Cardiac Sympathetic Stimulation Research Articles

QT-interval prolongation, paroxysmal ventricular arrhythmias, and convulsive syncope.

A patient with prolonged QTc interval, paroxysmal ventricular tachycardia, and syncope was studied. Her syncopal episodes were often precipitated by stress or unexpected stimuli. Neurological evaluation showed no abnormalities. Right and left stellate ganglion blockade and intravenous atropine, calcium gluconate, and digoxin did not shorten QTc-interval duration. Ventricular pacing and intravenous phenobarbital suppressed ventricular tachyarrhythmias. Sodium diphenylhydantoin (Dilantin Sodium®) produced QTc shortening and controlled ectopic rhythms. Neural influence on synchrony of ventricular repolarization may predispose to the paroxysmal arrhythmias associated with this syndrome. Central nervous and asymmetrical cardiac sympathetic nervous stimulation may produce an increase in temporal dispersion of repolarization and a prolonged refractory period, thus facilitating reentrant rhythms and tachyarrhythmias. Sodium diphenylhydantoin shortens repolarization and effective refractory period and increases the conduction velocity of ectopic ventricular impulses, reducing temporal dispersion and suppressing reentrant rhythms. QT-prolongation syndromes are potentially lethal and may account for a number of cases of "atypical epilepsy."

Angina pectoris.

Cardiac ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) uptake is reduced in chronic heart failure, and its reduction is reported to relate to the decrease in exercise capacity. Reduced ¹²³I-MIBG uptake may predict an inadequately reduced adrenergic drive to the heart during cardiac sympathetic stimulation, including exercise. However, there is little information about the relationship between cardiac ¹²³I-MIBG uptake at rest and norepinephrine (NE) release during exercise in relation to the exercise capacity in the failing heart. The aim of this study was to examine whether cardiac ¹²³I-MIBG uptake at rest can predict cardiac sympathetic activity during exercise in patients with chronic heart failure. We determined how cardiac ¹²³I-MIBG uptake at rest relates to NE overflow from the heart during symptom-limited graded exercise in such patients. <b>Methods:</b> Twelve patients (mean ± SD, 52 ± 12 y) with chronic stable heart failure performed symptom-limited graded exercise tests under catheterizations with a 4-min stage using a supine bicycle ergometer within 2 wk after ¹²³I-MIBG imaging. NE concentrations in the arterial and coronary sinus blood (NE_A and NE_CS, respectively) were measured at each exercise stage, and NE overflow was approximated by the difference between NE_CS and NE_A (NE_CS−A). <b>Results:</b> The left ventricular ejection fraction at rest was 47% ± 16% and peak oxygen uptake was 17.7 ± 5.1 mL/kg/min. The heart-to-mediastinum uptake ratio of the delayed ¹²³I-MIBG image (1.00∼1.72; mean ± SD, 1.30 ± 0.19) correlated with NE_CS−A at peak exercise (<i>r</i> = 0.80, <i>P</i> &lt; 0.01) and peak heart rate (<i>r</i> = 0.73, <i>P</i> &lt; 0.01) but not with peak oxygen uptake. <b>Conclusion:</b> Cardiac ¹²³I-MIBG uptake of the delayed image can predict the degree of the increase in adrenergic drive to the heart during sympathetic stimuli induced by exercise in patients with chronic heart failure.

Effect of ganglionic blockade on the responses of coronary blood flow to cardiac sympathetic stimulation in the dog.

The effects of ganglionic blockade were studied on the changes in coronary blood flow and myocardial contraction produced by electrical stimulation of the left cardiac sympathetic nerves in anesthetized open-chest dogs. Stimulation of the left ventral ansa subclavia (AS) and the ventrolateral cervical cardiac nerve (VLCCN) produced 2 peaks of increase in coronary blood flow, in myocardial contractile force (MCF) and in left ventricular pressure (LVP). The first peak was, in some experiments, preceded by an initial transient decrease in coronary blood flow. Bilateral cervical vagotomy or intravenous injection of atropine did not affect the initial changes in coronary blood flow. In dogs pretreated with intravenous propranolol or practolol, the stimulation of either AS or VLCCN evoked a prolonged decrease in coronary blood flow without appreciable changes in systemic blood pressure and myocardial contractility. The decrease in coronary flow resulting from AS stimulation was blocked not only by intravenous injection of phentolamine but also by hexamethonium (C6) given into the pericardial cavity or in the coronary artery. On the other hand, the decrease elicited by stimulation of VLCCN was abolished by phentolamine but not influenced by intracoronary and intrapericardial C6, while hypotension and brady-cardia produced by cervical vagosympathetic stimulation were completely blocked by C6. From the present data, it may be concluded that in coronary vessels there exist adrenergic alpha receptors corresponding to the sympathetic vasoconstrictor nerve of which preganglionic fibers terminate in the stellate and inferior cervical ganglia, and that the intracardiac ganglion cells play little role in the coronary vasoconstrictor response after beta adrenergic receptor blockade.

Cardio-selective beta-adrenoceptor blockade and the coronary circulation.

After blockade of myocardial, but not coronary vascular beta-adrenoceptors by practolol, cardiac sympathetic stimulation or exogenously administered noradrenaline gave rise to coronary vasoconstriction, possibly due to stimulation of coronary alpha-adrenoceptors.

Effects of right and left cardiosympathetic nerve stimulation on blood flow in the major coronary arteries of the anaesthetized dog.

Left cardiac sympathetic nerve stimulation in anaesthetized open-chest dogs produced more pronounced flow changes in the left circumflex than in the anterior descending or right coronary arteries. Right cardiac sympathetic stimulation produced no consistent change in the distribution of flow among these vessels. These observations suggest that the left and right cardiac sympathetic nerve terminals differ in their ventricular myocardial distribution.

