J. C. & Eves, N. D. The haemodynamic response to incremental increases in negative intrathoracic pressure in healthy humans. Exp. Physiol. 103, 581–589 (2018).
Baumbach, G. L. Effects of increased pulse pressure on cerebral arterioles. Hypertension 27, 159–67 (1996).
Hirata, K., Yaginuma, T., O’Rourke, M. F. & Kawakami, M. Age-related changes in carotid artery flow and pressure pulses: possible implications for cerebral microvascular disease. Stroke 37, 2552–6 (2006).
Henskens, L. H. et al. Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension 52, 1120–6 (2008).
Winklewski, P. J. et al. Wavelet transform analysis to assess oscillations in pial artery pulsation at the human cardiac frequency. Microvasc. Res. 99, 86–91 (2015).
Frydrychowski, A. F., Wszedybyl-Winklewska, M., Bandurski, T. & Winklewski, P. J. Flow-induced changes in pial artery compliance registered with a non-invasive method in rabbits. Microvasc. Res. 82, 156–62 (2011).
Jolly, T. A. et al. Early detection of microstructural white matter changes associated with arterial pulsatility. Front. Hum. Neurosci. 7, 782 (2013).
Beggs, C. B. et al. Dirty-Appearing White Matter in the Brain is Associated with Altered Cerebrospinal Fluid Pulsatility and Hypertension in Individuals without Neurologic Disease. J. Neuroimaging 26, 136–43 (2016).
Magnano, C. et al. Cine cerebrospinal fluid imaging in multiple sclerosis. J. Magn. Reson. Imaging 36, 825–34 (2012).
Rickards, C. A., Ryan, K. L., Cooke, W. H., Lurie, K. G. & Convertino, V. A. Inspiratory resistance delays the reporting of symptoms with central hypovolemia: association with cerebral blood flow. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R243–50 (2007).
Kiviniemi, V. et al. Ultra-fast magnetic resonance encephalography of physiological brain activity - Glymphatic pulsation mechanisms? J. Cereb. Blood Flow Metab. 36, 1033–45 (2016).
Weippert, M., Behrens, K., Rieger, A., Kumar, M. & Behrens, M. Effects of breathing patterns and light exercise on linear and nonlinear heart rate variability. Appl. Physiol. Nutr. Metab. 40, 762–8 (2015).
Mason, H. et al. Cardiovascular and respiratory effect of yogic slow breathing in the yoga beginner: what is the best approach? Evid. Based Complement. Alternat. Med. 2013, 743504 (2013).
Wang, H., Zhang, H., Song, G. & Poon, C. S. Modulation of Hering-Breuer reflex by ventrolateral pons. Adv. Exp. Med. Biol. 605, 387–92 (2008).
St Croix, C. M., Morgan, B. J., Wetter, T. J. & Dempsey, J. A. Fatiguing inspiratory muscle work causes reflex sympathetic activation in humans. J. Physiol. 529, 493–504 (2000).
Winklewski, P. J. et al. Effect of Maximal Apnoea Easy-Going and Struggle Phases on Subarachnoid Width and Pial Artery Pulsation in Elite Breath-Hold Divers. PLoS One 10, e0135429 (2015).
Schroth, G. & Klose, U. Cerebrospinal fluid flow. II. Physiology of respiration-related pulsations. Neuroradiology 35, 10–15 (1992).
Chen, L., Beckett, A., Verma, A. & Feinberg, D. A. Dynamics of respiratory and cardiac CSF motion revealed with real-time simultaneous multi-slice EPI velocity phase contrast imaging. Neuroimage 122, 281–7 (2015).
Dreha-Kulaczewski, S. et al. Inspiration is the major regulator of human CSF flow. J. Neurosci. 35, 2485–91 (2015).
Lachowska, K., Bellwon, J., Narkiewicz, K., Gruchala, M. & Hering, D. Long-term effects of device-guided slow breathing in stable heart failure patients with reduced ejection fraction. Clin. Res. Cardiol. 108, 48–60 (2019).
Bertisch, S. M., Hamner, J. & Taylor, J. A. Slow Yogic Breathing and Long-Term Cardiac Autonomic Adaptations: A Pilot Study. J. Altern. Complement. Med. 23, 722–729 (2017).
Cui, R. et al. Wavelet coherence analysis of spontaneous oscillations in cerebral tissue oxyhemoglobin concentrations and arterial blood pressure in elderly subjects. Microvasc. Res. 93, 14–20 (2014).
Grinsted, A., Moore, J. C. & Jevrejeva, S. Application of the cross wavelet transform and wavelet coherence to geophysical time series. Nonlinear Process. Geophysics 11, 561–566 (2004).
Lachaux, J.P. et al. Clin. Neurophysiol. 32, 157 (2002).
