Experimental cardiac allograft vasculopathy in mice.
Cardiac allograft vasculopathy is the most common cause of death in heart transplant recipients after the first postoperative year. The pathogenesis of cardiac allograft vasculopathy is not clearly defined. To better study this disease, a genetically well-defined and reproducible animal model such as the mouse is needed. We performed heterotopic, intraabdominal heart transplantation between two inbred strains of mice. The B10.A strain served as donors, and the B10.BR strain served as recipients. No immunosuppressive therapy was administered. The allografts in groups I (n = 6) and II (n = 6) were harvested at 30 and 50 days after operation, respectively. All allografts had palpable contractions at the time of harvest. The cardiac allografts from both groups showed mild to moderate acute cellular rejection. In groups I and II, 55% +/- 26% and 60% +/- 18% of arteries showed intimal thickening, respectively. Pathologically, the vascular lesions were characterized with varying degrees of intimal thickening, subendothelial mononuclear cell infiltration and fibrosis, frequent disruption of the internal elastic lamina, and perivascular inflammation. These findings are characteristic of cardiac allograft vasculopathy seen clinically. Isografts (n = 6) showed no vascular lesions. The heterotopic transplantation of B10.A-strain hearts into B10.BR recipients provides a useful murine model for future studies in the pathogenesis and treatment of cardiac allograft vasculopathy.
Ardehali
A
A
Department of Surgery, UCLA Medical Center 90024.
Billingsley
A
A
Laks
H
H
Drinkwater
D C
DC
Sorensen
T J
TJ
Drake
T A
TA
D000818:Animals; D001160:Arterioles / Q000473:pathology; D003327:Coronary Disease / Q000209:etiology / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005355:Fibrosis; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology*; D006084:Graft Rejection / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000473:pathology