Effects of hypoxia on diaphragm relaxation rate during fatigue

Van Lunteren, Erik, Augusto Torres, and Michelle Moyer.Effects of hypoxia on diaphragm relaxation rate during fatigue. J. Appl. Physiol. 82(5):1472-1478, 1997.Skeletal muscle fatigue is associated with aslowing of relaxation rate. Hypoxia may increase the rate at whichfatigue occurs, but, surprisingly, mild to moderate hypoxia has notbeen found to augment the degree of slowing of relaxation duringfatigue. The present study tested the hypothesis that severe hypoxiainteracts with fatigue in slowing the rate of muscle relaxation andthat this can be modulated by altering membranous ionic conductances.Rat diaphragm muscle strips were studied in vitro while aerated with95% O₂-5%CO₂ (normoxia) or 95%N₂-5%CO₂ (hypoxia). During continuous0.1-Hz stimulation, relaxation rate and force remained stable overtime, and relaxation rate was not slowed by hypoxia. Hypoxiaaccelerated force decline during continuous 5-Hz but not intermittent20-Hz stimulation. During both 5- and 20-Hz stimulation, relaxationrate became slower over time as force declined, the extent of which wasincreased significantly by hypoxia. The extent of hypoxia-augmentedslowing of relaxation rate during fatigue increased over time and was greater than expected for a given degree of force loss. 4-Aminopyridine did not attenuate or partially attenuated, whereas loweringextracellular Clconcentration fully attenuated, the hypoxia-induced prolongation ofrelaxation rate during repetitive stimulation. Thushypoxia slows relaxation rate to a greater extent than expected for a given degree of force decline, an effect that increases over time, isat most partially attenuated by loweringK⁺ conductance, and is fullyattenuated by lowering membranousCl conductance.