Measurement of the activation time of oxidative phosphorylation in isolated mouse hearts.

The purpose of this study was to develop a technique for determination of the dynamic regulation of oxidative myocardial metabolism in the mouse. The response time of myocardial oxygen consumption (MVO(2)) to a step in heart rate was determined in Langendorff-perfused mouse hearts. We examined the effect of glucose-only perfusate and glucose combined with 1, 3, or 6 mM pyruvate. Left ventricular systolic pressure (LVSP) decreased, yet the rate-pressure product (RPP) and MVO(2) increased with upward steps in heart rate. Pyruvate increased LVSP, RPP, and MVO(2) at the lower concentrations; however, when 6 mM pyruvate was added, LVSP and RPP became depressed while MVO(2) remained elevated. The mean response time of oxygen consumption to a step in heart rate from 270 to 350 beats/min was 9.8 s (n = 7) in the glucose-only perfused hearts. Perfusion with glucose plus 6 mM pyruvate decreased the response time to 5.3 s. These results are similar to those found in the rabbit heart and lay the groundwork for further examination of the dynamic regulation of oxidative myocardial metabolism in genetically altered mice. We concluded that the activation time of oxidative phosphorylation in the mouse is similar to that in larger species, despite the high mitochondrial content and natural heart rate of the mouse.