ENDOTHELIAL STUNNING AND MYOCYTE RECOVERY AFTER REPERFUSION OF JEOPARDIZED MUSCLE - A ROLE OF L-ARGININE BLOOD CARDIOPLEGIA

Ischemia and reperfusion may damage myocytes and endothelium in jeopar dized hearts. This study tested whether (1) endothelial dysfunction (r educed nitric oxide release) exists despite good contractile performan ce and (2) supplementation of blood cardioplegic solution with nitric oxide precursor L-arginine augments nitric oxide and restores endothel ial function. Among 30 Yorkshire-Duroc pigs, 6 received standard gluta mate/aspartate blood cardioplegic solution without global ischemia, Tw enty-four underwent 20 minutes of 37 degrees C global ischemia. Six re ceived normal blood reperfusion, In 18, the aortic clamp remained in p lace 30 more minutes and ail received 3 infusions of blood cardioplegi c solution, In 6, the blood cardioplegic solution was unaltered; in 6, the blood cardioplegic solution contained L-arginine (a nitric oxide precursor) at 2 mmol/L; in 6, the blood cardioplegic solution containe d the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L -NAME) at 1 mmol/L. Complete contractile and endothelial recovery occu rred without ischemia, In jeopardized hearts, complete systolic recove ry followed infusion of blood cardioplegic solution and of blood cardi oplegic solution plus L-arginine, Conversely, contractility recovered approximately 40% after infusion of normal blood and blood cardioplegi c solution plus L-NAME. Postischemic nitric oxide production fell 50% in the groups that received blood cardioplegic solution and blood card ioplegic solution plus L-NAME but was increased in the group that rece ived blood cardioplegic solution L-arginine, In vivo endothelium-depen dent vasodilator responses to acetylcholine recovered 75% +/- 5% of ba seline in the blood cardioplegic solution plus L-arginine group, but l ess than 20% of baseline in other jeopardized hearts, Endothelium-inde pendent smooth muscle responses to sodium nitroprusside were relativel y unaltered, Myeloperoxidase activity (neutrophil accumulation) was si milar in the blood cardioplegic solution (without ischemia) and blood cardioplegic solution plus L-arginine groups (0.01 +/- 0.002 vs 0.013 +/- 0.003 mu g/gm tissue), Myeloperoxidase activity was raised substan tially to 0.033 +/- 0.002 mu g/gm after exposure to normal blood and t o 0.025 +/- 0.003 mu g/gm after infusion of blood cardioplegic solutio n and was highest at 0.053 +/- 0.01 mu g/gm with exposure to blood car dioplegic solution plus L-NAME in jeopardized hearts. The discrepancy between contractile recovery and endothelial dysfunction in jeopardize d muscle can be reversed by adding L-arginine to blood cardioplegic so lution.