CARDIAC VERSUS CORONARY DILATOR EFFECTS OF SD-3211, A NEW NONDIHYDROPYRIDINE CALCIUM-ANTAGONIST, IN ISOLATED, BLOOD-PERFUSED DOG HEARTS

被引：12
作者：
YONEYAMA, F [1 ]
YAMADA, H [1 ]
SATOH, K [1 ]
TAIRA, N [1 ]
机构：
[1] TOHOKU UNIV,SCH MED,DEPT PHARMACOL,SENDAI,MIYAGI 980,JAPAN
来源：
CARDIOVASCULAR DRUGS AND THERAPY | 1990年 / 4卷 / 06期
关键词：
CORONARY DILATOR; NEGATIVE DROMOTROPIC EFFECT; NONDIHYDROPYRIDINE CALCIUM ANTAGONIST; SD-3211;
D O I：
10.1007/BF02026494
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Coronary and cardiac effects of SD-3211 were compared in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. SD-3211 was administered intraarterially. In all preparations SD-3211 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate, and in high doses atrial standstill occurred. The dose that produced a 15% decrease in sinus rate was about 5.6 times the dose that doubled coronary blood flow. In AV node preparations, when injected into the artery supplying the AV node, the drug produced an increase in AV conduction time, and in high doses second- or third-degree AV block occurred. The dose that produced a 15% increase in AV conduction time was about 1.6 times the dose that doubled coronary blood flow. In the same preparations the drug slightly increased AV conduction time only at high doses when injected into the artery supplying the His-Purkinje-ventricular system. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. The dose that produced a 50% decrease in the force of contraction of the paced papillary muscle was about 50 times the dose that doubled coronary blood flow. The drug was virtually ineffective on ventricular automaticity. In short, in doses that doubled coronary blood flow, SD-3211 depressed only AV nodal conduction. This cardiovascular profile differs from those of diltiazem and verapamil, which do not discriminate between coronary vasculature and the SA and the AV node.
引用
收藏
页码：1469 / 1476
页数：8
相关论文
共 22 条
  • [1] Nishimura K., Miyawaki N., Yamauchi H., Iso T., Tissue selectivity of the novel calcium antagonist sesamodil fumarate in isolated smooth muscles and cardiac muscles, Arzneimitt Forsch (Drug Res), 40, pp. 244-248, (1990)
  • [2] Taira N., Effects of diltiazem and other calcium-antagonists on cardiac functions and coronary blood flow as assessed in blood-perfused dog-heart preparations, New Drug Therapy with a Calcium Antagonist: Diltiazem Hakone Symposium '78, pp. 91-103, (1979)
  • [3] Taira N., Differences in cardiovascular profile among calcium antagonists, The American Journal of Cardiology, 59, pp. 24B-29B, (1987)
  • [4] Kawada M., Satoh K., Taira N., Profile of coronary vasodilator and cardiac actions of bepridil revealed by use of isolated, blood-perfused heart preparations of the dog, J Cardiovasc Pharmacol, 5, pp. 604-612, (1983)
  • [5] Taira N., Kawada M., Satoh K., Cardiac versus coronary vasodilator actions of KB-944, a new calcium antagonist, assessed in isolated, blood-perfused heart preparations of dogs, J Cardiovasc Pharmacol, 5, pp. 359-356, (1983)
  • [6] Hosono M., Taira N., coronary vasodilator versus cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in the dog heart, J Cardiovasc Pharmacol, 9, pp. 633-640, (1987)
  • [7] Kubota K., Hashimoto K., Selective stimulation of the parasympathetic preganglionic nerve fibres in the excised and blood-perfused SA node preparation of the dog, Naunyn Schmiedebergs Arch Pharmacol, 278, pp. 135-150, (1973)
  • [8] Hashimoto K., Iijima T., Hashimoto K., Taira N., The isolated and cross-circulated AV node preparation of the dog, Tohoku J Exp Med, 107, pp. 263-275, (1972)
  • [9] Endoh M., Hashimoto K., Pharmacological evidence of autonomic nerve activities in canine papillary muscle, Am J Physiol, 218, pp. 1459-1463, (1970)
  • [10] Litchfield J.T., Wilcoxon F., A simplified method of evaluating dose-effect experiments, J Pharmacol Exp Ther, 96, pp. 99-113, (1949)
123