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The effect of sodium nitroprusside on the chronic allograft damage in a rat model of renal transplantation
The Effect of Sodium Nitroprusside on the Chronic Allograft Damage in a Rat Model of Renal Transplantation A. Soots, L. Krogerus, I. Lautenschlager, and J. Ahonen
O
NE OF THE INFLUENCING factors of chronic allograft rejection is suggested to be ischemia-reperfusion injury. We have developed a rat kidney transplant model, which, after an early inflammatory episode, results in chronic rejection under triple-drug treatment within 40 to 60 days.1 The purpose of this study was to investigate the effect of a vasodilating drug, sodium nitroprusside,2 on the development of chronic allograft damage in this experimental model. MATERIALS AND METHODS Renal transplantations were performed in a strain combination of DA (RTIa)-⬎ BN (RTIn) as described previously.1 In one group of animals, the grafts were with flushed and stored in Euro-Collins containing sodium nitroprusside (10⫺5 mmol), and in the other group, without nitroprusside. Triple-drug immunosuppression of methyl prednisolone (MP) 2 mg/kg, azathioprime (AZA) 2 mg/kg, and cyclosporine A (CyA) 5 mg/kg was given daily. The grafts were harvested at day 40 after transplantation, and chronic allograft damage index (CADI) was used to evaluate the characteristic histopathologic changes.3 The CADI was formed from the characteristic changes of chronic rejection: interstitial inflammation and fibrosis, glomerular sclerosis, mesangial matrix increase, vascular intimal thickening, and tubular atrophy.3
RESULTS
Sodium nitroprusside significantly decreased the histologic changes of chronic rejection in the graft, and the CADI values in the nitroprusside group were significantly lower at day 40 after transplantation than in those without nitroprusside (3.7 ⫾ 4.2 vs 8.6 ⫾ 1.8, P ⬍ .05). The most significantly affected by nitroprusside perfusion were two components of the CADI, tubular atrophy (0.6 ⫾ 0.9 vs 2.5 ⫾ 0.6, P ⬍ .001) and interstitial fibrosis (0.8 ⫾ 0.9 vs 1.9 ⫾ 0.8, P ⬍ .05). The other components the CADI were also somewhat decreased in the nitroprusside group, but the differences were not significant.
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
DISCUSSION AND CONCLUSIONS
Sodium nitroprusside is a potent nitric oxide donor and effective in the regulation of vascular tone.2 The use of nitroprusside in the perfusion solution of lung and liver grafts has been shown to improve circulation and prevent ischemia-reperfusion injury of the organs in experimental models.4,5 In our study, sodium nitroprusside perfusion diminished the development of histologic changes of chronic allograft damage in this rat model of renal transplantation. The most significant effect of nitroprusside was recorded in tubular atrophy and interstitial fibrosis. The possible clinical benefit of this drug should be investigated.
REFERENCES 1. Soots A, Lautenschlager I, Krogerus L, et al: Transplantation 65:42, 1998 2. McHugh J, Cheek DJ: Am J Crit Care 7:131, 1998 3. Isoniemi H, Krogerus L, von Willebrand E, et al: Kidney Int 41:155, 1992 4. Yamashita M, Scmid RA, Ando K, et al: Ann Thorac Surg 62:791, 1996 5. Rodrigues JV, Guibert EE, Quintana A, et al: J Surg Res 87:201, 1999
From the Departments of Surgery (A.S., I.L., J.A.), Pathology (L.K.), and Virology (I.L.), Helsinki University Central Hospital, Helsinki, Finland. Supported by grants from Helsinki University Hospital Funds (EVO). Address reprint requests to Dr A. Soots, Transplant Unit Research Laboratory, Department of Surgery, Helsinki University Central Hospital, Kasarmikatu 11-13, FIN-00130 Helsinki, Finland.
0041-1345/01/$–see front matter PII S0041-1345(00)02469-6 853
Transplantation Proceedings, 33, 853 (2001)
O
NE OF THE INFLUENCING factors of chronic allograft rejection is suggested to be ischemia-reperfusion injury. We have developed a rat kidney transplant model, which, after an early inflammatory episode, results in chronic rejection under triple-drug treatment within 40 to 60 days.1 The purpose of this study was to investigate the effect of a vasodilating drug, sodium nitroprusside,2 on the development of chronic allograft damage in this experimental model. MATERIALS AND METHODS Renal transplantations were performed in a strain combination of DA (RTIa)-⬎ BN (RTIn) as described previously.1 In one group of animals, the grafts were with flushed and stored in Euro-Collins containing sodium nitroprusside (10⫺5 mmol), and in the other group, without nitroprusside. Triple-drug immunosuppression of methyl prednisolone (MP) 2 mg/kg, azathioprime (AZA) 2 mg/kg, and cyclosporine A (CyA) 5 mg/kg was given daily. The grafts were harvested at day 40 after transplantation, and chronic allograft damage index (CADI) was used to evaluate the characteristic histopathologic changes.3 The CADI was formed from the characteristic changes of chronic rejection: interstitial inflammation and fibrosis, glomerular sclerosis, mesangial matrix increase, vascular intimal thickening, and tubular atrophy.3
RESULTS
Sodium nitroprusside significantly decreased the histologic changes of chronic rejection in the graft, and the CADI values in the nitroprusside group were significantly lower at day 40 after transplantation than in those without nitroprusside (3.7 ⫾ 4.2 vs 8.6 ⫾ 1.8, P ⬍ .05). The most significantly affected by nitroprusside perfusion were two components of the CADI, tubular atrophy (0.6 ⫾ 0.9 vs 2.5 ⫾ 0.6, P ⬍ .001) and interstitial fibrosis (0.8 ⫾ 0.9 vs 1.9 ⫾ 0.8, P ⬍ .05). The other components the CADI were also somewhat decreased in the nitroprusside group, but the differences were not significant.
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
DISCUSSION AND CONCLUSIONS
Sodium nitroprusside is a potent nitric oxide donor and effective in the regulation of vascular tone.2 The use of nitroprusside in the perfusion solution of lung and liver grafts has been shown to improve circulation and prevent ischemia-reperfusion injury of the organs in experimental models.4,5 In our study, sodium nitroprusside perfusion diminished the development of histologic changes of chronic allograft damage in this rat model of renal transplantation. The most significant effect of nitroprusside was recorded in tubular atrophy and interstitial fibrosis. The possible clinical benefit of this drug should be investigated.
REFERENCES 1. Soots A, Lautenschlager I, Krogerus L, et al: Transplantation 65:42, 1998 2. McHugh J, Cheek DJ: Am J Crit Care 7:131, 1998 3. Isoniemi H, Krogerus L, von Willebrand E, et al: Kidney Int 41:155, 1992 4. Yamashita M, Scmid RA, Ando K, et al: Ann Thorac Surg 62:791, 1996 5. Rodrigues JV, Guibert EE, Quintana A, et al: J Surg Res 87:201, 1999
From the Departments of Surgery (A.S., I.L., J.A.), Pathology (L.K.), and Virology (I.L.), Helsinki University Central Hospital, Helsinki, Finland. Supported by grants from Helsinki University Hospital Funds (EVO). Address reprint requests to Dr A. Soots, Transplant Unit Research Laboratory, Department of Surgery, Helsinki University Central Hospital, Kasarmikatu 11-13, FIN-00130 Helsinki, Finland.
0041-1345/01/$–see front matter PII S0041-1345(00)02469-6 853
Transplantation Proceedings, 33, 853 (2001)