0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Prevention of Intra-abdominal Abscesses and Adhesions Using a Hyaluronic Acid Solution in a Rat Peritonitis Model FREE

Michel M. P. J. Reijnen, MD; Jacques F. G. M. Meis, MD, PhD; Victor A. Postma; Harry van Goor, MD, PhD
[+] Author Affiliations

From the Departments of Surgery (Drs Reijnen and van Goor and Mr Postma) and Medical Microbiology (Dr Meis), University Hospital Nijmegen, Nijmegen, the Netherlands.


Arch Surg. 1999;134(9):997-1001. doi:10.1001/archsurg.134.9.997.
Text Size: A A A
Published online

Hypothesis  Hyaluronic acid (HA)–based bioresorbable membrane and 0.4% HA solution reduce intra-abdominal adhesion and abscess formation in a rat peritonitis model.

Design  Randomized laboratory experiment.

Setting  A university hospital.

Interventions  In 72 male Wistar rats, a bacterial peritonitis was induced using the cecal ligation and puncture model. Animals were randomized to receive isotonic sodium chloride solution (group 1), HA-carboxymethylcellulose bioresorbable membrane (group 2), or 0.4% HA solution (group 3). Half of each group were killed at day 7 and half at day 21, and adhesions were scored in a blind fashion. The presence and sizes of intra-abdominal abscesses were noted. Cultures were taken for bacterial analysis.

Main Outcome Measures  Intra-abdominal adhesions and abscesses.

Results  The median severity of adhesions was significantly lower in group 3 compared with group 1 rats at day 7 (II [range, I-IV] vs IV [range, I-IV], respectively; P=.02) and at day 21 (II [range, I-III] vs IV [range, II-IV], respectively; P=.02). There was no significant difference between group 2 and group 1 rats on either day. At day 7, abscesses larger than 2 cm were found in 6 of 12 group 1 rats and in 4 of 12 group 2 rats, but in 0 of 11 group 3 rats (P=.01). At day 21, 0 of 11 group 3 rats had an intra-abdominal abscess, in contrast to 4 (33%) of 12 group 1 rats and 5 (45%) of 11 group 2 rats. All cultures of abscesses revealed polymicrobial flora.

Conclusion  Adhesion and abscess formation are reduced using a 0.4% HA solution, and not HA-carboxymethylcellulose bioresorbable membrane, in a rat model of generalized bacterial peritonitis.

Figures in this Article

INTRA-ABDOMINAL infection is accompanied by fibrin deposition in the abdominal cavity. This fibrin deposition may lead to adhesion and abscess formation. Both entities have significant clinical relevance. Intra-abdominal abscesses are an important cause of morbidity and mortality in patients with generalized peritonitis. Adhesions are the main cause of intestinal obstruction in the developed world. Furthermore, adhesions are responsible for 15% to 20% of cases of infertility and are associated with chronic abdominal and pelvic pain.13

Numerous agents have been investigated in the prevention of adhesions, eg, dextran, corticosteroids, phosphatidylcholine, phospholipase inhibitors, non–steroidal anti-inflammatory drugs, heparin, and tissue plasminogen activator.4 Agents particularly interfering with coagulation and fibrinolysis, eg, heparin and tissue plasminogen activator, have also been studied in the prevention of intra-abdominal abscess formation. However, clinical experience with these agents is limited, mainly because of fear of bleeding complications.

Recently, hyaluronic acid (HA) derivates have been shown to be successful in preventing postsurgical adhesions in experimental and clinical studies.511 Hyaluronic acid is a biocompatible, nontoxic, high-molecular-weight polyanionic polysaccharide consisting of repeating units of alternating N-acetylglucosamine and D-glucuronic acid. It is found in all tissues and body fluids of vertebrates.12 Hyaluronic acid has a stabilizing effect on extracellular matrices. Furthermore, it interacts with cell surfaces to modify cell behavior.12,13

Becker et al5 demonstrated a significant reduction of intra-abdominal adhesion formation following colectomy using a bioresorbable membrane consisting of HA and carboxymethylcellulose bioresorbable membrane (HA-CMC). In another study, use of an HA solution diminished de novo adhesion formation following gynecological procedures.6 The antiadhesive effect of these agents has not been assessed in an infectious environment, nor has their influence on intra-abdominal abscess formation.

