On-pump coronary artery bypass surgery activates human myocardial NF-κB and increases TNF-α in the heart

Daniel R. Meldrum, David A. Partrick, Joseph C. Cleveland, Robert Shenkar, Kirstan K. Meldrum, Azad Raiesdana, Alfred Ayala, John Brown, Alden H. Harken

Research output: Contribution to journalArticle

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Abstract

Purpose. Myocardial tumor necrosis factor alpha (TNF) production and nuclear factor kappa B (NF-κB) activation has been demonstrated in chronic heart failure and experimental models of acute ischemia-reperfusion injury. Further, a cause and effect relationship has been established between these events and cardiomyocyte apoptosis following such conditions. It remains unknown, however, whether the myocardial injury associated with coronary artery bypass surgery (CAB) results in myocardial NF-κB activation and TNF production. We hypothesized that CAB with cardiopulmonary bypass ("on-pump") activates human myocardial NF-κB and increases TNF in the heart. Methods Patients, 18 to 65 years of age, scheduled for elective cardiac surgery but without other preexisting disease were considered eligible for the study. Biopsies of human myocardium were obtained before and after cardiopulmonary bypass and myocardial TNF levels were determined by ELISA and cytotoxicity assay, and NF-κB activation was determined by electrophoretic mobility shift assay (n = 6 patients). NF-κB activation was quantitated with gel densitometry. Results. The clinical characteristics of the study patients were as follows (means ± SEM): mean age (y) 50.0 ± 5.7, male 6 (100%), cardiopulmonary bypass time (min) 107 ± 37.7, cross-clamp time (min) 68 ± 17.6, number of CAB 3.0 ± 1.1, and length of hospital stay (d) 4.8 ± 0.9. Before CAB, myocardial TNF-α levels were 251 ± 22 pg/g and 33 ± 9 U/g, as determined by ELISA and cytotoxicity assay, respectively. Following CAB, human myocardial TNF-α levels increased to 892 ± 71 pg/g (P = 0.0008) and 141 ± 11 U/g (P = 0.0042), as determined by ELISA and cytotoxicity assay, respectively. Before CAB, the ratio of bound to unbound NF-κB DNA was 0.009 ± 0.0007 and after CAB the ratio was 0.24 ± 0.01 (P < 0.0001). Conclusion. This study represents the initial demonstration that coronary artery bypass grafting results in an activation of NF-κB and an increase of TNF in the heart.

Original languageEnglish
Pages (from-to)175-179
Number of pages5
JournalJournal of Surgical Research
Volume112
Issue number2
DOIs
StatePublished - Jun 15 2003

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NF-kappa B
Coronary Artery Bypass
Tumor Necrosis Factor-alpha
Cardiopulmonary Bypass
Enzyme-Linked Immunosorbent Assay
Length of Stay
Preexisting Condition Coverage
Densitometry
Electrophoretic Mobility Shift Assay
Reperfusion Injury
Cardiac Myocytes
Thoracic Surgery
Myocardium
Theoretical Models
Heart Failure
Gels
Apoptosis
Biopsy
DNA
Wounds and Injuries

ASJC Scopus subject areas

  • Surgery

Cite this

Meldrum, D. R., Partrick, D. A., Cleveland, J. C., Shenkar, R., Meldrum, K. K., Raiesdana, A., ... Harken, A. H. (2003). On-pump coronary artery bypass surgery activates human myocardial NF-κB and increases TNF-α in the heart. Journal of Surgical Research, 112(2), 175-179. https://doi.org/10.1016/S0022-4804(03)00122-7

On-pump coronary artery bypass surgery activates human myocardial NF-κB and increases TNF-α in the heart. / Meldrum, Daniel R.; Partrick, David A.; Cleveland, Joseph C.; Shenkar, Robert; Meldrum, Kirstan K.; Raiesdana, Azad; Ayala, Alfred; Brown, John; Harken, Alden H.

In: Journal of Surgical Research, Vol. 112, No. 2, 15.06.2003, p. 175-179.

Research output: Contribution to journalArticle

Meldrum, DR, Partrick, DA, Cleveland, JC, Shenkar, R, Meldrum, KK, Raiesdana, A, Ayala, A, Brown, J & Harken, AH 2003, 'On-pump coronary artery bypass surgery activates human myocardial NF-κB and increases TNF-α in the heart', Journal of Surgical Research, vol. 112, no. 2, pp. 175-179. https://doi.org/10.1016/S0022-4804(03)00122-7
Meldrum, Daniel R. ; Partrick, David A. ; Cleveland, Joseph C. ; Shenkar, Robert ; Meldrum, Kirstan K. ; Raiesdana, Azad ; Ayala, Alfred ; Brown, John ; Harken, Alden H. / On-pump coronary artery bypass surgery activates human myocardial NF-κB and increases TNF-α in the heart. In: Journal of Surgical Research. 2003 ; Vol. 112, No. 2. pp. 175-179.
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abstract = "Purpose. Myocardial tumor necrosis factor alpha (TNF) production and nuclear factor kappa B (NF-κB) activation has been demonstrated in chronic heart failure and experimental models of acute ischemia-reperfusion injury. Further, a cause and effect relationship has been established between these events and cardiomyocyte apoptosis following such conditions. It remains unknown, however, whether the myocardial injury associated with coronary artery bypass surgery (CAB) results in myocardial NF-κB activation and TNF production. We hypothesized that CAB with cardiopulmonary bypass ({"}on-pump{"}) activates human myocardial NF-κB and increases TNF in the heart. Methods Patients, 18 to 65 years of age, scheduled for elective cardiac surgery but without other preexisting disease were considered eligible for the study. Biopsies of human myocardium were obtained before and after cardiopulmonary bypass and myocardial TNF levels were determined by ELISA and cytotoxicity assay, and NF-κB activation was determined by electrophoretic mobility shift assay (n = 6 patients). NF-κB activation was quantitated with gel densitometry. Results. The clinical characteristics of the study patients were as follows (means ± SEM): mean age (y) 50.0 ± 5.7, male 6 (100{\%}), cardiopulmonary bypass time (min) 107 ± 37.7, cross-clamp time (min) 68 ± 17.6, number of CAB 3.0 ± 1.1, and length of hospital stay (d) 4.8 ± 0.9. Before CAB, myocardial TNF-α levels were 251 ± 22 pg/g and 33 ± 9 U/g, as determined by ELISA and cytotoxicity assay, respectively. Following CAB, human myocardial TNF-α levels increased to 892 ± 71 pg/g (P = 0.0008) and 141 ± 11 U/g (P = 0.0042), as determined by ELISA and cytotoxicity assay, respectively. Before CAB, the ratio of bound to unbound NF-κB DNA was 0.009 ± 0.0007 and after CAB the ratio was 0.24 ± 0.01 (P < 0.0001). Conclusion. This study represents the initial demonstration that coronary artery bypass grafting results in an activation of NF-κB and an increase of TNF in the heart.",
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AU - Meldrum, Daniel R.

