Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

Background  

Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow.     

Functional measurements based on feature tracking of cine magnetic resonance images identify left ventricular segments with myocardial scar

Background

New sensors for intelligent remote monitoring of the heart should be developed. Recently, a cutaneous force-frequency relation recording system has been validated based on heart sound amplitude and timing variations at increasing heart rates.

Aim

To assess sensor-based post-exercise contractility, diastolic function and pressure in normal and diseased hearts as a model of a wireless telemedicine system.

Methods

We enrolled 150 patients and 22 controls referred for exercise-stress echocardiography, age 55 ± 18 years. The sensor was attached in the precordial region by an ECG electrode. Stress and recovery contractility were derived by first heart sound amplitude vibration changes; diastolic times were acquired continuously. Systemic pressure changes were quantitatively documented by second heart sound recording.

Results

Interpretable sensor recordings were obtained in all patients (feasibility = 100%). Post-exercise contractility overshoot (defined as increase > 10% of recovery contractility vs exercise value) was more frequent in patients than controls (27% vs 8%, p < 0.05). At 100 bpm stress heart rate, systolic/diastolic time ratio (normal, < 1) was > 1 in 20 patients and in none of the controls (p < 0.01); at recovery systolic/diastolic ratio was > 1 in only 3 patients (p < 0.01 vs stress). Post-exercise reduced arterial pressure was sensed.

Conclusion

Post-exercise contractility, diastolic time and pressure changes can be continuously measured by a cutaneous sensor. Heart disease affects not only exercise systolic performance, but also post-exercise recovery, diastolic time intervals and blood pressure changes – in our study, all of these were monitored by a non-invasive wearable sensor.     

Hemodynamic and therapeutic effects of intravenous dopamine

The effects of intravenous dopamine were evaluated in 10 patients with severe but stable coronary artery disease, 17 consecutive patients with primary cardiogenic shock and 3 with severe congestive heart failure and oliguria. Dopamine infusion at 10 μg/kg·min in the 10 patients increased cardiac output by 35%, left ventricular peak dP/dt by 38%, left ventricular minute work index by 44% and mean systolic ejection rate by 7% (P < 0.01); heart rate, aortic pressure, left ventricular end-diastolic pressure and tension-time index were unchanged. For oxygen, potassium and lactate, arterial and coronary sinus values, coronary arteriovenous oxygen differences and myocardial extraction were unchanged. Hemodynamically 13 of the 17 patients in shock responded favourably to dopamine infusion (0.5 to 15 μg/kg·min), with decrease in heart rate, increase in systolic arterial pressure from 75 to 100 mm Hg (P <0.001), decrease in ventricular filling pressure from 20 to 16 mm Hg (P < 0.01) and increase in urine output from 10 to 100 ml/h (P < 0.01). Eleven of those patients survived the shock episode. A close relation was observed between the hemodynamic response to dopamine, survival from the shock episode and the time between onset of shock and initiation of therapy. Low rates of dopamine infusion induced diuresis in the three patients with severe cardiac failure.Dopamine thus seems to improve the mechanical efficiency of the heart in coronary artery disease. Cardiac output is selectively increased and myocardial ischemia does not appear to be induced; those beneficial effects as well as presumably specific action on renal flow and natriuresis, improve immediate survival from cardiogenic shock and severe heart failure.     

Theoretical analysis of rest and exercise hemodynamics in patients with total cavopulmonary connection

The objective of this study was to determine the impact of a total cavopulmonary connection on the main hemodynamic quantities, both at rest and during exercise, when compared with normal biventricular circulation. The analysis was performed by means of a mathematical model of the cardiovascular system. The model incorporates the main parameters of systemic and pulmonary circulation, the pulsating heart, and the action of arterial and cardiopulmonary baroreflex mechanisms. Furthermore, the effect of changes in intrathoracic pressure on venous return is also incorporated. Finally, the response to moderate dynamic exercise is simulated, including the effect of a central command, local metabolic vasodilation, and the "muscle pump" mechanism. Simulations of resting conditions indicate that the action of baroreflex regulatory mechanisms alone can only partially compensate for the absence of the right heart. Cardiac output and mean systemic arterial pressure at rest show a large decrease compared with the normal subject. More acceptable hemodynamic quantity values are obtained by combining the action of regulatory mechanisms with a chronic change in parameters affecting mean filling pressure. With such changes assumed, simulations of the response to moderate exercise show that univentricular circulation exhibits a poor capacity to increase cardiac output and to sustain aerobic metabolism, especially when the oxygen consumption rate is increased above 1.2-1.3 l/min. The model ascribes the poor response to exercise in these patients to the incapacity to sustain venous return caused by the high resistance to venous return and/or to exhaustion of volume compensation reserve.     

