The electron-microscopic morphology, mitochondrial respiratory rates and respiratory control ratios, and the histochemical distribution of mitochondrial enzymes were studied in the ventricular myocardium of young female rats during the time-course of repeated exercise by swimming. Following swimming between a total of 140 and 180 hours (at the rate of 6 hours a day, 6 days a week) there was a large increase in mitochondrial mass. The respiratory rate of these mitochondria showed no change with α-ketoglutarate, succinate, or pyruvate, and slight increase with glutamate. With only the latter substrate, however, a considerable increase of the mitochondrial respiratory control ratio was observed. Already at this stage of exercising, which represented an optimum physical condition of the animals, some scattered degenerative foci in the myocardium were noted showing fusion, swelling, clumping and reduction of mitochondrial cristae, and disoriented indistinct myofilaments in which the sarcomere bands could not be seen. These foci showed decrease of histochemically detectable succinic dehydrogenase and β-hydroxybutyric dehydrogenase. In advanced stages of exercising (for 361-490 hours of swimming) the animals showed physical exhaustion and were unable to maintain the same rate of exercising. The distribution and extent of the above focal degenerative changes in the myocardium of these animals were considerably more pronounced, and this was paralleled by a return of the mitochondrial respiratory control ratio (with glutamate) to the base level; there was no change in the respiratory rates with any of the substrates, however. There was no change in the Ca++- and Mg++-activated, histochemically demonstrable, ATPase levels in the myocardium during the entire time-course of exercising. The findings suggest that the increase of mitochondrial mass is a compensatory response to exercise and this increase brings about focal regions of hypoxia during over-exercise, responsible for the degenerative changes. The respiratory control increase with glutamate, at the stage of optimum exercise, possibly represents a regulatory mechanism limiting amino acid catabolism via the tricarboxylic acid cycle during high overall anabolic activity. © 1968.
