Evaluation of Autologous Substitute Vascular Graft Developed from Rectus-Sheath Under Cyclosporine Immunosuppression in Dogs (2nd Phase)
*Tibor Németh, DVM, PhD, László Kóbori, MD, Gábor Dallos, MD, Ferenc Perner, MD, PhD, DSc, Maarten J.H. Slooff, Koert P. de Jong
The experimental study aimed to testify an alternative technique for autologous vessel replacement eliminating the relatively high (10-40%) incidence of postoperative complications (e.g., rejection, thrombosis) of currently used vascular allografts in the field of transplantation surgery. The novel vascular autograft is developed from the rectus sheath with an internal mesothelial cover within the same individual. During the 1st phase of the project authors had managed to confirm the feasibility of the new technique in a short term pilot study. The 2nd phase of this project evaluated the longer term survival of the rectus sheath autograft and the effect of Cyclosporine immunosuppression with respect to the expectable vascular media-degenerative effect of the drug.
Eight autologous rectus sheath (RS) grafts were developed, prepared around a standard glass stick (diameter: 7mm, length: 20mm) as a tube and implanted as a vascular conduit between two cut ends of the right-sided external iliac artery via end-to-end single anastomosis technique using 7/0 polypropylene in eight dogs. The contralateral artery was left intact as control. 70 IU/kg iv. heparin-sodium was applied to decrease the hemostasis activity and Cyclosporine was administered orally (10mg/kg b.i.d.) for 3 months postoperatively. Physical examination (general state, circulation and femoral pulse quality) as well as Doppler ultrasonographic evaluation (graft patency) was performed regularly to follow up the survival and function of the autografts. 3 months after surgery the autografts were removed and submitted to thorough macroscopic and histopathological (HE, fibrin staining, immunohistochemistry: VIII. factor, CD 34, electron microscopy) examination.
Two of the eight RS grafts suffered from stenosis and complete closure at the proximal anastomosis at the end of the first two weeks, six of them remained intact and patent confirmed by the normal pulse quality and the Doppler ultrasonographic findings (median flow rate was 370 cm/sec) up to the end of the follow up period. At harvesting RS autografts seemed to be vital vessel-like structures without either aneurysm or thrombosis. The median maximum dilation of the grafts in the middle was 1.5mm. The histopathological evaluation revealed proved vitality as well as a proendothel cell layer formation covering the internal surface of the conduit. The mesothelial layer has completely disappeared. Elastic fibers, smooth muscle elements appeared in conjunction with the signs of angiogenesis within the wall of the RS grafts. There was no evidence of media degeneration related to the Cyclosporine administration.
The study revealed that the RS grafts are able to function and behave as patent vascular substitute autografts with a longer term survival. The two complicated cases might have been related to technical mistakes. Neither aneurysm nor thrombosis were detected. Histopathological findings have indicated the gradual integration of the graft developing proendotelial monolayer replacing the disappeared mesothelium. The expected vascular degenerative effect of the Cyclosporine was not detected.