Lysis and Absorption of Fibrin Sealant (Tissucol/Tisseel)

Abstract

In order to determine the optimal fibrin thrombin adhesive system (FTAS) composition for resistance to fibrinolysis, in vivo lysis was tested by adding increasing amounts of the fibrinolysis inhibitor aprotinin to ¹²⁵I-FS; urokinase and plasminogen were administered in vitro while measuring protein and iodine¹²⁵ release. The correlation between protein and iodine¹²⁵ release clearly reflects the interdependence of these parameters; disjunction of radioactivity from the protein molecule was ruled out. In vivo, fibrinolysis is inhibited to a nearly unlimited extent by aprotinin. In vivo, aprotinin improves fibrinolysis inhibition only up to a maximum of 1500 KIU/ml clot, thereby significantly altering the maximum elimination of ¹²⁵iodine and FS half-life as well. Higher doses of aprotinin applied in vivo remain without effect upon FS stability. In human surgery, the addition of aprotinin to FS is recommended for strictly hemostatic application only, not for tissue synthesis such as nerve and microvessel anastomoses in plastic reconstructive surgery.

The aim of the second study was to investigate the degradation of fibrinogen thrombin adhesive system (FTAS) and the process of wound healing after partial kidney resection in rats using ETAS for induction of local hemostasis. In 28 rats partial kidney resection was performed bilaterally. Hemostasis was achieved with FTAS. Four experimental groups were formed. Group F (n = 3): hemostasis with unlabeled FTAS, subcutaneous injection of 0.1 ml = 60μCi Na ¹²⁵I. Group G (n = 3): hemostasis with unlabeled FTAS, subcutaneous injection of 0.1 ml = 60μCi ¹²⁵I-labeled FTAS, Group H (n = 6): hemostasis with ¹²⁵I-labeled ETAS. Group I (n = 16): treated like group H. In groups F-H ¹²⁵I elimination in 24-h urine samples was determined with a gamma-scintillation counter. Pairs of animals in group I were killed after 2, 6, 12, and 24 h and 3, 7, 14, and 21 days.

Kidneys were examined under the light and electron microscope and by auto-radiography. In animals of groups G and H two peaks of ¹²⁵I excretion were observed: one peak within the first 48 h postoperatively which corresponded to the amount of free iodine injected with FTAS (FTAS contains 15% free iodine) and a second peak after 120 h which was most probably due to the degradation of FIAS. Fibrinolysis was not observed. FTAS was resorbed mainly by macrophages. The time course of wound healing paralleled that of physiological fibrinogen concentration. Renal parenchymal damage was not observed.