Matthew N. Levy

Brief Reviews Sympathetic-Parasympathetic Interactions in the Heart

• It is generally recognized that the two divisions of the autonomic nervous system exert antagonistic efFects on various aspects of the performance of the heart. However, these opposing influences are not algebraically additive; complicated interactions exist. Two major types of peripheral interactions have been described. The first type is manifested as an accentuated antagonism between the two divisions. In the second type, the peripheral components of one division are activated as a consequence of activity in the other; this will be designated reciprocal excitation.

Depression of Ventricular Contractility by Stimulation of the Vagus Nerves

In three different types of canine heart preparations, it was demonstrated that efferent vagal stimulation exerts a potent, negative inotropic influence upon the ventricular myocardium. In the paced, isovolumetric, left ventricle preparation, vagal stimulation evoked a reduction of left ventricular systolic pressure which, within limits, varied directly with the magnitude of the stimulus. Supramaximal stimulation elicited a mean reduction of 23% in the peak pressure generated by the left ventricle. No differences could be detected between the effects of the right and left vagi upon ventricular contractility. The percentage changes induced by vagal stimulation upon ventricular contractility in the paced heart were less than the percentage changes in heart rate induced in the spontaneously beating heart. In a pumping heart preparation in which a constant rate of venous return was delivered to the left atrium, vagal stimulation consistently elicited an appreciable elevation of left ventricular end diastolic ...

Functional Distribution of the Peripheral Cardiac Sympathetic Pathways

The functional peripheral cardiac sympathetic pathways of the dog were delineated in isovolumetric left ventricle preparations. In unpaced hearts, supramaximal stimuli at 2 cycles/sec to the right stellate ganglion caused the heart rate to increase 2.8 times more than stimuli applied to the left side. In paced hearts, such stimuli evoked rises in left ventricular systolic pressure which were 2.3 times greater when applied to the left than to the right stellate ganglion. Tonic cardiac sympathetic impulses appear to funnel through the stellate ganglia. Decentralization of the stellate ganglia abolished the ventricular responses to stimulation of the carotid baroreceptors and cephalic ischemia. Approximately two thirds of the tonic and baroreceptor reflex influences to the left ventricle entered the stellate ganglia from lower segments of the thoracic paravertebral chain, and one third entered from the communicating rami of the stellate ganglia. The ratio of the effects of complete decentralization of the left to those of decentralization of the right stellate ganglion was 1.6, both with respect to eliminating sympathetic tone and abolishing the baroreceptor reflex.

Sympathetic and Parasympathetic Interactions upon the Left Ventricle of the Dog

In canine, isovolumetric, left ventricle preparations, stimulation of the cardiac end of a cut cervical vagus nerve evokes a biphasic change of left ventricular systolic pressure (LVSP). Characteristically, there is a definite reduction of LVSP during the stimulus, followed by a slight increase of LVSP after cessation of stimulation. The magnitude of the reduction of LVSP during vagal stimulation is considerably augmented when sympathetic activity is increased either directly (by electrical stimulation of the left stellate ganglion) or reflexly (by lowering carotid sinus pressure). These results indicate that the effect of vagal stimulation is mediated, at least in part, by antagonizing the positive inotropic influence of the prevailing sympathetic nervous activity. The mechanism of the poststimulation rebound is unknown. It may be due to cardiac sympathetic fibers in the canine vagosympathetic nerve trunks and to the release of catecholamine-like substances in the myocardium.

Effects of Repetitive Bursts of Vagal Activity on Heart Rate

The effect of the timing of discrete bursts of efferent vagal impulses on heart rate was determined in anesthized dogs. Two modes of stimulation were employed. In the first mode, one stimulus burst was delivered per cardiac cycle. As the time from the beginning of the P wave to the vagal stimulus (P-St interval) was progessively increased, there was first a progressive lengthening of the cardiac cycle (P-P interval), then a rapid decrease in P-P interval, and finally a gradual augmentation of the P-P interval. The amplitudes of curves of P-P interval as a function of P-St interval increased as the number of stimuli per burst was augmented, with 10 stimuli/burst yielding nearly maximal effects. Vagal stimuli applied at P-St intervals which coincided with the negative-slope (d[P-P]/d[P-St]) region of such curves tended to evoke sinus arrhythmias. With 5 stimuli/burst or more, these arrhythmias were pronounced and consisted of alternate short and long P-P intervals. In the second mode of stimulation, bursts of stimuli were delivered to the vagus nerve at a frequency independent of heart rate. The cardiac pacemaker tended to become synchronized in some fixed ratio of vagal stimuli to P waves, and this tendency became greater the larger the number of stimuli per burst of impulses. Within any range of synchronization, a paradoxical effect was manifest--increasing frequencies of vagal stimulation produced increasing rather than decreasing heart rates.

Paradoxical Effect of Vagus Nerve Stimulation on Heart Rate in Dogs

In the anesthetized, open-chest dog, electrical stimulation of the cardiac ends of the transected cervical vagus nerves produced effects on heart rate and A-V transmission that were dependent upon the P-St interval, i.e., the-time from the beginning of the P wave to the beginning of the stimulus. When one vagal stimulus was delivered per cardiac cycle, the pacemaker response curve (curve of the P-P interval as a function of the P-St interval) was sinusoidal in configuration, with a maximum at a P-St interval of 135 msec and a minimum at 349 msec. The mean P-P interval was 568 msec, and the mean amplitude of the pacemaker response curve was 58 msec. In any given experiment, the range of P-P intervals encompassed by the pacemaker response curve defined a range of frequencies over which S-A nodal rhythm became synchronized with the activity in the vagus nerves. Over such a range, increases in the frequency of vagal stimulation evoked paradoxical increases in heart rate. On either side of this range of synchronization, vagal stimulation elicited pronounced rhythmic oscillations of P-P and P-R intervals. The frequency of such oscillations was equal to the difference between the vagal stimulation frequency and the mean heart rate. The oscillations in P-R interval were approximately 180° out of phase with the oscillations in P-P interval.

