Protective effects of bepridil on calcium injury of anoxic myocytes isolated from adult rat heart ventricular muscle.
Cardiac myocytes allowed to recover after the isolation procedure in a well-oxygenated medium were resistant to an extracellular Ca++ concentration of 1.5 mM. At least 90% of the isolated myocytes maintained their initial rod-shaped form after a 1-hr incubation, as well as 85% of their ATP and a low cellular content of calcium. At concentrations less than 10(-5) M, bepridil had no effect on these cells. On the other hand, when the myocytes were incubated in anaerobic conditions, 1.5 mM Ca++ was deleterious: the number of viable cells decreased by about 50%, ATP levels were lowered by 70% and the total cell calcium content increased by more than 100%. Bepridil had a biphasic effect on anaerobic cells. At concentrations below 10(7) M, the drug had a beneficial action. It restored cell viability and cellular ATP to 77 and 100% when compared to their respective level in the absence of Ca++. However, at concentrations higher than 10(-6) M, bepridil decreased the number of viable cells as well as their ATP content. At optimal concentrations, bepridil lowered the cellular calcium to its level in aerobic conditions. Without calcium addition, anoxic cells accumulated Na+ and lost K+. Calcium addition decreased Na+ accumulation by 68% and prevented the loss of K+. The Na+ and K+ content of the cells were not affected by bepridil. However, it is noteworthy that, at 10(-4) M, bepridil decreased dramatically the potassium content of the cells. In aerobic conditions, the calcium resistance of isolated ventricular myocytes may still be enhanced by Fluozol, a fluorocarbon compound which increases oxygen solubility in water.
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D015764:Bepridil; D002118:Calcium / Q000378:metabolism / Q000633:toxicity*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D010100:Oxygen; D011188:Potassium / Q000032:analysis; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000032:analysis
D002121:Calcium Channel Blockers; D011759:Pyrrolidines; D015764:Bepridil; D000255:Adenosine Triphosphate; D012964:Sodium; D011188:Potassium; D010100:Oxygen; D002118:Calcium