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Feeding a vitamin E deficient diet to rats for 10 weeks was found to decrease myocardial creatine phosphate, ATP, ATP/ADP ratio, NAD+, NADP+, and NADPH, whereas the level of ADP was increased without any changes in the levels of AMP, total adenine nucleotides, NADH, and ATP/AMP ratio. The levels of ATP and pyridine nucleotides were restored fully, whereas creatine phosphate was restored partially on feeding a normal diet for 4 weeks to animals previously on the vitamin E deficient diet for 10 weeks. Vitamin E deficiency was found to increase cardiac lactate, pyruvate, and lactate/pyruvate ratio and decrease the activities of lactate dehydrogenase and malate dehydrogenase. The activity of Na+–K+-stimulated, ouabain-sensitive ATPase was markedly elevated in the hearts of animals on the vitamin E deficient diet. The ATP-dependent calcium accumulation by the sarcoplasmic reticular fraction in the absence and presence of P1 or oxalate was greater in the vitamin E deficient heart. Vitamin E deficiency also increased the Ca2+-stimulated ATPase activity of the cardiac sarcoplasmic reticulum. Although myocardial contractility of the hearts from vitamin E deficient rats was depressed, no damage to the ultrastructures of mitochondria and sarcoplasmic reticulum was apparent. These results indicate marked alterations in myocardial metabolism due to vitamin E deficiency and it is suggested that such changes are due to abnormalities in the processes of both energy production and utilization.

The hind leg skeletal muscles of about 215-day-old genetically dystrophic hamsters (BIO strain 14.6) were found to contain subnormal concentrations of creatine phosphate, ATP, total adenine nucleotides, and NAD+ in comparison with those from the control animals. On the other hand, the levels of lactate, NADH, and NADPH were elevated without any significant changes in pyruvate, AMP, ADP, and NADP+ in the dystrophic muscle. The ratios of ATP/ADP and ATP/AMP were decreased and those of lactate/pyruvate, NADH/NAD+, and NADPH/NADP+ were increased in the dystrophic muscle. There are a number of similarities between the dystrophic and asphyxiated muscles with respect to energy metabolism; however, the possibility is not ruled out at present that the hypoxic-like changes in energy metabolism of the dystrophic muscle are due to mechanisms other than oxygen lack. The activity of glucose-6-phosphate dehydrogenase was increased whereas the activities of α-glycerophosphate dehydrogenase, glyceraldehyde phosphate dehydrogenase, lactate dehydrogenase, myokinase, and creatine phosphokinase were decreased in the dystrophic muscle. On the basis of our earlier and present results it is suggested that changes in the high energy phosphate stores in the genetically dystrophic hamster muscle are due to defects in both the processes of energy production and utilization.

Solutions of adenosine triphosphate (ATP) were injected into the left coronary artery of isolated nonperfused dog hearts kept for 30 to 180 minutes at temperatures varying from 4 to 34°C. The amount of ATP administered varied from 0.5 to 7 /xmoles/g heart. The left ventricles of the ATP-treated hearts had a higher content of adenine nucleotides and of phosphocreatine than did the left ventricles of control hearts not exposed to ATP. This effect was temperature-dependent and was maximal at 14°C. Glycogen disappearance in the hypothermic myocardial tissue was markedly slowed in a dose-dependent fashion by the administration of ATP. Injections of adenine and adenosine were without effect.An analysis of the intra-and extracellular distribution of simultaneously administered adenosine-8-14 C-triphosphate and adenosine triphosphate-a-32 P shows that the injected ATP was mainly split into ADP, AMP, adenosine, and inorganic phosphate and indicates that a minor percentage of these fission products entered the myocardial cells, some of the ADP and AMP being rephosphorylated there to ATP. The results suggest that intravascular introduction of ATP into the arrested hypothermic heart might help in the survival of the organ. ADDITIONAL KEY WORDS ATP penetration into cells heart conservationtissue storage hypothermia myocardial glycogenolysis