PMID: 7536397Apr 1, 1995Paper

How cyclosporine modifies histological and molecular events in the vascular wall during chronic rejection of rat cardiac allografts

The American Journal of Pathology
P K KoskinenP J Häyry

Abstract

Accelerated allograft arteriosclerosis (chronic rejection) has emerged as a major factor affecting long-term survival of human cardiac allografts. The underlying mechanism of this disorder remains unclear. The purpose of this study was to investigate the effect of cyclosporine on the development of cardiac allograft arteriosclerosis at the cellular and molecular level. Heterotopic rat cardiac allografts from DA donors to WF recipients, with a strong genetic disparity in major histocompatibility complex and non-major histocompatibility complex loci, were used. The allograft recipients received triple-drug immunosuppression consisting of methylprednisolone (0.5 mg/kg/day), azathioprine (2 mg/kg/day), and three different doses of cyclosporine A (CsA; 5, 10, and 20 mg/kg/day). The grafts were removed 3 months after transplantation and processed for histology and immunohistochemistry. Low dose CsA (5 mg/kg/day) was associated with a severe form of intimal cell accumulation and intimal thickening in epicardial arteries and in smaller intramyocardial arterioles with nearly occluded vessel lumens 3 months after transplantation. The intermediate dose CsA (10 mg/kg/day) significantly inhibited arterial intimal thickening but was not effi...Continue Reading

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