Right ventricular function in acute myocardial ischaemia

A haemodynamic examination of 10 dogs was carried out at rest, during volume loading and after ligation of the right coronary artery in the presence of a closed pericardium. Ligation of the right coronary artery led to haemodynamic signs of depression of right ventricular function--a drop in systolic pressure and an increase in end diastolic pressure, together with a shift of the functional curve to the right and downwards. Overall performance of the heart (cardiac output and the mean systemic pressure, also fell. Our results show that the depression of the systolic function of the myocardium in the presence of right ventricular infarction can be an important factor in the genesis of low cardiac output syndrome observed in clinical situations. Its pathophysiological mechanisms and some of the clinical consequences are discussed.     

Atrioventricular nonuniformity of pericardial constraint

Physiologists and clinicians commonly refer to "pressure" as a measure of the constraining effects of the pericardium; however, "pericardial pressure" is really a local measurement of epicardial radial stress. During diastole, from the bottom of the y descent to the beginning of the a wave, pericardial pressure over the right atrium (P(pRA)) is approximately equal to that over the right ventricle (P(pRV)). However, in systole, during the interval between the bottom of the x descent and the peak of the v wave, these two pericardial pressures appear to be completely decoupled in that P(pRV) decreases, whereas P(pRA) remains constant or increases. This decoupling indicates considerable mechanical independence between the RA and RV during systole. That is, RV systolic emptying lowers P(pRV), but P(pRA) continues to increase, suggesting that the relation of the pericardium to the RA must allow effective constraint, even though the pericardium over the RV is simultaneously slack. In conclusion, we measured the pericardial pressure responsible for the previously reported nonuniformity of pericardial strain. P(pRA) and P(pRV) are closely coupled during diastole, but during systole they become decoupled. Systolic nonuniformity of pericardial constraint may augment the atrioventricular valve-opening pressure gradient in early diastole and, so, affect ventricular filling.     

Assessment of haemodynamic changes and acid-base equilibrium during hypovolaemia and after infusion of plasma substitutes in dogs

The following haemodynamic values were determined in anaesthetized mongrel dogs: heart rate, systolic blood pressure in the ascending aorta, left ventricular pressure at the peak dp/dt, left ventricular end-diastolic pressure, time interval from Q in ECG to the onset of the systolic wave of dp/dt, time interval from Q in ECG to peak dp/dt, maximum rate of left ventricular pressure rise, femoral arterial flow, and certain indices of left ventricular contractility. It was concluded from the results of these experiments that infusion of a modified gelatin solution Fluigel prevented haemodynamic and metabolic changes produced by experimental hypovolaemia more effectively than infusion of Plasmagel.     

Haemodynamics in the first seconds after coronary artery occlusion.

The changes in cardiac and in total haemodynamics, occurring during the first seconds of occlusion and the subsequent desocclusion of coronary arteries were studied on 28 dogs. The most intensive changes were observed after the trunk occlusion of the left coronary artery. Simultaneously with decreasing blood inflow into the myocardium its contractility and the systolic pressure in the left ventricle and the outflow from the coronary sinus began to fall rapidly. The systolic pressure in the left ventricle decreased within the first 10 s from 24 to 13-15 kPa (180 to 100-110 mm Hg), which means that the systolic pressure fell about 1 kPa (7-8 mm Hg) per second, or 0.5-0.6 kPa (4-5 mm Hg) per systole. At the same time the end-diastolic pressure in the left ventricle also increased from zero to 3-4 kPa (25-30 mm Hg). After the trunk desocclusion of the left coronary artery the systolic pressure in the left ventricle proceeded to fall by about 2-3 kPa (15-22 mm Hg). Only then, 20-25 s after the desocclusion, blood flow in the left coronary artery began to rise intensively and 4-6 s later the myocardial contractility and the systolic pressure in the left ventricle also increased. After unclamping (50-60 s), there was an overshoot of haemodynamic values above preocclusive values and then followed the compensatory phase. This phase lasted 80-90 s and on its peak the pressure and flow parameters increased by about 50-60% above preocclusive values. During the occlusion of ramus interventricularis anterior or ramus circumflexus for 30-60 s the haemodynamic parameters changed only slightly. The same was observed during trunk occlusion of the right coronary artery (30-60 s), but in that case many extrasystoles occurred.     

Haemodynamic effects of intravenous morphine in patients with acute myocardial infarction complicated by severe left ventricular failure.

