The control of peritendinous adhesions using topical beta-aminopropionitrile base

The Lindsay chicken foot tendon model was utilized to test the effect of topically applied beta-aminopropionitrile base upon the tensile strength of peritendinous adhesions following tenolysis of a scarified flexor tendon. The agent reduced by one-third the force required to effect tendon gliding and flexion of the joints in the involved digit. The results show that topical beta-aminopropionitrile is effective in the control of peritendinous adhesions and, therefore, achieves sufficient depth of penetration topically to affect the peritendinous location. No adverse effects of the topically applied agent were demonstrated. The principle of topical therapeutics that may have significant benefits to patients with tendon injuries is demonstrated.     

Cross-linked cartilage acellular matrix film decreases postsurgical peritendinous adhesions

Cartilage extracellular matrix contains antiadhesive and antiangiogenic molecules such as chondromodulin-1, thrombospondin-1, and endostatin. We have aimed to develop a cross-linked cartilage acellular matrix (CAM) barrier for peritendinous adhesion prevention. CAM film was fabricated using decellularized porcine cartilage tissue powder and chemical cross-linking. Biochemical analysis of the film showed retention of collagen and glycosaminoglycans after the fabrication process. Physical characterization of the film showed denser collagen microstructure, increased water contact angle, and higher tensile strength after cross-linking. The degradation time in vivo was 14 d after cross-linking. The film extract and film surface showed similar cell proliferation, while inhibiting cell migration and cell adhesion compared to standard media and culture plate, respectively. Application of the film after repair resulted in similar tendon healing and significantly less peritendinous adhesions in a rabbit Achilles tendon injury model compared to repair only group, demonstrated by histology, ultrasonography, and biomechanical testing. In conclusion, the current study developed a CAM film having biological properties of antiadhesion, together with biomechanical properties and degradation profile suitable for prevention of peritendinous adhesions.     

Prevention of peritendinous adhesions following flexor tendon injury with seprafilm

Peritendinous adhesions are the most important complication of flexor tendon injury. In this study, Seprafilm was used for the prevention of peritendinous adhesions following flexor tendon repair. Seprafilm Bioresorbable Membrane (Genzyme Corporation, Cambridge, MA) contains sodium hyaluronate and carboxymethyl cellulose. Thirty New Zealand white male rabbits were divided equally into 3 groups. In all groups, the deep flexor tendon of the third finger of the left back foot was cut and repaired by Kessler-Tajima suture technique. In the first study group following tendon repair, Seprafilm was wrapped around the repaired tendon. In the second study group, sodium hyaluronate gel was injected to the operation field after tendon repair. In the control group, no external material was applied to the field. The study groups had better range of motion. Histopathologically, study groups had less adhesions compared with the control groups. As a result, it was concluded that in rabbit the peritendinous adhesions following flexor tendon repairs could be lowered with Seprafilm and hyaluronic acid.     

Injectable ibuprofen: preliminary evaluation of its ability to decrease peritendinous adhesions

Peritendinous adhesions continue to limit the full return of hand function following flexor tendon injury and repair. Pilot studies in rabbits demonstrated the ability of ibuprofen (Motrin) to reduce intra-abdominal adhesions. In this study, ibuprofen injected at the site of flexor tendon repair significantly reduced the restrictive effects of peritendinous adhesions in primates.     

Fleece bound sealing prevents pleural adhesions

This study assessed the value of haemostatic fleece (HF) in prevention of pleural adhesions in an experimental animal model. Forty rats were randomly assigned to four equal groups and underwent bilateral thoracotomy. In Group 1 standardized defects of 5 mm were generated in the visceral and the opposite parietal pleura without further coverage. In Group 2 a 5-mm piece of HF (TachoSil) was applied onto the intact pleura. In Group 3 a standardized pleural defect was completely covered by HF. The same kind of defect was only partially covered by HF in group 4 animals. Autopsy at 6 weeks (n=5, each group) revealed the fleece widely unchanged and covered by a smooth serous membrane. After 12 weeks (n=5, each group) the fleece had been completely resorbed. Histological studies revealed the area of the defect covered by regular mesothelium. In all animals pleural adhesions were detected only in the area without fleece coverage. In this experimental model HF prevented the development of pleural adhesions. This property may have clinical impact in patients with some probability of re-thoracotomy enabling to reduce the risk of pleural adhesions significantly.     

