CARDIOPROTECTIVE EFFECT OF L-ARGININE IN MYOCARDIAL-ISCHEMIA AND REPERFUSION IN AN ISOLATED WORKING RAT-HEART MODEL

Background Studies in myocardial ischemia and reperfusion have demonst rated damage to endothelium, impaired production and release of vasoac tive substances such as nitric oxide, and marked alteration in endothe lium-dependent relaxatin of the coronary vasculature. This study was d esigned to examine the cardioprotective effect of exogenous administra tion of L-arginine, a precursor of nitric oxide, during ischemia and r eperfusion, particularly using oxygenated crystalloid cardioplegia. Me thods. Seventy energy-depleted isolated working rat hearts were arrest ed by cardioplegia and subjected to 60 min normothermic global ischemi a followed by 10 min nonworking and 30 min working reperfusion (Gr 1). L-arginine (3mM or 10mM) was added to the cardioplegic solution (Gr 2 ,3 respectively), reperfusion (Gr 6,7 respectively), throughout the ex periment (Gr 4,5 respectively), and with Nw-nitro-L-arginine methyl es ter (L-NAME), a competitive inhibitor of nitric oxide synthase (Gr 8). Results. At 30 min of working heart reperfusion, compared to control, all arginine containing groups (Gr 2-7) exhibited a significant impro ved recovery of cardiac output (64.7+/-21.2, 98.1+/-21.1, 90.9+/-11.7, 88.9+/-16.2, 83.1+/-7.4, and 90.8+/-10.6, mean +/- SD% Gr 2 to 7 resp ectively, vs Gr 1 36.3+/-20%, p<0.01). Significant recovery improvemen t was observed also in other hemodynamic parameters (coronary now, aor tic peak pressure), as well as biochemical recovery assessed by O-2 co nsumption ratio, release of lactic dehydrogenase at reperfusion and re generation of ATP. The L-NAME group had a significant poorer hemodynam ic and biochemical recovery. L-arginine had no effect on the preischem ic hemodynamic parameters. Conclusions. These results support the cumu lative data considering L-arginine as a cardioprotective agent in post ischemic reperfusion injury.