Increased Tolerance of Ventricular Function and Energy Metabolism to Hypoxia in Cardiomyopathic Hamsters

To study the responses of myocardial function and metabolism to hypoxia in normal hamsters and cardiomyopathic hamsters (Bio 14.6), left ventricular pressure was measured in an isolated isovolumically beating heart preparation, and myocardial high energy phosphates (ATP and creatine phosphate), inorganic phosphate, and intracellular pH were also measured by 31P nuclear magnetic resonance spectroscopy. In 20-week-old cardiomyopathic hamsters, the heart weight was increased and the baseline left ventricular developed pressure, peak positive dP/dt, and peak negative dP/dt were decreased, indicating depression of left ventricular function. In control hamsters, left ventricular end-diastolic pressure rose markedly (+481 ± 70%), and left ventricular developed pressure decreased (-57 ± 6%) during 30 mins period of hypoxic perfusion. Correspondingly, myocardial content of ATP (-42 ± 17%) and creatine phosphate (-48 ± 14%) was decreased and that of inorganic phosphate was increased (+185 ± 127%). Intracellular pH was also decreased (-0.20 ± 0.13). In contrast, cardiomyopathic hamsters, showed a relatively slight increase slight increase in left ventricular end-diastolic pressure (+106 ± 83%, P < 0.01 vs. control hamsters), although the decrease in left ventricular developed pressure (-50 ± 5%) was comparable to that in control hamsters. The recovery of left ventricular end-diastolic pressure and developed pressure during reoxygenation was better in cardiomyopathic hamsters. The decrease in myocardial ATP (-13 ± 26%, P < 0.01 vs. control hamsters), the increase in inorganic phosphate (+95 ± 88%, P < 0.05 vs. control hamsters), and the decrease in intracellular pH (-0.06 ± 0.06, P < 0.01 vs. control hamsters) during hypoxia were much less marked in cardiomyopathic hamsters. Only the decrease in creatine phosphate (-32 ± 16%) was comparable to that in control hamsters. Thus, in cardiomyopathic hamsters, the deterioration of left ventricular diastolic function, systolic function, and myocardial energy metabolism during hypoxia was mild compared with the change in control healthy hamsters. This increased tolerance of cardiomyopathic hearts to hypoxia may be related to alteration in myocardial contractile proteins and/or energy utilization, or substrate availability.