cAMP pulse during preservation inhibits the late development of cardiac isograft and allograft vasculopathy.
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.
Wang
C Y
CY
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Aronson
I
I
Takuma
S
S
Homma
S
S
Naka
Y
Y
Alshafie
T
T
Brovkovych
V
V
Malinski
T
T
Oz
M C
MC
Pinsky
D J
DJ
D000818:Animals; D003327:Coronary Disease / Q000517:prevention & control*; D000242:Cyclic AMP / Q000627:therapeutic use*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D016027:Heart Transplantation; D007962:Leukocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009926:Organ Preservation; D011183:Postoperative Complications / Q000517:prevention & control*; D011184:Postoperative Period; D013481:Superoxides / Q000037:antagonists & inhibitors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D004791:Enzyme Inhibitors; D013481:Superoxides; D009569:Nitric Oxide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases