Tumor necrosis factor-α 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)-α 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-α, interleukin-2, interferon-γ, and inducible nitric oxide synthase expression. Eight of 26 recipients (30.8%) developed RV failure. Seven of these 8 (87.5%) expressed TNF-α, but only 4 of the 18 (22.2%) who did not develop RV failure expressed TNF-α (P<0.005). As a predictor of RV failure. TNF-α 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-α to 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-α to expression to cardiac myocytes. Reverse transcriptase-polymerase chain reaction detected interferon-γ, 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-α expression in donor heart cardiac myocytes seems to predict the development of RV failure in patients early after heart transplantation.