Using an animal model of generalized bacterial peritonitis, we studied the effect of an HA-CMC bioresorbable membrane and an HA solution on intra-abdominal adhesion and abscess formation.

STUDY DESIGN

Seventy-two male Wistar rats (Harlan Nederland, Zeist, the Netherlands) weighing 250 to 325 g were allowed to become accustomed to laboratory conditions for 1 week before experimental use. Animals were housed at 21°C with a day-night cycle of 12 hours. They had free access to water and standard rodent chow (Hope Farms BV, Woerden, the Netherlands). The study protocol was approved by the Animal Ethics Review Committee of the Faculty of Medicine, University of Nijmegen, Nijmegen, the Netherlands.

In all rats, a bacterial peritonitis was induced by performing a cecal ligation and puncture (CLP) procedure, using the methods of Wichterman et al.14

Food was withheld from the animals for 12 hours before the first operation. On day 0, rats were weighed and anesthetized with a mixture of halothane (Fluothane; Zeneca, Cheshire, England), nitrous oxide, and oxygen. Before the operation, the abdomen was shaved and disinfected with 70% alcohol. Via a 3-cm midline laparotomy, the cecum was dissected without damaging the vascularization and was filled backwards with feces. Thereafter, the cecum was ligated just distal to the ileocecal valve, with a 3.0 polyglactin suture (Vicryl; Ethicon Inc, Somerville, NJ), and at the antimesenterial site the cecum was punctured once with a 19-gauge needle. The abdominal wall was closed in 2 layers with a 3.0 polyglactin suture. Immediately after operation, rats received a single dose of gentamicin sulfate (Centrafarm Services BV, Etten-Leur, the Netherlands), 6 mg/kg, intramuscularly and buprenorphine hydrochloride (Temgesic, Reckitt and Colman Products Ltd, Amstelveen, the Netherlands), 0.1 mg/kg, subcutaneously. All animals were resuscitated with 10 mL of isotonic sodium chloride solution administered subcutaneously.

On day 1, animals were weighed, the abdomen was reopened under anesthesia, and peritoneal fluid samples were taken and collected in an envelope (BBL Port-A-Cul; Becton Dickinson, Cockeysville, Md) for microbiological examination. The abdominal cavity was rinsed with 10 mL of isotonic sodium chloride solution, and the cecum was resected. Before closure of the abdomen, animals were randomly assigned to receive 8 mL of isotonic sodium chloride solution (group 1, n=24), 4×4 cm HA-CMC bioresorbable membrane (Seprafilm; Genzyme Corporation, Cambridge, Mass) wrapped around the cecal resection site and 2×3 cm under the midline incision (group 2, n=24), or 8 mL of 0.4% HA solution (Sepracoat Genzyme Corporation) instilled throughout the whole abdominal cavity (group 3, n=24).

After 1 and 3 weeks, respectively, half of the animals in each group were weighed and killed using carbon dioxide asphyxiation. Adhesions were scored in a blinded manner by one of us (H.v.G.) according to the method of Zuhlke et al,15 whereby grade 0 means no adhesions and grade IV means firm extensive adhesions that are only dissectable with sharp instruments, with organ damage almost unavoidable. Sites of adhesions scored included the midline, the upper abdomen (liver), the parietal peritoneum, the omentum, and between the bowel loops.

If present, the size of abscesses was noted. An abscess was defined as a walled-off collection containing purulent material. Samples were taken from the abscesses for microbiological examination.

BACTERIAL CULTURES

Samples of peritoneal fluid and abscesses were cultured semiquantitatively in aerobic and anaerobic conditions. Columbia III agar with 5% sheep blood (Becton & Dickinson, Etten-Leur, the Netherlands), Levine-eosin-methylene blue agar (Oxoid, Haarlem, the Netherlands), and fastidious anaerobic agar (Tapley, Bury, England) with or without kanamycin, were used for cultures.

After 24 and 48 hours of incubation at 37°C, bacteria were identified using standard procedures.

STATISTICAL ANALYSIS

The statistical tests used are given within the text. Tests were performed on a personal computer using commercially available software (Stat Xact program; Statcon, Witzenhausen, Germany). Statistical significance was achieved at P<.05. All tests were 2-tailed.

