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Ischemic preconditioning preserves creatine phosphate and intracellular pH
1Third Division, Faculty of Medicine, Kyoto University, Japan.
Insights
Ischemic preconditioning preserves cardiac energy stores and intracellular pH during ischemia. This protection, particularly of intracellular pH, is key to reducing infarct size and preserving heart function.
Area of Science:
- Cardiovascular Physiology
- Cellular Metabolism
- NMR Spectroscopy
Background:
- Ischemic preconditioning mitigates ATP depletion and cellular damage during ischemia.
- The roles of creatine phosphate (CP) and intracellular pH (pHi) in this protective effect require further definition.
Purpose of the Study:
- To investigate the influence of CP and pHi on the protective mechanisms of ischemic preconditioning.
- To quantify serial changes in CP and pHi during sustained ischemia following preconditioning.
Main Methods:
- Utilized 31P-NMR spectroscopy to measure CP and pHi in porcine hearts.
- Assessed ultrastructural changes alongside biochemical markers.
- Employed a preconditioning protocol of intermittent ischemia/reperfusion followed by sustained ischemia.
Main Results:
- Preconditioning significantly preserved CP and ATP levels during sustained ischemia compared to controls.
- Intracellular pH (pHi) was significantly higher in preconditioned hearts.
- Ultrastructural damage was reduced in the preconditioned group.
Conclusions:
- Ischemic preconditioning preserves cardiac CP and pHi during sustained ischemia.
- Protective effects may involve CP overshoot or reduced ATP consumption.
- Preservation of pHi, likely due to reduced ATP consumption, suggests a greater role in infarct size reduction than CP or ATP alone.
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.