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


METHODS
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.
West Virginia University, Department of Surgery, Morgantown, WV 26506-9238, USA.
Ganga
G
Prabhakar
Linda
L
Vona-Davis
David
D
Murray
Paresh
P
Lakhani
Gordon
G
Murray
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism; D006019:Glycolysis / Q000187:drug effects; D007275:Injections, Intravenous; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008026:Ligation; D008279:Magnetic Resonance Imaging; D008297:Male; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D015425:Myocardial Reperfusion / Q000379:methods; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D010710:Phosphates / Q000032:analysis / Q000378:metabolism*; D010725:Phosphocreatine / Q000494:pharmacology / Q000627:therapeutic use*; D010759:Phosphorus Isotopes; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D010710:Phosphates; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate