METABOLIC CHANGES IN THE AUTOTRANSPLANTED BABOON HEART

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Abstract

Chronic denervation of the heart leads to depletion of tissue catecholamines, giving rise to metabolic abnormalities, including a reduction in cardiac glucose oxidation. Impaired glucose oxidation could cause an increased oxidation of fat, which in turn could lead to development of coronary artery disease. Cardiac glucose oxidation (using 14C-(U),D-glucose) was studied in female baboons, before, and three to five weeks after, autotransplantation. Systemic arterial and coronary sinus samples were analyzed for total CO2 content, O2 content, 14CO2, glucose, lactate, pH, PCO2, and PO2. Tissue for metabolite assays (adenosine-5‘-triphosphate7 [ADP] and creatine phosphate [CP]; glucose-6-phosphate [G6P] and fructose 6-phosphate [F6P] was obtained from the right ventricle before and after auto-transplantation in some animals. There were no significant changes. Tissue was also obtained postmortem for analysis of noradrenaline, soluble tyrosine hydroxylase activity, and contractile and regulatory proteins. There was a large decrease in tissue noradrenaline, suggesting almost total sympathetic denervation. The level of tyrosine hydroxylase activity shows that the denervated heart can synthesize dopamine. There were no detectable changes in the contractile or regulatory proteins. In six of the nine baboons successfully studied, there was a distinct decrease in the oxidation of glucose after auto-transplantation (P<0.05). This indicates that the removal of the sympathetic and parasympathetic nerve supply to the heart affects the ratio of glucose oxidized to other substrates.

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