Cardiac Failure in the Dog as a Consequence of Exogenous Hyperthyroidism
Thirty dogs were made hyperthyroid by feeding them 1 g/kg USP thyroid powder or injecting 1.2 mg/kg of 1-thyroxine/day. Seven of the 30 dogs used had surgically induced mild valvular lesions of the right heart to determine whether preexistent organic disease was a requisite to the induction of failure in hyperthyroidism.
At 2 to 27 months the animals were subjected to cardiac catheterization for measurement of cardiac work and metabolism in vivo. The animals were then killed and the levels of the high energy phosphate compounds creatine phosphate (CP) and the adenine nucleotides (ATP+ADP) in the heart were measured as an index of the net efficiency of the processes of oxidative phosphorylation.
By hemodynamic or histopathologic criteria, 13 dogs showed signs of failure, only 3 of which had preexistent valvular lesions. The failure was not accompanied by a decreased efficiency of oxidative phosphorylation. Net levels of CP and ATP + ADP in the myocardium were normal. Preliminary studies with sarcosomes isolated from 5 animals also revealed normal P/O ratios in 3 dogs with and in 2 without signs of cardiac failure. Liver mitochondria isolated from these same 5 animals all demonstrated decreased P/O ratios. Decreased myocardial extractions of both glucose and pyruvate occurred with failure, suggesting some degree of myocardial hypoxia with increased intracellular glycolysis. Areas of relative hypoxia may exist in a hypertrophied myocardium of the hyperthyroid animal.
- uncoupling of oxidative phosphorylation
- myocardial substrate metabolism
- liver mitochondria
- high energy phosphates
- thyrotoxic heart failure
- Accepted December 26, 1966.
- © 1967 American Heart Association, Inc.