Fluvastatin in combination with RAD significantly reduces graft vascular disease in rat cardiac allografts

Clare R. Gregory, Steven Katznelson, Stephen M Griffey, Andrew E. Kyles, Edwin R. Berryman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background. RAD is a potent immunosuppressive agent that has been shown to be effective in preventing acute and chronic allograft rejection in animal models. The HMGCoA reductase inhibitors have been found to reduce the incidence of graft vascular disease (GVD) in heart transplant patients and in animal models. This study was designed to investigate the effects of fluvastatin or pravastatin in a rodent model of GVD produced using low doses of RAD to prevent acute rejection. Methods. Hearts from Fisher 344 rats were heterotopically transplanted to Lewis rat recipients. RAD was administered orally at 0.5 mg/kg per day for days 0 to 14 and then 0.25 mg/kg per day for an additional 85 days to prevent acute rejection but allow for the development of GVD. Pravastatin (20 mg/kg per day) or fluvastatin (2 or 6 mg/kg per day) was added to the RAD treatment. At the end of a 100-day treatment period, the hearts were harvested for morphometric and histopathologic examinations. Results. Rats treated with fluvastatin, at either dose, had a significant (P≤0.0239) decrease in coronary arterial intimal thickening (GVD) of approximately 43%. Rats treated with pravastatin had a 22% reduction in GVD that did not reach statistical significance. Treatment with fluvastatin, but not pravastatin, decreased the degree of endomyocardial mononuclear cell infiltration seen with RAD administered alone. Conclusions. Fluvastatin significantly decreased GVD in a rat model produced using low-dose RAD immunosuppression. To a lesser extent, pravastatin also decreased GVD in this model. These data lend further support for the study of fluvastatin, pravastatin, and other HMG-CoA reductase inhibitors for the prevention of GVD in cardiac transplant patients.

Original languageEnglish (US)
Pages (from-to)989-993
Number of pages5
JournalTransplantation
Volume72
Issue number6
StatePublished - Sep 27 2001

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fluvastatin
Vascular Diseases
Allografts
Pravastatin
Transplants
Animal Models
Tunica Intima
Hydroxymethylglutaryl-CoA Reductase Inhibitors

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Gregory, C. R., Katznelson, S., Griffey, S. M., Kyles, A. E., & Berryman, E. R. (2001). Fluvastatin in combination with RAD significantly reduces graft vascular disease in rat cardiac allografts. Transplantation, 72(6), 989-993.

Fluvastatin in combination with RAD significantly reduces graft vascular disease in rat cardiac allografts. / Gregory, Clare R.; Katznelson, Steven; Griffey, Stephen M; Kyles, Andrew E.; Berryman, Edwin R.

In: Transplantation, Vol. 72, No. 6, 27.09.2001, p. 989-993.

Research output: Contribution to journalArticle

Gregory, CR, Katznelson, S, Griffey, SM, Kyles, AE & Berryman, ER 2001, 'Fluvastatin in combination with RAD significantly reduces graft vascular disease in rat cardiac allografts', Transplantation, vol. 72, no. 6, pp. 989-993.
Gregory, Clare R. ; Katznelson, Steven ; Griffey, Stephen M ; Kyles, Andrew E. ; Berryman, Edwin R. / Fluvastatin in combination with RAD significantly reduces graft vascular disease in rat cardiac allografts. In: Transplantation. 2001 ; Vol. 72, No. 6. pp. 989-993.
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abstract = "Background. RAD is a potent immunosuppressive agent that has been shown to be effective in preventing acute and chronic allograft rejection in animal models. The HMGCoA reductase inhibitors have been found to reduce the incidence of graft vascular disease (GVD) in heart transplant patients and in animal models. This study was designed to investigate the effects of fluvastatin or pravastatin in a rodent model of GVD produced using low doses of RAD to prevent acute rejection. Methods. Hearts from Fisher 344 rats were heterotopically transplanted to Lewis rat recipients. RAD was administered orally at 0.5 mg/kg per day for days 0 to 14 and then 0.25 mg/kg per day for an additional 85 days to prevent acute rejection but allow for the development of GVD. Pravastatin (20 mg/kg per day) or fluvastatin (2 or 6 mg/kg per day) was added to the RAD treatment. At the end of a 100-day treatment period, the hearts were harvested for morphometric and histopathologic examinations. Results. Rats treated with fluvastatin, at either dose, had a significant (P≤0.0239) decrease in coronary arterial intimal thickening (GVD) of approximately 43{\%}. Rats treated with pravastatin had a 22{\%} reduction in GVD that did not reach statistical significance. Treatment with fluvastatin, but not pravastatin, decreased the degree of endomyocardial mononuclear cell infiltration seen with RAD administered alone. Conclusions. Fluvastatin significantly decreased GVD in a rat model produced using low-dose RAD immunosuppression. To a lesser extent, pravastatin also decreased GVD in this model. These data lend further support for the study of fluvastatin, pravastatin, and other HMG-CoA reductase inhibitors for the prevention of GVD in cardiac transplant patients.",
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AU - Gregory, Clare R.

