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Biomedical subjects

R L Verrier

Publications and source records attributed to R L Verrier.

At least 73 records · Page 4Linked to original sources
PubMed1986

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 2.1 mEq/L induced by hemodialysis decreased the repetitive extrasystole threshold by 30% and the ventricular fibrillation threshold by 25% (p less than 0.01). The increase in ventricular vulnerability following acute coronary occlusion was markedly augmented by concomitant potassium depletion. Thus, hypokalemia enhances the propensity for ventricular fibrillation in the normal as well as in the ischemic canine heart. These findings shed light on clinical observations of enhanced susceptibility to life-threatening arrhythmias during acute myocardial ischemia in hypokalemic patients.

Animals↗
PubMed1986

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 (1.0 microgram X kg-1 X min-1) caused a brief rise and a subsequent prolonged fall in serum potassium concentration, which was accompanied by a decline in ventricular fibrillation threshold when baroreceptor activation was prevented. After pretreatment with the beta1 adrenoceptor blocking agent metoprolol (0.5 mg X kg-1), adrenaline did not alter vulnerability to ventricular fibrillation but still elicited hypokalaemia. In contrast, selective beta2 adrenoceptor blockade (ICI 118551, 100 micrograms X kg-1) prevented the adrenaline induced lowering of serum potassium concentration but not of ventricular vulnerability. Muscarinic receptor activation by methacholine (3.0 micrograms X kg-1 X min-1) had no effect on serum potassium concentration but increased the ventricular fibrillation threshold by 30%. When methacholine was administered concomitantly with adrenaline the decline in serum potassium concentration persisted, but the increase in ventricular vulnerability was completely prevented. It is concluded that in the normal canine myocardium adrenaline produces an increase in vulnerability that is mediated through beta 1 adrenoceptors and that the beta 2 adrenoceptor mediated hypokalaemia is dissociated from electrophysiological effects of adrenaline. Parasympathetic nervous system activation does not influence serum potassium concentrations but opposes the effects of adrenaline on susceptibility to ventricular fibrillation.

Adrenergic beta-Antagonists↗
PubMed1986

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. An intriguing new approach involves changing the serum concentration of amino acid precursors of the central neurotransmitters that modulate autonomic traffic. Considerable evidence indicates that accumulation of serotonin in the brain reduces sympathetic neural activity. When L-tryptophan or 5-hydroxytryptophan is administered with phenelzine (a monoamine oxidase inhibitor) and carbidopa (a selective peripheral L-amino acid decarboxylase inhibitor) to raise brain serotonin, a significant increase in myocardial electrical stability is observed. This effect results from a decrease in cardiac sympathetic tone as indicated by selective denervation and nerve recording studies. Enhancing serotoninergic neurotransmission can also significantly reduce vulnerability to VF during acute coronary artery occlusion. The effect of augmenting serotoninergic activity without the use of enzyme inhibitors has been investigated by administering agents such as melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl) pyrazine (MK-212). Each of these substances increases cardiac electrical stability. The protective influence is unaffected by bilateral vagotomy but is blocked by the specific serotonin antagonist methergoline. Diminution of cardiac sympathetic drive appears to be the main mechanism of action. Thus, neurochemical interventions can exert a profound effect on cardiac electrical stability. Recent advances in neurochemistry and psychopharmacology promise new insights into the problem of sudden death and suggest a fresh approach for the management of life-threatening arrhythmias.

Animals↗
PubMed1986

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. Calcium channel blocking agents, by virtue of their broad spectrum of action, can interrupt the cascade of events leading to arrhythmias. In experimental animals, verapamil has been shown to reduce vulnerability to ventricular fibrillation during sympathetic stimulation and to prevent spontaneous fibrillation during both myocardial ischaemia and reperfusion. Comparable antifibrillatory effects have been observed with diltiazem and prenylamine. Tiapamil is effective during sympathetic stimulation and myocardial ischaemia but not during reperfusion. Nifedipine appears to exert a moderate antifibrillatory influence during myocardial ischaemia and is ineffectual in preventing reperfusion-induced fibrillation. These observations indicate that calcium channel blocking agents differ considerably in their ability to suppress arrhythmias during myocardial ischaemia and reperfusion. Their effectiveness appears to depend critically both on the pathophysiologic mechanisms and on the pharmacologic profile of the individual agent.