The haemodynamic effects of intravenous morphine sulphate (0.2 mg/kg body weight) were measured in 10 patients with acute myocardial infarction complicated by severe left ventricular failure. Fifteen minutes after morphine injection there was a significant fall in mean heart rate (from 109 to 101 beats/min) and mean systemic arterial pressure (from 80 to 65 mm HG), and a small fall in mean cardiac index (from 2.4 to 2.21/min/m2). Haemodynamic changes at 45 minutes were similar. Neither stroke index nor indirect left ventricular filling pressure (measured as pulmonary artery end-diastolic pressure) were consistently improved 15 or 45 minutes after injection. The useful action of morphine in relieving distressing cardiac dyspnoea is not adequately explained by systemic venous blood pooling. These results suggest that the effects of morphine on the central nervous system are more important.     

Effects of nitric oxide synthesis inhibition with or without nitric oxide inhalation on responses to systemic cocaine administration in rats

The effects of N^ω-nitro-L-arginine methyl ester (L-NAME) i.v. and nitric oxide (NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats. Cocaine (4 mg/kg/min i.v.) produced seizures then isoelectric electrocephalographic (isoEEG) activity as well as an initial increase in systolic blood pressure and heart rate, then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME (2 mg/kg/min i.v.) for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8). Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. NO inhalation (80 ppm) did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular system (lower dose for arrhythmias and asystole), but does not affect the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.     

Control and interaction of the cardiovascular and respiratory systems in anuran amphibians

In anuran amphibians, respiratory rhythm is generated within the central nervous system (CNS) and is modulated by chemo- and mechanoreceptors located in the vascular system and within the CNS. The site for central respiratory rhythmogenesis and the role of various neurotransmitters and neuromodulators is described. Ventilatory air flow is generated by a positive pressure, buccal force pump driven by efferent motor output from cranial nerves. The vagus (cranial nerve X) also controls heart rate and pulmocutaneous arterial resistance that, in turn, affect cardiac shunts within the undivided anuran ventricle; however, little is known about the control of central vagal motor outflow to the heart and pulmocutaneous artery. Anatomical evidence indicates a close proximity of the centers responsible for respiratory rhythmogenesis and the vagal motoneurons involved in cardiovascular regulation. Furthermore, anurans in which phasic feedback from chemo- and mechanoreceptors is prevented by artificial ventilation exhibit cardiorespiratory interactions that appear similar to those of conscious animals. These observations indicate interactions between respiratory and cardiovascular centers within the CNS. Thus, like mammals and other air-breathing vertebrates, the cardio-respiratory interactions in anurans result from both feedback and feed-forward mechanisms.     

Can changes in sarcolemmal membranes account for the altered inotropic responsiveness in hypertrophied heart?

Hypertrophy is an adaptive mechanism of the heart subjected to pressure overload. Ultrastructural, electrophysiological and mechanical changes occur during this adaptation. A decrease in the inotropic responsiveness of the hypertrophied heart has often been observed as compared to the normal heart. Four sarcolemmal mechanisms that could account for this modification have been described. The mechanism of action of each system (calcium channel, alpha-and beta-adrenergic systems, (Na+,K+)-ATPase) of the hypertrophied heart has been compared to that of the normal heart. In spite of the paucity of results available relating to the calcium channel, the lengthening of the action potential in every case of compensatory hypertrophy could be explained by an altered functioning of the calcium channel. alpha- and beta-adrenergic systems in the hypertrophied heart could be modified at the receptor level itself, or at another level in the cascade of events under their control. For example, two different models of hypertrophy showed a decreased inotropic responsiveness correlated to a defect in the GS regulatory protein. The modification of the ouabain-receptor (Na+,K+)-ATPase mediates a decrease and a prolongation of the inotropic response. According to the modifications of each system, a direct relationship does not seem to exist between the stimulated membrane system and the inotropic responsiveness of the hypertrophied heart.     

Effects of atropine and propranolol on the respiratory, circulatory, and ECG responses to high altitude in man