Effects of Respiratory Center Activity on the Heart

Rhythmic fluctuations in heart rate and ventricular contractility at the frequency of the respiratory movements were observed in innervated, isovolumetric, canine, left ventricle preparations. The heart rate and contractility waves probably represent the radiation of activity from the respiratory centers to the cardiac autonomic centers within the central nervous system. In spontaneously beating hearts, the respiratory cardiac arrhythmia is mediated via the vagi predominantly, although a slight arrhythmia is still evident after bilateral vagotomy. The greater the vagal tone, the greater is the amplitude of the arrhythmia. In paced hearts, the contractility waves exhibit significantly greater phase lags than do the heart rate waves in unpaced beats. The magnitude of the contractility waves varies inversely with the respiratory frequency. These waves are more prominent after bilateral vagotomy. Therefore, sympathetic influences appear to predominate in the mediation of the contractility waves, although the change in wave amplitude after vagotomy must be ascribed partly to the deceleration of respiratory frequency which occurs after vagotomy. The contractility waves represent rhythmic augmentations of contractility above a base line level after vagal section.

Outflow Resistance as an Independent Determinant of Cardiac Performance

In the modified heart-lung preparation of the dog, sudden increases in outflow resistance were imposed during the diastolic interval between two beats. The changes in cardiac performance which were recorded during the first beat at higher resistance represent the response to augmented resistance per se, since there was no change in the initial length or initial tension of the ventricular myocardial fibers. Increased resistance elicited an immediate elevation of the peak aortic systolic pressure. This pressure rise was a direct function of the magnitude of the outflow resistance, and the effect was enhanced at higher left atrial pressures. Peak aortic flow and stroke volume were inversely related to the magnitude of the outflow resistance. At slight to moderate increases of resistance, stroke work was relatively unaffected; with more severe augmentations of resistance, however, stroke work varied inversely with outflow resistance. Arterial compliance played an important role in the ventricular response. For any given increase of resistance, the reductions of peak aortic flow and ventricular power were more severe when the arterial system was more rigid. It is concluded that the limits of cardiac performance are determined by the initial conditions, such as fiber length or tension, previous activity, temperature, and nervous and humoral factors. Within these limits, however, ventricular performance is determined by the afterload, of which the outflow impedance is an integral component.

The Influence of Erythrocyte Concentration upon the Pressure-Flow Relationships in the Dog's Hind Limb

Since alterations in cell-plasma ratios are of paramount importance in the assessment of peripheral resistance, a study of pressure-flow relations was made in which blood having wide hematocrit values was perfused through a dogs hind limb in which collateral circulation has been excluded. When vessels were moderately dilated by denervation, the relative apparent viscosity was not affected by the perfusion pressure. When, however, the vessels were maximally dilated after a preceding period of anoxia, the relative apparent viscosity was found to become greater as perfusion pressure was progressively reduced. The in vivo relative apparent viscosity did not significantly exceed that of plasma until the erythrocyte concentration reached 30 per cent.

Inhibition of cardiac vagal effects by neurally released and exogenous neuropeptide Y.

Neuropeptide Y (NPY) attenuates vagal effects on cardiac cycle length, presumably by inhibiting the release of acetylcholine from vagal nerve endings. We sought to determine if NPY inhibited the vagal effects on atrioventricular (AV) interval and atrial contraction in a manner similar to its inhibition of the vagal effects on cycle length. In 19 anesthetized dogs we measured the vagal effects on cycle length, AV Interval, and atrial contraction before and after 3-minute trains of sympathetic stimulation or before and after exogenous NPY (20 μg/kg i.v.). Three minutes after 10-Hz sympathetic stimulation, the vagal effects on cycle length and AV interval were attenuated by 52 ± 9% and 63 ± 8%, respectively. Phentolamine significantly augmented this attenuation, but propranolol had no appreciable effect. In the control group of animals or in the group that received phentolamine, the vagal effects on atrial contraction measured before and after sympathetic stimulation were not significantly different. In these two groups, however, the basal atrial contraction was reduced substantially after the cessation of sympathetic stimulation. Propranolol prevented this reduction in atrial contraction. After propranolol, the vagal effects on atrial contraction 3 minutes after sympathetic stimulation were attenuated by 31 ± 6%. Exogenous NPY had no direct effect on cycle length, AV interval, or atrial contraction, but exogenous NPY did persistently inhibit the vagal effects on each of these cardiac processes. Three minutes after NPY was given, the vagal effects on cycle length, AV interval, and atrial contraction were inhibited by 62 ± 7%, 69 ± 5%, and 68 ± 5%, respectively. We conclude that NPY attenuates the vagal effects on the atrial myocardium and on the sinus and AV nodes. In the absence of β-blockade, the inhibitory effect of neurally released NPY on the vagally induced decreases in atrial contraction may be masked by the reduction in the atrial contraction that occurs after sympathetic stimulation.