Permeability alterations after surgical trauma in normal rabbit peritoneum.
ABSTRACT To investigate whether surgical trauma in a rabbit adhesion formation model and the administration of normal saline (N/S), icodextrin (ID) and/or dimetindene maleate (DM) changes the permeability of the normal rabbit parietal peritoneum.
A total of 45 female rabbits were operated on for adhesion formation and were euthanized 10 days later. In some rabbits, ID or N/S was instilled intraabdominally during operation, whereas in others DM was infused intravenously. In others, ID plus DM or no agent was used. Specimens were obtained postoperatively and were mounted between Ussing chambers. Amiloride was used to investigate Na(+) channels. Transmesothelial resistance (R(TM)) was determined as a permeability indicator. Results: Amiloride increased the R(TM) of both surfaces. Surgical trauma increased R(TM) and partially inhibited the effect of amiloride. ID and N/S increased R(TM) and inhibited the effect of amiloride. Use of DM did not change R(TM) and did not inhibit the effect of amiloride. Use of ID plus DM slightly increased R(TM), but the effect of amiloride was blocked.
Surgical trauma impairs the permeability of the normal rabbit parietal peritoneum. ID or N/S surmounted this effect, but DM did not, suggesting that surgical trauma is a diffuse process. Antiadhesion measures influence peritoneal physiology.
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ABSTRACT: Intra-abdominal adhesion formation causes significant post-operative morbidity. Controlled studies using animal models have been carried out to assess the tolerability and preventive efficacy of icodextrin solution (a biodegradable, biocompatible, glucose polymer). Reduction of adhesion formation was first evaluated in a rabbit double uterine horn model, applying 10-75 ml of 7.5 and 20%, or 50 ml of 2.5-20% icodextrin solution post-operatively. Significant increases in adhesion free sites (P < 0.005) were observed with volumes > or =25 ml, and at concentrations > or =4%. Efficacy of 50 ml 4 and 20% icodextrin was then evaluated both during and after surgery, demonstrating significant reductions in adhesion formation (P < 0. 002). In one study, intra- plus post-operative use of 4% icodextrin produced the greatest reduction of non-surgical site adhesions; in others, the post-operative effect was predominant. Post-surgical administration of 50 ml 4% icodextrin in a rabbit sidewall model also resulted in more adhesion-free animals, and a significant reduction (P < 0.001) in areas of adhesion formation and reformation. In a rat infection potentiation model, 4% icodextrin produced no difference in mortality, abscess formation or overall abscess score. These data suggest that 4% icodextrin offers a well-tolerated and effective means of reducing post-surgical adhesion formation.Human Reproduction 08/2000; 15(8):1764-72. · 4.67 Impact Factor
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ABSTRACT: Adhesion-related readmissions are frequent sequelae to gynaecological surgery. Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions. Rapid absorption limits the effectiveness of solutions such as Ringer's lactated saline (RLS). This pilot study assessed the safety, tolerability and preliminary effectiveness of a non-viscous, iso-osmolar solution of 4% icodextrin, an alpha-1,4 glucose polymer with prolonged intraperitoneal residence, in reducing adhesions after laparoscopic gynaecological surgery. Women aged > or = 18 years, requiring laparoscopic adnexal surgery (n = 62), were entered into a randomized, open-label, assessor-blinded, multicentre study to compare 4% icodextrin with RLS. Treatments were coded in blocks of four with equal randomization to each group, and pre-allocated to consecutively numbered patients. At least 100 ml per 30 min was used for intra-operative lavage, with 1 l instilled post-operatively. Per protocol analysis included all eligible patients (n = 53); reformation analysis required one or more baseline adhesion (n = 42). Incidence, extent and severity of post-operative adhesions were assessed at second-look laparoscopy after 6-12 weeks. Procedures were video-taped for third party, blinded assessment. Safety and tolerability (laboratory variables, adverse events, clinical follow-up) were good with no difference between treatments. A shift analysis of incidence-ranked adhesions (n = 53) showed apparent improvements in more patients with icodextrin than RLS (37 versus 15%; not significant). Adhesion score reduction (n = 42) was more frequent in icodextrin- than RLS-treated patients: incidence (52 versus 32%), extent (52 versus 47%), and severity (65 versus 37%). Despite greater baseline adhesions, median reformation was less after icodextrin (24%) than RLS (60%). The pilot study group sizes were not powered for statistical significance. In this preliminary study, 4% icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery. A Phase III pivotal study is currently in progress.Human Reproduction 04/2002; 17(4):1031-8. · 4.67 Impact Factor
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ABSTRACT: The purpose of this study was to determine the effects of diphenhydramine hydrochloride and methylprednisolone in peritoneal adhesions. Forty-eight male rats were used in the study. The rats were anesthetized by 5 mg/kg ketamine hydrochloride. After opening the abdomen, 10 longitudinal incisions of 2 to 3 cm in length were made on the right parietal peritoneum, and a 2 cm(2) peritoneal layer was excised from the left abdominal wall. The abdomen was closed with 3/0 silk suture. Group I was the control group, group II was given 10 mg/kg diphenhydramine intravenously, group III was given 20 mg/kg methylprednisolone intravenously, and group IV was administered both of the drugs in the above doses. A blood sample of 2 mL was taken from the rats on the 14th day after the operation. The animals were then sacrificed. The abdomen was opened and abdominal adhesions were examined. A tissue sample of 1 g was taken from the abdominal incision line. Albumin, zinc, and hemoglobin levels and leucocyte counts in the blood were determined as well as hydroxyproline levels in the tissue. Numbers of adhesions were as follows: 9 in group I, 3 in group II, and 2 in group III. No adhesion was observed in group IV. Albumin, zinc, and hemoglobin levels and leucocyte counts were found to be similar in all groups. Hydroxyproline levels in the tissue were significantly lower in groups III and IV than in groups I and II (P <0.05). Diphenhydramine and methylprednisolone reduced postoperative adhesions significantly in rats. Further investigations are needed in order to use these drugs as antiadhesive agents in humans.The American Journal of Surgery 07/2001; 181(6):512-5. · 2.52 Impact Factor