Sequential monitoring of intragraft cytokine mRNA expression in relation to diastolic left ventricular wall thickness and function early after heart transplantation.

Abstract

Because production of immune regulatory proteins may play a role in early graft dysfunction after heart transplantation, we analyzed whether intragraft cytokine messenger RNA (mRNA) expression levels are associated with diastolic left ventricular function in cardiac allografts. We intensively monitored 16 cardiac allograft recipients during the first 3 months after transplantation. The mRNA expression levels of tumor necrosis factor (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF-beta), platelet derived growth factor (PDGF-A), and basic fibroblast growth factor (bFGF) were measured in endomyocardial biopsies (n = 123) by quantitative RT-PCR. To determine diastolic allograft function, concurrent M-mode and two-dimensional Doppler echocardiograms were analyzed for the following parameters: left ventricular total wall thickness, maximal early and atrial mitral flow velocity, deceleration time of maximal early mitral flow velocity, and isovolumetric relaxation period. During the first 3 months post-transplant an overall decrease in mRNA expression levels of almost all measured cytokines was observed, which paralleled an improvement in diastolic left ventricular wall thickness and function. However, no straightforward relationship could be found between a specific cytokine mRNA expression pattern and the studied echocardiographic parameters. Our data suggest that the improvement in diastolic left ventricular function is associated with a general reduction of inflammation within the allograft, rather than related to a specific cytokine expression pattern.