[Basic amino acid, L-arginine aggravates ischemia-reperfusion injury]

Abstract

Basic amino acid, L-arginine has been known to have several biological actions including nitric oxide production. The real effects caused by L-arginine administration to heart has not been fairly understood in the setting of ischemia-reperfusion process. The effects of L-arginine on recovery of myocardial contractile function and oxidative metabolism were studied in a model of reversible global normothermic ischemic injury using an isolated, buffer-perfused rabbit heart preparation. 1 mM L-arginine or vehicle was infused into hearts for 2 minutes at the onset of 35 minutes of ischemia in L-arg. group or in control group, respectively. Oxygen consumption (MVO2), lactate release into coronary vessels, and cardiac function including developed pressure, +dp/dt, -dp/dt and diastolic pressure-volume relationship (PVR) were measured and high energy phosphates were also evaluated by 31P-NMR spectroscopy. Endothelial function was also evaluated by acetylcholine (Ach) infusion with monitoring of constant perfusion pressure. L-arginine caused a significant increase in the PVR and profund decline in systolic function when compared to control group. MVO2 was significantly impaired to cause a decrease of high energy phosphates (phosphocreatine and ATP). Lactate release into coronary vessels on reperfusion was significantly higher in L-arg group than that in control group, suggesting a promotion of anaerobic glycolysis. Deterioration of endothelial function and smooth muscle function of artery were evidenced by Ach infusion test. Although the mechanisms of injury are speculatory, possible mechanisms of this injury are stimulation of nitric oxide production by L-arginine and cation change, especially calcium accumulation. We concluded that L-arginine was able to cause aggravation of ischemia-reperfusion injury with reduced contractile function and mitochondrial function and increased anaerobic glycolysis after ischemia-reperfusion in an isolated model of reversible ischemic injury.