Allo- and autotransplantation of carotid artery--a new model of chronic graft vessel disease: evaluation by magnetic resonance imaging and histology.
BACKGROUND
Graft vessel disease is a special form of accelerated arteriosclerosis. Because immunological and nonimmunological factors can contribute to graft vessel disease, we developed a model that enables the study of both factors simultaneously.


METHODS
A carotid artery was allografted from DA to Lewis rats, with the excised native artery autografted on the contralateral side. Five groups of six to seven rats were treated for 8 weeks with vehicle (placebo) or cyclosporine (CsA) (0.3, 1, 3, and 10 mg x kg(-1) x day(-1)), which was administered using subcutaneous osmotic minipumps. The carotid lumen area was estimated in vivo at 2, 4, and 8 weeks by magnetic resonance imaging (MRI); CsA blood levels were determined twice. Carotid neointimal thickening and medial and luminal area were measured with histological techniques.


RESULTS
MRI showed bulging of the allografts but not autografts. Bulging disappeared over time with narrowing of the allograft lumina estimated by both MRI and histology. Histologically, vehicle-treated animals developed a massive neointima, which was inhibited in a dose-dependent manner by CsA. Autografts remained normal except for minimal subintimal thickening of two of four arteries in the group given the highest dose of CsA. Cellular rejection was detected in the allografts of all but the highest-dose group. The CsA blood levels were similar to those used in man at the two lower doses and about 10-fold higher at the highest dose.


CONCLUSIONS
Subintimal thickening did not correlate with in vivo lumen size, a phenomenon that we have previously described for balloon catheter-induced lesions. CsA blood concentrations similar to those used in patients suppressed neointima formation in part, and 10-fold higher concentrations almost completely suppressed neointima formation.
Wehr
S
S
Transplantation Department, Sandoz Pharma Ltd., Basel, Switzerland.
Rudin
M
M
Joergensen
J
J
Hof
A
A
Hof
R P
RP
D000818:Animals; D001835:Body Weight; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000473:pathology / Q000637:transplantation*; D016572:Cyclosporine / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control; D008279:Magnetic Resonance Imaging; D011180:Postmortem Changes; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014181:Transplantation Immunology; D014182:Transplantation, Autologous / Q000401:mortality / Q000473:pathology; D014184:Transplantation, Homologous / Q000401:mortality / Q000473:pathology
D016572:Cyclosporine