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.

• Authors: Y Abe, Y Kitada, A Narimatsu, A Tobe
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 192 Issue 2 Pg. 279-85 (Jan 10 1991) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2032560 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cardiotonic Agents
• Pyridazines
• Pyridones
• Dobutamine
• Adenosine Triphosphate
• MCI 154
• Milrinone
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Calcium (metabolism)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Coronary Disease (drug therapy, physiopathology)
• Dobutamine (therapeutic use)
• Dogs
• Female
• Hemodynamics (drug effects)
• Male
• Milrinone
• Myocardial Contraction (drug effects)
• Myocardium (metabolism)
• Pyridazines (pharmacology, therapeutic use)
• Pyridones (therapeutic use)
• Ventricular Function, Left (drug effects)