AU - Partrick, David A.

AU - Cleveland, Joseph C.

AU - Shenkar, Robert

AU - Meldrum, Kirstan K.

AU - Raiesdana, Azad

AU - Ayala, Alfred

AU - Brown, John

AU - Harken, Alden H.

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Y1 - 2003/6/15

N2 - Purpose. Myocardial tumor necrosis factor alpha (TNF) production and nuclear factor kappa B (NF-κB) activation has been demonstrated in chronic heart failure and experimental models of acute ischemia-reperfusion injury. Further, a cause and effect relationship has been established between these events and cardiomyocyte apoptosis following such conditions. It remains unknown, however, whether the myocardial injury associated with coronary artery bypass surgery (CAB) results in myocardial NF-κB activation and TNF production. We hypothesized that CAB with cardiopulmonary bypass ("on-pump") activates human myocardial NF-κB and increases TNF in the heart. Methods Patients, 18 to 65 years of age, scheduled for elective cardiac surgery but without other preexisting disease were considered eligible for the study. Biopsies of human myocardium were obtained before and after cardiopulmonary bypass and myocardial TNF levels were determined by ELISA and cytotoxicity assay, and NF-κB activation was determined by electrophoretic mobility shift assay (n = 6 patients). NF-κB activation was quantitated with gel densitometry. Results. The clinical characteristics of the study patients were as follows (means ± SEM): mean age (y) 50.0 ± 5.7, male 6 (100%), cardiopulmonary bypass time (min) 107 ± 37.7, cross-clamp time (min) 68 ± 17.6, number of CAB 3.0 ± 1.1, and length of hospital stay (d) 4.8 ± 0.9. Before CAB, myocardial TNF-α levels were 251 ± 22 pg/g and 33 ± 9 U/g, as determined by ELISA and cytotoxicity assay, respectively. Following CAB, human myocardial TNF-α levels increased to 892 ± 71 pg/g (P = 0.0008) and 141 ± 11 U/g (P = 0.0042), as determined by ELISA and cytotoxicity assay, respectively. Before CAB, the ratio of bound to unbound NF-κB DNA was 0.009 ± 0.0007 and after CAB the ratio was 0.24 ± 0.01 (P < 0.0001). Conclusion. This study represents the initial demonstration that coronary artery bypass grafting results in an activation of NF-κB and an increase of TNF in the heart.

AB - Purpose. Myocardial tumor necrosis factor alpha (TNF) production and nuclear factor kappa B (NF-κB) activation has been demonstrated in chronic heart failure and experimental models of acute ischemia-reperfusion injury. Further, a cause and effect relationship has been established between these events and cardiomyocyte apoptosis following such conditions. It remains unknown, however, whether the myocardial injury associated with coronary artery bypass surgery (CAB) results in myocardial NF-κB activation and TNF production. We hypothesized that CAB with cardiopulmonary bypass ("on-pump") activates human myocardial NF-κB and increases TNF in the heart. Methods Patients, 18 to 65 years of age, scheduled for elective cardiac surgery but without other preexisting disease were considered eligible for the study. Biopsies of human myocardium were obtained before and after cardiopulmonary bypass and myocardial TNF levels were determined by ELISA and cytotoxicity assay, and NF-κB activation was determined by electrophoretic mobility shift assay (n = 6 patients). NF-κB activation was quantitated with gel densitometry. Results. The clinical characteristics of the study patients were as follows (means ± SEM): mean age (y) 50.0 ± 5.7, male 6 (100%), cardiopulmonary bypass time (min) 107 ± 37.7, cross-clamp time (min) 68 ± 17.6, number of CAB 3.0 ± 1.1, and length of hospital stay (d) 4.8 ± 0.9. Before CAB, myocardial TNF-α levels were 251 ± 22 pg/g and 33 ± 9 U/g, as determined by ELISA and cytotoxicity assay, respectively. Following CAB, human myocardial TNF-α levels increased to 892 ± 71 pg/g (P = 0.0008) and 141 ± 11 U/g (P = 0.0042), as determined by ELISA and cytotoxicity assay, respectively. Before CAB, the ratio of bound to unbound NF-κB DNA was 0.009 ± 0.0007 and after CAB the ratio was 0.24 ± 0.01 (P < 0.0001). Conclusion. This study represents the initial demonstration that coronary artery bypass grafting results in an activation of NF-κB and an increase of TNF in the heart.

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