Cardiac failure in patients with valvar heart disease after use of propranolol to control atrial fibrillation.

When digitalis fails to control atrial fibrillation propranolol may be useful in slowing the ventricular rate (Besterman and Friedlander, 1965 ; Rowlands et al., 1965). The beta-adrenergic blockade which propranolol causes may induce or aggravate cardiac failure, as cardiac sympathetic nervous stimulation is an important factor supporting myocardial function (Gaffney and Braunwald, 1963). Therefore it is likely that in some patients propranolol may control the heart rate at the expense of myocardial efficiency. This paper reports the cases of four patients with atrial fibrillation and chronic valvar heart disease in whom propranolol was used to control the ventricular rate when digitalis had failed. In each case, though the rate was adequately controlled, heart failure occurred.

Catecholamine-induced myocardial hypoxia in the presence of impaired coronary dilatability independent of external cardiac work ∗

Surface electrocardiograms were taken in vagotomized cats over areas of the left ventricle. An adjustable nonoccluding restriction device prevented part of the coronary arterial supply from dilating. Under these circumstances, brief stimulation of the cardiac sympathetic nerves or reflex stimulation of the adreno-sympathetic system through electrically induced muscular “exercise,” or intravenous injection of catecholamines (epinephrine, norepinephrine) caused regularly marked elevations of the S-T segment and the T wave, even if concomitant augmentation of cardiac mechanical work was only minimal. Identical electrocardiographic changes were elicited by exogenous anoxia (breathing 100 per cent nitrogen), and by more complete coronary constriction. By contrast, no S-T displacement occurred despite coronary restriction when heavy work loads were imposed upon the heart by noncatecholamine influences, namely, tachycardia produced by electrical stimulation of the right atrium, or high rises of the blood pressure produced by intravenous injection of angiotensin II, or both combined. Neurogenic and blood-borne catecholamines cause severe regional myocardial hypoxia when the normal compensatory coronary dilatation is impaired. Such catecholamine-induced myocardial hypoxia is not caused by the concomitant augmentation of cardiac mechanical work which these neurohormones usually elicit, but by their specific biochemical oxygen-wasting properties. Our findings agree with the clinical experience that in patients with coronary sclerosis attacks of angina pectoris are ordinarily triggered by sympathetic-stimulating, catecholamine-liberating conditions (exercise, emotions and other stresses), and prevented by various antiadrenergic measures. Contrary to traditional belief, it is suggested that anginal symptoms do not occur because “the heart works harder” but because certain areas of the myocardium whose coronary vessels have lost the ability for compensatory dilatation are exposed to the biochemical hypoxiating influence of acute catecholamine discharges accompanying various stresses. Except in cases of far advanced coronary sclerosis, the term “coronary insufficiency” is to be understood as meaning inability of the coronary circulation to compensate by adequate dilatation for sympathogenic (catecholamine-induced) excessive myocardial oxygen losses.

Myocardial extraction and production of catechol amines.

Stimulation of the cardiac sympathetic efferent nerves is accompanied by a release of catechol amines in coronary blood. This release is a function of stimulation intensity and occurs even when stroke volume and coronary outflow are maintained constant. Comparison between the ethylenediamine and the trihydroxyindole methods for the analysis of plasma catechol amines shows both quantitative and qualitative differences, with only the results with the latter method showing a consistent relationship to the hemodynamic changes observed during cardiac sympathetic stimulation. The acutely synipatheetomized heart extracts catechol amines from coronary blood in the absence of nervous stimulation. The patterns of extraction observed indicate that the quantity of catechol amines in the myocardium can modify the extent of extraction in the unstimulated state as well as the extent of release during stimulation. Continued stimulation of the cardiac sympathetics is accompanied by at least a partial depletion of the myoeardial catechol amine stores. These stores appear to be repleted by circulating catechol amines, since the response to any given intensity of stimulation can be potentiated by a prior norepinephrine infusion. Dichloroisoproterenol prevents neither the myocardial extraction of catechol amines in the unstimulated state nor the release of catechol amines during sympathetic stimulation; it does lessen or abolish the cardiody-namic effects of sympathetic stimulation. Data are presented which indicate that a direct coronary vasoconstriction is one of the consequences of cardiac sympathetic nerve stimulation, the vasodilatation usually observed being due, at least in part, to overriding metabolic factors.

Influence of cardiac sympathetic and vagal nerve stimulation on the relation between left ventricular diastolic pressure and myocardial segment length.

During the continuous and simultaneous recording of left ventricular diastolic pressures and changes in the length of a segment of left ventricular myocardium it was demonstrated that neither cardiac sympathetic nor vagal efferent nerve stimulation produces a change in ventricular myocardial extensibility. It was further shown that, at the heart rates studied, autonomic nerve stimulation does not modify the end-diastolic pressurelength curve. These data indicate that, during cardiac sympathetic stimulation, the augmented ventricular stroke work from any given end-diastolic Pressure is accomplished without a change in end-diastolic fiber length. Evidence was obtained, however, which suggests that the abbreviation of diastole at high imposed heart rates or large stroke volumes may leave an inadequate time for ventricular relaxation to take place and for inertial and viscous factors to be dissipated. Under these circumstances, sympathetic stimulation, by shortening systole and thereby lengthening diastole, permits the ventricle to remain on its "normal" pressure-length curve. This component of cardiac sympathetic efferent activity is peculiarly appropriate to the tachycardia that occurs with increased sympathetic outflow to the heart.