家兎低酸素灌流心における verapamil の心筋保護作用
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概要
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Effects of calcium antagonist verapamil on myocardial calcium and contractility were studied in isolated rabbit hearts perfused with bicarbonate buffered salt solution containing 0.56 mM Ca and gassed with 95% N_2+5% CO_2. Thirty minutes hypoxic perfusion was performed after 20min of equilibration with the perfusate gassed with 95% O_2 +5% CO_2. Submaximum active tension (AT) was rapidly reduced and reached cardiac arrest by hypoxic perfusion. Resting tension (RT) was significantly increased from 1.9±0.4g/g left ventricular muscle (LV) to 6.0±0.4g/g LV, and myocardial total Ca and mitochondrial Ca concentrations were markedly increased from 0.55 ± 0.03 pg/g LV and 12.6±0.8 nmole/mg protein to 0.97±0.07 μg/g LV and 19.6±1.2 nmole/mg protein, respectively, in the hypoxic hearts. Verapamil, 1×10^<-8>M to 1×10^<-6>M in the perfusate, significantly prevented these increases of RT and accumulation of myocardial Ca in hypoxia. Verapamil, however markedly reduced AT of the control hearts with aerobic perfusion, and norepinephrine (NE) reversed this depressant effect of 5×10^<-8>M verapamil. Administration of both verapamil (5×10^<-8>M) and NE (6.8μg/min) significantly prevented the increase in RT and accumulation of myocardial Ca in hypoxic hearts, but the reduced AT was not changed. These results suggest that verapamil may have a possible protective effect on hypoxic hearts under the increased sympathetic activity and/or administration of sympathomimetic amines in acute myocardial infarction or reperfusion after coronary intervention.
- 神戸大学の論文