Donald F. Leon

Autonomic Mechanisms in Hemodynamic Responses to Isometric Exercise

Selective autonomic blockade with intravenous propranolol, practolol, atropine, and combined atropine-propranolol was utilized to elucidate the role of the autonomic nervous system in the hemodynamic responses in young adult male volunteers to handgrip sustained at 30% of maximal voluntary contraction for 3 min. The initial 30 s of the tachycardia response was found to be mediated by withdrawal of vagal dominance, as evidenced by blockade of this response by prior atropinization. The mid and late portion of the heart rate response curve was demonstrated to be sympathetic in origin, since it was unaffected by atropine, but was suppressed by combined atropine-propranolol blockade. Sympathetic stimulation appears to be a secondary mechanism for increasing the heart rate, however, as it becomes operative only after the first mechanism of vagal withdrawal has been utilized. This was confirmed by the finding that beta adrenergic receptor blockade alone had little effect on the heart rate response curve. The pressor response to handgrip was accompanied by increased cardiac output and no change in calculated systemic vascular resistance. After propranolol, handgrip resulted in increased peripheral resistance and an equivalent rise in arterial pressure, but no increase in cardiac output. It was concluded that the increase in resistance was the result of sympathetically induced vasoconstriction. This response was shown to be independent of peripheral beta adrenergic receptor blockade by the use of practolol, a cardio-selective beta adrenergic receptor-blocking drug which caused identical hemodynamic responses to those observed after propranolol. Left ventricular ejection time (corrected for heart rate) was prolonged by handgrip. The increased afterload imposed on the left ventricle by sustained handgrip may explain the prolongation of ejection time index. Preejection period was prolonged by SHG after propranolol and shortened after atropine. In addition to confirming the previously defined role of the parasympathetic nervous system, this study delineates the role of the sympathetic nervous system in the heart rate and pressor responses to sustained handgrip.

Effect of the Thyroid State on Myocardial Contractility and Ventricular Ejection Rate in Man

Although the circulatory changes in various thyroid states are well known, the alterations of myocardial contractility of hypothyroidism and hyperthyroidism have remained controversial. The changes in the length of the ejection time (ET) and isovolumic contraction time (ICT) are used as indicative of alterations in inotropic state of the myocardium. Isovolumic contraction time, ejection time, and pre-ejection period were measured externally in 10 normal, 13 hyperthyroid, and five hypothyroid subjects. Cardiac outputs, mean rate of left ventricular ejection index, and predicted ejection times were calculated. More shortening of ICT and ET in hyperthyroid and more prolongation of these intervals in hypothyroid subjects than could be attributed to other factors were interpreted as indicative of increased and decreased myocardial contractility, respectively. Catecholamine depletion in hyperthyroid subjects with adequate administration of intramuscular reserpine induced no changes in cardiac output and oxygen consumption and caused no alteration in different phases of ventricular systole; consequently it had no effect on enhancement of hyperthyroid myocardial contractility.

Reflex heart rate control in man.

Abstract In summary, the relative roles of the parasympathetic and sympathetic nervous systems in baroreceptor reflex heart rate control have been studied in eleven normal young men. These data have been compared to the results of similar studies in a heart transplant subject. The findings indicate that in normal conscious men, reflex parasympathetic stimulation and withdrawal primarily control heart rate responses to changes in blood pressure. Beta-adrenergic activity, while influencing basal heart rate plays little, if any, role in baroreceptor reflex heart rate control. The Valsalva maneuver may be used as an effective measure of parasympathetic integrity but it may not be used as a reliable index of sympathetic integrity. The pharmacologically denervated heart is similar in terms of reflex responses to the surgically denervated heart in conscious man. The heart rate responses to Valsalva maneuver, amyl nitrite inhalation, and phenylephrine infusion should be reliable indices of parasympathetic reinnervation of the transplanted heart should reinnervation occur.