Sheppard, L. W., Vuksanovic, V., McClintock, P. V. E. & Stefanovska, A. Oscillatory dynamics of vasoconstriction and vasodilation identified by time-localized phase coherence. Physics Med. Biol. 56, 3583–3601 (2011).
Sheppard, L. W., Stefanovska, A. & McClintock, P. V. E. Testing for time-localized coherence in bivariate data. Physical Rev. E. 85, 4–16 (2012).
Iatsenko, D. et al. Evolution of cardiorespiratory interactions with age. Philos. Trans. A. Math. Phys. Eng. Sci. 371, 20110622 (2013).
Early vertebrate heart
Jawless fish (Infraphylum Agnatha)
Among the most primitive vertebrates in evolutionary history are the agnathans, which include the living hagfish and lampreys (Yasuhiro et al. 2012 ). The oldest fossil of the hagfish was found in Pennsylvania and dates back to around 300 My (Bardack, 1991 ) however, agnathans are believed to have evolved over 450 My (Diogo, 2010 ). Living agnathans lack defining characteristics seen in other vertebrates, such as the absence of a calcified jaw (Alexander, 1986 ) as well as only a partly calcified skull with a cartilaginous vertebral column (Bishopric, 2005 ).
Living agnathans have a circulatory system which consists of the main ‘systemic (or brachial)’ heart and three accessory hearts (Fig. 2). The ‘portal’ heart is used to pump blood from the intestines to the liver, the ‘cardinal’ heart pumps blood from the head to the body and ‘caudal’ heart pumps blood from the trunk and kidneys to the rest of the body. The circulatory system is similar to that of a worm and shares with it both open and closed blood vessels (Jorgensen et al. 1998 ). In comparison with other vertebrates, agnathans also have a different sinus venosus (SV), which makes studying the agnathan circulatory system essential when investigating cardiac evolution. The SV is attached to the left side of the atrium, which has a collagenous wall. A layer of collagen and muscle marks the boundary between the SV and the atrium. Underneath the atrium is a single ventricle, which is attached via an elongated atrioventricular (AV) canal. Small amounts of myocardium can be noted inside the canal, which incorporates a two-leafed AV valve without any defining papillary muscles (Icardo et al. 2016 ).
The circulatory system of the hagfish has not changed in millions of years, with majority of species showing great diversity in habitats, behaviour and environments (Murphy, 1967 ). As living agnathans such as the hagfish are demersal (e.g. ‘bottom-dwellers’) they have adapted to an environment that requires low arterial blood pressure along with low cardiac power. A few characteristics specific to this demersal adaptations include hypoxia-tolerant heart muscle, an extended action potential, as well as the widely spaced intervals in the contractile tissue of the myocardium along with an accessory portal heart supplying the liver.
Lobe-finned fish (Superclass Sarcopterygii)
Due to oxygen deficiency and the high metabolic cost of obtaining oxygen from water, vertebrates were forced to make their way out of the ocean and on to land 350–400 Mya. This transition gave the heart a more complex role in terms of blood convection and gas transport. The ability to obtain oxygen straight out of the air called for a redesign of the gas chamber, as the small capillaries inside the gills could no longer function efficiently (Jorgensen, 2010 ).
Anatomical, physiological, genetic and fossil studies have provided evidence that the sacropterygians are a probable vertebrate ancestor to the tetrapods (or sister group alt. Superclass Tetrapoda sensu Ruggiero et al. 2015 Bassi et al. 2010 ) and appear in the evolutionary timeline in the Late Devonian period (385–355 Mya Prothero, 2015 ). The most studied sarcopterygian circulatory system is that of lungfish (Class Dipnoi), which have two main sites of blood oxygenation. Lungfish primarily use gills to breathe when aquatic, but as they inhabit stagnant ponds and swampland, which are often threatened with drought, lungfish adopted a vascularised lung supplied by two pulmonary arteries that enables them to breathe outside aquatic environments in times of hypoxia (Alexander, 1986 Bettex et al. 2014 ). With very few exceptions, and in comparison with exclusively aquatic fish, oxygenated blood flow moving out of pulmonary circulation in extant lungfish species does not directly continue into systemic circulation. Instead, it moves back into the heart, where it is then pumped into systemic circulation, ultimately creating dual circulation, the first ever seen in vertebrate evolutionary history. The reason dual circulation was required was because the vascular resistance needed in pulmonary circulation was so high as to dissipate the majority of the kinetic energy conveyed to the blood by the heart (Jorgensen, 2010 ). As a result of this adjustment, the heart of the lungfish is highly specialised in order to preserve separation of oxygenated and deoxygenated blood through its body cavities (Icardo et al. 2005 ).
Generally, sarcopterygians breathe by pulling in water through their mouth and out through their gills. A capillary network on each side of their pharynx (throat) allows the fish to pull in oxygen from the water and into their circulatory system, which is then pumped to individual cells (Park et al. 2014 ). Generally, bony fish have a two-chambered heart (one atrium and one ventricle) which makes up 0.2% of their mass (Bettex et al. 2014 ) however, these are subdivided into a linear series of a total of four different compartments: a SV, atrium, ventricle and conus arteriosus (CA Holmes, 1975 ).
