Direct detrimental effects of L-arginine upon ischemia--reperfusion injury to myocardium.
The effects of L-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 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-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. L-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 MVO2 and high energy phosphates (phosphocreatine and ATP), measured by 31P-NMR spectroscopy, were significantly impaired in L-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]L-arginine to [15N]nitrate/nitrite using gas chromatography/mass spectroscopy) was not increased by L-arginine administration. Thus, we conclude that L-arginine acts synergistically with ischemia reperfusion to augment myocardial injury, which includes inhibition of oxidative metabolism and mitochondrial function.
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000097:blood; D010084:Oxidation-Reduction / Q000187:drug effects; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*
D009569:Nitric Oxide; D001120:Arginine