Ventricular fibrillation induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity: Effect of nifedipine

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Abstract

Sympathetic hyperactivity plays a major role in the genesis of malignant arrhythmias during acute myocardial ischemia. An experimental model in which life-threatening arrhythmias are specifically and consistently induced by the interaction between acute myocardial ischemia and left stellate gangllon stimulation has been developed in alpha-chloralose anesthetized cats. In this preparation, drugs that share antiischemic, antiadrenergic, and specific electrophysiologic effects, such as verapamil, diltiazem, and amiodarone, were most effective. To evaluate the relative role of these different properties in mediating the effect of antiarrhythmic drugs, we used this same model to test nifedipine, a calcium channel blocker that is able to counteract the consequences of sympathetic stimulation on coronary circulation but has no electrophysiologic properties at concentrations relevant in the clinical setting. Nifedipine (15 μg/kg) prevented the occurrence of ventricular fibrillation in 10 of 13 animals (77%). Its efficacy was independent of changes in the peripheral hemodynamics. Plasma concentrations of nifedipine were within the therapeutic range in humans. To evaluate if this rather striking protective effect was specifically related to the prevention of the deleterious consequences of sympathetic stimulation, the effect of nifedipine on ventricular fibrillation threshold was studied in an additional group of 13 cats in the nonischemic state, during acute myocardial ischemia and during ischemia plus sympathetic stimulation. Nifedipine did not modify ventricular fibrillation threshold in nonischemic or in ischemic conditions. However, nifedipine specifically prevented the further reduction in ventricular fibrillation threshold occurring when sympathetic stimulation was superimposed on acute ischemia. These data suggest that the extension of ischemic damage by sympathetic stimulation is an important progenitor of arrhythmogenic action during acute ischemia. Agents such as nifedipine that can specifically counteract this effect may be useful in preventing life-threatening arrhythmias, even if they lack direct electrophysiologic properties.

Original languageEnglish
Pages (from-to)37-43
Number of pages7
JournalAmerican Heart Journal
Volume116
Issue number1 PART 1
DOIs
Publication statusPublished - 1988

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Ventricular Fibrillation
Nifedipine
Myocardial Ischemia
Cardiac Arrhythmias
Ischemia
Cats
Coronary Circulation
Chloralose
Adrenergic Antagonists
Amiodarone
Diltiazem
Anti-Arrhythmia Agents
Calcium Channel Blockers
Verapamil
Theoretical Models
Hemodynamics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Ventricular fibrillation induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity: Effect of nifedipine",
abstract = "Sympathetic hyperactivity plays a major role in the genesis of malignant arrhythmias during acute myocardial ischemia. An experimental model in which life-threatening arrhythmias are specifically and consistently induced by the interaction between acute myocardial ischemia and left stellate gangllon stimulation has been developed in alpha-chloralose anesthetized cats. In this preparation, drugs that share antiischemic, antiadrenergic, and specific electrophysiologic effects, such as verapamil, diltiazem, and amiodarone, were most effective. To evaluate the relative role of these different properties in mediating the effect of antiarrhythmic drugs, we used this same model to test nifedipine, a calcium channel blocker that is able to counteract the consequences of sympathetic stimulation on coronary circulation but has no electrophysiologic properties at concentrations relevant in the clinical setting. Nifedipine (15 μg/kg) prevented the occurrence of ventricular fibrillation in 10 of 13 animals (77{\%}). Its efficacy was independent of changes in the peripheral hemodynamics. Plasma concentrations of nifedipine were within the therapeutic range in humans. To evaluate if this rather striking protective effect was specifically related to the prevention of the deleterious consequences of sympathetic stimulation, the effect of nifedipine on ventricular fibrillation threshold was studied in an additional group of 13 cats in the nonischemic state, during acute myocardial ischemia and during ischemia plus sympathetic stimulation. Nifedipine did not modify ventricular fibrillation threshold in nonischemic or in ischemic conditions. However, nifedipine specifically prevented the further reduction in ventricular fibrillation threshold occurring when sympathetic stimulation was superimposed on acute ischemia. These data suggest that the extension of ischemic damage by sympathetic stimulation is an important progenitor of arrhythmogenic action during acute ischemia. Agents such as nifedipine that can specifically counteract this effect may be useful in preventing life-threatening arrhythmias, even if they lack direct electrophysiologic properties.",
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T1 - Ventricular fibrillation induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity

T2 - Effect of nifedipine

AU - Priori, Silvia G.

