Protective Effect of Benidipine Against the Abnormal Electrical Activity in Single Ventricular Myocytes of the Guinea Pig Under Simulated Ischemic Conditions and Reperfusion.

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  • Tokuno Tomoaki
    Department of Pharmacology & Therapeutics Faculty of Pharmaceutical Sciences,Nagoya City University,3-1 Tanabedori,Mizuhoku,Nagoya 467-8603,Japan
  • Muraki Katsuhiko
    Department of Chemical Pharmacology,Facultyof Pharmaceutical Sciences,Nagoya City University,3-1 Tanabedori,Mizuhoku,Nagoya 467-8603,Japan
  • Watanabe Minoru
    Department of Chemical Pharmacology,Facultyof Pharmaceutical Sciences,Nagoya City University,3-1 Tanabedori,Mizuhoku,Nagoya 467-8603,Japan
  • Imaizumi Yuji
    Department of Pharmacology & Therapeutics Faculty of Pharmaceutical Sciences,Nagoya City University,3-1 Tanabedori,Mizuhoku,Nagoya 467-8603,Japan

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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(pH7.4)to the modified one, which contained no glucose, 8mM K+ and 30mM sodium-D, L-lactate and was gassed with 90% argon −10%CO2(pH6.6).Under the simulated ischemia for 20min, EAs such as delayed afterdepolarization, early afterdepolarization, automatic activity or transient inward current were observed in about 37% of myocytes driven electrically at 1Hz.Irreversible hypercontracture occurred in myocytes of 10% or less.Upon reperfusion with the standard solution, EAs and hypercontracture were oberved 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 10min with 10nM 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.

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  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 82 (3), 199-209, 2000

    公益社団法人 日本薬理学会

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