In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.

The combination of two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.

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.

Evaluation of a new bioadhesive copolymer (ADAL) to seal corneal incisions.

OBJECTIVE: To evaluate the efficacy and clinical tolerance of a new acrylic copolymer tissue adhesive, ADAL, in corneal surgery. METHODS: Corneal incisions were performed on 24 New Zealand albino rabbits. The incision was either sealed with ADAL bioadhesive, hydrated with balanced salt solution, or closed with 10-0 nylon surgical sutures. The incisions underwent weekly tensile strength testing and clinical, histopathologic, and confocal microscopy evaluations. RESULTS: Clinical evaluation revealed good sealing and no incision leakage in any group. There was no anterior chamber reaction in any case. Compared with the hydrated group, there was somewhat more incisional vascularization and localized corneal opacity in the ADAL group, but there were no cases of severe corneal opacity or neovascularization. On histologic analysis, a slightly larger inflammatory reaction was noted in the ADAL group compared with the hydrated group. Tensile strength during the first week was statistically significantly greater in the ADAL group (2.93 Newtons) than in the control groups (1.40 Newtons, hydrated group; 1.43 Newtons, sutured group) (P < 0.001). Confocal microscopy study revealed a unique dendritic keratocyte shape and structure resembling shiny crystalline particles after disappearance of the adhesive from the cornea. CONCLUSIONS: Corneal surgical incisions sealed with ADAL adhesive have superior tensile strength in the first postoperative week compared with incisions closed with sutures or hydrated with salt solution. Thereafter, findings in both groups became similar. The use of ADAL adhesive was not associated with any deleterious effects during the corneal incision-healing process compared with hydration or sutures.

[Comparative study between different conjunctival tissue adhesives]. / Estudio comparativo entre diferentes adhesivos conjuntivales.

PURPOSE: To evaluate efficacy and clinical and histopathological tolerance of a new acrylic tissue adhesive (ADAL-2) compared to sutures (Vicryl) and other available tissue adhesives (Tisuacryl) for their use in conjunctival surgery. METHODS: This was an experimental study performed in New Zealand albino rabbits with conjunctival dissection and closure by ADAL-2. Groups treated with Vicryl and Tisuacryl were compared regarding efficacy, clinical, and histological tolerance at 7, 28 and 42 days. RESULTS: Efficacy was similar in the three methods of conjunctival repositioning evaluated. Tolerance to ADAL-2 was similar to that of Vicryl suture and tolerance to ADAL-2 was superior to that to Tisuacryl. Histopathological results with ADAL-2 and Tisuacryl are similar. CONCLUSIONS: ADAL-2 tissue adhesive is an efficient and very well tolerated alternative for conjunctival closure in ophthalmic surgery.

Mediastinal fibrin glue: hemostatic effect and tissue response in calves.

There is continued controversy regarding the effectiveness and potential adverse effects of fibrin glue. Thus, we chose to evaluate it in a model of experimental calf aortic valve replacement that has been previously well established. Concentrated fibrinogen and topical thrombin were sprayed to form a thin layer of fibrin glue over the mediastinal tissues of 20 consecutive calves undergoing aortic valve replacement. Chest tube outputs of these animals were compared with those of the preceding 20 consecutive calves undergoing aortic valve replacement without fibrin glue. All procedures were performed by the same surgeon, and no other technical changes were made between the two series. Total postoperative chest tube output (mean +/- standard error) was 553 +/- 50 mL for the calves treated with fibrin glue and 1,155 +/- 103 mL for the control calves (p less than 0.001). On histological examination of mediastinal tissues from 5 treated calves killed 6 weeks after operation, there was no evidence of inflammation, fibrosis, or residual fibrin. To our knowledge, this is the first controlled laboratory study to show that fibrin glue spray is an effective hemostatic agent and that it produces no long-term tissue reaction.