Myocardial preconditioning significantly reduced infarct size compared with controls (0.3% vs 38.1%; p<0.0001), with the loss of protection paralleling the time course of glycogen repletion.
Myocardial preconditioning reduces infarct size in rats by depleting glycogen stores and attenuating intracellular acidosis during subsequent prolonged ischemia.
Absolute Event Rate: 0.3% vs 38.1%
p-value: p=<0.0001
BACKGROUND: Although previous investigators have demonstrated that myocardial preconditioning reduces infarct size, the mechanisms of cardioprotection associated with preconditioning are not completely understood. METHODS AND RESULTS: To test the hypothesis that preconditioning (four 5-minute episodes of ischemia each followed by 5 minutes of reperfusion) reduces infarct size by depleting cardiac glycogen stores and attenuating the degree of intracellular acidosis during subsequent prolonged left coronary artery occlusion, preconditioned and control rats were subjected to 45 minutes of left coronary artery occlusion and 120 minutes of reflow immediately after preconditioning (groups 1P and 1C, respectively) or after 30 minutes (groups 2P+30m and 2C), 1 hour (groups 3P+60m and 3C), or 6 hours (groups 4P+360m and 4C) of nonischemic recovery after preconditioning but before prolonged ischemia. In each group, cardiectomy was performed in selected rats immediately before prolonged ischemia for cardiac glycogen assay. In selected animals, 31P magnetic resonance spectroscopy was performed to monitor intracellular pH and measure high-energy phosphate levels during ischemia and reperfusion. Group 1P rats demonstrated marked glycogen depletion after preconditioning compared with controls (0.72 +/- 0.39 n = 9 versus 5.67 +/- 1.73 n = 12 mg glucose/g wet wt; p < 0.001 versus group 1C) that was associated with attenuation of intracellular acidosis during ischemia, as measured by 31P magnetic resonance spectroscopy (6.8 +/- 0.3 n = 11 versus 6.2 +/- 0.3 n = 9 pH units; p < 0.01), and marked infarct size reduction (0.3 +/- 0.6% n = 7 versus 38.1 +/- 11.3% n = 7, infarct size divided by risk area; p < 0.0001). During ischemia, there were no differences in myocardial ATP or phosphocreatine levels or in any hemodynamic determinant of myocardial oxygen demand between groups 1P and 1C. In preconditioned rats that were allowed to recover before ischemia (groups 2P+30m, 3P+60m, and 4P+360m), the time course of glycogen repletion paralleled the loss of protection from ischemic injury. CONCLUSIONS: Glycogen depletion and the attenuation of intracellular acidosis during ischemia appear to be important factors in delaying irreversible injury and reducing infarct size in this animal model of myocardial preconditioning.
Wolfe et al. (Mon,) conducted a other in Myocardial ischemia-reperfusion injury. Myocardial preconditioning vs. Control (no preconditioning) was evaluated on Infarct size (infarct size divided by risk area) (p=<0.0001). Myocardial preconditioning significantly reduced infarct size compared with controls (0.3% vs 38.1%; p<0.0001), with the loss of protection paralleling the time course of glycogen repletion.
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