Hypoxic-induced damage of rabbit heart muscle has been quantitated in terms of the release of intracellular enzymes (including creating phosphokinase, CPK) into the extracellular space, a gain in tissue Na+ and Ca2+, a loss of tissue K+, the depletion of the adenosine triphosphate (ATP) and creatine phosphate (CP) reserves, and ultrastructural damage. This ultrastructural damage incolves the disruption of the plasmalemma, swelling and distortion of the mitochondria, disruption of the myofilaments, and the development of contraction bands. In isolated Langendorff-perfused rabbit hearts perfused under either aerobie (pO2 greater than 80.0 kPa [600 mm Hg]) or hypoxie (pO2 less than 0.80 kPa [6 mmHg]) conditions, and either with or without glucose substrate, 0.5-1.0 mg/litre dl verapamil reduced the amount of ultrastructural damage caused by hypoxie perfusion. Verapamil (0.5-1.0 mg/litre) also reduced the rate at which the hypoxie muscle gained Na+ and lost K+; it reduced the rate at which the endogenous stores of ATP and CP were depleted and, provided that the extracellular phase contained Ca2+, it decreased the rate at which CPK appeared in the coronary effluent. Verapamil failed to prevent the hypoxie muscle from gaining Ca2+. These results are discussed in terms of a possible protective effect of dl verapamil on hypoxie heart muscle.

The ability of several beta-adrenoceptor antagonists with partial agonist activity (dl-oxprenolol, dl-acebutolol and dl-practolol) to attenuate the release of CPK that occurs during hypoxia (pO2 less than 0.8 kPa [6 MMHg]) has been studied and compared with the protection provided by dl-propranolol. dl-propranolol attenuated the hypoxic-induced release of CPK. The activity resided in the l isomer. dl-oxprenolol, acebutolol, and practolol were either less effective than propranolol in preventing CPK release, or they exacerbated the release. The protective effect of dl-propranolol extended to the hypoxic hyperthyroid heart but not to hearts that were perfused under aerobic (pO2 greater than 80 kPa [600 mmHg]) Ca2+-free conditions.

Experiments were undertaken to further investigate the protective effect of methylprednisolone sodium succinate on hypoxic heart muscle. Hypoxia was induced in isolated Langendorff perfused rat and rabbit hearts by gassing the perfusate with 95% N2 + 5% CO2. The hypoxia-induced damage was quantitated in terms of an altered ultrastructure and increased resting tension. When added at the start of the hypoxic episode 6 X 10(-5) mol.litre-1 methylprednisolone sodium succinate protected the fine ultrastructure of the heart, and delayed the increase in resting tension. This protective effect could not be accounted for in terms of the sodium succinate moiety.