Sound Pressure Correlates of the Second Heart Sound An Intracardiac Sound Study

The sound pressure correlates of the second heart sound were studied in 22 patients during diagnostic cardiac catheterization. Simultaneous right ventricular and pulmonary artery pressures were recorded with equisensitive catheter-tip micromanometers together with the external phonocardiogram and ECG. In 12 patients having normal pulmonary vascular resistance (group 1), pulmonic closure sound was coincident with the incisura of the pulmonary artery pressure curve which in turn was separated from the right ventricular pressure trace by an interval denoted hangout. The duration of this interval varied (33-89 msec), was independent of pulmonary artery pressure or resistance and was felt to be primarily a reflection of the capacitance of the pulmonary vascular tree. The absolute value of this interval during inspiration was very similar to the splitting interval and, when subtracted from the Q-P2 interval, the remaining interval (QRV) was almost identical to the Q-A2 interval, indicating that the actual duration of right and left ventricular systole is nearly equal. Awareness of the existence of the hangout interval and its hemodynamic determinants offers a reasonable mechanism to explain the audible expiratory splitting of the second heart sound found in patients with idiopathic dilatation of the pulmonary artery following atrial septal defect repair and in one additional patient studied with mild valvular pulmonic stenosis. In nine patients with elevated pulmonary vascular resistance approaching systemic levels (group 2), the absolute value of the hangout interval was markedly reduced (15-28 msec) consistent with the decrease in capacitance of the pulmonary vascular bed and the increased pulmonary vascular resistance known to occur in pulmonary hypertension. In those patients where the duration of right and left ventricular systole were nearly equal, narrow splitting of the second heart sound was present. In those patients where selective prolongation of right ventricular systole occurred, the narrow hangout interval persisted, but the splitting interval was prolonged proportionate to the increased duration of right ventricular systole.

Hemodynamic Observations after Cardiac Transplantation

Abstract Hemodynamic observations were performed one and six months after cardiac transplantation in a 46-year-old man. Cardiac catheterization revealed normal pressures at rest and a slightly decreased cardiac index. Total cardiac denervation was documented by absence of reflex changes in heart rate during physiologic and pharmacologic stimuli. Intracardiac electrocardiography demonstrated both donor and recipient p waves, the former always controlling the heart rate. Observations during atrioventricular dissociation indicated that the transplanted heart has active atrial transport. The denervated heart responded to the stress of muscular exercise. Cardiac output increased predominantly by increasing stroke volume, although delayed increments in heart rate occurred. After complete beta-adrenergic blockade, the response of the heart rate to exercise was attenuated but not completely blocked. These findings suggest that whereas circulating catecholamines have an important role in cardiac acceleration durin...

Right atrial ectopic rhythms. Experimental production in man

Abstract Endocardial pacing at a variety of sites in the right atrium and coronary sinus was accomplished in 19 healthy young volunteers. The spatial orientation of the P wave induced by pacing at each site was determined from the 12 lead electrocardiogram. In each instance, the mean vector of the resultant P wave was directed toward a point on the opposite circumference of a spheroid; the walls of this spheroid were made up of the atrial myocardium and its supporting structure. The results of these studies in normal individuals support and further define those of previous experimental studies of coronary sinus rhythm and are in agreement with earlier demonstrations that P waves induced at multiple sites within the left atrium are oriented in a predictable fashion. The P waves resulting from right atrial pacing were of normal duration and the P-R intervals were rate-dependent. At any fixed pacing rate the P-R interval resulting from pacing at the ostium of the coronary sinus was shorter than the control P-R interval at the same paced rate but never less than 0.12 sec. These ectopic atrial rhythms were artificially induced in normal hearts. Fibrosis resulting from heart disease involving the atria may cause disturbances in conduction; in such cases the P waves arising from ectopic foci may not be entirely predictable. At no time did right atrial pacing at any point remote from the sinoatrial tissue result in normally directed P waves in normal hearts.