In order to analyze the respiratory, cardiovascular, and ECG responses to acute hypoxic hypoxia, three experimental series were carried out in a randomized manner on 11 healthy, unacclimatized volunteers at rest during standardized stepwise exposure to 6000 m (PAO2 35.2 +/- 2.9 mmHg/4.7 +/- 0.4 kPa) in a low-pressure chamber a) without (control), b) with propranolol, and c) with atropine combined with propranolol. The results show that hypoxic hyperventilation and alveolar gases are not affected by activation of the sympatho-adrenal axis or by parasympathetic withdrawal. Sympathetic activity, however, increases heart rate, stroke volume (pulse pressure), estimated cardiac output and systolic blood pressure, whereas decreased parasympathetic activity increases heart rate and estimated cardiac output, but lowers stroke volume. The fall in peripheral resistance, observed during progressive hypoxia in all three groups, is thought to be due to hypoxia-induced depression of the vasomotor center. At altitude catecholamine secretion and vagal withdrawal synergistically account in the ECG for the R-R shortening, the relative Q-T lengthening, the elevation of the P wave and the ST-T flattening. Probable direct hypoxic effects on the heart are the increase in P-Q duration and the minor but still significant depression of the T wave. It is concluded that at altitude increased sympatho-adrenal and decreased parasympathetic activity is without effect on hypoxic hyperventilation, but accounts for most of the cardiovascular and ECG changes. Diminution of sympathetic activity and imminent vagotonia arising after acute ascent to 6000 m probably reflect hypoxia of the central nervous system.     

Difference of arterial pressure regulatory mechanism between awake and anesthetized human subjects

This experiment was conducted to clarify difference of arterial pressure regulatory mechanism between awake and anesthetized human subjects. In 18 subjects who were scheduled for surgical operations, passive tilting test was performed both in awake and anesthetized conditions. Arterial pressure and heart rate were measured during four types of tilting test, i.e., 1. supine-10 degrees head down tilt 2. 10 degrees head down tilt-supine 3. supine-10 degrees head up tilt 4. 10 degrees head up tilt-supine. Relative changes in arterial pressure and heart rate in response to these four tilting tests were compared. After postural changes, all anesthetized subjects showed significant arterial pressure changes followed by restoration of arterial pressure towards control level with opposite changes of heart rate. This initial arterial pressure changes were mainly induced by shift of blood due to gravity and subsequent arterial pressure and heart rate changes were mainly by baro-receptor reflex. On the other hand, awake subjects showed transient increase of heart rate immediately after tilting followed by arterial pressure rise 2 to 3 seconds later in all four tilting tests. However, arterial pressure did not change so remarkably as in anesthetized condition and remained almost constant during tilting test. In awake subjects, their arterial pressure was regulated rapidly and reflex control of arterial pressure was masked. This rapid regulation of arterial pressure may be induced directly by higher central nervous system.     

Extracardiac versus cardiac haemocoelic pulsations in pupae of the mealworm (Tenebrio molitor L.)

Pulsations in mechanical pressure of the pupal haemocoele were investigated by means of simultaneous recording from multiple sensors. It has been determined that cardiac and extracardiac haemocoelic pulsations are each regulated by substantially different and quite independent physiological mechanisms. At the beginning and in the middle of the pupal interecdysial period the anterograde heartbeat and extracardiac pulsations occur in similar, but not identical periods. During the advanced pharate adult stage, there appear almost uninterrupted pulsations from different sources: cardiac, extracardiac, intestinal, and the ventral diaphragm.Extracardiac pulsations are associated with pressure peaks of 200-500 Pa, occurring at frequencies of 0.3-0.5 Hz. The effect of heartbeat on haemocoelic pressure is very small, 100- to 500-fold smaller, comprising only some 1 or 2 Pa during the vigorous anterograde systolic contractions. Accordingly, extracardiac pulsations are associated with relatively large abdominal movements from 30-90 μm whereas heartbeat produces movements of only 100-500 nm. This shows that extracardiac pulsations can be easily confused with the anterograde heartbeat. It does not seem realistic to assume that the relatively weak insect heart, and not the 100- to 500-fold more powerful extracardiac system of abdominal pump, could be at all responsible for selective accumulation of haemolymph in anterior parts of the body, for inflation of wings or enhancement of tracheal ventilation.It has been established that thermography from the pericardial region is not specific for the heartbeat. It records subepidermal movement of haemolymph resulting from the actions of both dorsal vessel and extracardiac pressure pulses as well. Shortly before adult eclosion the cardiac and extracardiac pulsations occasionally strike in concert, which profoundly increases the flow of haemolymph through pericardial and perineural sinuses. The relatively strong extracardiac pulsations cause passive movements of various visceral organs, tissue membranes, or tissue folds, giving thus a false impression of an authentic pulsation of tissues. In addition, extracardiac pulsations cause rhythmical movements of haemolymph between various organs, thus preventing haemolymph occlusion at the sites where the heart does not reach. It has been emphasized, finally, that the function of the autonomic nervous system (coelopulse), which integrates extracardiac pulsations, depends on homeostatic moderation of excessive or deficient conditions in insect respiration and haemolymph circulation.     