Oxygen enters the capillaries through the gills and is transported in the blood via the aortic arches, down through the pulmonary arteries and into the lungs, where it is further oxygenated (Icardo et al. 2005 Bettex et al. 2014 ). In contrast to other osteichthyan (bony) fishes (e.g. Superclass Actinopterygii), the ventral aortic arches are shortened in a lungfish so that they arise closer to the heart (Holmes, 1975 ). Afferent brachial arteries include the aortic arches between the ventral aorta and the gill capillaries, and the efferent brachial aorta between the gill capillaries and the dorsal aorta. The oxygenated blood then travels through a set of pulmonary veins which unite into a single vein. The now single pulmonary vein empties into the left side of the atria. Blood returning from circulation also enters the atria but via the SV, which has shifted to the right side of the heart. It is here that the oxygenated blood is partially mixed with returning deoxygenated blood from systemic circulation (Icardo et al. 2005 Bettex et al. 2014 ). The CA has become subdivided into two compartments by an intricate spiral fold (Holmes, 1975 ). The atria and ventricle are separated by the atrioventricular plug, or cushion. Lungfish have the beginning of a separation in the atria by a pulmonalis fold, and also the separation of the ventricle know as a vertical septum. Therefore, only partial mixing of the blood takes place as oxygenated blood is diverted into the aorta, whereas the deoxygenated blood is diverted back towards the gills and the lungs (Icardo et al. 2005 Bettex et al. 2014 ). In a hypoxic environment where the lungfish must rely primarily on obtaining oxygen from the air, the capillaries in the gills partially vasoconstrict, but the pulmonary vessels remain open (Bettex et al. 2014 ).
The Australian lungfish (Neoceratodus forsteri Order Ceradontiformes) is considered the most primitive of the dipnoids in that it primarily relies on its gills for respiration. The primary cardiovascular anatomical difference relative to other exclusively aquatic bony fish is the pulmonary artery, which arises from both of the six efferent brachial arteries. The African lungfish (Propterus sp. Order Lepidosireniformes) relies more on its lungs than its gills for respiration, and instead of breaking up into a network of capillaries, two of the aortic arches are carried directly to the dorsal aorta. The South American lungfish (Lepidosiren paradoxa Order Lepidosireniformes) is the most advanced, as it obtains the majority of its oxygen from the air. The efferent and afferent brachial arteries are in constant communication so that most of the blood flow bypasses the gills (which are still used for carbon dioxide excretion Holmes, 1975 ).
Relationship between blood pressure time series and ventricular dynamics of the heart - Biology
THE HEART IS NOT A PUMP:
A REFUTATION OF THE PRESSURE PROPULSION PREMISE OF HEART FUNCTION
Ralph Marinelli 1 Branko Fuerst 2 Hoyte van der Zee 3 Andrew McGinn 4 William Marinelli 5 James D. Stewart 6 Michael Duffy 7
1. Rudolf Steiner Research Center, Royal Oak, MI
2. Dept. of Anesthesiology, Albany Medical College, Albany, NY
3. Dept. of Anesthesiology and Physiology, Albany Medical College, NY
4. Cardiovascular Consultants Ltd., Minneapolis, MN. Department of Medicine, University of Minnesota, MN
5. Hennipen County Medical Center and Dept. of Medicine, University of Minnesota, MN
6. Rudolf Steiner Archive & e.Lib, Fremont, MI
7. Emerson College, UK
In 1932, Bremer of Harvard filmed the blood in the very early embryo circulating in self-propelled mode in spiralling streams before the heart was functioning. Amazingly, he was so impressed with the spiralling nature of the blood flow pattern that he failed to realize that the phenomena before him had demolished the pressure propulsion principle. Earlier in 1920, Steiner, of the Goetheanum in Switzerland had pointed out in lectures to medical doctors that the heart was not a pump forcing inert blood to move with pressure but that the blood was propelled with its own biological momentum, as can be seen in the embryo, and boosts itself with "induced" momenta from the heart. He also stated that the pressure does not cause the blood to circulate but is caused by interrupting the circulation. Experimental corroboration of Steiner's concepts in the embryo and adult is herein presented.
The fact that the heart by itself is incapable of sustaining the circulation of the blood was known to physicians of antiquity. They looked for auxiliary forces of blood movement in various types of `etherisation' and `pneumatisation' or ensoulement of the blood on its passage through the heart and lungs. With the dawn of modern science and over the past three hundred years, such concepts became untenable. The mechanistic concept of the heart as a hydraulic pump prevailed and became firmly established around the middle of the nineteenth century.
