Kolár F, Papousek F, MacNaughton C, Pelouch V, Milerová M, Korecky B
Department of Developmental Cardiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Mol Cell Biochem. 1996 Oct-Nov;163-164:253-60. doi: 10.1007/BF00408666.
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.
目的是确定与受体原位心脏相比，用环孢素A（CsA）治疗大鼠是否会对异位同种或异种移植心脏产生有害副作用。采用了四个实验组：近交系（Lewis）大鼠术后接受7天每天15mg·kg-1剂量的CsA免疫抑制或不进行免疫抑制，以及远交系（Wistar）大鼠接受相同日剂量的CsA治疗7天或21天。术后1个月，所有移植心脏的质量均下降，由此导致的萎缩与相对心肌纤维化有关。CsA治疗显著增加了所有移植心脏和受体心脏左右心室中胶原蛋白的浓度和含量。接受相同剂量CsA的近交系和远交系组的相应心脏之间，以及远交系组中接受7天或21天治疗的心脏之间，均未观察到明显差异。在离体灌注“工作”制剂上评估，CsA治疗后移植心脏和受体心脏均未观察到右心室机械功能障碍的迹象。移植心脏的最大稳态舒张压（RVDevP）及其上升速率[（+dP/dt）max]略高于相应的受体心脏，且CsA治疗组高于未治疗组，而所有组的收缩状态指数[（+dP/dt）/P]相似。数据表明，用CsA治疗大鼠可在异位心脏移植和受体原位心脏中诱导相似程度的纤维化，且不损害其收缩性能。