AU - Zuanetti, Giulio

AU - Schwartz, Peter J.

PY - 1988

Y1 - 1988

N2 - Sympathetic hyperactivity plays a major role in the genesis of malignant arrhythmias during acute myocardial ischemia. An experimental model in which life-threatening arrhythmias are specifically and consistently induced by the interaction between acute myocardial ischemia and left stellate gangllon stimulation has been developed in alpha-chloralose anesthetized cats. In this preparation, drugs that share antiischemic, antiadrenergic, and specific electrophysiologic effects, such as verapamil, diltiazem, and amiodarone, were most effective. To evaluate the relative role of these different properties in mediating the effect of antiarrhythmic drugs, we used this same model to test nifedipine, a calcium channel blocker that is able to counteract the consequences of sympathetic stimulation on coronary circulation but has no electrophysiologic properties at concentrations relevant in the clinical setting. Nifedipine (15 μg/kg) prevented the occurrence of ventricular fibrillation in 10 of 13 animals (77%). Its efficacy was independent of changes in the peripheral hemodynamics. Plasma concentrations of nifedipine were within the therapeutic range in humans. To evaluate if this rather striking protective effect was specifically related to the prevention of the deleterious consequences of sympathetic stimulation, the effect of nifedipine on ventricular fibrillation threshold was studied in an additional group of 13 cats in the nonischemic state, during acute myocardial ischemia and during ischemia plus sympathetic stimulation. Nifedipine did not modify ventricular fibrillation threshold in nonischemic or in ischemic conditions. However, nifedipine specifically prevented the further reduction in ventricular fibrillation threshold occurring when sympathetic stimulation was superimposed on acute ischemia. These data suggest that the extension of ischemic damage by sympathetic stimulation is an important progenitor of arrhythmogenic action during acute ischemia. Agents such as nifedipine that can specifically counteract this effect may be useful in preventing life-threatening arrhythmias, even if they lack direct electrophysiologic properties.

AB - Sympathetic hyperactivity plays a major role in the genesis of malignant arrhythmias during acute myocardial ischemia. An experimental model in which life-threatening arrhythmias are specifically and consistently induced by the interaction between acute myocardial ischemia and left stellate gangllon stimulation has been developed in alpha-chloralose anesthetized cats. In this preparation, drugs that share antiischemic, antiadrenergic, and specific electrophysiologic effects, such as verapamil, diltiazem, and amiodarone, were most effective. To evaluate the relative role of these different properties in mediating the effect of antiarrhythmic drugs, we used this same model to test nifedipine, a calcium channel blocker that is able to counteract the consequences of sympathetic stimulation on coronary circulation but has no electrophysiologic properties at concentrations relevant in the clinical setting. Nifedipine (15 μg/kg) prevented the occurrence of ventricular fibrillation in 10 of 13 animals (77%). Its efficacy was independent of changes in the peripheral hemodynamics. Plasma concentrations of nifedipine were within the therapeutic range in humans. To evaluate if this rather striking protective effect was specifically related to the prevention of the deleterious consequences of sympathetic stimulation, the effect of nifedipine on ventricular fibrillation threshold was studied in an additional group of 13 cats in the nonischemic state, during acute myocardial ischemia and during ischemia plus sympathetic stimulation. Nifedipine did not modify ventricular fibrillation threshold in nonischemic or in ischemic conditions. However, nifedipine specifically prevented the further reduction in ventricular fibrillation threshold occurring when sympathetic stimulation was superimposed on acute ischemia. These data suggest that the extension of ischemic damage by sympathetic stimulation is an important progenitor of arrhythmogenic action during acute ischemia. Agents such as nifedipine that can specifically counteract this effect may be useful in preventing life-threatening arrhythmias, even if they lack direct electrophysiologic properties.

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