The heart, an organ weighing about three hundred grams, is supposed to `pump' some eight thousand liters of blood per day at rest and much more during activity, without fatigue. In terms of mechanical work this represents the lifting of approximately 100 pounds one mile high! In terms of capillary flow, the heart is performing an even more prodigious task of `forcing' the blood with a viscosity five times greater than that of water through millions of capillaries with diameters often smaller than the red blood cells themselves! Clearly, such claims go beyond reason and imagination. Due to the complexity of the variables involved, it has been impossible to calculate the true peripheral resistance even of a single organ, let alone of the entire peripheral circulation. Also, the concept of a centralized pressure source (the heart) generating excessive pressure at its source, so that sufficient pressure remains at the remote capillaries, is not an elegant one.
Our understanding and therapy of the key areas of cardiovascular pathophysiology, such as septic shock, hypertension and myocardial ischemia are far from complete. The impact of spending billions of dollars on cardiovascular research using an erroneous premise is enormous. In relation to this, the efforts to construct a satisfactory artificial heart have yet to bear fruit. Within the confines of contemporary biological and medical thinking, the propulsive force of the blood remains a mystery. If the heart really does not furnish the blood with the total motive force, where is the source of the auxiliary force and what is its nature? The answer to those questions will foster a new level of understanding of the phenomena of life in the biological sciences and enable physicians to rediscover the human being which, all too often, many feel they have lost.
Implicit in the notion of pressure propulsion in the cardiovascular system are the following four major concepts.
(1) Blood is naturally inert and therefore must be forced to circulate.
(2) There is a random mix of the formed particles in the blood.
(3) The cells in the blood are under pressure at all times.
(4) The blood is amorphous and is forced to fill its vessels and thereby takes on their form.
However, there are observations that challenge these notions. It is seen that the blood has its own form, the vortex, which determines rather than conforms to the shape of the vascular lumen and circulates in the embryo with its own inherent biological momentum before the heart begins to function. Just as an inert vortex in nature pulses radially and longitudinally, we tentatively assume that blood is also free to pulse and is not subject to the pulse-restricting pressure implied in the pressure propulsion concept. The blood is not propelled by pressure but by its own biological momenta boosted by the heart.
When the heart begins to function, it enhances the blood's momentum with spiraling impulses. The arteries serve a subsidiary mimical heart function by providing spiraling boosts to the circulating blood. In so doing the arteries dilate to receive the incoming blood and contract to deliver an impulse to increase the blood's momentum.
The history of the pressure propulsion premise goes back to Galileo and Leonardo da Vinci. The concept of the heart functioning as a pressure pump that forces the blood, assumed to be amorphous and inanimate, into its vessels and taking on the shape of its vessels was suggested by Borelli 1 , a student and a close friend of Galileo, who observed the spiraling heart and compared its function to wringing the water out of a wet cloth. Borelli did not confirm his conjecture with experiments but was supported by misleading drawings of the left ventricle found later in Leonardo's work. In Leonardo's Notebooks the left ventricle wall was shown to be of uniform thickness as one expects to find in a pressure chamber. (See Fig. 1-A.)
However, quite the contrary, the left ventricle wall thickness varies by about 1800%, as we found by dissecting bovine hearts. The thickness ranges from 0.23 cm in the apex to 4.3 cm in the equatorial area. The apex wall is so soft and weak that it can be pierced with the index finger. The peculiar variability in the ventricular wall thickness is not in keeping with the idea of the heart being a pressure generator. However, one could conceive of such a wall configuration as maximizing the moment inertia with no static pressure in the ventricle.The thin, flexible, cone shaped apex and suspension from the aorta suggest the accommodation of a twisting function especially, when taking into account the spiral orientation of the myocardial muscle layers2. (See Fig. 1-B.)
The rotary motion of the heart, arteries, and blood has been measured or detected by several investigators 2 , 18 , 19 . With slight variations, the erroneous sketch in Leonardo's Notebooks has been used in most biology, physiology, and medical texts during the last few hundred years as well as in most modern anatomy texts in the last decades. Thus, false sketches have served to bear witness to a false premise. (See Fig. 1-C.)
William Harvey (1578-1657) attended the University of Padua while Galileo was on its Faculty. He seemed to be deciding in favor of momentum propulsion from his own experiments focusing on the blood flow and pressure propulsion probably under the influence of Borelli who focused on heart motion. At times he implied a momentum propulsion concept: "The auricle (atria) throws the blood into the ventricle" and "the ventricle projects the moving blood into the aorta." "The blood is projected by each pulsation of the heart." At other times he used expressions that imply a pressure propulsion concept. "The heart squeezes out the blood." "The blood is forced into the aorta by contraction of the ventricle." In a few cases he speaks of the pressure of the blood. However, he also used neutral terms, "the blood is transferred, transfused, transmitted, and sent" - from place to place.
