Protective effect of benidipine against the abnormal electrical activity in single ventricular myocytes of the guinea pig under simulated ischemic conditions and reperfusion.
Induction of electrical abnormalities (EAs) under simulated ischemic conditions and after reperfusion was measured from single cardiac myocytes isolated from guinea pig ventricle using whole-cell voltage or current clamp with perforated patch variation. Conditions of simulated ischemia were produced by the exchange of medium from the standard one oxygenated with 95% O2-5% CO2 gas (pH 7.4) to the modified one, which contained no glucose, 8 mM K+ and 30 mM sodium-D,L-lactate and was gassed with 90% argon-10% CO2 (pH 6.6). Under the simulated ischemia for 20 min, EAs such as delayed afterdepolarization, early afterdepolarization, automatic activity or transient inward current were observed in about 37% of myocytes driven electrically at 1 Hz. Irreversible hypercontracture occurred in myocytes of 10% or less. Upon reperfusion with the standard solution, EAs and hypercontracture were observed in about 43% and 22% of cells, respectively. Glibenclamide-sensitive current was detected during ischemia, but tended to be enhanced during reperfusion. Amplitude of Ca2+ current and ATP-sensitive K+ current after reperfusion varied widely with time and from cell to cell. When myocytes were pretreated for 10 min with 10 nM benidipine, a 1,4-dihydropyridine derivative Ca2+ blocker, the incidence of EAs and hypercontracture was markedly reduced, suggesting the protective effect of benidipine against cardiac cell injury during ischemia and reperfusion.
Tokuno
T
T
Department of Pharmacology & Therapeutics, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuhoku, Nagoya, Japan.
Muraki
K
K
Watanabe
M
M
Imaizumi
Y
Y
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine