Mechanism of protection by verapamil and nifedipine from anoxic injury in isolated cardiac myocytes.
This study was designed to determine whether slow Ca2+ channel blocking agents exert a direct protective effect on the anoxic myocardial cell and, if so, what the mechanism of protection is. Isolated Ca2+-tolerant rat cardiac myocytes were incubated under aerobic or anaerobic conditions, with or without verapamil or nifedipine, in the resting and contractile state. Protection against cell injury was assessed by preservation of rod-shaped morphology, cellular ATP levels, intracellular ionic composition, and lactate dehydrogenase release. Resting myocytes incubated anaerobically lost their rod-shaped appearance, accumulated Na+ and lost K+, and suffered a significant loss of cellular ATP. The release of lactate dehydrogenase into the medium was increased twofold, indicating significant membrane injury. Verapamil (1 microM) or nifedipine (1 microM) did not afford any protection against anoxic injury as measured by these parameters. Furthermore, on reoxygenation, anoxic verapamil- and nifedipine-treated myocytes had significantly higher cellular Ca2+ levels than control aerobic cells. When anoxic myocytes were paced at a rate of 300/min for 10 min, there were marked decreases in the number of rod-shaped cells and cellular ATP levels, whereas identically paced aerobic cells sustained no significant injury. Verapamil (1 microM) or nifedipine (1 microM) protected cells paced at 300/min from anoxic injury, but the cells were unable to sustain contraction rates at the frequency of the imposed pacing.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000032:analysis; D000860:Hypoxia / Q000473:pathology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000032:analysis / Q000473:pathology*; D009543:Nifedipine / Q000627:therapeutic use*; D051381:Rats; D014700:Verapamil / Q000627:therapeutic use*
D014700:Verapamil; D009543:Nifedipine; D002118:Calcium