Bcl-xL gene transfer inhibits Bax translocation and prolongs cardiac cold preservation time in rats

Background - Apoptosis is an important cause of early graft loss after heart transplantation. Bcl- xL was reported to protect the heart against normothermic ischemia and reperfusion injury. In this study, we determined whether overexpression of Bcl- xL could inhibit tissue injury resulting from prolonged cold preservation followed by warm reperfusion of heart transplants. Methods and Results - Lewis rat hearts were transduced with an adenovirus vector harboring Bcl- xL cDNA ( AxCAhBclxL) 4 days before collection of tissue. After preservation in University of Wisconsin solution at 4 degrees C for 24 hours, the heart was either perfused with a Langendorff device ex vivo or used for heterotopic heart transplantation in vivo. Bcl- xL gene transfer significantly reduced the infarct size (23.0 +/- 2.6% versus 47.7 +/- 7.0% in saline control and 48.6 +/- 6.1% in vector control, P < 0.01) after 2- hour reperfusion at 37 degrees C with the Langendorff device and significantly decreased creatine kinase release (0.82 +/- 0.27 IU, versus 1.57 +/- 0.33 and 1.50 +/- 0.37 IU in saline and vector controls, respectively; P < 0.05). In heart transplantation, overexpresson of Bcl-xL inhibited Bax translocation from the cytosol to the mitochondria, resulting in decreased cytochrome c release from the mitochondria; it also significantly decreased cardiac cell apoptosis and improved graft survival rate after long cold preservation, followed by warm reperfusion. Conclusions - Bcl- xL gene transfer inhibited the translocation of Bax and prolonged the cold preservation time of cardiac transplants. This may be a potential therapeutic method in clinical practice.