DIRECT DETRIMENTAL EFFECTS OF L-ARGININE UPON ISCHEMIA-REPERFUSION INJURY TO MYOCARDIUM

The effects of L-arginine on recovery of myocardial contractile functi on and oxidative metabolism were investigated in a model of reversible global normothermic, ischemic injury using an isolated, buffer-perfus ed rabbit heart preparation, One mM L-arginine was infused into hearts for 2 min at the onset (group 1) of a 35 min period of ischemia or at the onset of reperfusion (group 2). In non-ischemic hearts, L-arginin e caused a slight increase in developed pressure but had no effects on diastolic pressure, oxygen consumption (MVO(2)), coronary flow, or la ctate production. When administered either before or after ischemia-re perfusion, L-arginine caused a significant increase in the diastolic p ressure-volume relationship (PVR) and decline in systolic function whe n compared to untreated control hearts receiving the same ischemic inj ury. Recovery of MVO(2) and high energy phosphates (phosphocreatine an d ATP), measured by P-31-NMR spectroscopy, were significantly impaired in L-arginine-treated hearts compared to reperfused control hearts. L actate release on reperfusion was also higher in both arginine-treated groups, Nitric oxide release into the coronary circulation (measured in separate experiments by the conversion of [N-15]L-arginine to [N-15 ]nitrate/nitrite using gas chromatography/mass spectroscopy) was not i ncreased by L-arginine administration. Thus, we conclude that L-argini ne acts synergistically with ischemia reperfusion to augment myocardia l injury, which includes inhibition of oxidative metabolism and mitoch ondrial function. (C) Academic Press Limited