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.
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.
Authors: Montserrat Rigol; Núria Solanes; Juan Fernandez-Armenta; Etelvino Silva; Adelina Doltra; Nicolas Duchateau; Aina Barcelo; Luigi Gabrielli; Bart Bijnens; Antonio Berruezo; Josep Brugada; Marta Sitges Journal: J Cardiovasc Transl Res Date: 2013-04-30 Impact factor: 4.132
Authors: Mohamed Zaid; Lorenzo Sala; Jan R Ivey; Darla L Tharp; Christina M Mueller; Pamela K Thorne; Shannon C Kelly; Kleiton Augusto Santos Silva; Amira R Amin; Pilar Ruiz-Lozano; Michael S Kapiloff; Laurel Despins; Mihail Popescu; James Keller; Marjorie Skubic; Salman Ahmad; Craig A Emter; Giovanna Guidoboni Journal: Front Med Technol Date: 2022-02-16
Authors: Jessica A Hiemstra; Songtao Liu; Mark A Ahlman; Karl H Schuleri; Albert C Lardo; Christopher P Baines; Kevin C Dellsperger; David A Bluemke; Craig A Emter Journal: Physiol Rep Date: 2013-12-05
Authors: Jessica A Hiemstra; Manuel Gutiérrez-Aguilar; Kurt D Marshall; Kyle S McCommis; Pamela J Zgoda; Noelany Cruz-Rivera; Nathan T Jenkins; Maike Krenz; Timothy L Domeier; Christopher P Baines; Craig A Emter Journal: Physiol Rep Date: 2014-06-24