Role of mitochondrial calcium metabolism in the altered contractility of pressure-hypertrophied right ventricular myocardium.

: Pressure-hypertrophied right ventricular myocardium (RVH) demonstrates paradoxically increased oxygen consumption (MVO2) related to increase- in vitro energy-linked mitochondrial calcium flux. The present experiments were designed to measure mitochondrial Ca retention in intact RVH and relate changes in mitochondrial Ca metabolism to altered RVH contractility and relaxation. Sixteen cats were pulmonary artery banded and their hearts plus paired controls were perfused with 45Ca-labeled Krebs-Henseleit (30 degrees C) at 120 beats/min for 10 min. Papillary muscles from both right ventricles were studied in a muscle bath. Mitochondria were isolated from the right ventricles and retained 45Ca measured. At the length at which active tension is developed (Lmax) papillary muscle abnormalities were, for reduced active tension, 6.9 gm/mm2 +/- 0.6 SE for control, 4.0 +/- 0.6 for RVH, p less than 0.001; for slower contraction rate, 40.8 gm/mm2/sec +/- 6.3 control, 16.9 +/- 2.8 RVH, p less than 0.001; for slower relaxation rate, 22.0 gm/mm2/sec "/0 1.5 control, 11.1+/- 1.6 RVH, p less than 0.001; for greater time to peak tension, 317 msec +/- 7 control, 408 +/- 13 RVH, p less than 0.001; for greater relaxation time, 590 msec +/- 29 control, 800 +/- 39 RVH, p less than 0.001. Retained 45Ca of mitochondria was increased from 16.75 +/- 0.96 nM/mg of protein for control, to 20.82 +/- 0.98 for RVH, p less than 0.005. This increase in mitochondrial 45Ca retention correlated (r = 0.93, p less than 0.001) with the decreased rate of papillary muscle relaxation. These data show an increased 45Ca retention of mitochondria in pressure-induced RVH and relate this biochemical abnormality to a decreased myocardial relaxation in this state.