Improvement of postischemic contractile dysfunction of dog heart by MCI-154, a novel cardiotonic agent.

Abstract:

:The effects of MCI-154, a cardiotonic agent which has direct effects on cardiac myofilaments, on postischemic contractile dysfunction were studied in dog heart subjected to a 30-min occlusion of the left anterior descending coronary artery followed by reperfusion, and compared with the effects of milrinone and dobutamine, that have largely cyclic AMP-dependent mechanisms of action. Regional myocardial contractility (segment shortening) and tissue ATP levels were severely depressed in reperfused myocardium. MCI-154 (0.3 and 1 microgram/kg per min) improved the regional function of postischemic myocardium and decreased left ventricular end-diastolic pressure and systemic aortic pressure when infused i.v. from 30 min after reperfusion. The improvement of regional function caused by MCI-154 (1 microgram/kg per min) was more pronounced than that caused by milrinone (1 microgram/kg per min) or dobutamine (1 microgram/kg per min), although the drugs produced an equal increase in cardiac performance (peak positive left ventricular dP/dt). These results suggest that MCI-154 produces a more pronounced improvement of regional myocardial function than milrinone and dobutamine, presumably by increasing the responses of the contractile protein system to Ca2+. In this respect, MCI-154 would be of much benefit for the treatment of postischemic left ventricular dysfunction.

journal_name

Eur J Pharmacol

authors

Abe Y,Kitada Y,Narimatsu A,Tobe A

doi

10.1016/0014-2999(91)90053-s

subject

Has Abstract

pub_date

1991-01-10 00:00:00

pages

279-85

issue

2

eissn

0014-2999

issn

1879-0712

pii

0014-2999(91)90053-S

journal_volume

192

pub_type

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