Fibrinolytic drugs prevent pericardial adhesions in the rabbit.

Epicardial adhesions are believed to form secondarily to impaired pericardial fibrinolytic activity. This activity was reconstituted in a rabbit pericardial adhesion model with single doses of the fibrinolytic agents tissue plasminogen activator (t-PA), t-PA analog (Fb-Fb-CF), and streptokinase (SK), resulting in reductions in the extent and tenacity of adhesion formation. Adhesions of the median strip of the anterior cardiac surface were reduced in area from 89% (n = 22) in controls, to 28% (n = 5) by treatment with Fb-Fb-CF (0.94 mg), and to 49% (n = 7) by treatment with SK (93,750 IU). A modified fabric of oxidized regenerated cellulose (mTC7) used to deliver the agent to the cardiac surface did not interfere with the activity of these agents (Fb-Fb-CF 19%, n = 14; SK 33%, n = 7). t-PA (0.94 mg) was also found to reduce adhesion formation in combination with mTC7 (4%, n = 4), although the appearance of significant postoperative bruising and bleeding resulted in a decision to terminate the treatment of further animals with t-PA with and without mTC7. Postoperative bruising, bleeding, and swelling, to a lesser extent, were associated with SK and Fb-Fb-CF. Despite the efficacy of the these fibrinolytic drugs further work is required to assess their safety before they are used clinically.

Synergistic effects of INTERCEED(TC7) and heparin in reducing adhesion formation in the rabbit uterine horn model.

Surgical adjuvants are commonly employed to reduce the frequency of postoperative adhesion development after reproductive pelvic surgery. The ability of indomethacin, promethazine dexamethasone, Intralipid, progesterone, and heparin to reduce adhesion formation in combination with INTERCEED(TC7) (Johnson and Johnson Medical, Inc., New Brunswick, NJ), an absorbable barrier that alone reduces adhesion formation, was examined in a rabbit uterine horn model. A significant reduction in adhesion formation was only observed with the combination of INTERCEED(TC7) plus heparin. In addition studies, heparin delivery by intraperitoneal (IP) lavage, intravenous injection, or intra-abdominal instillation failed to demonstrate efficacy. Similarly, heparin delivery with other barriers or IP instillates (carboxymethylcellulose or 32% Dextran 70) failed to reduce adhesion formation. We conclude that INTERCEED(TC7) can be efficaciously utilized as a carrier to deliver heparin to traumatized surfaces, thereby reducing adhesion formation.

Adhesion reformation: reduction by the use of Interceed (TC7) plus heparin.

Adhesions frequently develop after surgical procedures. Several groups have demonstrated that reduction of adhesion reformation is more difficult than reduction of adhesion formation. Previous studies have demonstrated the efficacy of Interceed (TC7) (oxidized regenerated cellulose) plus heparin in reducing adhesion formation. Adhesions were created using a previously standardized rabbit uterine horn model. After adhesiolysis, rabbits were assigned randomly to one of four groups: control, Interceed (TC7) alone, Interceed (TC7) plus 500 USP units heparin/horn, and Interceed (TC7) plus 1000 USP units heparin/horn. Adhesion reformation was evaluated 2 weeks later. Combination of the Interceed (TC7) barrier plus heparin resulted in a significant reduction of the adhesion reformation scores. It is concluded that Interceed (TC7) plus heparin is efficacious in reduction of both adhesion formation and adhesion reformation.

In vivo degradation of oxidized, regenerated cellulose.

Oxidized, regenerated cellulose (ORC) was surgically implanted on the uterine horns of rabbits, and its biodegradation was studied in vivo. Samples of peritoneal lavages, serum, and urine were collected during the degradation process and analyzed for carbohydrate components utilizing high-performance liquid chromatography with pulsed amperometric detection (h.p.l.c.-p.a.d.). Degradation was rapid, and oligomeric products were evident primarily in the peritoneal fluid from the implantation site, with no apparent accumulation in either the serum or the urine. The size distribution and the amount of the oligomeric products decreased after day one, and by day four peritoneal lavages were essentially free of oligomers. The structure of the products formed was consistent with the lability of the polymer in solution, and the kinetics of degradation paralleled the results of the previously reported in vitro studies. Rabbit peritoneal macrophages, when incubated with ORC in vitro were observed to readily ingest and hydrolyze the polymeric material. A mechanism of degradation consisting of chemical depolymerization, followed by enzymatic hydrolysis mediated by glycosidases endogenous to peritoneal macrophages, is proposed.

Biodegradation of oxidized regenerated cellulose.