Following CLP, all rats had symptoms of intra-abdominal sepsis. They demonstrated apathetic behavior, ocular exudates, piloerection, and diarrhea. These symptoms resolved within 2 days following the relaparotomy and removal of the necrotic, perforated cecum and peritoneal lavage. Weight loss was observed in the first week. After 1 week, rats regained weight. Differences in weight loss or weight gain were not statistically significant between the groups (P=.62, Mann-Whitney U test). Three (4%) of the 72 animals died. Survival in group 1 was 100% (24 of 24) compared with 96% (23 of 24) in group 2 and 92% (22 of 24) in group 3 (differences were not significant; P=.49, Fisher exact test). One rat died immediately after anesthesia, the other 2 rats, 1 and 4 days after CLP due to unknown causes. None of them died due to bleeding.

ADHESIONS

One week after CLP, significantly fewer rats in group 3 had grades III and IV adhesions (5/11 [45%]) than among group 1 rats (11/12 [92%]) (P=.03; Fisher exact test). There was no significant difference in the occurrence of grades III and IV adhesions between the rats in group 2 (9/12 [75%]) and group 1 rats. The most frequent sites of adhesions were the omentum, the lateral peritoneum, between the bowel loops, and the midline incision, in that order. Three weeks after CLP, 8 of 12 control rats and 6 of 11 rats in group 2 had grades III and IV adhesions, whereas in group 3 only 2 of 11 rats had grade III adhesions, and none had grade IV adhesions (P=.04; Fisher exact test).

The median severity of adhesions after 1 and 3 weeks is shown in Figure 1. The median severity of adhesions in group 3 rats was significantly lower at 1 week (II [range, I-IV]) and at 3 weeks (II [range, I-III]) compared with group 1 rats (1 week, IV [range, II-IV]; 3 weeks, IV [range, I-IV]) (P=.02 for both comparisons; Mann-Whitney U test). There was no difference in the median severity in group 2 rats after 1 week (IV [range II-IV]) or 3 weeks (III [range, I-III]) compared with group 1 rats.

Place holder to copy figure label and caption
Figure 1.

The median severity of adhesions 1 and 3 weeks after cecal ligation and puncture. Points represent adhesions in individual animals, with bars indicating median levels. Asterisk indicates P<.01, group 3 vs group 1. Group 1 rats received isotonic sodium chloride solution; group 2, a hyaluronic acid–carboxymethylcellulose bioresorbable membrane; and group 3, 0.4% hyaluronic acid solution.

Graphic Jump Location

Involvement of the omentum in adhesion formation was analyzed separately. At week 1, the median severity of omental adhesions was significantly lower in group 3 compared with group 1 animals (P=.02; Mann-Whitney U test). There was no difference in the appearance of omental adhesions between groups 1 and 2. At 3 weeks, no grade III or IV adhesions of the omentum were observed in group 3 rats, whereas in 33% of the group 1 rats and 33% of group 2 rats, grade III and/or IV adhesion of the omentum was found. The difference did not reach statistical significance (P=.06; Mann-Whitney U test).

ABSCESSES

Abscesses were predominantly located at the cecal resection site.

At day 7, 6 of 11 rats in group 3 had abscesses, whereas this was 10 of 12 rats in groups 1 and 2; in group 3, no abscesses larger than 2 cm were observed (P=.02; Fisher exact test).

At day 21, no abscesses were found in group 3, whereas 4 of 12 control rats and 5 of 11 rats in group 2 had an intra-abdominal abscess. This difference did not reach statistical significance (P=.09; Fisher exact test). An enterocutaneous fistula in conjunction with an abscess developed in 1 group 1 rat and 2 group 2 rats.

BACTERIAL CULTURES

Bacterial cultures taken at the day of cecal resection revealed a mixed aerobic and anaerobic flora of Proteus species, Escherichia coli, coliform gram-negative bacilli, anaerobic gram-negative rods, and Enterococcus and Staphylococcus species in concentrations of 107 to 109 colony-forming units/mL. A similar flora was found in cultures of abscesses present at day 7.