Animals↗
PubMed1984

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. There were no adverse effects of VFT measurement. Three patients had nonsustained ventricular tachycardia (VT) on 24-hour ambulatory monitoring and had VFTs of 10, 14, and 16 mA. In this group VF was induced without any preceding repetitive ventricular responses. Seven patients had no repetitive forms on ambulatory monitoring. Their VFTs ranged from 30 to greater than 40 mA (mean greater than 37). Repetitive extrasystoles were regularly observed in this group at current intensities which ranged from 53% to 80% of the VFT. Thus patients with manifest VT appear to have an enhanced vulnerability to VF. Single or multiple responses were not observed in these patients but appeared to be present in patients with coronary disease and no demonstrable rhythm disorder.

Aged↗
PubMed1983

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. There was a statistically significant correlation between the RET and ventricular fibrillation threshold (VFT) until left circumflex coronary artery flow was reduced by 90% of control values (r = 0.92). During reductions of CBF of 90% or greater, the VFT fell more than the RET and the RET/VFT ratio was disrupted. Total coronary occlusion, whether performed abruptly or gradually (5 minutes), likewise resulted in a disproportionate decline in VFT. During sustained total coronary occlusion, the VFT recovered to control values within 15 minutes, and the relationship between the RE and VF thresholds was restored. We conclude that the vulnerable period threshold for provoking repetitive extrasystole is a reliable index of vulnerability to VF during myocardial ischemia and remains so until nearly total occlusion of a major coronary vessel.

Animals↗
PubMed1983

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%). This effect was abolished by baroreceptor denervation. Neither drug altered mid-diastolic threshold or effective refractory period duration either before or after denervation. We conclude that alpha-receptor activation exerts no direct effect on ventricular excitability or refractoriness in the normal intact heart.

Animals↗
PubMed1983

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 +/- 1.3 to 16 +/- 2.3 mA, p less than 0.05) corresponding with the period of maximal activation of cardiac sympathetic preganglionic fibers (from 4.4 +/- 0.2 to 6.3 +/- 0.5 impulses/sec). Coronary sinus blood flow and oxygen tension decreased significantly. All these changes persisted for 5 to 6 minutes, thereafter returning to control levels despite continued obstruction of the coronary artery. A transient but significant reduction in ventricular fibrillation threshold also occurred with release of the occlusion but was unaccompanied by increases in sympathetic neural discharge. Bilateral stellectomy completely prevented the ventricular fibrillation threshold changes observed during coronary artery occlusion. However, there was no change in coronary sinus oxygen tension or blood flow. During reperfusion, stellectomy increased rather than decreased vulnerability to ventricular fibrillation. Stellectomy augmented the reactive hyperemic response to release-reperfusion. These findings indicate that enhanced cardiac sympathetic neural activity contributes to ventricular vulnerability associated with coronary artery obstruction. An opposite action results during release-reperfusion. Cardiac sympathetic neural discharge, by reducing the magnitude of reactive hyperemic response through influence on coronary vascular tone, exerts an antifibrillatory effect.

Animals↗
PubMed1983

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 0.01). These changes are known to be associated with the formation and distal embolization of platelet aggregates. These reductions in coronary blood flow were accompanied by significant decreases in the repetitive extrasystole (-40%) and ventricular fibrillation (-38%) thresholds. Prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet activation, in increasing doses of from 25 to 100 ng/kg/min caused a stepwise decrease in the frequency and magnitude of coronary blood flow fluctuations and restored the vulnerable period thresholds to control levels. Indomethacin (5 mg/kg), an inhibitor of cyclo-oxygenase activation and platelet thromboxane A2 production, produced similar results. The mechanism of coronary blood flow reduction appears to be mechanical blockade of the vessel lumen by platelet thrombi and production of myocardial ischemia. These results suggest that intracoronary platelet aggregation contributes to electrical destabilization of the myocardium and may predispose to ventricular fibrillation. A model is thus available for further investigating the role of platelets and antiplatelet drugs in modulating ventricular electrical stability.

Animals↗
PubMed1983

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. Intravenous propranolol (0.5 mg/kg), oxprenolol (0.5 mg/kg) and pindolol (0.05 mg/kg) were administered in 16 anesthetized dogs. The effects of the drugs on ventricular vulnerability were studied over a 2 hour period. Propranolol and oxprenolol raised the ventricular fibrillation threshold by 42 and 56%, respectively. In contrast, pindolol resulted in an elevation of only 25%. After depletion of endogenous norepinephrine stores using reserpine, pindolol led to a decrease of the ventricular fibrillation threshold, which was reversed by propranolol. These data indicate that intrinsic sympathomimetic activity of beta-adrenergic blocking agents substantially alters their ultimate effect on myocardial excitable properties.

