Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat.

Brain serotoninergic neurons are known to participate in cardiovascular regulation. Administration of the serotonin precursor 5-l-hydroxytryptophan in conjunction with the monamine oxidase inhibitor phenelzine and the selective peripheral l-amino acid decarboxylase inhibitor carbidopa has been shown to raise the repetitive extrasystole threshold in the canine heart. The present investigation demonstrates that this drug regimen increases the cerebrospinal fluid concentration of serotonin and its major metabolite, 5-hydroxyindoleacetic acid, by 330 and 830%, respectively.

Mechanisms of behaviorally induced arrhythmias.

Significant progress has been made in the past few years in defining the role of behavioral stress in the precipitation of cardiac arrhythmias. This is largely attributable to the development of relevant biobehavioral models and the advent of quantitative methods for assessing myocardial electrical stability in conscious animals. Classic and instrumental aversive conditioning has been shown to decrease electrical stability even in the normal heart.

Influence of beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties and serum potassium concentration in the anesthetized dog.

The influence of selective beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties was studied in 18 anesthetized dogs. Selective beta 2-adrenoceptor activation by salbutamol failed to alter myocardia excitability but significantly lowered serum potassium concentration. Excitability, refractoriness, and ventricular fibrillation threshold were also not changed after administration of 100 and 200 micrograms/kg of the selective beta 2-antagonist ICI 118,551.

Delayed myocardial ischemia induced by anger.

The objectives of this study were to develop a reproducible behavioral model that simulates the anger state and to characterize its influence on myocardial blood flow in both the normal and compromised coronary circulations. Fourteen mongrel dogs of both sexes were studied. The animals were instrumented for the recording of electrocardiogram, arterial blood pressure, and left circumflex coronary arterial blood flow.

Effects of adrenergic and muscarinic receptor stimulation on serum potassium concentrations and myocardial electrical stability.

The influence of adrenergic and muscarinic receptor activation on cardiac electrical stability and on serum potassium concentrations was studied in 23 anaesthetised dogs. The ventricular fibrillation threshold was assessed using the single stimulus technique. Adrenaline (1.

Effect of hypokalemia on susceptibility to ventricular fibrillation in the normal and ischemic canine heart.

To examine the impact of hypokalemia on cardiac electrical stability, the thresholds for repetitive extrasystole and ventricular fibrillation were determined before and after potassium depletion in 15 chloralose-anesthetized dogs. A reduction in serum potassium concentration from 3.6 to 2.

Neurochemical approaches to the prevention of ventricular fibrillation.

Current evidence indicates that susceptibility to ventricular fibrillation (VF) can be reduced by decreasing cardiac sympathetic activity and by increasing vagal tone. Pharmacological agents that favor such a pattern of autonomic outflow protect the heart against fibrillation. These include morphine sulfate, clonidine, digitalis drugs, and bromocriptine.

Protective effect of tiapamil against ventricular fibrillation during coronary artery occlusion.

Calcium channel antagonists differ in their effects on myocardial excitable properties. This study examines whether tiapamil (100 micrograms/kg/min intravenously) is capable of reducing the susceptibility to ventricular fibrillation (VF) during acute occlusion and reperfusion of the left anterior descending coronary artery. During occlusion, tiapamil elevated the VF threshold to 17.

Mechanisms involved in reperfusion arrhythmias.

Clinical and experimental studies indicate that reperfusion of the ischaemic myocardium may play an important role in the genesis of life-threatening arrhythmias. Reflow may occur as a result of abrupt cessation of coronary artery spasm or upon dislodgment of platelet aggregates with the attendant washout of products of cellular ischaemia. The released substances exert a transient but potent arrhythmogenic effect.

Vulnerability to ventricular fibrillation in patients with clinically manifest ventricular tachycardia.

Ventricular vulnerability may be assessed by measuring the threshold current for the induction of ventricular fibrillation (VF). This technique has been widely utilized in animal experimentation and has been safely applied in a small number of clinical studies. We measured the VF threshold (VFT), using the single stimulus technique in 10 patients with coronary artery disease just prior to the institution of cardiopulmonary bypass.

The repetitive extrasystole as an index of vulnerability to ventricular fibrillation during myocardial ischemia in the canine heart.

