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The effects of cadmium on coronary blood flow

Thesis/Dissertation ·
OSTI ID:5611543

In initial experiments isolated heart mitochondria were prepared from control rats using polytron homogenization and differential centrifugation at 4{degree} C. Mitochondrial respiratory characteristics were subsequently determined by polarographic methods at 37{degree}C. Dose-dependent actions of CdCl{sub 2} (0.1-100 {mu}M) were determined and compared with those of site-specific mitochondrial respiratory modifiers (ssMRMs). Cd acted solely as an inhibitor of isolated heart mitochondrial respiration. The dose-response curve was essentially asymptotic to the ordinate at the half-maximal inhibitory dose of 4 {mu}M. Pretreatment with mono- or dithiol reagents attenuated the inhibitory effects of Cd on mitochondrial respiration. Cd caused a dose-dependent inhibition of mitochondrial respiration whether added before or after the mitochondrial uncoupler CCCP. In parallel experiments concerned with the actions of Cd at the level of the intact organ, rat hearts were perfused with varying Cd concentrations (0.1 to 100 {mu}M) and/or various combinations of ssMRMs (KCN, CCCP, and Ca{sup ++}) under spontaneously beating (C) and potassium-arrested (A) conditions. Multiple cardiac functional and metabolic parameters: coronary flow (CF), oxygen extraction (FIO{sub 2}), oxygen consumption (MVO{sub 2}), heart rate (HR), peak pulse pressure (PP), rate of intraventricular pressure development (dP/dt), and systolic tension time index (STTI) were analyzed. Cd caused a dose- and time-dependent, biphasic reduction of CF without stimulating myocardial lactate release within the dose range of 0.1 to 10 {mu}M. In contrast, Cd had only dose- and time-dependent depressant effects on HR, PP, dP/dt, and MVO{sub 2}.

Research Organization:
Illinois Univ., Chicago, IL (USA)
OSTI ID:
5611543
Country of Publication:
United States
Language:
English