Endothelial linings: the effect of serine protease inhibition

The purpose of this investigation was to determine if the inhibition of the serine proteases, thrombin and plasmin, by heparin and epsilon-aminocaproic acid (EACA) would improve endothelial cell retention on synthetic grafts. Endothelium was harvested from the external jugular veins of mongrel dogs using an enzymatic technique. The cells were grown in tissue culture for 3-4 weeks, labeled with 111In oxine, inoculated (2000 cells/mm2) into fibronectin-coated 4 mm-diameter tubes of polyester elastomer (PE, Hytrel 4056, DuPont), and cultured for 18 hr. Each animal received iv heparin (100 U/kg) prior to implantation, and a 4 X 30-mm segment of the culture-lined PE was interposed in the dog's own carotid artery. After 6 hr of flow the grafts were perfusion fixed; the percentage of endothelial retention was determined by 111In counting, and the surfaces of the grafts were analyzed by scanning electron microscopy. Six experiments were performed in each of three treatment groups. Animals in Group I received no additional drugs. Group II animals received a continuous infusion of heparin at 30 U/kg/hr. Group III animals received a bolus of 200 mg/kg of EACA with the initial heparin dose and a continuous infusion of heparin at 30 U/kg/hr and EACA at 200 mg/kg/hr. Group I grafts retained an average of 36.1 +/- 23.3% of the cells; Group II retained 67.5 +/- 24.9%; and Group III retained 83.4 +/- 9.8%. Although continuous heparin infusion resulted in a trend (P = 0.067) toward better retention, a combined infusion of heparin and EACA resulted in significantly better retention (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)