Pyruvate mitigates oxidative stress during reperfusion of cardioplegia-arrested myocardium

E. Marty Knott, Jie Sun, Yu Lei, Myoung Gwi Ryou, Albert Yurvati, Robert T. Mallet

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19 Citations (Scopus)

Abstract

Background. Cardioplegic arrest and reperfusion of the myocardium imposes oxidative stress that could potentially inactivate metabolic enzymes and compromise energy production. This study determined the impact of cardioplegic arrest and reperfusion on activities of several oxidant-sensitive enzymes, and tested whether pyruvate, a natural metabolic fuel and antioxidant, mitigates oxidant stress, protects enzymes, and bolsters myocardial energy state after reperfusion. Methods. In situ swine hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, and then reperfused for 3 minutes with cardioplegia-free blood with or without approximately 12 mM pyruvate. Tissue metabolites and enzyme activities were measured in left ventricular myocardium snap frozen at 45 minutes of arrest and 3 minutes of reperfusion. Results. The 8-isoprostane content, a measure of lipid peroxidation, sharply increased upon reperfusion, coincident with a 70% decline in redox state of the intracellular antioxidant glutathione. Aconitase and glucose 6-phosphate dehydrogenase activities fell during arrest; creatine kinase and phosphofructokinase were inactivated upon reperfusion. Pyruvate suppressed 8-isoprostane formation, maintained glutathione redox state, and enhanced phosphocreatine phosphorylation potential, a measure of myocardial energy state, during reperfusion. Pyruvate reactivated creatine kinase and aconitase, which are at least partially mitochondrial enzymes, but did not protect the cytosolic enzymes glucose 6-phosphate dehydrogenase and phosphofructokinase. Conclusions. Administration of pyruvate upon reperfusion after cardioplegic arrest mitigates oxidative stress, protects mitochondrial enzymes and increases myocardial energy state. These results support therapeutic application of pyruvate-enhanced reperfusion to prevent cardiac injury after cardioplegic arrest.

Original languageEnglish
Pages (from-to)928-934
Number of pages7
JournalAnnals of Thoracic Surgery
Volume81
Issue number3
DOIs
StatePublished - 1 Mar 2006

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Induced Heart Arrest
Pyruvic Acid
Reperfusion
Myocardium
Oxidative Stress
8-epi-prostaglandin F2alpha
Enzymes
Aconitate Hydratase
Phosphofructokinases
Glucosephosphate Dehydrogenase
Creatine Kinase
Oxidants
Oxidation-Reduction
Glutathione
Antioxidants
Phosphocreatine
Lipid Peroxidation
Swine
Phosphorylation

Cite this

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title = "Pyruvate mitigates oxidative stress during reperfusion of cardioplegia-arrested myocardium",
abstract = "Background. Cardioplegic arrest and reperfusion of the myocardium imposes oxidative stress that could potentially inactivate metabolic enzymes and compromise energy production. This study determined the impact of cardioplegic arrest and reperfusion on activities of several oxidant-sensitive enzymes, and tested whether pyruvate, a natural metabolic fuel and antioxidant, mitigates oxidant stress, protects enzymes, and bolsters myocardial energy state after reperfusion. Methods. In situ swine hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, and then reperfused for 3 minutes with cardioplegia-free blood with or without approximately 12 mM pyruvate. Tissue metabolites and enzyme activities were measured in left ventricular myocardium snap frozen at 45 minutes of arrest and 3 minutes of reperfusion. Results. The 8-isoprostane content, a measure of lipid peroxidation, sharply increased upon reperfusion, coincident with a 70{\%} decline in redox state of the intracellular antioxidant glutathione. Aconitase and glucose 6-phosphate dehydrogenase activities fell during arrest; creatine kinase and phosphofructokinase were inactivated upon reperfusion. Pyruvate suppressed 8-isoprostane formation, maintained glutathione redox state, and enhanced phosphocreatine phosphorylation potential, a measure of myocardial energy state, during reperfusion. Pyruvate reactivated creatine kinase and aconitase, which are at least partially mitochondrial enzymes, but did not protect the cytosolic enzymes glucose 6-phosphate dehydrogenase and phosphofructokinase. Conclusions. Administration of pyruvate upon reperfusion after cardioplegic arrest mitigates oxidative stress, protects mitochondrial enzymes and increases myocardial energy state. These results support therapeutic application of pyruvate-enhanced reperfusion to prevent cardiac injury after cardioplegic arrest.",
author = "Knott, {E. Marty} and Jie Sun and Yu Lei and Ryou, {Myoung Gwi} and Albert Yurvati and Mallet, {Robert T.}",
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Pyruvate mitigates oxidative stress during reperfusion of cardioplegia-arrested myocardium. / Knott, E. Marty; Sun, Jie; Lei, Yu; Ryou, Myoung Gwi; Yurvati, Albert; Mallet, Robert T.

In: Annals of Thoracic Surgery, Vol. 81, No. 3, 01.03.2006, p. 928-934.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pyruvate mitigates oxidative stress during reperfusion of cardioplegia-arrested myocardium

AU - Knott, E. Marty

AU - Sun, Jie

AU - Lei, Yu

AU - Ryou, Myoung Gwi

AU - Yurvati, Albert

AU - Mallet, Robert T.

PY - 2006/3/1

Y1 - 2006/3/1

N2 - Background. Cardioplegic arrest and reperfusion of the myocardium imposes oxidative stress that could potentially inactivate metabolic enzymes and compromise energy production. This study determined the impact of cardioplegic arrest and reperfusion on activities of several oxidant-sensitive enzymes, and tested whether pyruvate, a natural metabolic fuel and antioxidant, mitigates oxidant stress, protects enzymes, and bolsters myocardial energy state after reperfusion. Methods. In situ swine hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, and then reperfused for 3 minutes with cardioplegia-free blood with or without approximately 12 mM pyruvate. Tissue metabolites and enzyme activities were measured in left ventricular myocardium snap frozen at 45 minutes of arrest and 3 minutes of reperfusion. Results. The 8-isoprostane content, a measure of lipid peroxidation, sharply increased upon reperfusion, coincident with a 70% decline in redox state of the intracellular antioxidant glutathione. Aconitase and glucose 6-phosphate dehydrogenase activities fell during arrest; creatine kinase and phosphofructokinase were inactivated upon reperfusion. Pyruvate suppressed 8-isoprostane formation, maintained glutathione redox state, and enhanced phosphocreatine phosphorylation potential, a measure of myocardial energy state, during reperfusion. Pyruvate reactivated creatine kinase and aconitase, which are at least partially mitochondrial enzymes, but did not protect the cytosolic enzymes glucose 6-phosphate dehydrogenase and phosphofructokinase. Conclusions. Administration of pyruvate upon reperfusion after cardioplegic arrest mitigates oxidative stress, protects mitochondrial enzymes and increases myocardial energy state. These results support therapeutic application of pyruvate-enhanced reperfusion to prevent cardiac injury after cardioplegic arrest.

AB - Background. Cardioplegic arrest and reperfusion of the myocardium imposes oxidative stress that could potentially inactivate metabolic enzymes and compromise energy production. This study determined the impact of cardioplegic arrest and reperfusion on activities of several oxidant-sensitive enzymes, and tested whether pyruvate, a natural metabolic fuel and antioxidant, mitigates oxidant stress, protects enzymes, and bolsters myocardial energy state after reperfusion. Methods. In situ swine hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, and then reperfused for 3 minutes with cardioplegia-free blood with or without approximately 12 mM pyruvate. Tissue metabolites and enzyme activities were measured in left ventricular myocardium snap frozen at 45 minutes of arrest and 3 minutes of reperfusion. Results. The 8-isoprostane content, a measure of lipid peroxidation, sharply increased upon reperfusion, coincident with a 70% decline in redox state of the intracellular antioxidant glutathione. Aconitase and glucose 6-phosphate dehydrogenase activities fell during arrest; creatine kinase and phosphofructokinase were inactivated upon reperfusion. Pyruvate suppressed 8-isoprostane formation, maintained glutathione redox state, and enhanced phosphocreatine phosphorylation potential, a measure of myocardial energy state, during reperfusion. Pyruvate reactivated creatine kinase and aconitase, which are at least partially mitochondrial enzymes, but did not protect the cytosolic enzymes glucose 6-phosphate dehydrogenase and phosphofructokinase. Conclusions. Administration of pyruvate upon reperfusion after cardioplegic arrest mitigates oxidative stress, protects mitochondrial enzymes and increases myocardial energy state. These results support therapeutic application of pyruvate-enhanced reperfusion to prevent cardiac injury after cardioplegic arrest.

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U2 - 10.1016/j.athoracsur.2005.08.046

DO - 10.1016/j.athoracsur.2005.08.046

M3 - Article

VL - 81

SP - 928

EP - 934

JO - Annals of Thoracic Surgery

JF - Annals of Thoracic Surgery

SN - 0003-4975

IS - 3

ER -