Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation

Myoung Gwi Ryou, Devin C. Flaherty, Besim Hoxha, Hunaid Gurji, Jie Sun, Lisa Michelle Hodge, Albert Yurvati, Robert T. Mallet

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16 Citations (Scopus)

Abstract

Background: Cardiopulmonary bypass-induced oxidative stress initiates inflammation that can damage the myocardium. This study tested whether cardioplegia enriched with the intermediary metabolite and antioxidant pyruvate dampens postbypass myocardial inflammation. Methods: Pigs were maintained on cardiopulmonary bypass while their hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, in which the crystalloid contained 188 mM glucose ± 24 mM pyruvate. Pigs were weaned from bypass after 30 minutes of whole blood reperfusion and recovered for 4 hours. Glutathione (GSH) and glutathione disulfide (GSSG) were measured in coronary sinus plasma to indirectly monitor myocardial GSH redox state (GSH/GSSG). Left ventricular myocardium was sampled 4 hours after cardiopulmonary bypass for analyses of C-reactive protein, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinase-2 (TIMP-2), and to assess neutrophil infiltration by histology and myeloperoxidase assay. Results: Coronary sinus GSH/GSSG fell 70% after cardiopulmonary bypass with control cardioplegia, but pyruvate cardioplegia produced a robust increase in coronary sinus GSH/GSSG that persisted for 4 hours after bypass. Myocardial C-reactive protein content increased 5.6-fold after control bypass, and neutrophil infiltration and myeloperoxidase activity also increased, but pyruvate-fortified cardioplegia prevented these inflammatory effects. Control cardioplegia lowered myocardial TIMP-2 content by 59% and increased matrix metalloproteinase-9 activity by 35% versus nonbypass sham values, but pyruvate cardioplegia increased TIMP-2 content ninefold versus control cardioplegia and prevented the increase in matrix metalloproteinase-9. Matrix metalloproteinase-2 was not affected by bypass ± pyruvate. Conclusions: Pyruvate-enriched cardioplegia dampens cardiopulmonary bypass-induced myocardial inflammation. Increased GSH/GSSG and TIMP-2 may mediate pyruvate's effects.

Original languageEnglish
Pages (from-to)1529-1535
Number of pages7
JournalAnnals of Thoracic Surgery
Volume90
Issue number5
DOIs
StatePublished - 1 Jan 2010

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Induced Heart Arrest
Cardiopulmonary Bypass
Pyruvic Acid
Glutathione Disulfide
Inflammation
Tissue Inhibitor of Metalloproteinase-2
Coronary Sinus
Matrix Metalloproteinase 9
Neutrophil Infiltration
Matrix Metalloproteinase 2
C-Reactive Protein
Peroxidase
Myocardium
Swine
Reperfusion
Oxidation-Reduction
Glutathione
Histology
Oxidative Stress
Antioxidants

Cite this

Ryou, Myoung Gwi ; Flaherty, Devin C. ; Hoxha, Besim ; Gurji, Hunaid ; Sun, Jie ; Hodge, Lisa Michelle ; Yurvati, Albert ; Mallet, Robert T. / Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation. In: Annals of Thoracic Surgery. 2010 ; Vol. 90, No. 5. pp. 1529-1535.
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title = "Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation",
abstract = "Background: Cardiopulmonary bypass-induced oxidative stress initiates inflammation that can damage the myocardium. This study tested whether cardioplegia enriched with the intermediary metabolite and antioxidant pyruvate dampens postbypass myocardial inflammation. Methods: Pigs were maintained on cardiopulmonary bypass while their hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, in which the crystalloid contained 188 mM glucose ± 24 mM pyruvate. Pigs were weaned from bypass after 30 minutes of whole blood reperfusion and recovered for 4 hours. Glutathione (GSH) and glutathione disulfide (GSSG) were measured in coronary sinus plasma to indirectly monitor myocardial GSH redox state (GSH/GSSG). Left ventricular myocardium was sampled 4 hours after cardiopulmonary bypass for analyses of C-reactive protein, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinase-2 (TIMP-2), and to assess neutrophil infiltration by histology and myeloperoxidase assay. Results: Coronary sinus GSH/GSSG fell 70{\%} after cardiopulmonary bypass with control cardioplegia, but pyruvate cardioplegia produced a robust increase in coronary sinus GSH/GSSG that persisted for 4 hours after bypass. Myocardial C-reactive protein content increased 5.6-fold after control bypass, and neutrophil infiltration and myeloperoxidase activity also increased, but pyruvate-fortified cardioplegia prevented these inflammatory effects. Control cardioplegia lowered myocardial TIMP-2 content by 59{\%} and increased matrix metalloproteinase-9 activity by 35{\%} versus nonbypass sham values, but pyruvate cardioplegia increased TIMP-2 content ninefold versus control cardioplegia and prevented the increase in matrix metalloproteinase-9. Matrix metalloproteinase-2 was not affected by bypass ± pyruvate. Conclusions: Pyruvate-enriched cardioplegia dampens cardiopulmonary bypass-induced myocardial inflammation. Increased GSH/GSSG and TIMP-2 may mediate pyruvate's effects.",
author = "Ryou, {Myoung Gwi} and Flaherty, {Devin C.} and Besim Hoxha and Hunaid Gurji and Jie Sun and Hodge, {Lisa Michelle} and Albert Yurvati and Mallet, {Robert T.}",
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Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation. / Ryou, Myoung Gwi; Flaherty, Devin C.; Hoxha, Besim; Gurji, Hunaid; Sun, Jie; Hodge, Lisa Michelle; Yurvati, Albert; Mallet, Robert T.