Adrenergic beta-Antagonists↗
PubMed1983

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 (0.5 micrograms X kg-1 X min-1) caused a fall in ventricular fibrillation threshold from 30 to 20 mA (P less than 0.001). Pretreatment with prostaglandin E1, I2 or nitroglycerin at doses which reduced mean arterial blood pressure by 0.7 to 1.3 kPa (5 to 10 mmHg) abolished the enhanced vulnerability produced by noradrenaline. Following baroreceptor denervation, these agents no longer afforded protection against the profibrillatory action of noradrenaline. We conclude that small doses of vasodilator agents can augment ventricular electrical stability. The mechanism for this protective action appears to be a decrease in cardiac sympathetic tone resulting from vasodilatation of baroreceptor areas.

Alprostadil↗
PubMed1982

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. Prostacyclin lowered the vulnerable period threshold in the normal animal. PGI2 had no effect on ventricular vulnerability when the blood pressure was controlled with phenylephrine and was not protective during either occlusion or release. However, when blood pressure was controlled, PGI2 did not reverse the vasoconstrictor and profibrillatory effects of ergonovine.

Animals↗
PubMed1982

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. Vagotomy reduced the frequency of CBF oscillations from 11.5 +/- 2.1 to 5.0 +/- 2.1 cycles/hr (p less than 0.05). The magnitude of the flow changes was reduced from 13.8 +/- 4.0 to 9.7 +/- 3.0 ml/min (NS). Bilateral cervical stellectomy reduced the frequency of CBF changes from 7.8 +/- 2.7 to 3.7 +/- 1.3 cycles/hr (p less than 0.025) and their magnitude from 10.6 +/- 2.5 to 5.6 +/- 1.8 ml/min (P less than 0.05). In five dogs in which cyclical CBF changes were reduced or abolished by decentralizing the stellate ganglia, electrical stimulation of the main body of the left ganglion evoked or enhanced the oscillations in two dogs, had no distinct effect in two dogs, and elicited no response in one dog. A 5-minute infusion of 0.5 microgram/kg/min and 0.75 microgram/kg/min epinephrine (four dogs) provoked the CBF changes in all animals for a period of 5 to 10 minutes. Blockade of muscarinic receptors by 0.2 mg/kg atropine resulted in a significant attenuation of flow changes, which may at least in part have been due to a direct effect of atropine on platelets. We conclude that cardiac sympathetic tone significantly influences the CBF pattern during critical coronary stenosis. While the afferent limb of the vagus may in part mediate this effect via a reflex increase of adrenal medullary catecholamines, the role of the efferent vagus awaits further clarification.

Animals↗
PubMed1982

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. The influence of sulfinpyrazone during acute myocardial ischemia was evaluated before and during a 10 minute occlusion of the left anterior descending coronary artery and after abrupt release of the occlusion. Although the drug afforded significant protection during coronary occlusion, it had no effect on the ventricular fibrillation threshold after reperfusion. Because potent cardiocardiac reflexes are elicited during ischemia, the influence of sulfinpyrazone on the ventricular fibrillation threshold was studied during norepinephrine infusion. Sulfinpyrazone attenuated the reduction of the ventricular fibrillation threshold during sympathetic humoral stimulation. Its effect was additive to beta adrenergic blockade with practolol and membrane stabilization with lidocaine. This investigation suggests that sulfinpyrazone exerts significant effects on ventricular vulnerability of both the normal and the ischemic myocardium. Further studies are needed to elucidate its precise mechanism of action.

Animals↗
PubMed1982

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. This report describes a series of studies designed to investigate the processes underlying cardiac vulnerability and the influence upon it of various psychological stresses. It is concluded that the primary mediator of ventricular vulnerability is the sympathetic nervous system. The efferent vagus appears to exert some protective influence against arrhythmias due to adrenergic stimulation. An appropriate clinical strategy for the treatment of malignant arrhythmias would therefore involve attempts to decrease cardiac sympathetic drive whilst at the same time enhancing vagal tone. Treatments are described which aim to bring this situation about by the use of clonidine, morphine sulphate, l-tryptophan and tyrosine. The use of neurochemical agents in this context appears promising.

Animals↗