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(Circulation Research. 2000;86:982.)
© 2000 American Heart Association, Inc.

Integrative Physiology

cAMP Pulse During Preservation Inhibits the Late Development of Cardiac Isograft and Allograft Vasculopathy

Catherine Y. Wang, Isaak Aronson, Shin Takuma, Shunichi Homma, Yoshifumi Naka, Tarek Alshafie, Viktor Brovkovych, Tadeusz Malinski, Mehmet C. Oz, David J. Pinsky

From the Departments of Surgery (C.Y.W., Y.N., M.C.O.), Physiology (I.A., T.A.), and Medicine (S.T., S.H., D.J.P.), College of Physicians and Surgeons, Columbia University, New York, NY, and Department of Chemistry and Institute for Biotechnology (V.B., T.M.), Oakland University, Rochester, Mich.

Correspondence to David J. Pinsky, MD, Columbia University, College of Physicians and Surgeons, PH 10 Stem, 630 W 168th St, New York, NY 10032. E-mail djp5{at}columbia.edu

Abstract—The causes of transplant-associated coronary artery disease remain obscure, and there is no known treatment. Preservation injury of murine heterotopic vascularized cardiac isografts caused a small, albeit significant, increase in neointimal formation; preservation injury of allografts markedly increased both the incidence and severity of transplant-associated coronary artery disease. As cAMP is an important vascular homeostatic mediator the levels of which decline during organ preservation, buttressing cAMP levels solely during initial preservation both improved acute allograft function and reduced the severity of transplant-associated coronary artery disease in grafts examined 2 months later. Inhibiting the cAMP-dependent protein kinase abrogated these beneficial effects. cAMP treatment was associated with an early reduction in leukocyte infiltration and a reciprocal decrease in superoxide and increase in NO levels. These data indicate that alloantigen-independent injury to the graft, which occurs at the time of cardiac preservation, can set in motion pathological vascular events that are manifest months later. Furthermore, a cAMP pulse during cardiac preservation reduces the incidence and severity of transplant-associated coronary artery disease.

Key Words: cAMP • protein kinase • heart transplantation • allograft arteriopathy • organ preservation

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