Age-dependent myocardial reinduction of apoptosis inhibitors under VAD in heart failure

Hemodynamic unloading using the ventricular assist device [VAD] results in partial functional recovery of failing hearts that show increased susceptib ility to cardiomyocyte apoptosis. The caspase cascade is the central elemen t of the apoptotic process in cells. We therefore tested expression shifts of left ventricular mRNA of caspases and their endogenous inhibitors from 1 5 patients with VAD support and successful bridging to transplantation usin g semiquantitative RT-PCR. Cardiac unloading was shown by the reduction in ventricular Pro-ANP mRNA under VAD. No alteration of mRNA expression under VAD could be observed for initiator caspases, for their selective inhibitor s or for apoptotic signal molecules from the mitochondrial intermembrane sp ace. Only two unselective cardiac IAPs (inhibitor of apoptosis protein) wer e increased under VAD with better recovery in younger patients. In conclusi on, our findings indicate that successful hemodynamic unloading by VAD supp ort causes only minor, age-dependent recovery in the expression of IAPs, wh ile presumed alterations in antiapoptotic modulator systems upstream of the caspase cascade still remain to be identified.