ISCHEMIC PRECONDITIONING PRESERVES CREATINE-PHOSPHATE AND INTRACELLULAR PH

被引:215
作者
KIDA, M
FUJIWARA, H
ISHIDA, M
KAWAI, C
OHURA, M
MIURA, I
YABUUCHI, Y
机构
[1] KYOTO UNIV,FAC MED,DEPT INTERNAL MED,DIV 3,SAKYO KU,KYOTO 606,JAPAN
[2] OTSUKA PHARMACEUT CO LTD,TOKUSHIMA,JAPAN
关键词
MYOCARDIAL ISCHEMIA; ATP; NUCLEAR MAGNETIC RESONANCE; INTRACELLULAR PH;
D O I
10.1161/01.CIR.84.6.2495
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. Ischemic preconditioning slows ATP depletion and ultrastructural damage during the final episode of ischemia. To define the influence of creatine phosphate (CP) and intracellular pH (pH(i)) on this effect, CP and pH(i) were serially measured in porcine hearts without collateral circulation by using P-31-NMR spectroscopy and ultrastructural examination. Methods and Results. Farm pigs weighing 12-15 kg were anesthetized with Fluothane. The control group underwent a single occlusion (20 minutes or 60 minutes); the preconditioned group underwent four episodes of 5-minute occlusion and 5-minute reperfusion followed by a sustained occlusion (20 minutes or 60 minutes). After ischemic preconditioning, CP increased to 115 +/- 11% (p < 0.05) of preischemic value and ATP decreased to 84 +/- 8% (p < 0.05) of preischemic value, but pH(i) returned to preischemic value. At 5 and 10 minutes of sustained ischemia, CP was significantly preserved in the preconditioned group (control group, 19 +/- 3% versus preconditioned group, 29 +/- 4% at 5 minutes; control group, 5 +/- 3% versus preconditioned group, 11 +/- 3% at 10 minutes; p < 0.05). At 15 and 20 minutes of sustained ischemia, ATP was significantly preserved in the preconditioned group (control group, 64 +/- 3% versus preconditioned group, 73 +/- 3% at 15 minutes; control group, 51 +/- 7% versus preconditioned group, 62 +/- 2% at 20 minutes; p < 0.05). At 10, 15, 20, and 25 minutes of sustained ischemia, pH(i) was significantly higher in the preconditioned group (control group, 6.5 +/- 0.05 versus preconditioned group, 6.7 +/- 0.1 at 10 minutes; control group, 6.3 +/- 0.05 versus preconditioned group, 6.6 +/- 0.06 at 15 minutes; control group, 6.1 +/- 0.1 versus preconditioned group, 6.4 +/- 0.1 at 20 minutes; control group, 6.0 +/- 0.2 versus preconditioned group, 6.3 +/- 0.1 at 25 minutes; p < 0.05). Ultrastructural changes were milder in the preconditioned group at 20 minutes of sustained ischemia. Conclusions. In addition to ATP and ultrastructure, preconditioning preserved CP and pH(i) during sustained ischemia. These protective effects might be due to overshoot phenomenon of CP and/or reduced ATP consumption. The relatively longer period of preservation of pH(i), which probably is the result of reduced ATP consumption, indicates its greater contribution to reducing infarct size than that of CP and ATP.
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收藏
页码:2495 / 2503
页数:9
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