實驗的低酸素負荷に依る心筋代謝の研究
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It is widely accepted that the primary causative mechanism of such a heart failure as in a long termed anemia, coronary disease or peripheral circulatory shock and the like is the impairment of energy yielding metabolism due to the myocardial hypoxia.In the present paper, effects of hypoxia on myocardial metabolism were investigated with special reference to formation and utilization of some intermediates of Krebs cycle or energy rich phosphate.Myocardial tissue was obtained from rabbit or rat that was placed in a chamber of low oxygen content (7% O_2) with one atmospheric pressure for 24 hours before sucrifice.1) Exposing the rabbits to a low oxygen atmosphere caused the increase of lactic acid and citric acid in cardiac muscle as well as in venous in blood.2) Oxygen consumption of the myocardial homogenate taken out from rats exposed to hypoxia was only half that of normal ones, while the activities of succinic or lactic dehydrogenase determined manometricaly showed no significant difference between the control and experimental group.3) Spectrophotometric analysis of DPN and DPNH in cardiac muscle revealed a interesting fact that decrease of DPN and unchange of DPNH lead to the reduction of DPN/DPNH ratio in the hypoxic cardiac muscle.4) Those results described above introduced the next investigation about citric acid formation in vitro by cardiac tissue, and it was found that marked decrease in citrate formation from pyruvate and oxaloacetate by hypoxic myocardial homogenate was recovered nearly to the normal level when boiled heart extract, DPN, or DPN and cocarboxylase was supplemented.5) Besides the impairment of citric acid formation, uptake of citrate in vitro by hypoxic rabbit myocardial homogenate, which was remarkably reduced, was observed to be restored to normal by supplementation with boiled heart extract or DPN. These facts indicated the mareked reduction of Pyruvate and Citrate oxydation in cardiac tissue under hypoxic condition.6) When α-ketoglutarate served as the substrate, the oxydative phosphorylation quotient expressed in P/O ratio was proved to be between 1.5 to 3.0 with normal rabbit heart mitochondria, while the quotient with hypoxic one dropped nearly to 1.0 which indicated the reduced coefficiency in energy transformation.7) Against to these facts which showed a reduction of energy yielding metabolism in hypoxic cardiac tissue, determination of activity of ATP-ase in soluble extract of myocardial homogenate gave no evidence of any difference between normal and experimental group. This effect is considered to suggest that the failure in utilization of energy might well be ruled out as the primary causative for the heart failure in hypoxia.
- 社団法人日本循環器学会の論文
- 1958-06-20
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- 實驗的低酸素負荷に依る心筋代謝の研究