The effects of a glycerin-based blood analog on the testing of bioprosthetic heart valves

Detailed comparisons of aortic valvular flow using saline, with that using a glycerin-based blood analog in a pulse duplicator are reported. The experiments were carried out to determine whether exposure to glycerin caused stiffening of bioprosthetic valve leaflets. For two pericardial bioprostheses and for a mechanical valve we observed a fluid-dependent systolic volume flow, a fluid-dependent regurgitation volume, and fluid-dependent systolic pressure differences. Volume flow changes, both forward and reverse, are independent of valve type. The observed pressure differences, while proportional to fluid density for the mechanical valve, are fluid dependent in a more complicated way for the pericardial valves. However, no trend of changing valvular performance was observed over as much as 80 days of glycerin exposure, indicating that it is unlikely that the fluid-dependent performance was caused by glycerin absorption by the valve leaflets. We conclude that valid performance comparisons between mechanical and bioprosthetic valves may be made using a glycerin-based fluid. Furthermore, it appears that any detailed analysis of the physical mechanisms of valvular flow dissipation will require a properly matched blood analog.     

Proctolin affects the activity of the cardiac ganglion, myocardium, and cardioarterial valves in Carcinus maenas hearts

The decapod crustacean heartbeat is initiated by the cardiac ganglion and is regulated by a variety of neuronal and hormonal inputs. In this paper we examine the effects of the peptide hormone proctolin which appears to have multiple sites of action in the shore crab, Carcinus maenas. To examine some of the potential sites of proctolin action we used three heart preparations: in situ intact and open hearts, and isolated hearts. We provide evidence in support of the hypothesis that proctolin affects cardiac activity at many levels. It acts at the cardiac ganglion to modulate burst rate and at the myocardium to alter contractile force. We calculated the relationship between contractility and ganglionic output of in situ hearts as the ratio of ventricular pressure or tension to amplitude of the electromyogram or intracellular excitatory junction potential. Large proctolin-induced changes in this ratio, which could not be accounted for by ganglionic output, membrane potential or input resistance suggest direct action on the myocardium. The greater increases in ventricular pressure than in tension in the in situ hearts may reflect proctolin-induced contraction of the cardioarterial valves. Finally, proctolin can possibly influence heart rate by action on the cardioregulatory nerves of the central nervous system. Accepted: 11 May 1998     

Regression of cardiac hypertrophy with drug treatment in spontaneously hypertensive rats

Left ventricular hypertrophy is an important complication of essential hypertension. Some antihypertensive drugs have been shown to allow regression of cardiac hypertrophy, both in spontaneously hypertensive rats and in hypertensive patients. Recent results show that the agents which interfere with the functions of the sympathetic nervous system, converting enzyme inhibitors and calcium antagonists are effective in reducing arterial blood pressure and regression of left ventricular hypertrophy. The use of vasodilators and diuretics may under certain circumstances, however, even exacerbate cardiac hypertrophy. Regression of left ventricular hypertrophy in hypertension does not appear to depend solely on reduction of arterial blood pressure. Other factors seem to modulate the myocardial response to antihypertensive treatment. Included among these mechanisms are neural, humoral, haemodynamic and biochemical factors. The available experimental data further suggest that some functional derangements and biochemical changes associated with hypertrophy may be reversed by antihypertensive treatment. There is, however, insufficient experience with human subjects to determine whether a reduction in left ventricular mass is associated with lower incidences of heart failure or mortality than may be achieved by adequate blood pressure control alone.     

Comparison of exercise effects on the hemodynamics of the Bio 14.6 cardiomyopathic hamster.

1. Comparisons of the effects of 4 and 16 weeks of exercise were made on; cardiac output, stroke volume, heart rate, left intraventricular systolic and diastolic pressures, dP/dt, and heart calcium in the Bio 14.6 cardiomyopathic and F1 B hamsters. 2. In the cardiomyopathic hamster the cardiac output, stroke volume, left intraventricular systolic pressure and dP/dt, which were all depressed in the age related sedentary animals, were increased by both periods of exercise. The left intraventricular diastolic pressure which was elevated was likewise decreased by both exercise periods. Only the 16 week exercise period decreased the resting heart rate. 3. In the normal F1 B hamster, both periods of exercise increased the cardiac output and stroke volume while the left intraventricular systolic pressure was decreased. Only the 16 week exercise decreased the resting heart rate and left intraventricular diastolic pressure and increased the left ventricular dP/dt. 4. Both periods of exercise increased the total heart calcium in the Bio 14.6 hamster while the heart calcium in the F1 B was increased only by the 16 week exercise period.