Cardiac hypertrophy after transplantation is associated with persistent expression of tumor necrosis factor-alpha

Background-The mechanisms that contribute to cardiac allograft hypertrophy are not known; however, the rapid progression and severity of hypertrophy s uggest that nonhemodynamic factors may play a contributory role. Tumor necr osis factor-alpha (TNF-alpha) is a cytokine produced in cardiac allografts and capable of producing hypertrophy and fibrosis; therefore, we suggest th at TNF-alpha may play a contributory role. Accordingly, the aims of our stu dy were to define the role of systemic hypertension in the development of h ypertrophy, characterize the histological determinants of hypertrophy, and characterize the expression of myocardial TNF-alpha after heart transplanta tion. Methods and Results-To separate the effect of hypertension from immune inju ry in the development of cardiac allograft hypertrophy, we measured the gai n in left ventricular mass by 2D echocardiography in heart transplant recip ients and lung transplant recipients who developed similar rates of systemi c hypertension. The gain in left ventricular mass was 73% in heart transpla nt recipients and 7% in lung transplant recipients (P <0.0001). By comparin g myocardial samples obtained during the first week after transplant and at 1 year, we found that there was a significant increase in total collagen c ontent (P <0.0001), collagen I (P <0.0001), collagen III (P <0.0001), and m yocyte size (P <0.0001). These changes were associated with persistent myoc ardial TNF-alpha expression. Conclusions-We suggest that the contribution of hypertension to cardiac all ograft hypertrophy is minimal and that persistent intracardiac expression o f TNF-alpha may contribute to the development of cardiac allog-aft hypertro phy.