Calcium tolerance of isolated rat heart cells.
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Biomedical subjects
Publications and source records attributed to F A Kruger.
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Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N2, 12%O2 and 4% CO2. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p less than 0.01) and a decrease in cyclic GMP (p less than 0.05) as compared to hearts perfused for 60 min with media gassed with 96% O2. 4% CO2.
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To determine whether hypoxia per se could initiate myocardial ribonucleic acid (RNA) synthesis, isolated rat hearts were subjected to varying degrees of hypoxic perfusion in a modified Langendorff apparatus. Following a 30-min aerobic stabilization period the hearts were perfused for 30 min with media gassed with mixtures containing O:96% O2, 4% CO2, balance N2. Immediately following the stress period, the hearts were perfused for an additional 30 min with oxygenated media containing radiolabeled uridine, and the incorporation into RNA was determined. Exposure of hearts to 48% O2 resulted in a slight but nonsignificant increase in uridine incorporation. Reduction of perfusate oxygen to 24% caused a significant increase in label incorporation into RNA over that of the aerobic controls. Further reductions in oxygen tension resulted in concomitant increases in uridine incorporation, with the highest levels seen following 30 min of anoxia. Performance was not significantly different from that of controls during the aerobic labeling period. Exposure of hearts to brief (5 min) anoxic perfusion also resulted in significant increases in RNA synthesis during the posthypoxic perfusion period. It is concluded that intermittent hypoxia can initiate the biochemical mechanisms which result in increased myocardial RNA synthesis.
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Anaerobically periused hearts from rats with experimentally induced hyperthyroidism exhibited accelerated deterioration of pacemaker activity and ventricular performance. The diminished anaerobic performance of hyperthyroid hearts was associated with decreased adenosine triphosphate (ATP) levels and a reduced rate of anaerobic glycolysis as reflected in decreased lactic acid production during 30 min of anoxic perfusion.Studies on whole heart homogenates demonstrated inhibition at the phosphofructokinase (PFK) step of the glycolytic pathway. Such inhibition was not demonstrated in the hyperthyroid heart cytosol. It is postulated that an inhibitor of PFK which resides dominantly in the particulate fraction is probably responsible for the diminished anaerobic glycolysis and performance of the hyperthyroid heart.
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Employing an isolated perfused rat heart preparation, we investigated the contribution of anaerobic metabolic energy to the performance, recoverability, and ultrastructure of the heart perfused at 32 degrees C in 5% albumin in Krebs-Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in the perfusate of the anaerobic substrate, glucose, resulted in marked improvement in electrical and mechanical performance of the heart and in enhanced recovery during the subsequent period of reoxygenation. Lactate production was fivefold greater in the glucose-supported anoxic heart than in the anoxic heart without glucose. Electron microscope sections of the hearts exposed to anoxia in the absence of glucose revealed alterations in mitochondrial morphology and dilatation of the longitudinal tubules. These morphologic changes during anoxia were averted by inclusion of glucose in the perfusion fluid. The data are consistent with the hypothesis that anaerobic energy generation plays a significant role in preserving myocardial function and structure and in promoting recoverability of the anoxic mammalian heart.
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