We tested whether treatment with exogenous L-arginine, the precursor of nitric oxide (NO), could protect the skeletal muscle from ischemia/reperfusion (I/R) injury. A rabbit hindlimb I/R model (2.5 h ischemia/2 h reperfusion) was used. Morphological changes were elucidated by morphometry. Plasma concentrations of malondialdehyde (pMDA), as well as L-arginine and L-citrulline content in the plasma and skeletal muscle were measured. I/R injury in the skeletal muscle was manifested by development of prominent interstitial edema (fraction of interfiber area was 26.23% vs 15.09% in sham operated control, p < .005) and severe microvascular constriction (capillary area was 11.41 microns2 vs 16.92 in control, p <.005). These changes were accompanied by increased pMDA levels, indicating a process of lipid peroxidation in the cell membranes. L-arginine treatment (4 mg/kg/min intravenously, for 1 h, infusion initiated 30 min before reperfusion) caused an intracellular accumulation of this amino acid in the SM. Intracellular concentrations of L-citrulline increased (201.0 mumol/dm3 after reperfusion vs 176.0 before ischemia onset, p < .005), suggesting stimulated endogenous NO synthesis. L-arginine treatment protected capillary constriction (capillary area was 17.64 microns2 vs 11.41 in the untreated animals, p < .0005) and reduced interstitial edema after reperfusion (fraction of interfiber area was 17.80% vs 26.23 in untreated animals, p < 0.005). The protective effect of L-arginine treatment on I/R injury of SM may be related to its ability to prevent microvascular constriction and reduce permeability disorders by the stimulation of endogenous NO production.

Department of Vascular Surgery University of Vienna Austria