S Canbaz, T Ege, M Ac?payam, E Duran
adhesion, aorta, hyaluronic acid, seprafilm, vascular surgery
S Canbaz, T Ege, M Ac?payam, E Duran. The Effect Of Hyaluronic Acid On Vascular Surgical Adhesions. The Internet Journal of Thoracic and Cardiovascular Surgery. 2004 Volume 7 Number 1.
Objective: Hyaluronic acid solutions and membranes have been shown experimentally to reduce adhesions following several surgical procedures. We purposed to investigate the efficacy of a bioresorbable membrane containing hyaluronic acid in preventing experimental vascular adhesions.
Methods: The abdominal aortas of twelve adult rabbits were explored, cleared from surrounding tissues and abraded following median laparotomy. In six animals, bioresorbable membrane (Seprafilm®) was wrapped around the abdominal aorta; no similar procedure was performed in the remaining six (control) animals. Two months later, the abdominal aortas were re-explored and periaortic adhesions were scored.
Results: Some clinically significant periaortic adhesions were observed at re-exploration in all the animals. The mean adhesion scores of the periaortic tissues were 2.83 ± 0.75 in animals treated with bioresorbable membrane and 3.16 ± 0.75 in the controls. The difference between the groups was not statistically significant (p>0.05).
Conclusion: The bioresorbable membrane did not significantly reduce the formation of adhesions after aortic vascular surgery. The use of hyaluronic acid for preventing adhesions was not effective, except for serosal membranes.
Repeated vascular surgical procedures are associated with increased technical difficulty and risk because of previously formed dense adhesions between the vessels and surrounding tissues. During dissection of the adhesive fibrous tissue around the vessels, more blood loss and other undesired events can occur. Surgical trauma initiates an inflammatory reaction, followed by increased vascular permeability and release of a fibrin-rich exudates 1. To diminish the formation of postoperative adhesions, investigators have used several procedures and agents to minimize surgical trauma and decrease the inflammatory reactions. Hyaluronic acid (HA) solutions and membranes have been shown experimentally to reduce adhesions following abdominal, orthopaedic and cardiac surgery, but not vascular surgery 1,2,3,4. Hyaluronic acid is a nonsulfated glycosaminoglycan component of the mammalian extracellular matrix, intra-articular synovial fluid and vitreous humor 5,6. It is responsible for lubricating moving tissues such as joints and muscles by binding water. We have investigated the efficacy of a bioresorbable membrane containing hyaluronic acid in preventing experimental vascular adhesions.
Material and Methods
Twelve adult rabbits (mean body mass 2.400 g) were used for the study. All animals received humane care in compliance with the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 86-23, revised 1985). The study protocol was approved by the local ethics committee of Trakya University.
Following standard skin preparation with povidone-iodine solution and shaving, median laparotomy was performed on all the animals, under general anaesthesia with 80 mg/kg ketamine hydrochloride (Ketalar®, Parke-Davis, Morris Plains, NJ) given intramuscularly. The peritoneum was opened at the midline and the part of the abdominal aorta between the renal arteries and the aortic bifurcation was explored and cleared from surrounding tissues. The anterior and lateral surfaces of the abdominal aorta were then strongly abraded with a sterile gauze. In six randomly selected animals, previously-prepared 1 x 4-cm strips of bioresorbable membrane composed of chemically modified sodium hyaluronate, carboxymethylcellulose and glycerol (Seprafilm®, Genzyme Corp., Cambridge, MA) was wrapped around the abdominal aorta in double layers. No additional procedure was performed in the other six animals. In all animals, the peritoneum was closed with continuous 4-0 polyglactin (Vickryl®, Ethicon, Cincinnati, OH) sutures. Finally, the laparotomy was closed in standard fashion.
All animals underwent re-laparotomy two months after the initial procedure. The abdominal aortas were re-explored and periaortic adhesions were scored blindly by two different surgeons using a 0-4 scale, which is generally used in experimental adhesion studies 2,7,8 (Table 1). Scores of 0 and 1 were noted in cases of no adhesion or minimal filmy adhesions, respectively. Scores of 2 or greater were considered clinically significant adhesions. Statistical analysis was performed using the Statistical Package for Social Sciences (Version-11, SPSS-Institute, Chicago, IL, USA). Variables were expressed as the mean ± standard deviation of the scores. The mean hyaluronic acid group and control group scores were compared using the Mann-Whitney U test, and p values less than 0.05 were considered significant.
