Assessment of cyclosporine A-induced ultrastructural changes in vascular wall using an experimental arterial autograft model.
The objective of this ultrastructural study was to assess the effects of cyclosporine A (CsA) in an experimental model of arterial autograft. Fifty female Sprague-Dawley rats weighing 250-300 g were employed. Using a microsurgical technique, an arterial autograft measuring approximately 5 mm in length was placed in the right common iliac artery. Two groups were established: group I (control), consisting of 25 animals subjected only to arterial autograft; and group II (pre- and postoperative CsA), also consisting of 25 animals which received a daily subcutaneous dose of 5 mg/kg CsA (Sandimmun, Sandoz) on the four days preceding the surgery and thereafter, until sacrifice. The animals were sacrificed on postoperative day 7, 14, 21, 30 and 50. The specimens (autografts) obtained were studied under transmission and scanning electron microscopes. In the control group, the process of endothelialization of the graft was completed by day 14. In the CsA-treated group, restoration of the endothelium took 50 days. The development of intimal hyperplasia was delayed in the treated group. There were no morphological changes in its structure when compared to the control group. The tunica media had thinned in the treated grafts, with loss of smooth muscle cells, fragmentation and lysis of the elastic lamina, presence of lipid-filled macrophages, and muscle cells with cytoplasmic lipid vacuoles. In our opinion, these results suggest that the action of CsA mainly targets on the endothelium and smooth muscle cells, exerting a toxic effect in an in vivo arterial graft model.
Buján
J
J
Department of Morphological Sciences and Surgery, Faculty of Medicine, University of Alcalá de Henares, Madrid, Spain.
Bellón
J M
JM
Jurado
F
F
Hernando
A
A
Contreras
L
L
D000818:Animals; D001158:Arteries / Q000637:transplantation* / Q000648:ultrastructure*; D016572:Cyclosporine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D008866:Microsurgery; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000637:transplantation* / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous / Q000502:physiology; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D017540:Tunica Media / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure
D007166:Immunosuppressive Agents; D016572:Cyclosporine