L-ARGININE REDUCES ENDOTHELIAL INFLAMMATION AND MYOCARDIAL STUNNING DURING ISCHEMIA-REPERFUSION

Background. This study evaluated whether the nitric oxide precursor L- arginine could reduce ischemia/reperfusion injury by preventing leukoc yte-endothelial interactions. Methods. Normothermic regional ischemia was induced in the open-chest working pig heart for 30 minutes followe d by 90 minutes of reperfusion. A preischemic 10-minute intravenous in fusion of 4 mg . kg(-1) min(-1) of L-arginine (n = 12) was compared wi th 12 control pigs. Nitric oxide release was measured from the coronar y sinus using an amperometric probe. Left ventricular function, malona ldehyde, creatine kinase, myocardial oxygen extraction, and the solubl e adhesion molecules (intracellular adhesion molecule-1, endothelial l eukocyte adhesion molecule-1, and vascular cell adhesion molecule-1) w ere measured. Results. Nitric oxide release was significantly reduced from baseline throughout ischemia/reperfusion only in the control grou p. Systolic and diastolic function, and myocardial oxygen extraction w ere also significantly decreased during early reperfusion in the contr ol compared with the L-arginine group. Peak creatine kinase release wa s not significantly different between groups. The incidence of ventric ular fibrillation, malonaldehyde release, and soluble intracellular ad hesion molecule-1, endothelial leukocyte adhesion molecule-1, and vasc ular cell adhesion molecule-1 were each significantly decreased during reperfusion in the L-arginine group. Conclusions. L-Arginine reduced lipid peroxidation, plasma levels of soluble adhesion molecules, myoca rdial stunning, and arrhythmias. These results support an excessive en dothelial injury/inflammatory response after regional ischemia/reperfu sion that can be ameliorated through augmented nitric oxide.