Oral ibuprofen: evaluation of its effect on peritendinous adhesions and the breaking strength of a tenorrhaphy

In a study of 21 primates, treatment with oral ibuprofen significantly reduced the force required for tendon gliding following flexor tendon injury in zone II. Tendons that were partially lacerated but not repaired required less force for tendon motion than those repaired. Ibuprofen also reduced the breaking strength of completely divided and repaired extensor tendons. The addition of a piece of chromic suture buried across the extensor tenorrhaphy site significantly increased the breaking strength of the repair in control and treated animals alike. These findings were observed at 4 and 6 weeks after tendon injury and repair. No adverse reactions to the medication were observed.     

Bioabsorbable membrane prevents adhesions to polypropylene mesh in rats

Summary Most of mesh materials used in the repair of ventral hernias lead to considerable adhesion formation. In this study we evaluated the effects of a bioabsorbable membrane composed of carboxymethylcellulose and hyaluronic acid (HA membrane) on adhesion formation in the presence of a polypropylene mesh used to repair an incisional hernia model in rats. We repaired the defects either primarily or by polypropylene mesh. The abdominal surface of the repairs were then covered by a piece of HA membrane in randomly selected groups. The presence and grade of adhesions to the repair or mesh were recorded on the 8th day. Tissue specimens were analyzed for the extent of mesothelial and collagenous tissue growth and the degree of inflammation. Dense adhesions developed on all of the defects repaired by polypropylene mesh alone. The HA membrane decreased adhesions significantly when used as a supplement over the mesh (p < 0.01). Histopathologically, the HA membrane further retarded mesothelial growth over the mesh, and decreased vascular proliferation, inflammatory cell infiltration (p < 0.01) and collagen content of the wound (p < 0.05). In our rat model, the HA membrane prevented most of the adhesions that would be expected to occur on the mesh. It decreased the local infiltration of white cells and neovascularization. The HA membrane seemed to be a suitable physical barrier in rats against adhesion formation without compromising the wound healing. However, these findings need to be confirmed in humans.     

Mitomycin-C prevents reformation of intra-abdominal adhesions after adhesiolysis.

BACKGROUND: Prevention of adhesions is central to surgical practice, because they cause significant morbidity. Inhibition of fibroblast proliferation is a way to prevent adhesions. Mitomycin-C (MMC) (Kyowa-Hakko-Kogyo Co, Ltd, Tokyo, Japan) is an alkylating agent that also inhibits fibroblast proliferation for up to a few weeks. We investigated the effect of MMC on the prevention of adhesion reformation. METHODS: Adhesions were generated by brushing the cecum and parietal peritoneum in 60 female Wistar albino rats. Ten days later, during a second laparotomy, adhesions were graded. After adhesiolysis, rats were divided into 3 groups. Group 1 was intraperitoneally administered 5 mL of saline solution, whereas groups 2 and 3 were intraperitoneally administered 0.5 mg/kg MMC in 5 mL of saline solution. MMC solution in the abdomen was completely rinsed and aspirated after 5 minutes in group 2 and after 10 minutes in group 3. Then, all the rats were administered 5 mL of saline solution intraperitoneally. After 10 days, adhesions were graded again during a third laparotomy. RESULTS: Both MMC groups had significantly lower adhesion scores compared with the control group (P <.001). No side effects from MMC were observed during the experiment. CONCLUSIONS: MMC was found to be very effective in preventing adhesion reformation.     

