Development of an animal model for assessment of the hemostatic efficacy of fibrin sealant in vascular surgery

Purpose. Sustained hemostatic function of fibrin sealant (FS) is crucial wh en it is used in cardiovascular surgery. The purpose of this study was to d evelop a model that can determine the long-term hemostatic efficacy of tiss ue sealants in a vascular surgery. Methods. To determine the ability of the model to detect differences in FS performance, various concentrations of FS were prepared and tested. Tensile strength of FS clots was determined in vitro using a tensiometer. Laparoto my was performed on 49 anesthetized rabbits, and a segment of the aorta was occluded, transected, and then sutured in an end-to-end fashion with four or eight interrupted 9-O sutures. The four-suture repair was covered with F S or placebo, and blood flow restored. Spilled blood was absorbed with gauz e and weighed to estimate blood loss. Four weeks after surgery the animals were euthanized and the vessels recovered for histology. Results. Average tensile strength of FS clots at 120, 90, and 60 mg/ml topi cal fibrinogen complex (TFC) concentration was 0.42 +/- 0.07 N, with no sig nificant difference among them. The lowest TFC concentration, 30 mg/ml, pro duced weaker clots than either 120 or 90 mg/ml (P < 0.05). All rabbits with four-suture anastomoses that were treated with placebo bled to death after the vessel was unclamped (n = 6). Treatment of suture line with standard F S concentration (120 mg/ml TFC, n = 8) sealed the anastomosis and prevented blood loss. Hemostasis was sustained for 4 weeks, allowing vascular healin g. All rabbits with the eight-suture anastomosis survived the operation but lost 42 +/- 9.2 ml blood (n = 5). Hemostatic efficacy of FS was unchanged when TFC was diluted to 90 mg/ml (n 6) but further dilution to 60 mg/ml wit h water (n 8) produced significantly less effective clots, with an average blood loss of 5.5 +/- 7.6 ml (P < 0.05) and two fatal clot failures postope ratively. When FS was diluted to 60 mg/ml TFC with a buffer, it maintained its hemostatic strength (n = 6). Further TFC dilution to 30 mg/ml led to co nsistent bleeding with an average blood loss of 35.3 +/- 10.3 ml (P < 0.001 , n = 6). Conclusions. The four-suture anastomosis of rabbit aorta offers a consisten t and reliable method for evaluating the short- and long-term hemostatic ef ficacy of FS products. This model is not only able to determine the functio nal differences in various concentrations of FS, but it is also sensitive t o detect the subtle changes in FS preparation (e.g., medium composition) th at is not detected by in vitro testing. (C) 2001 Academic Press.