Hemodynamics and mitochondrial energy metabolism in right heart hypertrophy after acute hypoxic stress

Excessive right heart hypertrophy was investigated under additional acute h ypoxic stress to find out a possible contribution of mitochondrial dysfunct ion to sudden heart failure. Severe right heart hypertrophy in rats was ind uced by exposure to hypobaric pressure (46 663 Pa) for 4 weeks. Heart rate, isovolumic pressure and coronary now were determined in the Langendorff mo de of perfusion. After normoxia, the hearts were subdued to acute hypoxia/r eoxygenation. Mitochondrial membrane potential was measured at the heart su rface by fluorometry using 2-(dimethylaminostyryl)-1-ethylpyridinium iodide (DASPEI). At the end of each experiment mitochondria were isolated and ATP synthesis, ATPase, as well as creatine kinase activity were determined. Co mpared to normal hearts the heart rate is decreased in the hypertrophied gr oup whereas right ventricular systolic and (end)diastolic pressure (adjuste d to isovolumetric maxims) are increased. Coronary flow is decreased. Cytos olic creatine phosphate ATP levels and ATP/ADP ratios are significantly (p < 0.01) decreased. Furthermore, ATP synthesis and creatine kinase activitie s are diminished. At high ADP, respiration is loosely coupled or partially uncoupled. Acute hypoxia is particularly deleterious to hypertrophied heart s: Mitochondrial membrane potential as measured by heart surface fluorometr y decreases extensively and is only very incompletely restored during reoxy genation. Rate-pressure product decreases precipitously and is restored dur ing reoxygenation only to a very low extent. The results indicate an insuff icient energy metabolism of mitochondria during acute hypoxia/reoxygenation which adds to the earlier described shifted isozyme pattern of myosin and decreased activities of myosin and sarcoreticular Ca2+ ATPase, leading to m yocardial failure in right heart hypertrophy.