In: Annals of Thoracic Surgery, Vol. 90, No. 5, 01.01.2010, p. 1529-1535.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation

AU - Ryou, Myoung Gwi

AU - Flaherty, Devin C.

AU - Hoxha, Besim

AU - Gurji, Hunaid

AU - Sun, Jie

AU - Hodge, Lisa Michelle

AU - Yurvati, Albert

AU - Mallet, Robert T.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background: Cardiopulmonary bypass-induced oxidative stress initiates inflammation that can damage the myocardium. This study tested whether cardioplegia enriched with the intermediary metabolite and antioxidant pyruvate dampens postbypass myocardial inflammation. Methods: Pigs were maintained on cardiopulmonary bypass while their hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, in which the crystalloid contained 188 mM glucose ± 24 mM pyruvate. Pigs were weaned from bypass after 30 minutes of whole blood reperfusion and recovered for 4 hours. Glutathione (GSH) and glutathione disulfide (GSSG) were measured in coronary sinus plasma to indirectly monitor myocardial GSH redox state (GSH/GSSG). Left ventricular myocardium was sampled 4 hours after cardiopulmonary bypass for analyses of C-reactive protein, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinase-2 (TIMP-2), and to assess neutrophil infiltration by histology and myeloperoxidase assay. Results: Coronary sinus GSH/GSSG fell 70% after cardiopulmonary bypass with control cardioplegia, but pyruvate cardioplegia produced a robust increase in coronary sinus GSH/GSSG that persisted for 4 hours after bypass. Myocardial C-reactive protein content increased 5.6-fold after control bypass, and neutrophil infiltration and myeloperoxidase activity also increased, but pyruvate-fortified cardioplegia prevented these inflammatory effects. Control cardioplegia lowered myocardial TIMP-2 content by 59% and increased matrix metalloproteinase-9 activity by 35% versus nonbypass sham values, but pyruvate cardioplegia increased TIMP-2 content ninefold versus control cardioplegia and prevented the increase in matrix metalloproteinase-9. Matrix metalloproteinase-2 was not affected by bypass ± pyruvate. Conclusions: Pyruvate-enriched cardioplegia dampens cardiopulmonary bypass-induced myocardial inflammation. Increased GSH/GSSG and TIMP-2 may mediate pyruvate's effects.

AB - Background: Cardiopulmonary bypass-induced oxidative stress initiates inflammation that can damage the myocardium. This study tested whether cardioplegia enriched with the intermediary metabolite and antioxidant pyruvate dampens postbypass myocardial inflammation. Methods: Pigs were maintained on cardiopulmonary bypass while their hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, in which the crystalloid contained 188 mM glucose ± 24 mM pyruvate. Pigs were weaned from bypass after 30 minutes of whole blood reperfusion and recovered for 4 hours. Glutathione (GSH) and glutathione disulfide (GSSG) were measured in coronary sinus plasma to indirectly monitor myocardial GSH redox state (GSH/GSSG). Left ventricular myocardium was sampled 4 hours after cardiopulmonary bypass for analyses of C-reactive protein, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinase-2 (TIMP-2), and to assess neutrophil infiltration by histology and myeloperoxidase assay. Results: Coronary sinus GSH/GSSG fell 70% after cardiopulmonary bypass with control cardioplegia, but pyruvate cardioplegia produced a robust increase in coronary sinus GSH/GSSG that persisted for 4 hours after bypass. Myocardial C-reactive protein content increased 5.6-fold after control bypass, and neutrophil infiltration and myeloperoxidase activity also increased, but pyruvate-fortified cardioplegia prevented these inflammatory effects. Control cardioplegia lowered myocardial TIMP-2 content by 59% and increased matrix metalloproteinase-9 activity by 35% versus nonbypass sham values, but pyruvate cardioplegia increased TIMP-2 content ninefold versus control cardioplegia and prevented the increase in matrix metalloproteinase-9. Matrix metalloproteinase-2 was not affected by bypass ± pyruvate. Conclusions: Pyruvate-enriched cardioplegia dampens cardiopulmonary bypass-induced myocardial inflammation. Increased GSH/GSSG and TIMP-2 may mediate pyruvate's effects.

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U2 - 10.1016/j.athoracsur.2010.06.010

DO - 10.1016/j.athoracsur.2010.06.010

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JO - Annals of Thoracic Surgery

JF - Annals of Thoracic Surgery

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