Background:
Off-pump coronary artery bypass grafting is associated with transient periods of myocardial
ischemia during revascularization resulting in myocardial contractile dysfunction
and oxidative injury. The purpose of this study was to investigate the efficacy of
ethyl pyruvate as a myocardial protective agent in a rat model of off-pump coronary
artery bypass grafting associated with transient myocardial dysfunction without infarction.
Methods:
Wistar rats were subjected to transient ischemia via 10 min occlusion of the LAD coronary artery followed by 10 min of reperfusion. Animals received an IV bolus of Ringer's solution as a control
(n = 10) or Ringer's ethyl pyruvate (n = 10) immediately before the initiation of ischemia and reperfusion. Myocardial ATP
and lipid peroxidation levels were quantified for an estimation of energetics and
oxidative stress, respectively. In vivo cardiac function was assessed throughout the
ischemia and reperfusion periods.
Results:
Ethyl pyruvate significantly increased myocardial ATP levels compared to controls
(2650 ± 759 nmol/g versus 892 ± 276 nmol/g, p = 0.04). Myocardial oxidative stress was significantly reduced in animals treated with
ethyl pyruvate compared to controls (70.4 ± 2.6 nmol/g versus 81.8 ± 2.4 nmol/g, p = 0.04). dP/dt max and cardiac output were significantly greater in the ethyl pyruvate group compared
to controls during ischemia and reperfusion.
Conclusions:
Ethyl pyruvate enhances myocardial ATP levels, reduces oxidative stress, and preserves
myocardial function in a model of transient ischemia/reperfusion injury not subject
to myocardial infarction.
Keywords
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References
- Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity.Ann Thorac Surg. 2001; 72: 1282-1288
- Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial.J Am Med Assoc. 2002; 287: 1405-1412
- Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2003; 125: 797-808
- Off-pump vs conventional coronary artery bypass grafting: early and 1-year graft patency, cost, and quality-of-life outcomes. A randomized trial.J Am Med Assoc. 2004; 291: 1841-1849
- Flow simulation of the intracoronary shunt tube for off-pump coronary artery bypass.Eur J Cardiac Thorac Surg. 2003; 23: 665-669
- Intracoronary shunt flow measurement for off-pump coronary artery bypass surgery.Heart Surg Forum. 2003; 6: 16
- l-Lactate transport into rat heart mitochondria and reconstruction of the l-lactate/pyruvate shuttle.Biochem J. 2002; 364: 101-104
- Pyruvate/dichloroacetate supply during reperfusion accelerates recovery of cardiac energetics and improves mechanical function following cardioplegic arrest.Eur J Cardiothorac Surg. 2001; 19: 865-872
- Pyruvate augments mechanical function via activation of the pyruvate dehydrogenase complex in reperfused ischemic immature rabbit hearts.J Surg Res. 1998; 79: 164-169
- Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase attentuates postischemic contractile dysfunction.Circulation. 1998; 98: II255-II261
- Free radical scavengers improve functional recovery of stunned myocardium in a model of surgical coronary revascularization.Surgery. 1987; 102: 334-340
- Glutathione protects against myocardial ischemia reperfusion injury by detoxifying peroxynitrite.J Mol Cell Cardiol. 2000; 32: 1669-1678
- Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury.J Mol Cell Cardiol. 1996; 28: 1759-1767
- Pyruvate enhances recovery of rat hearts after ischemia and reperfusion by preventing free radical generation.Am J Physiol Heart Circ Physiol. 1993; 265: H1571-H1576
- Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia.J Cardiovasc Pharmacol. 1999; 34: 651-659
- Pyruvate: metabolic protector of cardiac performance.Proc Soc Exp Biol Med. 2000; 223: 136-148
- Pyruvate restores contractile function and antioxidant defenses of hydrogen peroxide-challenged myocardium.J Mol Cell Cardiol. 2002; 34: 1173-1184
- Ringer's ethyl pyruvate solution ameliorates ischemia/reperfusion-induced intestinal mucosal injury in rats.Crit Care Med. 2001; 29: 1513-1518
- Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia.JTCVS. 2004; 127: 1262-1269
- Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice.Hum Gene Ther. 1993; 4: 419-431
- Extraction of adenosine triphosphate from microbial and somatic cells.Methods Enzymol. 1986; 133: 14-22
- Use of a new methylene blue derivative for determination of lipid peroxides in foods.Biochem Int. 1986; 12: 367-371
- A randomized comparison of off-pump and on-pump multivessel coronary artery bypass surgery.N Engl J Med. 2004; 350: 21-28
- Activation of stimulus-secretion coupling in pancreatic beta-cells by specific products of glucose metabolism.J Biol Chem. 1996; 271: 4838-4845
- Prevention of intracellular oxidative stress to lens by pyruvate and its ester.Free Radic Res. 1998; 28: 131-135
- Attenuation of sugar cataract by ethyl pyruvate.Mol Cell Biochem. 1999; 200: 103-109
- Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock.Am J Physiol Gastrointest Liver Physiol. 2002; 283: G212-G221
- Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation.Proc Natl Acad Sci USA. 2002; 99: 12351-12356
Article info
Footnotes
☆Presented at the 2003 American Heart Association Scientific Sessions, November 11, 2003.
Identification
Copyright
© 2005 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved.