alexa Phosphocreatine restores high-energy phosphates in ischemic myocardium: implication for off-pump cardiac revascularization.

Journal of Pharmacokinetics & Experimental Therapeutics

Author(s): Prabhakar G, VonaDavis L, Murray D, Lakhani P, Murray G

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Abstract BACKGROUND: High-energy phosphate metabolism is altered in the ischemic myocardium. We investigated the effects of in vivo administration of phosphocreatine (PCr) in a transient ischemic rat model to emulate off-pump myocardial revascularization. STUDY DESIGN: Rats received either PCr (100 mg/kg) or saline intravenously 1 hour before surgery. Regional ischemia was maintained for 12 minutes by ligation of the left anterior descending artery and compared with sham-operated animals. Cardiac tissue was studied for ATP, PCr, and inorganic phosphate (Pi) using (31)P-cryo-NMR. Results were compared by ANOVA. RESULTS: Levels of ATP were significantly (p < 0.01) lower in the ischemic hearts compared with controls; Pi and PCr remained unchanged. The PCr/Pi ratio was altered in ischemic hearts, reflecting an increased energy demand. PCr administration significantly (p < 0.01) elevated the content of PCr and ATP in both normal and ischemic hearts. CONCLUSIONS: PCr restores high-energy phosphates and attenuates metabolic stress during periods of myocardial ischemia in the rat. Preconditioning with PCr may serve as a useful adjunct to off-pump coronary revascularization. This article was published in J Am Coll Surg and referenced in Journal of Pharmacokinetics & Experimental Therapeutics

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