Cyclosporine mitigates graft coronary artery disease in murine cardiac allografts: Description and validation of a novel fully allogeneic model

Masashi Tanaka, Golnaz K. Mokhtari, Leora B. Balsam, David T Cooke, Theo Kofidis, Monika Zwierzchonievska, Robert C. Robbins

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: The effect of cyclosporine (CsA) on the development of graft coronary artery disease (GCAD) is controversial. We developed a novel allogeneic mouse model of heart transplantation and investigated the effect of CsA on acute rejection and GCAD. Methods: Hearts of FVB mice (H-2q) were heterotopically transplanted into 60 C57BL/6 mice (H-2b). CsA was administered to recipients at 10, 20 or 30 mg/kg/day for 10 or 30 days after transplantation. Untreated recipients as well as isograft recipients served as controls. Viability of the grafts was assessed daily by palpation. Parenchymal rejection was scored in grafts surviving 30 days in the 30-day treatment groups. GCAD was evaluated by the percentage of luminal narrowing, intima/media ratio and percentage of diseased vessels. Blood CsA and creatinine levels were also evaluated. Results were evaluated statistically. Results: All groups except the untreated control group and the allograft groups treated with 10 or 20 mg for 10 days showed significant graft survival (≥33% survival for 30 days). An inverse correlation was observed between CsA treatment dose, parenchymal rejection score and degree of GCAD in the 30-day treatment groups. However, graft survival in the 20-mg/kg/day group was significantly better than that in the 30-mg/kg/day group. Serum creatine levels showed no nephrotoxicity. Conclusions: Relatively high-dose CsA mitigated parenchymal rejection and GCAD of the mouse cardiac allografts. In addition, a valuable mouse model mimicking the clinical course of GCAD was achieved with CsA treatment of 20 mg/kg/day for 30 days.

Original languageEnglish (US)
Pages (from-to)446-453
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume24
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

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Cyclosporine
Allografts
Coronary Artery Disease
Transplants
Graft Rejection
Graft Survival
Isografts
Creatine
Palpation
Heart Transplantation
Inbred C57BL Mouse
Creatinine
Transplantation
Control Groups
Serum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Cyclosporine mitigates graft coronary artery disease in murine cardiac allografts : Description and validation of a novel fully allogeneic model. / Tanaka, Masashi; Mokhtari, Golnaz K.; Balsam, Leora B.; Cooke, David T; Kofidis, Theo; Zwierzchonievska, Monika; Robbins, Robert C.

In: Journal of Heart and Lung Transplantation, Vol. 24, No. 4, 04.2005, p. 446-453.

Research output: Contribution to journalArticle

Tanaka, Masashi ; Mokhtari, Golnaz K. ; Balsam, Leora B. ; Cooke, David T ; Kofidis, Theo ; Zwierzchonievska, Monika ; Robbins, Robert C. / Cyclosporine mitigates graft coronary artery disease in murine cardiac allografts : Description and validation of a novel fully allogeneic model. In: Journal of Heart and Lung Transplantation. 2005 ; Vol. 24, No. 4. pp. 446-453.
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abstract = "Background: The effect of cyclosporine (CsA) on the development of graft coronary artery disease (GCAD) is controversial. We developed a novel allogeneic mouse model of heart transplantation and investigated the effect of CsA on acute rejection and GCAD. Methods: Hearts of FVB mice (H-2q) were heterotopically transplanted into 60 C57BL/6 mice (H-2b). CsA was administered to recipients at 10, 20 or 30 mg/kg/day for 10 or 30 days after transplantation. Untreated recipients as well as isograft recipients served as controls. Viability of the grafts was assessed daily by palpation. Parenchymal rejection was scored in grafts surviving 30 days in the 30-day treatment groups. GCAD was evaluated by the percentage of luminal narrowing, intima/media ratio and percentage of diseased vessels. Blood CsA and creatinine levels were also evaluated. Results were evaluated statistically. Results: All groups except the untreated control group and the allograft groups treated with 10 or 20 mg for 10 days showed significant graft survival (≥33{\%} survival for 30 days). An inverse correlation was observed between CsA treatment dose, parenchymal rejection score and degree of GCAD in the 30-day treatment groups. However, graft survival in the 20-mg/kg/day group was significantly better than that in the 30-mg/kg/day group. Serum creatine levels showed no nephrotoxicity. Conclusions: Relatively high-dose CsA mitigated parenchymal rejection and GCAD of the mouse cardiac allografts. In addition, a valuable mouse model mimicking the clinical course of GCAD was achieved with CsA treatment of 20 mg/kg/day for 30 days.",
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AU - Balsam, Leora B.

AU - Cooke, David T

AU - Kofidis, Theo

AU - Zwierzchonievska, Monika

AU - Robbins, Robert C.

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