Protective Effects Of L-Arginine Preconditioning On Short Term Hibernating Myocardium In Rat Hearts In States Of Beating Or Cardioplegia Arrest

Objective The term hibernating myocardium was described as a special state of impaired myocardial and left ventricular function at rest due to reduced coronary blood flow. Hiberniting myocardium has been demonstrated to accur in many kinds of clinical syndromes. But there is few studies on protection and treatment of hibernating myocardium at present. A donor of endorgenous nitric oxide桳-Arginine has been confirmed having protective effects on ischemic myocardium. Whether it can provide protective effects on hibernating myocardium has not known yet, in this study, we are intented to examine whether L-Arginine has beneficial effects on hibernating myocardium in two different states of beating or cardioplegia arrest and to explore its mechanisms.Methods The isolated rat hearts were perfused on a Langendorff perfusion device .36 Sprague-Dawley rat hearts were randomly divided into six groups when balanced perfusion finished. Controlled group (CON n=6)received persistently normal-flow perfusion for 90 minutes; Hibernating group(HBN n=6)received persistently low-flow perfusion for 90 minutes;Hibernating梤eperfusion group(HR n=6) received persistent low-flow perfusion for 90 minutes and subsequent normal-flow perfusion for 30 minutes; L-Arginine preconditioning and beating heart group(HAR n=6) received low-flow perfusion with KHB containing L-Arginine (Immol/L) for 90 minutes and subsequent normal-flow perfusion without L-Arginine for SOminutes; L-Arginine preconditioning and cardioplegia arrest group(HAIR n=6)received low-flow perfusion with KHB containing L-Arginine(Immol/L) for 90 minutes, then cardioplegia arrest for 60 minutes and subsequent normal-flow perfusion without L-Arginine for 30minutes; hibernating and Cardioplegia arrest group(HIR n=6)received low-flow perfusion for 90 minutes, then cardioplegia arrest for 60 minutes and subsequent normal-flow perfusion for 30 minutes ;The effects of L-Arginine on hibernating myocardium were assesed by measurement of hemodynamic parameters expressed as a percentage of baseline value, Myocardial enzemys leakout, Lactate release, MDA and SOD content, Endothelial function(NO and ET content), Myocardial water content, Myocardial nucleotides content (ATP, ADP, AMP, TAN) and ultrastructural alterations during hibernating or reperfusion.Results First of all, In the way which we designed, We successfully set up the model of short-term hibernating myocardium in isolated perfused rat hearts. During low-flow perfusion, heart contractile function in either group was injuried and identically lower than baseline ones. ATP content decreased by 50% in HBN group compared with CON group, and ATP content also reduced respectively in HR, HAR, HAIR and HIR groups. During hibernation, heart contractile function(LVSP , 眃p/dt , LVDP) in HAR, HAIR groups was much better than in HR and HIR(P < 0. 05). The recovery value of contractile function in HAR, HAIR groups was much more than in HR and HIR groups (P < 0. 05) during reperfusion. Myocardial enzemys leakout, lactate release, MDA and ET contents were more in HR and HIR groups than in HAR, HAIR groups(P < 0.05)during hibernation .while they were fewer in HR and HAR groups than in HAIR and HIR groups(P <0. 001)during perfusion. The production of NO kept more in HAR, HAIR groups than in HR and HIR groups persistently. The water cotent in HAR , HAIR groups is higher than in HR and HIR groups. Cardiomyocytes were not found irreversible ultrastructural alterations in HR and HAR groups,But ultrastructural alterations indicated that injury of myocytes in HAIR and HIR groups were more severe than in other groups.Conclusions L-Arginine preconditioning provides exactllyprotective effects on short-term hibernating myocardium, and especially on those in state of beating, The probable mechanism is L-Arginine induces increased generation of endogenous NO and takes its multibiological effects.