In vivo administration of L-arginine at different time points during the course of myocardialischemia and reperfusion(MI/R)has been shown to differentially regulate postischemic apoptosis.Cardiacfunction is one of the most important indexes used to judge the degree of myocardial injury.The presentstudy attempted to determine whether in vivo administration of L-arginine at different stages of MI/R has adiverse influence on cardiac function of ischemic reperfused hearts and,if so,to investigate the mechanismsinvolved.Male adult rats were subjected to 30 min myocardial ischemia followed by 5 h reperfusion.Anintravenous L-arginine bolus was given either 10 min before and 50 min after reperfusion(early treatment)or3 h and 4 h after reperfusion(late treatment).Early treatment with L-arginine markedly increased the leftventricular systolic pressure(LVSP)and dP/dt_(max),and decreased myocardial nitrotyrosine content.In strictcontrast,late treatment with L-arginine resulted in a significant decrease in LVSP and dP/dt_(max)from 4 h to 5h after reperfusion,and increase in toxic peroxynitrite formation as measured by nitrotyrosine.These resultssuggest that the administration of L-arginine at different time points during the course of MI/R leads todiverse effects on cardiac dysfunction.Early supplementation decreased the nitrative stress and improvedleft ventricular function.However,late treatment with L-arginine increased the formation of peroxynitriteand aggravated cardiac functional injury. In vivo administration of L-arginine at different time points during the course of myocardial ischemia and reperfusion (MI / R) has been shown to be differentially regulate postischemic apoptosis. Cardiacfunction is one of the most important indexes used to judge the degree of myocardial injury. presentstudy attempted to determine whether in vivo administration of L-arginine at different stages of MI / R has adiverse on cardiac function of ischemic reperfused hearts and, if so, to investigate the mechanismsinvolved. Male adult rats were subjected to 30 min myocardial ischemia followed by 5 h reperfusion. An intravenous L-arginine bolus was given either 10 min before and 50 min after reperfusion (early treatment) or 3 h and 4 h after reperfusion (late treatment). Early treatment with L-arginine markedly increased the left ventricular systolic pressure ( LVSP) and dP / dt_ (max), and reduced myocardial nitrotyrosine content. In simplecontrast, late treatment with L-arginine resulted in a significant dec rease in LVSP and dP / dt max from 4 h to 5 h after reperfusion and increase in toxic peroxynitrite formation as measured by nitrotyrosine.These resultssuggest that the administration of L-arginine at different time points during the course of MI / R leads todiverse effects on cardiac dysfunction. Early supplementation decreased the nitrative stress and improvedleft ventricular function. Despite, late treatment with L-arginine increased the formation of peroxynitrite and aggravated cardiac functional injury.