The predominant bacteria found in abscesses at day 21 were Proteus species and E coli. The concentrations tended to be lower than those at day 7.

We demonstrated that 0.4% HA-solution reduces intra-abdominal abscess and adhesion formation in a clinically relevant model of generalized bacterial peritonitis, without adversely affecting morbidity and mortality. Similar results at 1 and 3 weeks after the insult indicate that this effect is long lasting.

Several studies have demonstrated the ability of HA solutions to prevent the formation of postsurgical adhesions in a noninfectious environment.810,16,17 Hyaluronic acid solutions reduce serosal trauma by precoating the peritoneal surfaces, which become damaged during surgery. As a consequence, peritoneal surfaces do not adhere to each other with fibrinous deposits and may heal without adhesion formation.

Intra-abdominal infection is a potent stimulus of peritoneal injury, inevitably leading to adhesion formation.18 Hyaluronic acid solution was used 24 hours after initial peritoneal injury to mimic clinical treatment of intra-abdominal infection. At that point, established intra-abdominal infection was found with fibrinous exudates and pus in the whole abdomen. Hence, a precoating effect of HA solution does not explain the reduction of adhesions and abscesses, and other mechanisms of action may be involved.

Several lines of evidence suggest that HA decreases inflammation, interferes with fibrin formation, and accelerates the healing of peritoneal tissue (Figure 2).1921 Inflammation is considered pivotal in adhesion and abscess formation.18,2224 Hyaluronic acid has been reported to inhibit the release of protease from peritoneal leukocytes and of oxygen radicals from macrophages and to scavenge free oxygen radicals.19,25,26 Macrophages carry a hyaluronate-CD44 receptor on their membrane, which is known to modulate the cytokine response.27,28

Place holder to copy figure label and caption
Figure 2.

The pathway for adhesion and abscess formation in the cecal ligation and puncture model and possible sites of action of hyaluronic acid.

Graphic Jump Location

Intra-abdominal infection markedly impairs fibrinolysis reflected by high concentrations of plasminogen-activating inhibitors in peritoneal tissue and fluid.23,24,29 Abolishing plasminogen-activating inhibitor activity is important to facilitate fibrin degradation and subsequently to reduce adhesion and abscess formation.30 In another rat experiment, a significantly lower plasminogen-activating inhibitor activity in the abdominal fluid was found 6 hours after instillation of HA solution compared with isotonic sodium chloride solution. This finding supports the thesis of a beneficial effect of HA on fibrinolysis.20

Hyaluronic acid accelerates the healing of various tissues, including the peritoneum, without excessive growth of connective tissue.20,21 Stimulation of mesothelial recovery indeed seems to protect against adhesion formation.31,32 Such a mechanism of action seems unlikely, since HA solution has disappeared from the abdominal cavity within 24 hours after instillation, before peritoneal healing takes place.

The surplus of HA solution used in our study may have had a "floating" effect on intra-abdominal organs, which in turn prevented adhesions. Although the same amount of isotonic sodium chloride solution had no influence on adhesion and abscess formation, this does not necessarily refute such an effect, because there is a substantial difference in viscosity and ability to be absorbed between the solutions. Hyaluronic acid installed in the abdominal cavity is probably absorbed similarly to peritoneal fluid, by the diaphragmatic stomata, and degraded in the same manner as endogenous HA, mainly in lymph and blood, but also in liver.33 Isotonic sodium chloride solution is absorbed by the whole peritoneum. More appropriate solutions to compare with 0.4% HA are methylhydroxypropylcellulose gel and the liquid phase of the HA-CMC bioresorbable membrane. It has recently been shown that methylhydroxypropylcellulose gel did not reduce adhesion and abscess formation in rats with intra-abdominal infection.30 The HA-CMC bioresorbable membrane that turns into a liquid phase after 24 hours did not seem to reduce adhesion and abscess formation.

