DIMETHYL-SULFOXIDE DEPRESSES SKELETAL-MUSCLE CONTRACTILITY

Dimethyl sulfoxide (DMSO) is commonly used in studies of skeletal muscle as a selective antioxidant (DMSO preferentially scavenges hydroxyl radicals) or as a solvent for drugs. The present experiments tested DMSO for direct effects on diaphragm contractile properties. Fiber bundles were removed from anesthetized rats, mounted in vitro at optimal length (37 degrees C), curarized, and stimulated directly. Protocol 1 tested for contractile depression and dose dependence by comparing bundles treated with DMSO (0.6-640 mM) with time- and stimulus-matched controls. Protocol 2 tested reversibility of 220 mM DMSO effects by using each bundle as its own control. DMSO decreased the relative forces developed during twitch and submaximal tetanic (30- and 60-Hz) contractions, shifting the force-frequency relationship down and to the right. These effects were strongly dose dependent and were reversed by DMSO washout. DMSO had no detectable effect on the forces developed during maximal tetany (200 Hz). DMSO depresses contractile function of diaphragm fibers by reversible dose-dependent inhibition of excitation-contraction coupling.