Subsequent investigators who helped to firmly establish the pressure propulsion concept were as follows: Stephen Hales (1677-1761) who inserted a glass tube into the artery of a horse and assumed that the column of blood was balanced out by static pressure. Jean-Leonard-Marie Poiseuille (1799-1869) discovered that arterial dilation was in phase with ventricular ejection. Therefore, he assumed that the dilation was the passive response to the pressure in the blood. Among other things he substituted a mercury manometer for the blood manometer of Hales. Carl Ludwig (1816-1895) invented the recording manometer by adding a float with writing pen and moving chart to Poiseuille's mercury manometer, and ushered in the age of continuous pressure recording. Finally, Scipione Riva-Rocci (1896-1903) perfected the sphygmomanometer in 1903 and brought the consideration of blood pressure into clinical practice.
The Problem and Its Proposed Solution
The problematic situation in cardiovascular physiology was expressed by Berne and Levy 3 who wrote: "The problem of treating pulsatile flow through the cardiovascular system in precise mathematical terms is virtually insuperable." A fundamental aspect of this problem relates to the fact that the major portion of our knowledge of cardiac dynamics has been deduced from pressure curves. In fact our knowledge of the system has two independent sources: experimentally determined facts and logically deduced concepts from the pressure propulsion premise. The situation is so confusing that some life scientists are considering chaos theory and mathematics to try to find the order in the system. It will be shown that the chaos derives from a mix of facts and conjectures and not from the nature of the phenomenon itself.
It is our purpose to demonstrate that Borelli's premise is incorrect and to propose the concept that the blood is propelled by a unique form of momentum. First, the aortic arch does not respond as expected if the blood in it were under pressure. The aorta is a curved tube as such it has the basic form of the widely used pressure sensitive element of the Bourdon tube gage * .
When the curved tube of the Bourdon gage is subject to positive pressure, it is forced to straighten out as one sees in a garden hose. When subject to a negative pressure, the tube's curvature is increased. During the systolic ejection (period when blood is ejected from ventricle), the aorta's curvature is seen to increase, signifying that the aorta is not undergoing a positive pressure, but rather is undergoing a negative pressure 4 .
We demonstrate that this negative pressure is that associated with the vacuum center of traveling vortices of blood. Thus the motion of the aorta, when considered as nature's own pressure sensor, contradicts the pressure propulsion premise. Of course, the swirling streams of the vortex have potential pressure, so any attempt to measure pressure will result in a positive pressure reading due to interrupted momenta.
Movement without applied pressure is movement with momentum, as we observe so dramatically in the long leaps of racing cats. It is also manifest in nature in flowing water in open streams, traveling tornadoes, and jet streams which are actually horizontal spirals of air and moisture that can be thousands of miles long and move around like meandering rivers in the upper atmosphere. A thrown ball in its trajectory also moves without pressure.
What about the measured blood pressure? The concept under consideration here is the well known ratio of force to area:
pressure = force/area (force per unit area)
The pressure is an arithmetical ratio derived from the average force of the moving blood, and as such, indicates the phenomenon of the moving blood indirectly. In a momentum system the pressure is a potential while the object is in motion and becomes manifest when the velocity is impeded:
momentum (mass x velocity) = impulse (force x time)
The blood moves with various velocities in its vortex streams. At the moment of impact of an object moving with momentum, the velocity decreases while the pressure of a certain magnitude appears.
Rudolf Steiner, scientist and philosopher, pointed out on several occasions that the blood moves autonomously 5 , and that the pressure is not the cause of blood flow but the result of it 6 . The clinicians of old used elaborate methods of describing the nature of the arterial pulse and the ictus cordis or the apex beat, which is the impulse of the heart against the chest wall. Many descriptive terms such as thready pulse of hypovolemic shock, collapsing or water-hammer pulse of aortic incompetence and `heaving' apical impulse of left ventricular hypertrophy, convey the intuitive understanding of the real mechanism of the heart's action.
An attempt to characterize left ventricular function by indices such as the maximal velocity of contraction (V max ) and the maximum change of left ventricular pressure with time (dP/dt max ) suggests the felt inadequacy of the simple pressure propulsion concept.
When fluid mass is subject to force in the form of a pressure, it will first resist movement because of its inertia and viscosity. In a pressure driven system the pressure rises faster than the fluid moves the pressure will peak before the fluid velocity peaks. However, when one simultaneously measures pressure and flow in the aorta, the peak flow markedly precedes the peak pressure. This phenomenon was observed as early as 1860 by Chauveau and Lortet and, as reported by McDonald 7 , it contradicts the law of inertia in the pressure propulsion concept. (See Fig. 2.) While this phase relationship actually confirms the momentum propulsion principle, it nevertheless remained a source of conjecture for a considerable period of time in the 1950s until it was `rescued' with the help of elaborate mathematical modeling for oscillating flow.