姜黄素对内毒素所致肾脏炎症的抑制作用

目的：肾脏的急慢性炎症与肾脏疾病的进展密切相关,本研究拟探讨姜黄素对内毒素（LPS）所致肾脏炎症的抑制作用。方法：SPF级昆明种小鼠40只,鼠龄6～8周,体重20～25g。小鼠分为3组：（1）正常对照组：腹腔注射生理盐水;（2）模型组（LPS组）：腹腔注射LPS（1mg/kg和5mg/kg）;（3）治疗组（LPS＋姜黄素）：动物先腹腔注射姜黄素（1mg/kg或5mg/kg）3d,然后腹腔注射LPS1mg/kg或5mg/kg。于处理后6h取材,切取部分肾组织用10%甲醛固定,HE染色,进行病理学观察。部分肾组织用于MCP-1mRNA检测。将肾小管上皮细胞（HK-2细胞）培养于KSF培养液中,设正常对照组给予正常培养液,LPS刺激组（1ng/ml,100ng/ml和10μg/ml）,LPS刺激＋姜黄素（5μmol/L和50μmol/L）处理组,分别培养4h和24h后收集细胞,应用Real-timePCR检测各组细胞MCP-1的表达。ELISA检测细胞培养上清液中MCP-1的表达。EMSA检测肾小管上皮细胞NF-κB的活性。结果：腹腔注射LPS（1mg/kg和5mg/kg）虽未引起光镜下肾脏组织的病理改变,但可显著增加小鼠肾脏MCP-1 mRNA的表达,分别增加20倍和26倍,而姜黄素处理可降低LPS所诱导的肾脏MCP-1 mRNA的表达,尤以LPS（1mg/kg）＋姜黄素（1mg/kg）为明显（下降至基础值的2.5倍）。应用不同浓度的LPS刺激HK-2细胞4h,HK-2细胞MCP-1 mRNA表达量显著增加,且呈剂量依赖的效应（分别增加1.60、2.15和14.7倍）。而以100ng/ml的LPS刺激HK-2细胞4h,观察姜黄素的干预作用,可见不同浓度的姜黄素（5μmol/L和50μmol/L）可显著抑制LPS所诱导的HK-2细胞MCP-1 mRNA的表达,且以50μmol/L姜黄素干预组为明显。同时ELSA检测细胞上清液中MCP-1的表达结果相似。EMSA结果显示NF-κB的DNA结合活性随LPS的浓度增加而增加,而应用姜黄素预处理后,由LPS所诱导的增高的NF-κB的DNA结合活性随之下降。结论：早期给予姜黄素治疗,能明显改善LPS诱导的小鼠肾脏趋化因子MCP-1的表达,从而发挥其肾脏损伤的保护功能;而体外研究表明姜黄素可抑制LPS所诱导的肾小管上皮细胞MCP-1表达,其作用可能与抑制细胞NF-κB的活性有关。     

Hyperglycemia prevents isoflurane-induced preconditioning against myocardial infarction.

BACKGROUND: Volatile anesthetics stimulate but hyperglycemia attenuates activity of mitochondrial adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that acute hyperglycemia interferes with isoflurane-induced preconditioning in vivo. METHODS: Barbiturate-anesthetized dogs (n = 79) were instrumented for measurement of hemodynamics. Myocardial infarct size and collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of normal saline (normoglycemic controls) or 15% dextrose in water to increase blood glucose concentrations to 300 or 600 mg/dl in the absence or presence of isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) in separate experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion. RESULTS: Myocardial infarct size was 26 +/- 1% of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2 and 13 +/- 1% during 0.5 and 1.0 MAC, respectively). Hyperglycemia alone did not alter infarct size (26 +/- 2 and 33 +/- 4% during 300 and 600 mg/dl, respectively). Moderate hyperglycemia blocked the protective effects of 0.5 MAC (25 +/- 2%) but not 1.0 MAC isoflurane (13 +/- 2%). In contrast, severe hyperglycemia prevented reductions of infarct size during both 0.5 MAC (29 +/- 3%) and 1.0 MAC isoflurane (28 +/- 4%). CONCLUSIONS: Acute hyperglycemia attenuates reductions in myocardial infarct size produced by isoflurane in dogs.     

Carbon dioxide pneumoperitoneum prevents intraperitoneal adhesions after laparotomy in rats

Purpose

The aim of this study was to assess whether carbon dioxide insufflation (CDI) pneumoperitoneum prevents intraperitoneal adhesions (IPAs).

Methods

Laparotomy was performed in 40 8-week-old Lewis rats and their bowels delivered through the wound and manipulated. The rats were divided into 4 groups, namely, those that would have laparotomy (Lp group, n = 15), Lp with CDI (Lp-CDI group, n = 15), Lp and bowel anastomosis (LpBA group, n = 5), and LpBA with CDI (LpBA-CDI group, n = 5). LpBA and LpBA-CDI group rats had 1 cm of ileum excised and end-to-end anastomosis performed. To accelerate IPA formation, all rats then had their bowels heated to 45°C for 40 seconds and 0.5 mL of Lewis rat blood spilled over them. Rats in the control group (n = 5) had Lp alone without heating or blood spillage. Pneumoperitoneum involved insufflating carbon dioxide into the peritoneal cavity through a cannula at the time of final abdominal closure to create pneumoperitoneum to a pressure of 5 mm Hg. All rats had relaparotomy 10 days after surgery and IPAs were assessed blindly using an IPA severity score (IPASS: 0 = no adhesions, 1 = no serosal tears during adhesiolysis, 2 = serosal tears during adhesiolysis, 3 = bowel perforation during adhesiolysis). Only the worst IPA in each rat was scored. Rats were killed after the peritoneum and bowels were excised for histopathology.

