The effects of repeated exposure to anoxia on intracellular calcium, glycogen and lactate in isolated ferret heart muscle.

Isolated cardiac tissue from the ferret was repeatedly exposed to anoxia while perfused with glucose-containing Tyrode solution. In one series of experiments, papillary muscles were injected with aequorin to measure intracellular Ca2+. On the first exposure to anoxia, the Ca2+ transients often increased, but on subsequent exposures this increase disappeared and eventually the Ca2+ transients declined on exposure to anoxia. This decline in the Ca2+ transients could be converted back to an increase by a 1 h exposure to an elevated (x5) glucose concentration. Exposure of aerobic muscles to 10 mM lactic acid caused a similar increase in the Ca2+ transients to that seen in early exposures to anoxia. In a second series of experiments, performed on Langendorff-perfused hearts, measurements were made of glycogen concentration preceding, and lactate production during, exposures to anoxia. At a constant level of glucose, glycogen concentration and lactate production were found to decline on repeated exposures to anoxia, and both were increased after a period of elevated glucose and reduced stimulation frequency. These results suggest that the response of the Ca2+ transients to anoxia is dependent on the metabolic status of the muscle. The increase in the Ca2+ transients during an early exposure to anoxia may be a consequence of lactic acid production due to accelerated glycolysis. Repeated exposures to anoxia reduce glycogen concentration and lactate production and this reduces the rise in the Ca2+ transients.