MITOCHONDRIAL CALCIUM CONTENT IN ISOLATED-PERFUSED HEART - EFFECTS OFINOTROPIC STIMULATION

We tested the hypothesis that in the intact heart, mitochondrial metab olism is activated by mitochondrial Ca2+ uptake during increased work. We measured left ventricular pressure (LVP), pyruvate dehydrogenase ( PDH) activity, and mitochondrial and A band elemental content by elect ron probe microanalysis (EPMA) in Langendorff-perfused hamster hearts under control conditions, after isoproterenol (10(-6) M) stimulation, and after increasing perfusion pressure from 60 to 100 mmHg. Hearts we re rapidly frozen, then EPMA was performed on cryosections cut from th e surface of the frozen hearts; PDH activity was measured from the sam e area. Isoproterenol and elevated perfusion pressure increased LVP by 185 +/- 21 and 58 +/- 14%, respectively, versus controls. PDH activit y increased from 10.4 +/- 1.5 (mean +/- SE) nmol . min(-1) . mg protei n(-1) (controls) to 21.6 +/- 3.5 (isoproterenol) and 18.5 +/- 3.2 nmol . min(-1) . mg . protein(-1) (increased perfusion pressure). There wa s no significant change in mitochondrial Ca-1 in response to isoproter enol [1.2 +/- 0.1 (mean +/- SE) mmol/kg dry wt] or increased perfusion pressure (1.1 +/- 0.1) versus controls (1.0 +/- 0.1). These results s uggest that, in the intact heart, mechanisms other than mitochondrial Ca2+ uptake may contribute to PDH activation and increased cardiac wor k.