Myocardial properties of the new dihydropyridine calcium antagonist isradipine compared to nifedipine with or without additional beta blockade in coronary artery disease.
Isradipine is a new dihydropyridine calcium antagonist with myocardial effects significantly different from those of nifedipine, as shown by in vitro and animal experimental data. Isradipine selectively inhibits the sinus node but not the atrioventricular conduction and its negative inotropic action is much less if administered in a dose of comparable peripheral effects. To study these effects in man, 40 patients with coronary artery disease were divided into 2 groups receiving either a continuous 30-minute intravenous infusion of 2 mg of nifedipine or 0.5 mg of isradipine, doses that resulted in a comparable afterload reduction (decrease of systemic vascular resistance: nifedipine -22.1%, isradipine -25%, p less than 0.001). Ten patients in each group received an additional intravenous bolus of 5 mg of propranolol at the end of the calcium antagonist administration to antagonize its induced adrenergic reflex mechanisms. The heart rate significantly increased after nifedipine only (+9.2%, p less than 0.001), experienced no change after isradipine and the nifedipine and propranolol combination and decreased after the combination of isradipine and propranolol (-9.6%, p less than 0.001). This resulted in a significant decrease of the rate pressure product with isradipine (-12.5%, p less than 0.001) but not with nifedipine. As a result of the afterload-induced adrenergic reflex mechanisms, the maximal derivative of the left ventricular pressure increased after isradipine administration (+13.5%, p less than 0.001) and was unchanged after nifedipine, which demonstrates the significantly less negative inotropic properties of isradipine as compared with nifedipine.
Mauser
M
M
Department of Cardiology, University of Tübingen, Federal Republic of Germany.
Voelker
W
W
Ickrath
O
O
Karsch
K R
KR
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D017275:Isradipine; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D011725:Pyridines; D011433:Propranolol; D009543:Nifedipine; D017275:Isradipine