The experiment was conceived, planned, and evaluated by the first author (S.C.) and was performed in the Experimental Laboratory at the Medical Faculty of Trakya University under the direction of Dr Duran. The first author, Dr Ege and Dr Acipayam performed the experiments, collected the data and performed the statistical analyses. All authors reviewed the results and discussed the conclusions.
Laparotomy was well tolerated by all the animals. There were no signs of infection, ileus, or vascular insufficiency. No deaths occurred in either group and no residual membrane was found in the HA group.
In all the animals, some clinically significant periaortic adhesions were observed at re-exploration. Adhesions were identical in all parts of the aorta by gross inspection. The adhesions in animals in both groups were usually scored grade 2 or 3. The mean adhesion scores from the periaortic tissue were 2.83 ± 0.75 in animals treated with the bioresorbable membrane and 3.16 ± 0.75 in the control animals. There was no statistically significant difference between the groups (study versus control, p>0.05).
The present study has demonstrated that use of a bioresorbable membrane did not reduce adhesion formation in aortic vascular surgery. The effect of covering the abdominal aorta with this membrane was not significant.
Adhesion formation is induced by mechanical injury, bleeding, ischemia, infection or foreign bodies. The most frequent mechanical injury is surgical intervention. Tissue injury occurs normally in all surgical procedures, by direct injury at sites of cutting, suturing, handling, dissecting or abrasive manipulations, or by indirect injury at adjacent sites in the surgical field from desiccation or thermal injury. It supposed that injury results in inflammation, fibrin accumulation and dense adhesions, especially when blood is present. Some preventative modalities have been used after surgical procedures, such as corticosteroids, non-steroidal antiinflamatory drugs, carboxymethylcellulose and synthetic barriers 1.
It is frequently reported in both clinical and laboratory studies that hyaluronic acid is beneficial for pericardial and peritoneal surgical adhesions. The preventative effect of hyaluronic acid solutions or membranes on postoperative adhesions has been shown in large scale studies. In all previous clinical applications, hyaluronic acid had been applied to the pericardial or peritoneal serosal membranes, or to intraocular or intra-articular sites 2,3,4,7,9,10,11. Positive results were obtained in most of these experimental and clinical studies. However, there has been no recent study in which this material was directly applied to the tissue. For this reason, reactions of tissues other than serosal membranes to hyaluronic acid have not been recognized.
Significant periaortic adhesions were observed in both groups. We think that severe abrasion of the entire aorta with a gauze aggravated the tendency to form adhesions in both groups. We do not normally confront such significant adhesions during surgical dissection. Detection of significant adhesions in both groups indicated that hyaluronic acid failed to prevent postoperative tissue adhesion, although the study involved only a small number of animals. The study has another limitation: the results were based on personal observation not objective criteria.
However, the findings could been supported by biochemical and histopathological studies. Also, the amount of newly synthesized collagen would provide a measure of adhesion formation if we assessed tissue hydroxyproline levels in periaortic tissue specimens 6. Perivascular adhesions are frequently observed in cases with PTFE or Dacron synthetic grafts. For this reason, similar studies which used synthetic grafts must be performed.
Hyaluronic acid membranes used as tissue coatings during vascular surgery do not inhibit the formation of undesired postoperative adhesions. Application of these bioresorbable barriers in the prevention of perivascular adhesions could not reduce the technical difficulty and risk of repeated vascular surgical procedures. This finding warrants further investigation.
We are grateful to Mr I. Uzun for help with surgical assistance and care of animals.
Dr. Suat CANBAZ, Trakya University, Medical Faculty, Department of Cardiovascular Surgery, 22030 Edirne, Turkey Phone: +90 284 235 76 56 Fax: +90 284 235 06 65 E.mail: firstname.lastname@example.org