Amrinone reduces ischaemia-reperfusion injury in rat heart.
We investigated the effects of amrinone on ischaemia-induced changes in myocardial function in isolated rat hearts. Isolated hearts from male Sprague-Dawley rats (150-275 g) were perfused with physiological salt solution at a constant flow rate. The effects of amrinone (30 microM) on left ventricular end diastolic pressure, positive and negative dP/dt, heart rate and coronary perfusion pressure were observed following global ischaemia and reperfusion. In normal hearts, amrinone had no effect on myocardial contractility, heart rate, coronary perfusion pressure or left ventricular end diastolic pressure. Ischaemia-reperfusion caused an increase in coronary perfusion pressure, left ventricular end diastolic pressure and creatine kinase outflow and amrinone (present from before ischaemia) decreased the rise in all of these parameters. However, when amrinone was added only after the ischaemia, it had no effect on coronary perfusion pressure or left ventricular end diastolic pressure. Thus, the effect on coronary perfusion pressure must be due to actions during the ischaemia phase. We suggest that amrinone has pharmacological properties which may be useful in reducing ischaemia-reperfusion injury. We speculate that this involves altering ischaemia-induced changes in intracellular Ca(2+) in the myocytes.
Rechtman
M P
MP
Prince Henry's Institute of Medical Research, Melbourne, Australia.
Van der Zypp
A
A
Majewski
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D020105:Milrinone; D000676:Amrinone; D015056:1-Methyl-3-isobutylxanthine