冠動脈結紮家兎心におよぼす非梗塞部の心筋代謝異常とそれにおよぼす副腎皮質ホルモンの効果
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概要
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It has been indicated that contractility of non-infarcted heart muscle is markedly reduced, and the administration of dexamethasone is effective in improving the functional disturbance in early stage of myocardial infarction. This study was performed to observe the changes of myocardial metebolism of non-infarcted area and to evaluate the effect of dexamethasone on them in rabbits in which experimental myocardial infarction was produced by ligating the left anterior descending coronary artery. Dexamethasone (3mg / kg body weight) was administered intramuscular injection to the rabbits twice, just after operation and 24 hours later. Hearts were analyzed for cAMP & its related enzymes and calcium & its subcellular distribution immediately after removal from animals. Myocardial cAMP contents were markedly decreased reaching 60% of that of the sham operated animals which were made a pericardial incision only, although there were no changes in adenylate cyclase and cAMP phosphodiesterase activities in the non-infarcted area at 48 hours after operation. Mitochondrial calcium contents of the infarcted and peri-infarcted areas were significantly increased by 139% and 267% respectively, compared to that of the sham operated hearts. Calcium accumulation was particularly pronounced in mitochondria among the subcellular fractions. In the non-infarcted area, no increase was observed in the total calcium contents, and mitochondria showed a trend of increase in its accumulation. The rate of calcium uptake was reduced in sarcoplasmic reticulum prepared from the operated hearts by 46%, associated with a marked reduction in calcium activated ATPase activity. Dose-responce curve of myocardial contractility to norepinephrine was significantly shifted to the right in the isolated perfused hearts from coronary ligated animals. Thus, it was suggested that the decrease in myocardial contractility of the non-infarcted area might be induced the metabolic disturbance of cAMP and calcium in acute myocardial infarction. These abnormalities of myocardial function and metabolism were markedly prevented by the administration of dexamethasone. In the sham operated animals, dexamethasone caused 47% increase in myocardial cAMP contents and 25% decrease in cAMP-phosphodiesterase activity, while there were no changes in myocardial contractility and adenylate cyclase activity. Under the condition of the elevated cAMP level induced by the dexamethasone administration, there was a significant decrease of calcium in mitochondria and heavy microsomes without any changes in total calcium contents. It was, thus, speculated that the amount of calcium available for myocardial contraction and metabolism was increased. The dose-reponce curve to norepinephrine was markedly shifted to the left in the sham operated hearts. These findings indicated that dexamethasone may act beneficially to improve the abnormalities of myocardial function and metabolism of non-infacted area in acute myocardial infarction.
- 神戸大学の論文