An observation in favor of the concept of the blood having its own momentum was reported by Noble 8 in 1968. By simultaneous pressure measurements in the left ventricle and the root of the aorta of a dog, he demonstrated that the pressure in the left ventricle exceeds the aortic pressure only during the first half of the systole and that the aortic pressure is actually higher during the second half. He found it paradoxical that the ejected blood from the ventricle continues into the aorta despite the positive pressure gradient. The erroneous concept of left ventricular pressure exceeding the aortic pressure during entire systole proposed by Wiggers in 1928 is still depicted in many modern texts of physiology. (See Fig. 3A and B.) Noble proposed that this type of pressure pattern could be a result of momentum flow however, this idea was overshadowed by the edifice of pressure propulsion.
The concept of pressure propulsion sent physiologists and scientists from diverse fields on a crusade that resulted in numerous hypotheses and theories about the cardiovascular system mechanics. The saying that, "fluid dynamists in the nineteenth century were divided into hydraulic engineers who observed what could not be explained and mathematicians who explained things that could not be observed," still stands true to this very day.
Steiner 6 indicated that embryology provides the clues for solving the problem of the circulation. In relation to this, Bremer 9 performed a remarkable series of observations of blood circulation in the very early chick embryo before the formation of the heart valves. He described the two streams of spiraling blood with different forward velocities in the single tube stage heart. Nevertheless, the blood is noted to have a definite direction of flow within the conduits and moves without an apparent propelling mechanism.These streams spiral around their own longitudinal axes and around each other. The streams appear to be a considerable distance apart, do not fill their vessels, and appear to be in discontinuous segments.
In a movie made by Bremer of the beating embryonic heart, one observes that the spiraling blood is boosted by the pulsating heart without creating turbulence in the blood. This suggests that the momentum transfer occurring between the heart and blood is in phase the heart must somehow sense the motion of the blood and respond to it in turn with a spiraling impulses at the same velocities as the blood, thereby combining blood and heart momenta.
It is assumed that heart muscle layers have the same velocity distribution pattern as the concentric streams of a free vortex to enable heart and blood motions to couple in multi-velocity phase. It was significant to observe that the movement of the heart occurred with minimal inward motion of the heart wall. That the streaming of the blood can be observed before the functioning of the heart is supported by observations that the circulation in the early chick embryo is maintained for around 10 minutes after the heart had been excised 10 . Moreover, the inherent mobility of the blood was highlighted by Pomerance and Davies 11 , who found an embryo that lived to term without a heart but was born dead and grossly disfigured. Thus, the composite view of the embryonic cardiovascular system tells us that the blood is not propelled by pressure, but rather moves with its own biological momentum and with its own intrinsic flow pattern.
Alternations of Liquid and Gas Vortices in the Blood
The existence of apparently empty space between and within the spiraling liquid stream can be explained as space filled with gas or vapor. However, this hypothesis appears absurd when considering that even small bubbles in the arterial side of circulation can result in significant embolism. Each 100 cm of arterial blood contains 0.3 ml of free physically dissolved oxygen, 2.6 ml of carbon dioxide and 1 ml of nitrogen.
The importance of the small amount of dissolved oxygen is recognized only in extreme cases of anemia when it becomes a significant alternative source of tissue oxygenation. When viewed in terms of a highly differentiated distribution of solid, liquid and vapor/gas components of the composite vortex, this amount of free gas assumes critical importance.
The fact that the gas is elusive in the escaping liquid blood is very much in accord with the finding that the blood, as individualized liquid and gas vortices, moves with pressure-free momentum. The vortex in tornadoes is a very stable cohesive configuration with a vacuum center strongly held together by a centripetal force system. It does not have the physical properties of amorphous gas under pressure that tends to expand.
To further elucidate our observations, we contrived a model ventricle with a sealed, inverted cone-shaped, 0.5 liter clear glass flask filled with water. The instrumentation consisted of installing two tubes within the flask connected to pressure transducers to record vacuum in the vortex center and the potential pressure impulse in the momentum of the swirling water. The signal of pressure versus time was displayed on the oscilloscope screen and also fed to the computer for further analysis. The `ventricle' was operated by holding it in the hand and giving it a wobble and twist simultaneously to create a vortex. To enhance visibility, we filled the canister with methylene blue colored water.
Even the most energetic operation resulted in virtually no motion of the water. With some experimenting we determined that unless the model ventricle had about 1/3 of its volume as air space, a vortex could not be formed. This led us to reason that the highly organized gas/rarified plasma is a necessary component of the blood vortex. This also raises the question of how the gas and fluid elements can express the life property of locomotion.
The idea of the composite blood cells-plasma-gas vortex is in accord with the `gaps' in the flow of the embryonic vessels. To evaluate how valid our model ventricle was, we measured its potential impulse pressure (blood pressure as it is typically measured) in the swirling water and the vacuum in its center and found them to be in the range of +130 to -180 mm Hg, respectively. (See Fig. 4.)