The lack of effect of the HA-CMC membrane in comparison with HA solution was surprising. The failure of HA-CMC membrane to reduce adhesions in an infectious environment is in accord with the findings of Medina and associates34 in a rabbit model of incomplete colon anastomosis and with additional findings in the rat CLP model (J. W. Burns, PhD, and H.v.G., oral communication, June 1998). It may be criticized that the HA-CMC bioresorbable membrane was only placed at operative sites, eg, the cecum resection site and under the midline incision, whereas peritoneal injury was generalized.18 This initially local therapy compared with HA solution may explain adhesion and abscess formation in other parts of the abdominal cavity. However, most abscesses were found at the sites where the HA-CMC membrane was located. The HA-CMC membrane may have acted as foreign material, which in the presence of bacteria increases the inflammatory reaction. The enterocutaneous fistula, seen in rats treated with the bioresorbable membrane, is a feature of increased inflammation, adhesion to the parietal peritoneum, and abscess formation. A compound of the membrane, CMC, has been reported to increase adhesion formation to injured parietal peritoneum in a rabbit model of peritoneal damage.35 Other studies, however, have shown the opposite.16,36

Early reduction of fibrinous adhesions in intra-abdominal infection results in bacteremia and subsequent mortality as described earlier.30 Increased mortality associated with HA solution was not found, probably as a result of antibiotic treatment. However, an antibiotic effect of HA solution was not ruled out. Recently, it has been suggested that HA confers resistance to phagocytosis of gram-positive organisms.37

Treatment of intra-abdominal infection with 0.4% HA solution prevents the formation of adhesions and abscesses. Further experiments are necessary to elucidate the mechanism(s) of action of HA solution in an infectious environment.

This work was supported by a grant from Genzyme BV, Naarden, the Netherlands.

Reprints: Harry van Goor, MD, PhD, Department of Surgery, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands (e-mail: h.vangoor@heel.azn.nl).

