Circulation, Vol 84, 2495-2503, Copyright © 1991 by American Heart Association
M Kida, H Fujiwara, M Ishida, C Kawai, M Ohura, I Miura and Y Yabuuchi
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 (pHi) on this
effect, CP and pHi were serially measured in porcine hearts without
collateral circulation by using 31P-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 less than 0.05) of
preischemic value and ATP decreased to 84 +/- 8% (p less than 0.05) of
preischemic value, but pHi 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 less than 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 less than 0.05). At 10, 15, 20, and 25 minutes of
sustained ischemia, pHi 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 less than 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 pHi 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 pHi, which probably is the result of reduced ATP
consumption, indicates its greater contribution to reducing infarct size
than that of CP and ATP.
ARTICLES
Ischemic preconditioning preserves creatine phosphate and intracellular pH
Third Division, Faculty of Medicine, Kyoto University, Japan.
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