Fibrin chain cross-linking, fibrinolysis, and in vivo sealing efficacy of differently structured fibrin sealants.

In this study, we compared the sealing characteristics and efficacy of a fibrin sealant with reduced plasminogen (FS-rplg) and a fibrin sealant with aprotinin as a fibrinolysis inhibitor (FS-apr). The relevant sealing characteristics including clot structure, fibrin chain cross-linking, and clot lysis were tested in the laboratory. The sealing efficacy was then investigated in a follow-up animal model to determine differences in the in vivo sealing properties. A total of 46 animals were available for the final analysis with 23 animals in each treatment arm. In conclusion, we saw differences in vitro between FS-rplg and FS-apr in ultrastructure and α-chain cross-linking rates as well as in the rate of fibrinolysis. These differences may explain the significantly enhanced sealing efficacy in FS-apr compared to FS-rplg shown in vivo in a rabbit intestinal model.

A comparison of a cyanoacrylate [corrected] glue (Glubran) vs. fibrin sealant (Tisseel) in experimental models of partial pulmonary resection and lung incision [corrected] in rabbits.

INTRODUCTION: Bronchopleural fistulas (BPF) and air leaks (AL) present major complications after pulmonary resection. Various tissue sealants have been proposed for their prevention, e.g., fibrin sealant (FS) and cyanoacrylate glues (CA). Contrary to the safety record of FS, substantial side effects such as foreign body reaction and impaired tissue integration have been reported for CA. This study compares the sealing efficacy and biocompatibility as well as side effects of FS and CA in experimental partial pulmonary resection and lung incision in rabbits. METHODS: 26 New Zealand white rabbits (3 kg) were randomized to one of the three groups: partial pulmonary resection (A, acute model; n = 7 FS/ 7CA), lung incision [2 (B; n = 3 FS/ 3 CA)], and 14-day observation period (C; n = 3 FS/ 3 CA). In all groups (A, B, and C), FS was considered as control and CA as treatment. Surgery was carried out in general anaesthesia and mechanical ventilation. For partial lung resection a median thoracotomy was performed and the apex of the left median lobe was resected and the parenchymal surface covered with 0.09 ml of FS and CA. The thoracic cavity was filled with ringer solution after 5 minutes. The inspiratory minute volume (IMV) was increased by 0.02 l after every 4th inspiration. In groups B and C, a left lateral thoracotomy was performed in the 4th intercostal space and the left median lobe was incised with a scalpel. The incision was covered with 0.5 ml of FS or CA. At autopsy (B and C) the operation site was assessed macroscopically. Histology was performed in all animals. RESULTS: In terms of sealing purposes, FS and CA yielded comparable results in all groups. CA elicited a substantial increase of tissue temperature in the acute phase immediately after application (A). After 14 days CA residues were found, whereas FS was completely degraded. Histology showed a pronounced inflammatory response to CA but not to FS. We conclude that although the effect of airtight sealing was equally satisfying, our results emphasize that FS is preferable to CA for the prevention of BPF and AL due to superior biocompatibility and degradability. Longterm effects of CA residues on pulmonary tissue require further experimental testing.

Skin graft fixation by slow clotting fibrin sealant applied as a thin layer.

Human fibrin sealant (FS) has been proven effective for skin grafting after severe burn, however no systematic evaluation of application conditions has been performed so far. In order to find the optimal FS amount for fixation of skin grafts to deep defects, we created four full thickness wounds (8 cmx4 cm) on the dorsum of six male pigs. Wounds were covered with unmeshed split thickness skin grafts and fixed either with a thin layer (0.05 ml/cm2) or a thick layer (0.15 ml/cm2) of fibrin sealant (FS) without additional sutures. Sutures served as controls. FS was used as a slow clotting spray (4-5 IUthrombin/ml). Outcome measurements revealed that hematoma formation (day of surgery) was more extensive and occurred more frequently in the suture group as compared to FS 0.05 ml/cm2 (p<0.05). Areas of graft dislocation tended to be larger in the suture group versus the FS 0.05 ml/cm2. The FS 0.05 ml/cm2 graft take on day 5 appeared to be enhanced in comparison to the suture group. Excellent outcome was notable on the final observation day (day 21) in the FS 0.05 ml/cm2 group with a take of 99.7% (IQR 96.1-100%). Corresponding values in the FS 0.15 ml/cm2 group were 96.9% (IQR 92.2-99%) and 95.9% (IQR 93.2-98%) in the suture group. The results indicate, that the usage of a sprayed thin FS layer (0.05 ml/cm2) in a slow clotting rate (4-5 IUthrombin/ml) is an appropriate fixation method in split thickness skin transplantation.