The cumulative nature of pyruvate's dual mechanism for myocardial protection.
Pyruvate (PYR) supplementation protects myocardium from ischemia reperfusion injury. This study was designed to characterize and quantify the mechanism underlying this protection: specifically whether this ability resides in PYR's metabolic effect or in its antioxidant effect. Isolated perfused rat hearts (n = 6/group) were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 10 min of reperfusion (RP). Glucose was the sole metabolic substrate (Control) or was supplemented with PYR (5 mM) during (a) EQ only (PYREQ group), (b) RP only (PYRRP group), or (c) EQ and RP (PYREQ-RP group). Left ventricular developed pressure (DP) and +/- dP/dt were recorded throughout the experiment. ATP concentrations and intracellular pH were determined by 31P NMR spectroscopy. Myocardial creatinine kinase (CK) activity was assayed at end EQ and end RP. In vitro, purified CK was assayed and, after exposure to H2O2 (200 microM) and increasing concentrations of PYR (0-6 mM) for 10 min, reassayed to determine the antioxidant effect of PYR. In all cases PYR improved recovery of mechanical function at end RP (DP: Control, 11 +/- 1%; PRYRP, 23 +/- 6%; PYREQ, 34 +/- 8%; PRYEQ&RP, 53 +/- 7%; P < 0.05 between all groups and Control). Ischemic contracture was delayed in hearts that received PYR during EQ (PYREQ and PYREQ&RP: 17.8 +/- 0.2 vs 12.5 +/- 0.3 min, P < 0.001). PYR during EQ (PYREQ and PYREQ&RP) led to higher end ischemic ATP levels (32 +/- 4% vs 14 +/- 3%, P < 0.001) and a more acidic end ischemic pH (5.92 +/- 0.02 vs 5.98 +/- 0.03 in Control and PYRRP, P < 0.05). PYREQ&RP showed the highest end reperfusion ATP levels (55 +/- 7% vs 38 +/- 4%, P < 0.05 vs other groups).(ABSTRACT TRUNCATED AT 250 WORDS)
Crestanello
J A
JA
Division of Cardiothoracic Surgery, Medical College of Pennsylvania, Philadelphia 19129, USA.
Kamelgard
J
J
Whitman
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley
D011773:Pyruvates; D009243:NAD; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D003402:Creatine Kinase