Improvement of ischemic myocardial dysfunction by nisoldipine in relation to its coronary vasodilating action.
We examined the cardioprotective effect of nisoldipine against myocardial dysfunction during ischemia and reperfusion in comparison with those of diltiazem and nifedipine in rabbit hearts perfused at constant pressure. These calcium antagonists were administered to the hearts before 60 min of ischemia. They inhibited the increase of end-diastolic pressure during ischemia in a dose-dependent manner. Diltiazem at 1.0 microM, nifedipine at 3.0 microM and nisoldipine at 0.01 microM produced the maximal cardioprotective effect. Nisoldipine had a beneficial effect with less negative inotropic effect than those of diltiazem and nifedipine and it produced a significant increase of coronary flow during reperfusion. When the vascular component was eliminated under constant flow perfusion, nisoldipine also showed the cardioprotective effect. Nisoldipine did not produce any beneficial effect without the inhibition of the increase in end-diastolic pressure during ischemia nor did it do so without the increase of reperfusion flow. Therefore, the nisoldipine-increased coronary flow during reperfusion as well as the inhibition of ischemic contracture by nisoldipine seems to play a crucial role in improving the myocardial dysfunction of ischemic-reperfused hearts.
Umeda
M
M
Pharmacology Institute, Bayer Yakuhin, Ltd., Kobe, Japan.
Saida
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D015737:Nisoldipine / Q000494:pharmacology / Q000627:therapeutic use*; D010477:Perfusion; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D015737:Nisoldipine; D004110:Diltiazem; D009543:Nifedipine