AU - Katznelson, Steven

AU - Griffey, Stephen M

AU - Kyles, Andrew E.

AU - Berryman, Edwin R.

PY - 2001/9/27

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N2 - Background. RAD is a potent immunosuppressive agent that has been shown to be effective in preventing acute and chronic allograft rejection in animal models. The HMGCoA reductase inhibitors have been found to reduce the incidence of graft vascular disease (GVD) in heart transplant patients and in animal models. This study was designed to investigate the effects of fluvastatin or pravastatin in a rodent model of GVD produced using low doses of RAD to prevent acute rejection. Methods. Hearts from Fisher 344 rats were heterotopically transplanted to Lewis rat recipients. RAD was administered orally at 0.5 mg/kg per day for days 0 to 14 and then 0.25 mg/kg per day for an additional 85 days to prevent acute rejection but allow for the development of GVD. Pravastatin (20 mg/kg per day) or fluvastatin (2 or 6 mg/kg per day) was added to the RAD treatment. At the end of a 100-day treatment period, the hearts were harvested for morphometric and histopathologic examinations. Results. Rats treated with fluvastatin, at either dose, had a significant (P≤0.0239) decrease in coronary arterial intimal thickening (GVD) of approximately 43%. Rats treated with pravastatin had a 22% reduction in GVD that did not reach statistical significance. Treatment with fluvastatin, but not pravastatin, decreased the degree of endomyocardial mononuclear cell infiltration seen with RAD administered alone. Conclusions. Fluvastatin significantly decreased GVD in a rat model produced using low-dose RAD immunosuppression. To a lesser extent, pravastatin also decreased GVD in this model. These data lend further support for the study of fluvastatin, pravastatin, and other HMG-CoA reductase inhibitors for the prevention of GVD in cardiac transplant patients.

AB - Background. RAD is a potent immunosuppressive agent that has been shown to be effective in preventing acute and chronic allograft rejection in animal models. The HMGCoA reductase inhibitors have been found to reduce the incidence of graft vascular disease (GVD) in heart transplant patients and in animal models. This study was designed to investigate the effects of fluvastatin or pravastatin in a rodent model of GVD produced using low doses of RAD to prevent acute rejection. Methods. Hearts from Fisher 344 rats were heterotopically transplanted to Lewis rat recipients. RAD was administered orally at 0.5 mg/kg per day for days 0 to 14 and then 0.25 mg/kg per day for an additional 85 days to prevent acute rejection but allow for the development of GVD. Pravastatin (20 mg/kg per day) or fluvastatin (2 or 6 mg/kg per day) was added to the RAD treatment. At the end of a 100-day treatment period, the hearts were harvested for morphometric and histopathologic examinations. Results. Rats treated with fluvastatin, at either dose, had a significant (P≤0.0239) decrease in coronary arterial intimal thickening (GVD) of approximately 43%. Rats treated with pravastatin had a 22% reduction in GVD that did not reach statistical significance. Treatment with fluvastatin, but not pravastatin, decreased the degree of endomyocardial mononuclear cell infiltration seen with RAD administered alone. Conclusions. Fluvastatin significantly decreased GVD in a rat model produced using low-dose RAD immunosuppression. To a lesser extent, pravastatin also decreased GVD in this model. These data lend further support for the study of fluvastatin, pravastatin, and other HMG-CoA reductase inhibitors for the prevention of GVD in cardiac transplant patients.

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