Effects of cyclosporine, tacrolimus and sirolimus on vascular changes related to immune response.
BACKGROUND
Despite the use of newer immunosuppressors such as sirolimus (SRL) and tacrolimus (TRL) in heart transplantation, the rate of humoral rejection has remained unchanged. The aim of this study was to analyze the immunologic and histologic effects of cyclosporine (CsA), SRL, and TRL in a porcine model of arterial transplantation.


METHODS
Each transplant recipient animal (n = 49) received an autograft and an allograft and was then allocated to one of four treatment groups and a 7- or 30-day follow-up period, as follows: a WOT group (without immunosuppressor treatment), 7 days (n = 6) and 30 days (n = 5); a CsA group, 7 days (n = 5) and 30 days (n = 6); an SRL group, 7 days (n = 7) and 30 days (n = 8); and a TRL group, 7 days (n = 6) and 30 days (n = 6). The presence of donor-specific antibodies (DSA) was tested at the end of the follow-up period. Morphometric parameters and inflammatory infiltration were analyzed in the explanted grafts.


RESULTS
At 30-day follow-up, SRL was the only treatment capable of suppressing DSA formation (0 of 7 vs 4 of 5 in the WOT group; p < 0.05). SRL completely prevented aneurismal dilation and reduced the number of macrophages in the allografts. TRL treatment achieved a greater reduction of T lymphocytes. CsA did not prevent the reduction in total vascular area at 7 days that was achieved with the SRL and TRL groups. Animals treated with CsA had the largest number of T lymphocytes and macrophages in both follow-up periods.


CONCLUSIONS
SRL prevented DSA formation and reduced the number of macrophages as compared with TRL and CsA.
Rigol
Montserrat
M
Department of Cardiology, Institut Clínic del Tòrax, Institut d'Investigacions Biomèdiques Agustí Pi Sunyer, Barcelona, Spain. mrigol@clinic.ub.es
Solanes
Núria
N
Sionis
Alessandro
A
Gálvez
Carolina
C
Martorell
Jaume
J
Rojo
Isabel
I
Brunet
Mercè
M
Ramírez
José
J
Roqué
Mercè
M
Roig
Eulàlia
E
Pérez-Villa
Fèlix
F
Barquín
Leire
L
Pomar
José Luís
JL
Sanz
Ginés
G
Heras
Magda
M
D000783:Aneurysm / Q000503:physiopathology / Q000517:prevention & control; D000792:Angiography; D000818:Animals; D000906:Antibodies / Q000032:analysis; D000917:Antibody Formation / Q000187:drug effects; D002452:Cell Count; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D020123:Sirolimus / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D013552:Swine; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors; D014019:Tissue Donors; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014664:Vasodilation / Q000187:drug effects
D000906:Antibodies; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus