Effects of aprindine on ischemia/reperfusion-induced cardiac contractile dysfunction of perfused rat heart.
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 metabolic 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 aprindine-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 contents, and a decrease in myocardial potassium and magnesium contents. Treatment of the perfused heart with either 10 or 30 microM 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 microM) improved neither cardiac contractile dysfunction, 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: suppression of transmembrane flux of substrates and enzymes, and prevention of accumulation of myocardial sodium during ischemia.
Kamiyama
T
T
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Tanonaka
K
K
Hayashi
J
J
Takeo
S
S
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001073:Aprindine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D000889:Anti-Arrhythmia Agents; D004573:Electrolytes; D001073:Aprindine