Furthermore, we constructed a glass `ventricle' with an attached `aorta' and showed that up to 50% of the volume of the liquid could be ejected by subjecting it to a rotary-wobbling impulse, without the inward motion of the `ventricular' wall.
A Well Known Vortex Function
It is well known that the pattern of blood flow through the heart significantly contributes to heart valve dynamics as has been shown by several studies utilizing contrast cineradiography and more recently color Doppler imaging. Taylor and Wade 12 confirmed stable vortex flow patterns behind the cusps of mitral and tricuspid valves visualizing the fine stream contrast injection. Furthermore, the vortex formation in the aortic sinus has not only been demonstrated in the model heart, but also visualized with three-directional magnetic resonance velocity mapping 13 . Without the vortex formation in the aortic sinus, it is conceivable that with the blood rushing out of the left ventricular outflow tract at one to two meters per second, the coronary arteries would be ill perfused, as is the case in severe aortic stenosis (narrowing), where high velocity blood flow does not allow for formation of the normal supravalvular vortices.
Evidence of Momentum Flow in the Adult
Not only is the blood flow well maintained in the embryo before the formation of the valves there are reports of adults in whom both infected tricuspid and pulmonary valves were surgically removed and not replaced by prosthetic valves, without significant problems 14 . Werner et al. 15 using two dimensional echocardiography observed that the mitral and aortic valves were open during external chest compression and that cardiac chambers were passive and did not change in size.
The Perpetual Vortex in the Ventricle
The widely used technique of cardiac output measurement using the thermodilution method is fraught with significant deviations of individual measurements. This technique is based on the principle of warm blood mixing with the bolus of cold saline in the ventricle and detecting the rise in temperature of the resulting mixture in the pulmonary artery. A final value is obtained by averaging the results of several measurements.
By measuring electrical conductivity at various locations in the left ventricle of a dog, Irisawa 16 was unable to show uniform mixing of saline. The conductivity records showed the swirling streams of blood of different concentrations of saline within the ventricles during systole and diastole (the dilation or expansion stage of the heart muscles that allows the heart cavities to fill with blood), further supporting the concept of the highly organized vortical patterns inside the chambers of the heart.
Brecher 17 conducted an experiment on a dog that demonstrated a region of continuous negative pressure in the ventricle by observing the continuous flow of Ringer's solution from a vessel outside the heart through a cannula positioned in the left ventricle via the atrial auricle. This further confirms our concept of the persistence of the vortex in the ventricle with its negative pressure center and positive pressure impulse potential in its swirling periphery throughout the cardiac cycle. Thus the heart as a minimum functional organ consists not only of its tissue but also of the perpetual vortex of blood which provides the perpetual vacuum in its center that probably helps to pull the blood back to the heart from capillaries and veins. The persistence of the vortex explains the anomaly to engineers of a supposed pump that retains 40 % of its charge with each ejection a pump is expected to eject close to 100 % of its charge. As a pump concept it is absurd as presented herein it is ingenious. Pettigrew 2 found three columns of spiraling blood in the left ventricle.
Orbiting Blood Corpuscles
In contrast to the parabolic velocity profile assumed by small particle suspensions in rigid tubes of small diameter under pressure, the cellular elements in the blood arrange themselves in a flow pattern in vivo, such that the heavier red blood cells orbit nearest the center with lighter platelets in more distant orbits surrounded by a sleeve of plasma at the vessel wall. Such an ordered arrangement of blood particle configuration in a sectional view of the arteries denies an omnidirectional pressure propulsion mechanism and confirms the vortex/momenta premise.
One can demonstrate this phenomenon of differentiation by mass in the vortex by allowing spheres chosen for convenience, same size (3 mm diameter), differently colored for different weight, to swirl freely in water. It will be seen that the heaviest spheres orbit nearest the center of rotation. The vortex orbital velocities increase as the orbits approach the center of rotation. On the contrary, during the time that a force couple is applied to rotate the vessel, creating a forced vortex, all of the spheres are forced out to the periphery where the velocities are the greatest as in a centrifuge.
To further confirm the existence of the free vortex velocity pattern in vivo, we probed the blood flow in the carotid artery by positioning a Doppler transducer at 900 to the wall to sense the blood's swirling motion and processed the Doppler echoes through a variable band pass filter looking for frequency (velocity) distribution patterns. We detected echoes from groupings of particles at 400 to 650 Hz, 650 to 900 Hz and below 200 Hz Doppler-shifted frequencies. These three groupings indicate three separate orbital regions and velocities. Preliminary observations point to a highly ordered distribution of the blood's cellular and plasma components.
Also, when moving through larger arteries the red cells are in toroidal shape, with their mass at the periphery to maximize the moment of inertia, and are assumed to rotate about their individual axes due to the phenomenon of vorticity (the creation of micro-vortices between swirling layers in the main vortex moving at different velocities). Thus we can expect to find that the billions of red cells are actually traveling in their own unique space as further evidence of the extreme order of the blood motion.
