235. Herpes Simplex Virus Vector Mediated Heme Oxygenase Gene Therapy of Heart Ischemia_Reperfusion

Heart transplantation is the preferred therapy for patients with a variety of end-stage heart diseases. Developments in the use of potent immunosuppressive drugs, technical innovations in transplant surgery, and improvements in postoperative care have significantly improved outcomes of heart transplantation. However, donor organs suffer from perturbations in endothelial cell function during required cold storage and subsequent warm reperfusion that can lead to organ injury (ischemia-reperfusion [I-R]). Thus development of methods for preserving endothelial cell function would contribute to transplant success. Considerable evidence supports an important role for heme oxygenase-1 (HO-1) in protection against I-R injury. HO-1 catabolizes heme into biliverdin, free iron and CO, the latter acting as an anti-inflammatory and anti-apoptotic agent. These actions presumably help suppress deleterious effects associated with transplant rejection, endotoxemia and hyperoxia.