Cardiac effects of acute administration of a protonophore in a rat model.

OBJECTIVES: Excessive use of uncoupling agents, previously used as weight loss agents, has led to the increase in body temperature and death. The aim of the present study was to evaluate the acute cardiac effects of mitochondrial protonophore in a rat model at a high dose, and its specific influence on cardiac substrate uptake.

METHODS: Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with the protonophore carbonyl cyanide m-chloro phenyl hydrazone (CCCP; 4 mg/kg) or vehicle (dimethyl sulfoxide). Blood pressure, heart rate (HR) and systolic function were recorded. Substrate uptake was monitored by radioactive tracers.

KEY FINDINGS: Compared to the control group, the respiratory rate and body temperature increased, the left ventricle was dilated, and systolic function transiently deteriorated in the CCCP group. There was no difference in blood pressure and HR between the two groups. In cardiac substrate uptake, glucose uptake showed a 95% increase (P < 0.05), and fatty acid uptake showed a 52% decrease (P < 0.05) in CCCP-administered group.

CONCLUSIONS: The deleterious effects on cardiac function and the changes in substrate uptake were observed when administered with the protonophore at a high dose.