The spiral theme is also apparent in the heart and vessel form and function. The musculature of the heart and arteries all the way down to the pre-capillaries is spirally oriented, and both the heart and arteries move spirally to augment the momenta of the blood 2 , (18) , 19 . The literature on anatomical and physiological considerations of the twisting motion of the heart and vessels is comprehensive and has recently been reviewed 2 . The fact that arterial endothelial cell orientation closely follows the blood flow patterns is well established 18 , (19) .
In a group of patients undergoing reconstructive vascular surgery of the lower extremities, Stonebridge and Brophy observed by direct angioscopic examination that the inner surface of arteries was organized in a series of spiral folds that sometimes protruded into the lumina. They commented that the folds occur as a result of spiral blood flow, which may be more efficient, requiring less energy to drive the blood through tapering and branching arterial system 19 . They also observed the vortexing blood with fiber optics in the region of the endoluminal folds. In relation to this, enthusiasts know that rifled gun barrels forcing spin on the bullet make it more stable in flight and therefore more accurate in reaching its target. In the vessels the blood "grooves" its own conduits for the purpose of enhancing its torsional impulse. However, these spiral folds are not found in excised arteries they are dynamics of living tissue.
The autonomic vortex movement of the blood discussed herein is inherent to the blood motion. It is not an accidental local disturbance often explained as turbulence or eddy currents, nor a localized phenomena with a single functional purpose as in heart valve dynamics. From a broader view it is to be expected that blood should so move, considering that fluids in nature tend to move curvilinearly, which is their path of least energy. The extreme expression of this tendency in nature, in terms of order, stability and minimal expenditure of energy are tornados and "jet" streams.
Potential Clinical Consequences
These observations should foster an accelerated understanding of the cardiovascular system through a reexamination of the vast amount of valuable experimental data gathered world wide. Since we have observed that the blood has a highly ordered dynamic form and an ordered blood corpuscle motion, and orientation, we should be able to develop devices and techniques to detect small deviations from group and individual norms and thus form a basis for very early diagnosis of cardiovascular disease, which remains the number one cause of death in the U.S. Novel, more effective therapies for cardiovascular disease hopefully will also evolve from this new perspective on cardiovascular physiology.
* The Bourdon tube gage is named after its inventor, Bourdon. Its pressure sensitive element consists of a circularly bent tube that is flattened to increase its sensitivity to pressure. When the tube is subjected to an internal positive pressure it tends to straighten when subjected to an internal negative pressure its radius of curvature is increased. The deformation of the tube is proportional to the pressure and is transmitted via links and gears to motions that turn a pointer on a scale calibrated to indicate pressure.
We thank Larry W. Stephenson, M.D., Chief of Cardiothoracic Surgery, Wayne State University School of Medicine, and Beverly Rubik, Ph.D., for their comments on this work.
1. Borelli, De Motu Animalium. Rome, 1681.
2. Marinelli, R., Penney, D.G., et al. 1991. Rotary motion in the heart and blood vessels: a review. Journal of Applied Cardiology 6: 421-431.
3. Berne, R., Levy, M., 1986. Cardiovascular Physiology. St. Louis, MO: C.V. Mossy Co., p. 105.
4. Rushmer, R.F., D.K. Crystal. 1951. Changes in configuration of the ventricular chambers during cardiac cycle. Circulation 4: 211-218.
5. Steiner, R., 1990. Psychoanalysis and Spiritual Psychology. Hudson, NY: Anthroposophic Press, p. 126.
6. Steiner, R., 1920. Spiritual Science and Medicine. London, England: Rudolf Steiner Press, 24-25.
7. McDonald, D.,1952. The velocity of blood flow in the rabbit aorta studied with high speed cinematography. Journal of Physiology 118: 328-329.
8. Noble, M.I., 1968. The contribution of blood momentum to left ventricular ejection in dog. Circulation Res. 26: 663-670.
9. Bremer, J. 1932. Presence and influence of spiral streams in the heart of the chick embryo. American Journal of Anatomy, 49: 409-440.
10. Manteuffel-Szoege, L., 1969. Remarks on blood flow. J. of Cardiovasc. Surg. 10: 22-30.
11. Pomerance, A., Davies, M. 1975. Pathology of the Heart London, England: Blackwell Scientific Publications, pp. 538-39.
12. Taylor, D.E.M., J.D. Wade. 1973. Pattern of blood flow in the heart. Cardiovascular Research 7:14-21.
13. Kilner P.J., Z. Y. Guang, et al. 1993. Helical and retrograde secondary flow patterns in the aortic arch studied by three-directional magnetic velocity mapping. Circulation 88: 2235-2247.
14. Arbulu, A., I. Asfaw. 1981. Tricuspid valvulectomy without prosthetic replacement. J. Thorac Cardiovasc Surg 82: 684-691.