Effects of Aprindine on Ischemia/Reperfusion-Induced Cardiac Contractile Dysfunction of Perfused Rat Heart

Abstract

ABSTRACT-The present study was undertaken to determine whether aprindine, a class Ib antiarrythymic agent, exerts beneficial effects on ischemia/reperfusion-induced cardiac contractile dysfunction and meta bolic derangement. Isolated rat hearts were subjected to 35-min global ischemia, followed by 60-min reperfusion, and functional and metabolic alterations of the heart were determined with or without aprin dine-treatment. Ischemia induced a cessation of left ventricular developed pressure (LVDP), a rise in left ventricular end-diastolic pressure (LVEDP), and an increase in myocardial sodium content and a decrease in myocardial potassium content. When the hearts were reperfused, little recovery of LVDP and sustained rise in LVEDP and perfusion pressure were observed. Ischemia/reperfusion resulted in a release of ATP metabolites and creatine kinase from perfused hearts, an increase in myocardial sodium and calcium con tents, and a decrease in myocardial potassium and magnesium contents. Treatment of the perfused heart with either 10 or 30 uM aprindine for the last 3 min of pre-ischemia improved contractile recovery during reperfusion and suppressed changes in myocardial ion content during ischemia and reperfusion. Treatment with the agent also attenuated the release of ATP metabolites and creatine kinase from the heart. However, treatment with high concentrations of aprindine (70 and 100 uM) improved neither cardiac contractile dys function, myocardial ionic disturbance nor the release of ATP metabolites and creatine kinase during reperfusion. Two possible mechanisms for the cardioprotection by the agent have been suggested: suppres sion of transmembrane flux of substrates and enzymes, and prevention of accumulation of myocardial sodium during ischemia.

Cardiac Arrhythmias - New Considerations

“…The inhibition of the outward K + currents showed the cardioprotective effect during reperfusion (Liu et al, 1993;Tosaki et al, 1996). The increase of intracellular concentration of Na + ions in myocardial cells, and Ca 2+ overload, can contribute to the rise of reoxygenation arrhythmias (Takeo et al, 1995;Kamiyama et al, 1996;Shinmura et al, 1997). Systemic hypoxia induced by hypoventilation changed the electrical stability of the rat heart in dependence on the LD cycle.…”

Chronobiological Aspects of the Heart Rhythm Disorders at the Change of Pulmonary Ventilation in Rat Model

“…In hypoxia/reoxygenation or ischemia/reperfusion models, more authors describe myocardial Ca 2+ accumulation. Ca 2+ overload in myocytes is one of the many causes of the reperfusion injury (Kamiyama et al, 1996;Mubagwa et al, 1997;Shinmura et al, 1997;Sharikabad et al, 2000). It was hypothetized that the delayed afterdepolarizations producing the substrate for arrhythmogenesis of the serious ventricular dysrhythmias (Ca-mediated, non re-entry arrhythmias) are the result of such Ca 2+ overload (Whalley et al, 1995).…”

“…The inhibition of the outward K + currents showed the cardioprotective effect during reperfusion (Liu et al, 1993;Tosaki et al, 1996). The increase of intracellular concentration of Na + ions in myocardial cells, and Ca 2+ overload, can contribute to the rise of reoxygenation arrhythmias (Takeo et al, 1995;Kamiyama et al, 1996;Shinmura et al, 1997). Systemic hypoxia induced by hypoventilation changed the electrical stability of the rat heart in dependence on the LD cycle.…”