Herslag  ADiamond  MPDeCherney  AH Adhesiolysis. Clin Obstet Gynecol. 1991;34395- 402
Link to Article
DeCherney  AHdiZerega  GS Clinical problem of intraperitoneal postsurgical adhesion formation following general surgery and the use of adhesion prevention barriers. Surg Clin North Am. 1997;3671- 688
Link to Article
DiZerega  GS Biochemical events in peritoneal tissue repair. Eur J Surg. 1997;577(suppl)10- 16
Kowalczyk  CLDiamond  MP The management of adhesive disease. Treutner  KHSchumpelick  VedsPeritoneal Adhesions. New York, NY Springer-Verlag NY Inc1997;315- 324
Becker  JMDayton  MTFazio  VW  et al.  Prevention of postoperative abdominal adhesions by a sodium hyaluronate–based bioresorbable membrane: a prospective, randomized, double-blind multicenter study. J Am Coll Surg. 1996;183297- 306
Diamond  MP Reduction of de novo postsurgical adhesions by intraoperative precoating with Sepracoat (HAL-C) solution: a prospective randomized, blinded, placebo-controlled multicenter study. Fertil Steril. 1998;691067- 1074
Link to Article
Diamond  MP Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, randomized, multicenter clinical study. Fertil Steril. 1996;66904- 910
Burns  JWSkinner  KColt  J  et al.  Prevention of tissue injury and postoperative adhesions by precoating tissues with hyaluronic acid solutions. J Surg Res. 1995;59644- 652
Link to Article
Urman  BGomel  VJetha  N Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation in the rat model. Fertil Steril. 1991;56563- 567
Yaacobi  YIsrael  AAGoldberg  EP Prevention of postoperative abdominal adhesions by tissue precoating with polymer solutions. J Surg Res. 1993;55422- 426
Link to Article
Alponat  ALaksminarasappa  SRYavuz  NGoh  PMY Prevention of adhesions by Seprafilm, an absorbable adhesion barrier: an incisional hernia model in rats. Am Surg. 1997;63818- 819
Fraser  JRELaurent  TCLaurent  UBG Hyaluronan: its nature, distribution and turnover. J Intern Med. 1997;24223- 77
Link to Article
Toole  BPKnudson  CBKnudson  WGoldberg  RLChi-Rossi  GBiswas  C Hyaluronate-cell interactions in morphogenesis and tumorigenesis. Wolff  JRedMesenchymal-Epithelial Interactions in Neural Development. New York, NY Springer-Verlag NY Inc1987;267- 278
Wichterman  KABaue  AEChaundry  IH Sepsis and septic shock: a review of laboratory models and a proposal. J Surg Res. 1980;29189- 201
Link to Article
Zuhlke  HVLorenz  EMStraub  EMSavvas  V Pathophysiology and classification of adhesions. Langenbecks Arch Chir Suppl II Verh Dtsch Ges Chir. 1990;1009- 1016
Peck  LSQuigg  JMFossum  GTGoldberg  EP Evaluation of CMC and HA solutions for adhesiolysis. J Invest Surg. 1995;8337- 348
Link to Article
Seeger  JMKaelin  LDStaples  EM  et al.  Prevention of postoperative pericardial adhesions using tissue-protective solutions. J Surg Res. 1997;6863- 66
Link to Article
van Goor  Hde Graaf  JSGrond  J  et al.  Fibrinolytic activity in the abdominal cavity of rats with peritoneal peritonitis. Br J Surg. 1994;811046- 1049
Link to Article
Suzuki  YYamaguchi  T Effects of hyaluronic acid on the macrophage phagocytosis and active oxygen release. Agents Actions. 1993;3832- 37
Link to Article
Weigel  PHFuller  GMLeBoeuf  RD A model for the role of hyaluronic acid and fibrin in early events during the inflammatory response and wound healing. J Theor Biol. 1986;119219- 226
Link to Article
Adzick  NSLongacker  MT Scarless fetal healing: therapeutic implications. Ann Surg. 1992;2153- 7
Link to Article
Hau  TPayne  WDSimmons  RL Fibrinolytic activity of the peritoneum during experimental peritonitis. Surg Gynecol Obstet. 1987;148415- 418
van Goor  HBlom  VJJvan der Meer  JSluiter  WJBleichrodt  RP Coagulation and fibrinolytic responses in human peritoneal fluid and plasma to bacterial peritonitis. Br J Surg. 1996;831133- 1135
Link to Article
Whawell  SAThompson  EMFlemming  KAThompson  JN Plasminogen activator inhibitor-2 expression in inflamed appendix. Histopathology. 1995;2775- 78
Link to Article
Greenwald  RAMay  WW Effect of oxygen-derived free radicals on hyaluronic acid. Arthritis Rheum. 1980;223455- 461
Link to Article
Akatzuka  MYamamoto  YTobetto  K  et al.  Suppressive effect of hyaluronic acid on elastase release from rat peritoneal leukocytes. J Pharm Pharmacol. 1993;45110- 114
Link to Article
Noble  PWLake  FRHenson  PMRiches  DW Hyaluronate activation of CD44 induces insulin growth factor-1 expression by a tumor necrosis-alpha–dependent mechanism in murine macrophages. J Clin Invest. 1993;912368- 2377
Link to Article
McKee  CMPenno  MBCowman  M  et al.  Hyaluronan fragments induce chemokine gene expression in alveolar macrophages. J Clin Invest. 1996;982403- 2413
Link to Article
Vipond  MNWhawell  SAThompson  JNDudley  HA Peritoneal fibrinolytic activity and intra-abdominal adhesions. Lancet. 1990;3351120- 1122
Link to Article
van Goor  Hde Graaf  JSKooi  K  et al.  Effect of recombinant tissue plasminogen activator on intra-abdominal abscess formation in rats with generalized peritonitis. J Am Coll Surg. 1994;179407- 411
Buckman  RFBuckman  PDHufnagel  HVGervin  AS A physiologic basis for the adhesion-free healing of deperitonealized surfaces. J Surg Res. 1976;2167- 76
Link to Article
Gervin  ASPuckett  CLSilver  D Serosal hypofibrinolysis: a cause of postoperative adhesions. Am J Surg. 1973;12580- 88
Link to Article
Fraser  JRELaurent  TC Turnover and metabolism of hyaluronan. Evered  DWhelan  JedsThe Biology of Hyaluronan. Chichester, Sussex Whiley-Interscience1989;41- 53
Medina  MPaddock  HNConnoly  RJSchwaitzberg  SD Novel antiadhesion barrier does not prevent anastomotic healing in a rabbit model. J Invest Surg. 1995;8179- 186
Link to Article
Holmdahl  LEAl-Jabreen  MRisberg  BO Role of fibrinolysis in the formation of postoperative adhesions. Wound Repair Regen. 1994;2171- 176
Link to Article
Diamond  MPDeCherney  AHLinskey  CB  et al.  Adhesion re-formation in the rabbit uterine horn model, I: reduction with carboxymethylcellulose. Int J Fertil. 1988;33372- 375
Moses  EAWessels  MRZalcman  K  et al.  Relative contributions of hyaluronic acid capsule and M protein to virulence in a mucoid strain of the group A Streptococcus. Infect Immun. 1997;6564- 71

Figures

Place holder to copy figure label and caption
Figure 1.

