The central role of the endothelium in graft coronary vasculopathy and heart transplantation.
BACKGROUND
Despite the successes and advances made in clinical heart transplantation, the number one culprit and greatest cause of death beyond the first year remains graft coronary vasculopathy. The study of the central role of the endothelium in the development of graft coronary vasculopathy has been aided by the numerous advances in basic science, which have enhanced our understanding of endothelial physiology.


METHODS
Several experimental strategies are reviewed, such as the in vivo porcine heterotopic heart transplantation model and the in vivo and in vitro exposure of coronary and renal arteries to immunosuppressive drugs. Other studies are reviewed, including vascular biology studies that examine the role of acute and chronic rejection, hypercholesterolemia, inhibition of endothelial nitric oxide synthase, denudation of the endothelium, and immunosuppressive drugs in coronary endothelial function and intimal hyperplasia; studies that assess the acute and remote effects of different cardioplegic and preservation solutions used for transplantation; and studies that test novel therapies for pulmonary endothelial dysfunction and hypertension.


RESULTS
These studies highlight the target factors that ensure preservation of the protective role of the coronary endothelium on the vascular wall, including the control of immunological damage, treatment of hypercholesterolemia, use of optimal cardioplegic and preservation strategies, and the prevention and treatment of pulmonary endothelial dysfunction after exposure to cardiopulmonary bypass and heart transplantation.


CONCLUSIONS
Further research should focus on improving human lymphocyte antigen matching of donor and recipients, improving immunosuppressive regimens, and preserving graft coronary endothelial function and the pulmonary circulation to positively modify the survival curve of transplant recipients.
Perrault
Louis P
LP
Research Centre, Department of Surgery, Montreal Heart Institute, Quebec, Canada. louis.perrault@icm-mhi.org
Carrier
Michel
M
D000818:Animals; D002314:Cardioplegic Solutions / Q000627:therapeutic use; D013504:Cardiovascular Surgical Procedures / Q000639:trends; D003327:Coronary Disease / Q000503:physiopathology* / Q000628:therapy*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology* / Q000601:surgery*; D006084:Graft Rejection / Q000209:etiology / Q000503:physiopathology; D016027:Heart Transplantation; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology / Q000628:therapy; D019188:Organ Preservation Solutions / Q000627:therapeutic use
D002314:Cardioplegic Solutions; D019188:Organ Preservation Solutions