Effects of antiplatelet agents in combination with endothelial cell seeding on small-diameter Dacron vascular graft performance in the canine carotid artery model.

The purpose of this study was to assess the success of endothelial cell-seeded and non-seeded small-diameter vascular grafts in dogs medicated with antiplatelet agents. Eighty dogs underwent bilateral carotid artery replacements with 6 cm lengths of 4 mm I.D. double-velour Dacron grafts. In each dog one graft was seeded with enzymatically derived autologous endothelial cells; the contralateral graft was nonseeded. The following anti-platelet medications were administered beginning 4 days preoperatively: aspirin (5 grains every day); dipyridamole (50 mg twice a day); aspirin plus dipyridamole (5 grains each day plus 50 mg twice a day); aspirin (1.25 grains every other day); ibuprofen (10 mg/kg/day); U-53,059, a cyclooxygenase inhibitor (3 mg/kg/day); and U-63557A, a thromboxane synthase inhibitor (10 mg/kg/day). Grafts were harvested 5 weeks postoperatively. Graft success was evaluated by patency, thrombus-free surface area, area endothelialized, and graft production of prostacyclin. None of the medications prevented neoendothelialization of seeded grafts. Mean patencies of endothelial cell-seeded grafts from medicated dogs were significantly greater than mean patencies of endothelial cell-seeded grafts from nonmedicated dogs. The cyclooxygenase inhibitors best maintained patency in nonseeded grafts. Thrombus-free surface areas of endothelial cell-seeded grafts from medicated dogs were significantly greater than from nonseeded control grafts from the medicated dogs. All medications impaired prostacyclin synthesis. We conclude that the combination of endothelial cell seeding plus antiplatelet medication is most efficacious in small-vessel grafting success and that high levels of prostacyclin production by vascular grafts are not necessary to maintain patency in dogs medicated with antiplatelet agents.

Growth of aortic smooth muscle cells from hypertensive obese and lean rats in homologous and heterologous sera.

Arterial smooth muscle cells (SMC) were derived from the medial thoracic aortas of three groups of rats: (a) obese, hyperlipidemic, hypertensive koletsky rats (OHT); (b) lean, normolipidemic, hypertensive koletsky rats (LHT) and (c) lean, normotensive Wistar rats (NT). The growth patterns of these cells were subsequently compared in tissue culture media (DMEM) supplemented with pooled 10% homologous or 10% heterologous sera. Morphologically the SMC from all three rat sources grew in culture in typical SMC hill and valley patterns. When the SMC from the three rat sources were cultured in DMEM supplemented with 10% newborn calf serum (NCS) there were no differences in final cell densities and morphologies between the cell types. However, SMC derived from OHT rat aortas grown in DMEM supplemented with pooled 10% homologous serum achieved lower cell densities than SMC derived from LHT and NT rat aortas in their respective homologous sera. There were no differences in final cell densities when LHT SMC and NT SMC were separately cultured inpooled heterologous sera derived from LHT, OHT or NT rats or when OHT cells were cultured in heterologous sera derived from either LHT or NT rats. The OHT serum preferentially affected only the growth and morphology of SMC derived from the obese, hyperlipidemic, hypertensive koletsky rats.

Endothelial cell seeding of small-diameter vascular grafts.

Small-diameter double velour dacron vascular grafts were seeded with autologous canine endothelial cells, implanted in the canine carotid arteries and the in vivo progress of graft luminal endothelial surfacing followed. Sixty-five percent of the experimental grafts were successfully seeded. Comparison of patency, endothelial cell coverage, thrombus-free surface, and inner capsule thickness between seeded and control grafts revealed enhancement of graft performance by cell seeding. Peroxidase-antiperoxidase staining was utilized to positively identify graft luminal endothelium.