title: Tumor necrosis factor-alpha is expressed in donor heart and predicts right ventricular failure after human heart transplantation.
abstract: BACKGROUND-Myocardial failure is an important problem after heart transplantation. Right ventricular (RV) failure is most common, although its mechanisms remain poorly understood. Inflammatory cytokines play an important role in heart failure. We studied the expression of tumor necrosis factor (TNF)-alpha and other cytokines in donor myocardium and their relationship to the subsequent development of RV failure early after transplantation. METHODS AND RESULTS-Clinical details were obtained, and ventricular function was assessed by transesophageal echocardiography in 26 donors before heart retrieval. A donor RV biopsy was obtained immediately before transplantation, and each recipient was followed for the development of RV failure. Reverse transcriptase-polymerase chain reaction was performed to detect TNF-alpha, interleukin-2, interferon-gamma, and inducible nitric oxide synthase expression. Eight of 26 recipients (30.8%) developed RV failure. Seven of these 8 (87.5%) expressed TNF-alpha, but only 4 of the 18 (22.2%) who did not develop RV failure expressed TNF-alpha (P<0.005). As a predictor of RV failure, TNF-alpha mRNA had a sensitivity of 87.5%, a specificity of 83.3%, a positive predictive value of 70%, and a negative predictive value of 93.7%. Western blotting demonstrated more TNF-alpha protein in the myocardium of donor hearts that developed RV failure (658+/-60 versus 470+/-57 optical density units, P<0.05). Immunocytochemistry localized TNF-alpha expression to cardiac myocytes. Reverse transcriptase-polymerase chain reaction detected interferon-gamma in 2 (7.7%), interleukin-2 in 1 (3.8%), and inducible nitric oxide synthase mRNA in 1 (3.8%) of the 26 donor hearts, none of which developed RV failure. CONCLUSIONS-TNF-alpha expression in donor heart cardiac myocytes seems to predict the development of RV failure in patients early after heart transplantation.
authors.affiliation: National Heart and Lung Institute at the Imperial College School of Medicine, Royal Brompton and Harefield Hospital, Harefield, Middlesex, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Birks
authors.forename: V J
authors.initials: VJ
authors.lastname: Owen
authors.forename: P B
authors.initials: PB
authors.lastname: Burton
authors.forename: A E
authors.initials: AE
authors.lastname: Bishop
authors.forename: N R
authors.initials: NR
authors.lastname: Banner
authors.forename: A
authors.initials: A
authors.lastname: Khaghani
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002303:Cardiac Output, Low / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011183:Postoperative Complications; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D014019:Tissue Donors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D018497:Ventricular Dysfunction, Right / Q000209:etiology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha