Clinical Use of Autologous Endothelial Cell-Seeded PTFE Vascular Grafts for Coronary Artery Revascularization
Eight patients (seven male and one female), 62–78 years old, with severe symptomatic coronary artery disease (CAD) received autologous endothelial cell (EC) seeded 4-mm poly-tetra-fluoro-ethylene (PTFE) vascular bypass grafts for coronary artery revascularization. EC seeded PTFE grafts were used in patients who lacked their own suitable bypass material for coronary revascularization. The PTFE grafts were seeded with autologous ECs in a multiple-step procedure prior to the elective coronary bypass operation.
A 5-cm long segment of a cutaneous vein was harvested with local an-esthesia. The ECs were removed enzymatically by 0.2% collagenase. The endothelial cells were cultured and multiplied in cell culture with modified Dul- becco’s Eagle Medium (DMEM). After 3–4 weeks, the number of endothelial cells was great enough to cover the luminal surface of a 20 cm-long 4 mm PTFE vascular graft. Prior to EC seeding, the luminal wall of the PTFE graft was prepared by the application of a matrix consisting of fibrin glue and human recombinant basic Fibroblast Growth Factor (bFGF). In a special rotating device called an “endostrabilisator,” the homologous spreading and adhesion of the ECs on the luminal surface of the graft was achieved after 3–4 hours. For the constitution of tight junctions between the luminal surface of the graft and the ECs, a period of 8–10 days of maturation was necessary under cell culture conditions prior to implantation.
Bypass surgery was performed under extracorporal circulation in cardioplegic arrest with Bretschneider solution, using conventionel surgical techniques to perform the end-side coronary anastomoses with running 7x0 prolene sutures.
The eight patients received 19 coronary artery bypass grafts. Two patients had already had previous bypass operations with occluded vein grafts. In one patient, the aortic valve was replaced simultaneously because of severe aortic stenosis. For the revascularization of the left anterior descending artery (LAD), the left internal thoracic artery (LIMA) was used in six cases. Twelve aorto-coronary bypasses were performed with the EC seeded PTFE grafts to revascularize the LAD in one case, the first diagonal branch (Dl) in one case, the ramus intermedius (RIM) in two cases, the first marginal branch of the circumflex artery in three cases, the circumflex artery itself in two cases, and the right coronary artery (RCA) in four cases. In one patient, an additional saphenous vein graft was used to revascularize the RIM.
The postoperative course of all patients was without complications. Wound complications and perioperative myocardial infarctions did not occur.
After a mean postoperative follow-up of 420 (174–717) days, all patients are free from angina pectoris and clinically asymptomatic. Angiographic controls of the aorto-coronary PTFE bypass grafts after the operation showed patent bypasses in all cases except one EC seeded PTFE graft to the RCA, which was occluded asymptomatically and realized by angiography 20 months after the implantation. All 18 patent EC seeded PTFE bypass grafts showed a smooth luminal borderline without stenotic regions, angiographically. The angioscopic evaluation confirmed the angiographic results. The endoluminal graft surface was glossy white and smooth without any fibrin, platelet, or erythrocyte deposits, as the percutaneous transluminal angioscopic evaluation showed. In vitro experiments under cell culture conditions with EC seeded 4-mm PTFE grafts under physiological pulsatile flow conditions confirmed the adhesion and survival of the EC lining of the PTFE grafts. After an initial wash-out of ECs — within the first 15–30 minutes after the application of the pulstile flow — 60–80% of the ECs stayed adherent to the graft wall and were resistant to the applied shear forces.
Further evaluations and a larger population of patients who received an EC seeded PTFE graft as a coronary artery bypass will prove if the encouraging patency rate of 91% in the mean 420 days after implantation will last. Improving the biocompatibility of cardiovascular implants by seeding with vital endothelial cells may offer unestimated benefits in the development of cardiovascular implants, including new bioprosthetic valve implants and artificial hearts.
KeywordsLeft Anterior Descend Right Coronary Artery Luminal Surface PTFE Graft Left Internal Thoracic Artery
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