The in vitro solubilization and degradation of regenerated cellulose was studied under conditions which approximate those found in vivo, when the material is used as an adhesion barrier to assist normal wound repair. Factors affecting solubilization which were examined included the effects of serum or plasma, and the presence of hydrolytic enzymes. Products of the solubilization and degradation processes were examined by high performance liquid chromatography coupled with pulsed amperometric detection. The oxidized polymer readily undergoes chain shortening to give oligomers which, in the presence of plasma or serum, are further hydrolyzed to smaller fragments, including glucuronic acid and glucose. Proposed mechanisms of degradation are discussed.

Adhesion re-formation in the rabbit uterine horn model: I. Reduction with carboxymethylcellulose.

Adhesion re-formation frequently complicates the performance of adhesiolysis in reproductive pelvic surgery. To assess the ability of carboxymethylcellulose (CMC) to reduce adhesion re-formation, a rabbit uterine horn model was employed. Adhesions were created at laparotomy by scraping a 5-cm segment of each uterine horn. This injury reproducibly creates adhesions. Two weeks later, repeat laparotomy was performed, at which time all adhesions were lysed by sharp dissection. Animals were then randomly assigned to the control or CMC (20 mL of 2% solution) group. Necropsy was performed 2 weeks later. At both the second operative procedure and the time of necropsy, adhesions were graded in a blind fashion for severity and tenacity. There was no difference in adhesion score in the control and CMC-treated rabbits at the time of adhesiolysis. Subsequently, at the time of necropsy, the mean adhesion reformation score in the control group was 3.96 (median = 4.0). In contrast, adhesion re-formation in the CMC-treated group was significantly less (mean score = 2.15; median = 2.0; sign test, P less than .01). In summary, CMC significantly reduced adhesion re-formation in the rabbit uterine horn model. The mechanism by which CMC was able to reduce adhesion reformation is uncertain, but may be related to "hydroflotation" or "siliconizing" effects.

Assessment of carboxymethylcellulose and 32% dextran 70 for prevention of adhesions in a rabbit uterine horn model.

The ability of solutions of carboxymethylcellulose (CMC) and 32% dextran 70 to reduce postoperative adhesion formation was examined using a rabbit uterine-horn scrape model. Utilization of 50 mL of 32% dextran 70 did not reduce adhesion formation compared with control rabbits. However, intraperitoneal instillation of CMC significantly reduced postoperative adhesion formation. An inverse correlation was established between either the concentration of CMC employed (1%, 2%, and 3%) or the volume of 2% CMC employed (20, 30, 40, and 50 mL) and the extent of adhesion formation. It is concluded that in this animal model CMC, but not 32% dextran 70, was able to retard postoperative adhesion formation.

Adhesion reduction in the rabbit uterine horn model using an absorbable barrier, TC-7.

Use of a resorbable barrier (TC-7) to reduce adhesion formation was examined in the rabbit uterine horn model. Early evaluation (four days) established that the material remained where initially placed. Examination at two, four and eight weeks postoperatively in both control and treated groups revealed that the extent of adhesion formation did not change as a function of time. When compared to control animals without TC-7, the treated rabbits has a significant reduction (P less than .01) in postoperative adhesion formation. No complications from use of this fabric were noted, and no gross remnants were noted at the two-week time point. TC-7 appears to be an efficacious barrier for reducing adhesion formation in the rabbit uterine horn model.

A model for sidewall adhesions in the rabbit: reduction by an absorbable barrier.

Despite use of surgical adjuvants, pelvic adhesions frequently develop following infertility surgery. Recently a resorbable biocompatible material, TC 7, has been designed to be used as a barrier to reduce adhesion formation. Reproducibly severe sidewall adhesions were only able to be created in one of six models tested. The model consisted of the following steps: excision of a full thickness 2 x 2-cm musculoperitoneal tissue mass, scraping of an adjacent 2-cm length of uterine horn, tamponading of all bleeding, and suturing (6-0 Vicryl) of normal tube and sidewall so as to directly approximate the traumatized tissues. Studies were conducted in 13 rabbits after creation of the bilateral sidewall and horn lesions, each serving as its own control. Choice of control and TC 7 sides was determined randomly. Adhesion formation was examined 2 weeks postoperatively. No residual material was noted at that time. Adhesion scores were the composite total of extent (0-4), type (0-4), and tenacity (0-3) of sidewall adhesions, and were significantly reduced on the TC 7 side as compared with the control side (mean 6.8 +/- 0.4 vs 9.0 +/- 0.3, median 6 vs 9, sign test P = 0.0032). No complications of use of the barrier were noted. It is concluded that use of TC 7, a resorbable biocompatible barrier, was able to significantly reduce postoperative adhesion formation on the rabbit sidewall.