Direct Detrimental Effects of -Arginine Upon Ischemia–Reperfusion Injury to Myocardium

The effects of -arginine on recovery of myocardial contractile function and oxidative metabolism were investigated in a model of reversible global normothermic, ischemic injury using an isolated, buffer-perfused rabbit heart preparation. One m -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, -arginine caused a slight increase in developed pressure but had no effects on diastolic pressure, oxygen consumption (MVO2), coronary flow, or lactate production. When administered either before or after ischemia-reperfusion, -arginine caused a significant increase in the diastolic pressure-volume relationship (PVR) and decline in systolic function when compared to untreated control hearts receiving the same ischemic injury. Recovery of MVO2and high energy phosphates (phosphocreatine and ATP), measured by31P-NMR spectroscopy, were significantly impaired in -arginine-treated hearts compared to reperfused control hearts. Lactate 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 [15N] -arginine to [15N]nitrate/nitrite using gas chromatography/mass spectroscopy) was not increased by -arginine administration. Thus, we conclude that -arginine acts synergistically with ischemia reperfusion to augment myocardial injury, which includes inhibition of oxidative metabolism and mitochondrial function.