Results

Pneumoperitoneum resolved in approximately 5 days. There were no associated side effects. The Lp-CDI group had significantly lower IPASS than the Lp group (0.23 ± 0.46 vs 1.07 ± 1.18, P < .05), and the LpBA-CDI group had significantly lower IPASS than the LpBA group (1.50 ± 0.61 vs 2.40 ± 0.55, P < .05). Histopathology showed pneumoperitoneum had no effect on the peritoneum or bowels.

Conclusions

Our results suggest that CDI pneumoperitoneum appears to prevent IPA, especially between bowel-bowel IPA.     

Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury

Purpose  

Primary graft dysfunction still represents a major challenge in liver transplantation. We herein studied in an isolated rat liver perfusion model whether a multidrug donor preconditioning (MDDP) can not only reduce but also completely prevent cold ischemia–reperfusion injury.     

Omentum prevents intestinal adhesions to mesh graft in abdominal infections and serosal defects

Background Many studies have evaluated the use of grafts in the reconstruction of abdominal wall defects. In this study, the effects resulting from the presence or absence of the omentum were evaluated in the setting of infection or serosal defects in the formation of adhesions in abdominal closures using mesh grafts. Methods For this study, 60 Wistar albino rats were divided into six groups. A circular 3.79-cm² fascioperitoneal defect was created. After group-specific procedures, defects were reconstructed using polypropylene mesh grafts. In group C (control group), only a mesh graft recontruction was performed, whereas group O (O for omentectomy) underwent an omentectomy plus mesh closure. In group SD (serosal defect group), the cecum was abrased with a brush before mesh closure. Group SDO underwent cecal abrasion plus an omentectomy. In group I (infection group), the intraabdominal space was filled with 1 ml of solution containing 100,000 colony-forming units (CFUs) of Escherichia coli per milliliter. Group IO received the same same amount of E. coli solution plus an omentectomy before mesh closure. After 28 days, the groups were evaluated by intraabdominal and blood cultures, grading of intraabdominal adhesions, graft–organ adhesions, proportion of adhesions to graft size, and histopathologic studies. The results were statistically evaluated using one-way variant analysis and Scheffe’s and Fisher’s definite chi-square tests. Results For the groups in which the greater omentum was preserved, intestinal adhesions to the graft surface were less frequently observed, especially in cases with intraabdominal infections and serosal defects (p < 0.05). Conclusions Preservation of the greater omentum reduces the formation of intestinal adhesions, especially in cases with underlying infections and serosal defects in abdominal closures using mesh grafts. This could be beneficial in related clinical situations in lowering the rate of intestinal fistulas, erosions, and obstructions that can be attributed to the formation of adhesions.     

The effects of a combination of hyaluronic and amniotic membrane on the formation of peritendinous adhesions after flexor tendon surgery in chickens

We have investigated the effects of the intra-operative application of a combination of hyaluronic acid and amniotic membrane on adhesions in the flexor tendons of a chicken model. We used 144 tendons which were partially divided and then repaired by a modified Kessler technique. There were four test groups: group 1, simple tendon repair, group 2, repair site wrapped with amniotic membrane, group 3, hyaluronic acid injected around the repair site, and group 4, repair site wrapped with amniotic membrane and hyaluronic acid injected within it. At three and six weeks, the extent of the adhesions and the healing of the tendon were evaluated macroscopically and histologically. The range of movement of the toe and tensile strength of the repaired tendons were measured at 20 weeks. The least adhesions were observed in group 4 but no significant difference was found in the healing of the tendons. Overall, the intra-operative application of a combination of hyaluronic acid and amniotic membrane appears to be effective in preventing adhesions of the flexor tendon.     

Prevention of peritendinous adhesions using a hyaluronan‐derived hydrogel film following partial‐thickness flexor tendon injury

Peritendinous adhesions are an important complication of flexor tendon injury. Three hyaluronan (HA)‐derived biomaterials were evaluated for the reduction of peritendinous adhesions following partial‐thickness tendon injury in rabbits. Rabbits (n = 24) were divided into three groups (n = 8 per group), which were used for gross evaluation, histologic assessment, or biomechanical testing. The fourth and third toes from both hindpaws of each rabbit were randomly assigned to one of four treatments: (i) untreated control, (ii) Seprafilm®, (iii) Carbylan?‐SX in situ crosslinked hydrogel, and (iv) preformed Carbylan?‐SX film. Rabbits were sacrificed at 3 weeks postsurgery and evaluated anatomically, histologically, and mechanically. All materials used reduced adhesions relative to untreated controls for all three evaluations. Both the gross anatomic and histologic results revealed that Carbylan?‐SX film was statistically superior to Seprafilm® and Carbylan?‐SX gel in preventing tendon adhesion formation. In biomechanical tests, the Carbylan?‐SX film‐treated hindpaws required the least force to pull the tendon from the sheath. This force was statistically indistinguishable from that required to extrude an unoperated tendon (n = 8). Carbylan?‐SX gel was less effective than Carbylan?‐SX film but superior to Seprafilm® for all evaluations. A crosslinked HA‐derived film promoted healing of a flexor tendon injury without the formation of fibrosis at 3 weeks postoperatively. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:562–569, 2008     

Heat preconditioning prevents enterocyte mitochondrial damage induced by surgical manipulation

BACKGROUND: The small intestine is susceptible to free radical-induced damage and our earlier work has shown that surgical manipulation of the intestine results in generation of oxygen free radicals, leading to mucosal damage. Heat preconditioning has been shown to offer protection against various stresses including oxidative stress and this study looked at the effect of heat preconditioning on surgical manipulation-induced intestinal mitochondrial alterations. METHODS: Control and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Mitochondria were prepared from isolated enterocytes and structural and functional alterations were assessed. RESULTS: Surgical manipulation of the intestine resulted in mitochondrial alterations as seen by ultrastructural changes and altered lipid composition. Mitochondria were functionally impaired as evidenced by altered calcium flux, decreased respiratory control ratio, and increased tetrazolium dye reduction and swelling. Along with this, biochemical alterations such as increased lipid and protein oxidation were seen following surgical manipulation. Mild heat preconditioning of the animal prevented these damaging effects. CONCLUSIONS: These studies suggest that stress in the small intestine due to surgery can affect enterocyte mitochondrial structure and function and these effects can be prevented by mild whole body hyperthermia prior to surgery.     

Silicon prevents post laminectomy epidural root adhesions an experimental study in rats

Summary An experimental study was designed to test the efficacy of a silicon barrier around a nerve root in order to prevent post operative epidural root scar adhesions. In 32 Sprague-Dawely rats a lumbar nerve root was microsurgically exposed bilaterally. In 16 animals a silicon tube, prepared with a longitudinal cut along half of its wall, was placed around one nerve root, while the contralateral side served as control. In another group of 12 animals, an autologous subcutaneous fat graft was placed on the exposed root. A group of 4 animals served as the control group which had not been operated upon.No post operative neurological deficit was observed in any of the animals. All animals were sacrificed 60 days after the operation and a block of tissue including the nerve roots were resected bilaterally without removal of the silicon or fat graft. Longitudinal and transverse cuts of the roots were stained with Haematoxilin and Eosin and with Masson's trichrome collagen stain.The roots in the unoperated control group were clean of any scar tissue. In 13 out of 16 animals, silicon prevented scar formation around the root as opposed to scar adhesions around control root on the contralateral side and as compared to unoperated roots. In the silicon group, adhesions penetrated only through the longitudinal narrow cut edge of the tube. Fat did not prevent adhesions in 11 out of 12 animals.We conclude that a silicon barrier is an effective method preventing post operative epidural root scarring in rats.     

Phosphatidylcholine prevents postoperative peritoneal adhesions: an experimental study in the rat

Phosphatidylcholine (PC) is the main constituent of the surface-active material coating peritoneal mesothelium. It may prevent postoperative adhesion formation through production of a lubricant film on mesothelial defects. We therefore examined the effect of its soluble form on surgically induced intraabdominal adhesions in rats. The adhesions were induced at laparotomy by any of four different operative models. PC was administered intraperitoneally (20 mg/rat) or intravenously (20 mg/rat or 50 mg/rat) at the end of the operation and on the second and third postoperative day. It was found that the degree of postoperative adhesion formation was significantly reduced by the intraperitoneal injection of PC in all 4 models. In contrast, no effect was achieved by the intravenous injection of PC, not even at a very high dose level. Our results suggest that soluble PC administered intraperitoneally might be a potent adjunct in postoperative adhesion prevention.