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On perfusing the isolated rat heart for 7 min with substrate-free hypoxic medium, the contractile force, rate of change of contractile force, time to peak tension, and heart rate declined whereas resting tension increased. The coronary flow and the pH of the perfusate reached maximum and minimum values, respectively, within 2 min of hypoxia whereas the optical density of the perfusate at 260 mμ increased progressively over the 7 min of perfusion with hypoxic medium. The levels of glycogen, creatine phosphate, and ATP declined whereas the concentrations of lactate, ADP, AMP, creatine, and P i increased during the 1st min of hypoxia at which time the contractile force and heart rate decreased by about 20% of the control values. During the 1st min of hypoxia the diminution in phosphate potential and creatine phosphate/P i ratio was found to be of greater magnitude than that in the contractile force. Between 2 and 7 min of perfusion with hypoxic medium a marked reduction in contractile force occurred without appreciable changes in the coronary flow, the phosphate potential, the levels of ADP and AMP, and creatine phosphate/P i ratio. No change in myocardial lipids occurred under the present experimental conditions whereas changes in the electrical activity, time for half relaxation, norepinephrine stores, and mitochondrial structure lagged behind the changes in the high energy phosphate stores due to hypoxia. Although a clear relation between changes in the cardiac function and any one biochemical parameter throughout the period of hypoxia is not apparent from this study, the onset of failure of the hypoxic heart to generate contractility may be considered due to an insufficiency in the process of energy generation. The complete inability of the hypoxic heart to develop contractile force may be due to abnormalities in the processes of energy utilization subserving the mechanisms for the maintenance of ionic gradient and excitation–contraction coupling.
Dhalla et al. (Sat,) studied this question.