Improvement of postischemic contractile dysfunction of dog heart by MCI-154, a novel cardiotonic agent.
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.
Abe
Y
Y
Research Center, Mitsubishi Kasei Corporation, Yokohama, Japan.
Kitada
Y
Y
Narimatsu
A
A
Tobe
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004280:Dobutamine / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D011724:Pyridazines; D011728:Pyridones; D004280:Dobutamine; D000255:Adenosine Triphosphate; C052228:MCI 154; D020105:Milrinone; D002118:Calcium