The effects of L-arginine mono(2-mercaptoethanesulfonate) on the ischemic and reperfused heart

We evaluated the effectiveness of L-arginine mono(2-mercaptoethanesulfonate) (argimesna) to limit the extent of myocardial damage resulting from 60 minutes of severe ischemia followed by 30 minutes of reperfusion in the Langendorff-perfused rabbit heart. Argimesna is a sulfhydryl group containing molecule which has no effect on glutathione status or on the total thiol pool. The effects of 10 ^-6 M argimesna were compared with those of 10 ^-6 M L-arginine and of 10 ^-6 M sodium salt of 2-mercaptoethanesulfonate (mesna). Pretreatment of the hearts with 10 ^-6 M argimesna resulted in marked myocardial protection, measured in terms of improved recovery of developed pressure (p <0.01), reduced release of creatine kinase (p <0.01), maintenance of mitochondrial function and increased stores of ATP on reperfusion. On reperfusion less oxidative stress developed, as indicated by less accumulation of oxidized glutathione (p <0.01). These effects were specific for argimesna; no significant protection could be found for mesna and L-arginine. The beneficial effects of argimesna could not be explained by hemodynamic differences or effects on anaerobic metabolism. Neither is it likely that argimesna acts as a free radical scavenger at the concentrations employed. The protection may be achieved by maintenance of -SH groups during ischemia and reperfusion.