The median severity of adhesions 1 and 3 weeks after cecal ligation and puncture. Points represent adhesions in individual animals, with bars indicating median levels. Asterisk indicates P<.01, group 3 vs group 1. Group 1 rats received isotonic sodium chloride solution; group 2, a hyaluronic acid–carboxymethylcellulose bioresorbable membrane; and group 3, 0.4% hyaluronic acid solution.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

The pathway for adhesion and abscess formation in the cecal ligation and puncture model and possible sites of action of hyaluronic acid.

Graphic Jump Location

Tables

References

Herslag  ADiamond  MPDeCherney  AH Adhesiolysis. Clin Obstet Gynecol. 1991;34395- 402
Link to Article
DeCherney  AHdiZerega  GS Clinical problem of intraperitoneal postsurgical adhesion formation following general surgery and the use of adhesion prevention barriers. Surg Clin North Am. 1997;3671- 688
Link to Article
DiZerega  GS Biochemical events in peritoneal tissue repair. Eur J Surg. 1997;577(suppl)10- 16
Kowalczyk  CLDiamond  MP The management of adhesive disease. Treutner  KHSchumpelick  VedsPeritoneal Adhesions. New York, NY Springer-Verlag NY Inc1997;315- 324
Becker  JMDayton  MTFazio  VW  et al.  Prevention of postoperative abdominal adhesions by a sodium hyaluronate–based bioresorbable membrane: a prospective, randomized, double-blind multicenter study. J Am Coll Surg. 1996;183297- 306
Diamond  MP Reduction of de novo postsurgical adhesions by intraoperative precoating with Sepracoat (HAL-C) solution: a prospective randomized, blinded, placebo-controlled multicenter study. Fertil Steril. 1998;691067- 1074
Link to Article
Diamond  MP Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, randomized, multicenter clinical study. Fertil Steril. 1996;66904- 910
Burns  JWSkinner  KColt  J  et al.  Prevention of tissue injury and postoperative adhesions by precoating tissues with hyaluronic acid solutions. J Surg Res. 1995;59644- 652
Link to Article
Urman  BGomel  VJetha  N Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation in the rat model. Fertil Steril. 1991;56563- 567
Yaacobi  YIsrael  AAGoldberg  EP Prevention of postoperative abdominal adhesions by tissue precoating with polymer solutions. J Surg Res. 1993;55422- 426
Link to Article
Alponat  ALaksminarasappa  SRYavuz  NGoh  PMY Prevention of adhesions by Seprafilm, an absorbable adhesion barrier: an incisional hernia model in rats. Am Surg. 1997;63818- 819
Fraser  JRELaurent  TCLaurent  UBG Hyaluronan: its nature, distribution and turnover. J Intern Med. 1997;24223- 77
Link to Article
Toole  BPKnudson  CBKnudson  WGoldberg  RLChi-Rossi  GBiswas  C Hyaluronate-cell interactions in morphogenesis and tumorigenesis. Wolff  JRedMesenchymal-Epithelial Interactions in Neural Development. New York, NY Springer-Verlag NY Inc1987;267- 278
Wichterman  KABaue  AEChaundry  IH Sepsis and septic shock: a review of laboratory models and a proposal. J Surg Res. 1980;29189- 201
Link to Article
Zuhlke  HVLorenz  EMStraub  EMSavvas  V Pathophysiology and classification of adhesions. Langenbecks Arch Chir Suppl II Verh Dtsch Ges Chir. 1990;1009- 1016
Peck  LSQuigg  JMFossum  GTGoldberg  EP Evaluation of CMC and HA solutions for adhesiolysis. J Invest Surg. 1995;8337- 348
Link to Article
Seeger  JMKaelin  LDStaples  EM  et al.  Prevention of postoperative pericardial adhesions using tissue-protective solutions. J Surg Res. 1997;6863- 66
Link to Article
van Goor  Hde Graaf  JSGrond  J  et al.  Fibrinolytic activity in the abdominal cavity of rats with peritoneal peritonitis. Br J Surg. 1994;811046- 1049
Link to Article
Suzuki  YYamaguchi  T Effects of hyaluronic acid on the macrophage phagocytosis and active oxygen release. Agents Actions. 1993;3832- 37
Link to Article
Weigel  PHFuller  GMLeBoeuf  RD A model for the role of hyaluronic acid and fibrin in early events during the inflammatory response and wound healing. J Theor Biol. 1986;119219- 226
Link to Article
Adzick  NSLongacker  MT Scarless fetal healing: therapeutic implications. Ann Surg. 1992;2153- 7
Link to Article
Hau  TPayne  WDSimmons  RL Fibrinolytic activity of the peritoneum during experimental peritonitis. Surg Gynecol Obstet. 1987;148415- 418
van Goor  HBlom  VJJvan der Meer  JSluiter  WJBleichrodt  RP Coagulation and fibrinolytic responses in human peritoneal fluid and plasma to bacterial peritonitis. Br J Surg. 1996;831133- 1135
Link to Article
Whawell  SAThompson  EMFlemming  KAThompson  JN Plasminogen activator inhibitor-2 expression in inflamed appendix. Histopathology. 1995;2775- 78
Link to Article
Greenwald  RAMay  WW Effect of oxygen-derived free radicals on hyaluronic acid. Arthritis Rheum. 1980;223455- 461
Link to Article
Akatzuka  MYamamoto  YTobetto  K  et al.  Suppressive effect of hyaluronic acid on elastase release from rat peritoneal leukocytes. J Pharm Pharmacol. 1993;45110- 114
Link to Article
Noble  PWLake  FRHenson  PMRiches  DW Hyaluronate activation of CD44 induces insulin growth factor-1 expression by a tumor necrosis-alpha–dependent mechanism in murine macrophages. J Clin Invest. 1993;912368- 2377
Link to Article
McKee  CMPenno  MBCowman  M  et al.  Hyaluronan fragments induce chemokine gene expression in alveolar macrophages. J Clin Invest. 1996;982403- 2413
Link to Article
Vipond  MNWhawell  SAThompson  JNDudley  HA Peritoneal fibrinolytic activity and intra-abdominal adhesions. Lancet. 1990;3351120- 1122
Link to Article
van Goor  Hde Graaf  JSKooi  K  et al.  Effect of recombinant tissue plasminogen activator on intra-abdominal abscess formation in rats with generalized peritonitis. J Am Coll Surg. 1994;179407- 411
Buckman  RFBuckman  PDHufnagel  HVGervin  AS A physiologic basis for the adhesion-free healing of deperitonealized surfaces. J Surg Res. 1976;2167- 76
Link to Article
Gervin  ASPuckett  CLSilver  D Serosal hypofibrinolysis: a cause of postoperative adhesions. Am J Surg. 1973;12580- 88
Link to Article
Fraser  JRELaurent  TC Turnover and metabolism of hyaluronan. Evered  DWhelan  JedsThe Biology of Hyaluronan. Chichester, Sussex Whiley-Interscience1989;41- 53
Medina  MPaddock  HNConnoly  RJSchwaitzberg  SD Novel antiadhesion barrier does not prevent anastomotic healing in a rabbit model. J Invest Surg. 1995;8179- 186
Link to Article
Holmdahl  LEAl-Jabreen  MRisberg  BO Role of fibrinolysis in the formation of postoperative adhesions. Wound Repair Regen. 1994;2171- 176
Link to Article
Diamond  MPDeCherney  AHLinskey  CB  et al.  Adhesion re-formation in the rabbit uterine horn model, I: reduction with carboxymethylcellulose. Int J Fertil. 1988;33372- 375
Moses  EAWessels  MRZalcman  K  et al.  Relative contributions of hyaluronic acid capsule and M protein to virulence in a mucoid strain of the group A Streptococcus. Infect Immun. 1997;6564- 71

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 41

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles