Pravastatin decreases cold ischemia--but not alloantigen-dependent transplant arteriosclerosis.
BACKGROUND
Alloantigen mismatch and cold ischemia have been shown to induce transplant arteriosclerosis. Pravastatin (PR) decreases arteriosclerosis probably related to an immunosuppressive effect. Statins possess other nonimmune properties that may be beneficial to transplantation. We studied the effect of PR on cold ischemia and alloantigen-induced transplant arteriosclerosis in syngeneic (SYN) and allogeneic (ALLO) aortic transplantation models.


METHODS
Lewis rats served as the donors and recipients for SYN transplants and Brown Norway rats were donors for ALLO transplants. Aortic segments that had been preserved at 4 degrees C in Euro-Collins solution for 0 or 24 hours were transplanted to the infrarenal aorta of the recipients PR (10 mg/kg/d) was administered for 12 weeks prior to morphometric studies. Areas of intimal thickness and its relation to total vessel area were calculated. Lipid levels were measured at 12 weeks.


RESULTS
Aorta rings preserved for 24 hours showed marked intimal thickening compared to controls (SYN, CI 0 hours = 21.5% +/- 16.5% vs SYN, CI 24 hours = 50.7 +/- 9.5%, P <.05). PR significantly decreased thickening (SYN, CI 24 hours + PR = 41.7 +/- 12.2 (P <.05) vs SYN, CI 0 hours on SYN, CI 24 hours). There was a nonsignificant decrease in thickening among ALLO transplants treated with PR (ALLO = 31.4 +/- 15.9 vs ALLO + PR = 23.8 +/- 18.8; P >.05). PR had no effect on lipid levels. PR decreases cold ischemia induced transplant arteriosclerosis in this syngeneic aortic transplant model, but does not affect an alloantigen-mediated process. The beneficial effect of PR is not related to its lipid-lowering properties but probably to a nonimmune effect.
Domínguez
J
J
Department of Urology, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 437 Depto. C, Santiago, Chile. javierdomi@hotmail.com
Schultz
M
M
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D003080:Cold Temperature; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007511:Ischemia; D007519:Isoantigens; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000473:pathology / Q000502:physiology*; D014185:Transplantation, Isogeneic / Q000473:pathology / Q000502:physiology; D017539:Tunica Intima / Q000473:pathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007519:Isoantigens; D017035:Pravastatin