Work and oxygen consumption of isolated right ventricular papillary muscle in experimental pulmonary hypertension
Right-sided myocardial mechanical efficiency (work output/metabolic energy input) in pulmonary hypertension can be severely reduced. We determined the contribution of intrinsic myocardial determinants of efficiency using papillary muscle preparations from monocrotaline-induced pulmonary hypertensive (MCT-PH) rats. The hypothesis was tested that efficiency is reduced by mitochondrial dysfunction in addition to increased activation heat reported previously. Right ventricular (RV) muscle preparations were subjected to 5 Hz sinusoidal length changes at 37°C. Work and suprabasal oxygen consumption (VO2) were measured before and after cross-bridge inhibition by blebbistatin. Cytosolic cytochrome c concentration, myocyte cross-sectional area, proton permeability of the inner mitochondrial membrane (PP IMM), and monoamine oxidase (MAO)-A and glucose 6-phosphate dehydrogenase (G-6-PDH) activities and phosphatidylglycerol (PG) and cardiolipin (CL) contents were determined. Mechanical efficiency ranged from 23 to 11% in control (n = 6) and from 22 to 1% in MCT-PH (n = 15) and correlated with work (r2 = 0.68, P < 0.0001) but not with VO2 (r2 = 0.004, P = 0.7919). VO2 for cross-bridge cycling was proportional to work (r2 = 0.56, P = 0.0005). Blebbistatin-resistant VO2 (r2 = 0.32, P = 0.0167) and IMM PP (r2 = 0.36, P = 0.0110) correlated inversely with efficiency. Together, these variables explained the variance of efficiency (coefficient of multiple determination R2 = 0.79, P = 0.0001). Cytosolic cytochrome c correlated inversely with work (r2 = 0.28, P = 0.0391), but not with efficiency (r2 = 0.20, P = 0.0867). G-6-PDH, MAO-A and PG/CL increased in the RV wall of MCT-PH but did not correlate with efficiency. Reduced myocardial efficiency in MCT-PH is due to activation processes and mitochondrial dysfunction. The variance of work and the ratio of activation heat reported previously and blebbistatin-resistant VO2 are discussed.