Myocardial fibrosis and right ventricular function of heterotopically transplanted hearts in rats treated with cyclosporin.

The aim was to determine whether treatment of rats with cyclosporin A (CsA) leads to deleterious side effects on heterotopically iso- or allotransplanted hearts when compared with recipient native in situ hearts. Four experimental groups were employed: inbred (Lewis) rats receiving either no immunosuppression or CsA at a dose of 15 mg.kg-1 per day 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 surgery, the mass of all transplanted hearts decreased and resulting atrophy was associated with relative myocardial fibrosis. Treatment with CsA significantly increased the concentration and content of collagen in the right and left ventricles of all transplanted and recipient hearts. 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 treatment in both transplanted and recipient hearts. The maximal steady state developed pressure (RVDevP) and the rate of its development [(+dP/dt)max] were slightly higher in transplants than in the corresponding recipients, and in CsA-treated versus untreated hearts, while the index of contractile state [(+dP/dt)/P] was similar in all groups. The data 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.