The Effect of Atrial Contraction on Left Ventricular Performance in Valvular Aortic Stenosis

The instantaneous response of the left ventricle to loss or recovery of effective atrial contraction was studied in 12 patients with valvular aortic stenosis by producing A-V dissociation by electrical pacing of the ventricles so that some ventricular contractions were preceded by an effective atrial contraction while others were not. A conventional hydraulic formula relating size of the aortic valve orifice, pressure gradient, and flow was used to estimate beat to beat stroke volume. A properly timed atrial contraction augmented left ventricular performance in all patients, increasing stroke volume index from 14 to 55% (mean, 27%) and stroke work from 17 to 85% (mean, 45%).The contribution of atrial contraction to integrated cardiac performance was studied in six of the same patients by comparing cardiac performance with right atrial pacing and right ventricular pacing. With right atrial pacing, each ventricular contraction was preceded by an atrial contraction, while with right ventricular pacing many ventricular contractions were not preceded by atrial contraction. Right atrial pacing increased cardiac index in four of six patients: The mean increase for the total group was 13% and the mean increase in left ventricular minute work index was 17%.Although atrial contraction was capable of augmenting left ventricular performance in all patients studied, loss or recovery of effective atrial systole did not always alter integrated cardiac performance. Factors influencing atrial contribution remain poorly understood. Atrial contraction does not appear to have an unusual effect on the performance of the hypertrophied left ventricle.

Hemodynamic Effects of Practolol at Rest and during Exercise

The effects of practolol, a new beta-adrenergic blocking agent, and propranolol were studied in volunteers. At rest, practolol caused a very small reduction in cardiac index (CI), 190 ml, P < 0.25, and preejection period (PEP) lengthened 3 msec, P < 0.025. In contrast, propranolol caused a reduction in CI of 770 ml, P < 0.001. Heart rate (HR) slowed 10 beats/min, P < 0.001, stroke volume index (SVI) fell 6 ml, P < 0.005, PEP lengthened 16 msec, P < 0.001, and peripheral vascular resistance (PVR) increased 419 dynes-sec-cm−5, P < 0.001. Practolol reduced the increase in CI caused by an isoproterenol infusion by 65%, P < 0.005, by blocking the increase in HR by 73%, P < 0.05. Practolol also reduced the shortening of PEP and LVET caused by isoproterenol. PVR decreases due to isoproterenol were not blocked by practolol although they were slightly attenuated, P < 0.025. Practolol reduced the increase in CI caused by exercise by 22%, P < 0.05, by blocking the increase in HR by 29%, P < 0.01. Practolol also reduced the increase in tension-time index due to exercise by 25%, P < 0.025.Practolol has little effect on the performance of the normal heart at rest. It does block the cardiac effects of isoproterenol and exercise, largely through chronotropic mechanisms. The reductions in pressure-time relationships with exercise indicate reduced oxygen consumption by the heart, and therefore imply a therapeutic benefit in exercise-induced angina.

The experimental production of coronary sinus rhythm in man

Abstract Coronary sinus rhythm was produced experimentally in 8 patients, utilizing the bipolar pacing catheter in the os of the coronary sinus. The distinction between coronary sinus rhythm and upper nodal rhythm is again seen to be an arbitrary one. The value of the P-R interval in coronary sinus rhythm and its relation to A-V block is discussed.

Venous systolic thrill and murmur in the neck: A consequence of severe tricuspid insufficiency

A palpable venous systolic thrill and murmur at the base of the neck are described as new physical findings in five patients with severe tricuspid regurgitation. In two of these patients, the tricuspid valve had been resected as treatment for infective endocarditis related to intravenous drug abuse. The third patient had severe chronic pulmonary disease with right heart failure. The fourth patient had a complex congenital defect in which the mitral valve served as the venous atrioventricular valve and was severely incompetent. The fifth patient suffered from long-standing rheumatic mitral and tricuspid disease with pulmonary hypertension 10 years after placement of a mitral prosthesis. From these observations, it is apparent that pulsatile retrograde flow in the cervical veins resulting from severe right-sided atrioventricular valve incompetence can produce a palpable systolic thrill and murmur at the base of the neck.