MYOCARDIAL FIBROSIS AND RIGHT-VENTRICULAR FUNCTION OF HETEROTOPICALLYTRANSPLANTED HEARTS IN RATS TREATED WITH CYCLOSPORINE

The aim was to determine whether treatment of rats with cyclosporin A (CsA) leads to deleterious side effects on heterotopically iso- or all otransplanted hearts when compared with recipient native in situ heart s. Four experimental groups were employed: inbred (Lewis) rats receivi ng either no immunosuppression or CsA at a dose of 15 mg.kg(-1) per da y for 7 days after surgery, and outbred (Wistar) rats receiving CsA at the same daily dose for either 7 or 21 days. One month following surg ery, the mass of all transplanted hearts decreased and resulting atrop hy was associated with relative myocardial fibrosis. Treatment with Cs A significantly increased the concentration and content of collagen in the right and left ventricles of all transplanted and recipient heart s. No appreciable difference was observed between corresponding hearts of inbred and outbred groups receiving the identical dose of CsA, and between hearts in outbred groups treated for either 7 or 21 days. No signs of right ventricular mechanical dysfunction, as assessed on the isolated perfused 'working' preparation, were observed after CsA treat ment in both transplanted and recipient hearts. The maximal steady sta te developed pressure (RVDeVP) and the rate of its development [(+dP/d t)(max)] were slightly higher in transplants than in the corresponding recipients, and in CsA-treated versus untreated hearts, while the ind ex of contractile state [(+dP/dt)/P] was similar in all groups. The da ta suggest that treatment of rats with CsA can induce a similar degree of fibrosis both in heterotopic cardiac transplants and in recipient native hearts without impairment of their contractile performance.