Exercise-Evoked Metabolic Adaptations in Canine Myocardium




Stuewe, Steven Richard


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Stuewe, Steven Richard, Exercise-Evoked Metabolic Adaptations in Canine Myocardium. Doctor of Philosophy (Biomedical Sciences), November 1999; 128 pp; 4 tables; 17 figures; bibliography, 130 titles. Aerobic exercise training evokes adaptations in the myocardial contractile machinery that enhance cardiac functional capabilities, and the myocardium’s capacity to consume energy. Despite considerable investigative effort, the effects of exercise training on myocardial intermediary metabolism, the source of energy for cardiac function, have not been defined. The investigations described herein were undertaken to delineate the effects of aerobic exercise training on key rate-controlling enzymes of myocardial intermediary metabolism and energy transport, and to characterize the effects of acute exercise on cardiac messenger RNA transcripts encoding metabolic enzymes. To address these questions, dogs were conditioned by a 9 wk treadmill running program or cage rested for 4 wk. Exercise conditioning was documented by a significant decrease in heart rate at rest and during submaximal exercise. A panel of glycolytic and oxidative enzymes was measured in myocardial extracts. It was demonstrated that aerobic exercise training of dogs selectively increased capacities of key rate-controlling enzymes of each of the major pathways of intermediary metabolism in ventricular myocardium. In addition, it appeared that the training-evoked increases in enzyme activities were due to increased enzyme contents, not to changes in substrate affinity. The same training program was implemented to investigate the effects of aerobic exercise training on the myocardium’s energy shuttling system. Total creatine kinase (CK) activity and content of the CKMB isoenzyme were measured in canine myocardial extracts. It was demonstrated that aerobic exercise training increased total myocardial CK activity and CKMB content, although the CKMB isoenzyme remained minor component of the myocardial CK system. A third investigation was conducted to examine the effects of aerobic exercise on the abundance of messenger RNA (mRNA) encoding key enzymes involved in myocardial energy production and transport. Left ventricular myocardium was sampled 30 min after an exercise bout, and messenger RNA transcripts were analyzed by reverse transcriptase polymerase chain reaction. Exercise increased in the myocardial abundance of mRNA transcripts encoding glyceraldeheyde 3-phosphate dehydrogenase, citrate synthase, and the CK-M subunit. These mRNA enhancements could be responsible, at least in part, for exercise-evoked adaptations in myocardial metabolic enzymes demonstrated in the first two investigations.