The repetitive extrasystole threshold (RET) is a reliable measure of vulnerability to ventricular fibrillation (VF) during diverse interventions in the normal heart. Whether this relationship also holds during varying degrees of myocardial ischemia has not been adequately explored. In 15 chloralose-anesthetized dogs, circumflex coronary blood flow (CBF) was decreased progressively with the use of an externally applied balloon occluder.

Relationship between sympathetic neural activity, coronary dynamics, and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion.

The relationship between neural sympathetic discharge and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion was studied in 26 chloralose-anesthetized dogs. Preganglionic cardiac sympathetic impulse activity and ventricular fibrillation thresholds were separately determined before and during a 10-minute period of left anterior descending coronary artery occlusion and during release-reperfusion. Within 2 minutes of occlusion the ventricular fibrillation threshold was significantly decreased (from 25 +/- 1.

Intrinsic sympathomimetic activity and the effects of beta-adrenergic blocking drugs on vulnerability to ventricular fibrillation.

Beta-adrenergic blocking agents differ considerably in their effects on myocardial excitable properties. The possibility that intrinsic sympathomimetic activity might contribute to such differences has not been adequately explored. This study examined the influence of intrinsic sympathomimetic activity on the electrophysiologic effects of three agents with varying degrees of such activity.

Effect of alpha-adrenergic receptor stimulation on ventricular electrical properties in the normal canine heart.

We examined the effects of alpha-adrenergic stimulation on ventricular excitability, refractoriness, and vulnerability to fibrillation. Methoxamine or phenylephrine was infused in five dogs each before and after aortic arch and carotid sinus baroreceptor denervation, in doses which increased mean arterial blood pressure by 20 to 30 mm Hg. Methoxamine or phenylephrine caused an increase in the ventricular fibrillation threshold (VFT) (from 27% to 41%) and in the repetitive extrasystole threshold (RET) (from 28% to 39%).

Decreased vulnerability to ventricular fibrillation by vasodilator-induced baroreceptor sensitisation.

Vulnerability to ventricular fibrillation (VF) is affected by changes in systemic arterial blood pressure which are mediated through the sympathetic nervous system. We determined that small doses of a vasodilator drug can abolish the enhanced ventricular vulnerability induced by norepinephrine infusion. Noradrenaline (0.

Influence of intracoronary platelet aggregation on ventricular electrical properties during partial coronary artery stenosis.

Several clinical studies suggest that drugs which interfere with platelet function may protect persons at risk for sudden death. However, there is no direct evidence that intracoronary platelet aggregation produces cardiac arrhythmias. Induction of fixed partial coronary stenoses in dogs resulted in spontaneous cyclical reductions in coronary blood flow of 21 to 81% (p less than 0.

Effects of sulfinpyrazone on ventricular vulnerability in the normal and the ischemic heart.

The effects of sulfinpyrazone were studied in 33 chloralose-anesthetized dogs. Ventricular fibrillation thresholds, mid diastolic thresholds and duration of the effective refractory period were determined in the normal heart after intravenous administration of sulfinpyrazone, 30 mg/kg body weight. The drug significantly raised the ventricular fibrillation threshold by 24 percent and the mid diastolic threshold by 36 percent and prolonged the effective refractory period by seven percent.

Influence of the autonomic nervous system on coronary blood flow during partial stenosis.

Partial coronary stenosis produces cyclical changes in coronary blood flow (CBF) which are the result of spontaneous aggregation and disaggregation of platelet plugs at the site of occlusion. The possible influence of the autonomic nervous system on this phenomenon has not been hitherto determined. The present study was performed in 20 chloralose-anesthetized dogs in which the effects of bilateral vagotomy and stellectomy were examined during partial stenosis of the left circumflex coronary artery.

Effects of prostacyclin (PGI2) on vulnerability to ventricular fibrillation in the normal and ischemic canine heart.

Prostacyclin (PGI2) has been shown to have a number of beneficial effects on the cardiovascular system. However, its effects on ventricular electrical properties remain unexplored. We studied the effects of this naturally occurring humoral agent on ventricular vulnerability in the normal heart and in two models of myocardial ischemia: coronary artery occlusion and release and ergonovine-induced coronary vasoconstriction.

Experimental studies of psychophysiological factors in sudden cardiac death.

Earlier research in the field of sudden cardiac death is reviewed. Such studies have largely oriented towards the provocation of myocardial injury and asystole in normal animals. However, such investigations constitute an inadequate model to describe the clinical appearance of sudden death, where underlying coronary disease is often present and the precipitating event is usually ventricular fibrillation rather than asystole.