METABOLIC ALTERATIONS IN THE CHRONICALLY DENERVATED DOG HEART

Objectives: Previous studies have shown that chronic cardiac denervati on impairs myocardial glucose oxidation. To investigate this further w e tested whether the tissue content of glucose transporters, activity of glycolytic enzymes or metabolic capacity of pyruvate dehydrogenase were altered. Moreover, we investigated whether the decline in glucose utilization was associated with an upregulation of proteins and enzym es involved in fatty acid handling. Chronic cardiac denervation result s also in decreased left ventricular efficiency. We explored whether a lterations in mitochondrial properties could be held responsible for t his phenomenon. Methods: Twelve adult dogs were included in the study. In 6 of them chronic cardiac denervation was accomplished by surgical ablation of the extrinsic nerve fibers. The other 6 dogs were sham-op erated. Biopsies were obtained from the left ventricle after 4-5 weeks of denervation. The content or enzymatic activity of proteins involve d in fatty acid and glucose handling was assessed. Features of glutama te oxidation were measured in freshly isolated mitochondria. Results: The content or activity of a set of fatty acid handling proteins did n ot change during chronic cardiac denervation. In contrast GLUT1 conten t significantly increased in the chronically denervated left ventricle , while the active form of pyruvate dehydrogenase declined (p < 0.05). Glutamate oxidation characteristics in freshly isolated mitochondria were not affected by chronic denervation. Conclusion: The impairment o f glucose oxidation in the chronically denervated myocardium is most l ikely caused by a decline of pyruvate dehydrogenase in its active form . It is unlikely that the decrease in work efficiency is caused by alt erations in mitochondrial properties. (C) 1998 Elsevier Science B.V.