PREVENTION OF POSTOPERATIVE PERICARDIAL ADHESIONS WITH A HYALURONIC-ACID COATING SOLUTION - EXPERIMENTAL SAFETY AND EFFICACY STUDIES

Postoperative pericardial adhesions complicate reoperative cardiac procedures. Topical application of solutions containing hyaluronic acid have been shown to reduce adhesions after abdominal and orthopedic surgery. The mechanism by which hyaluronic acid solutions prevent adhesion formation is unknown but may be due to a cytoprotective effect on mesothelial surfaces, which would Limit intraoperative injury. In this study, we tested the efficacy and safety of hyaluronic acid coating solutions for the prevention of postoperative intrapericardial adhesion formation. Eighteen mongrel dogs underwent median sternotomy and pericardiotomy followed by a standardized 2-hour protocol of forced warm air desiccation and abrasion of the pericardial and epicardial surfaces. Group 1 (n = 6) served as untreated control animals. Group 2 (n = 6) received topical administration of 0.4% hyaluronic acid in phosphate-buffered saline solution at the time of pericardiotomy, at 20-minute intervals during the desiccation/abrasion protocol, and at pericardial closure. The total test dose was less than 1% of the circulating blood volume. Group 3 (n = 6) served as a vehicle control, receiving phosphate-buffered saline solution as a topical agent in a fashion identical to that used in group 2. At resternotomy 8 weeks after the initial operation, the intrapericardial adhesions were graded on a 0 to 4 severity scale at seven different areas covering the ventricular, atrial, and great vessel surfaces. In both the untreated control (group 1, mean score 3.2 +/- 0.4) and vehicle control (group 3, mean score 3.3 +/- 0.2) animals, dense adhesions were encountered. In contrast, animals treated with the hyaluronic acid solution (group 2, mean score 0.8 +/- 0.3) characteristically had no adhesions or filmy, transparent adhesions graded significantly less severe than either the untreated control (group 2 versus group 1, p < 0.001) or vehicle control (group 2 versus group 3, p < 0.001) animals. In separate experiments, six baboons were infused with 0.4% hyaluronic acid in phosphate-buffered saline solution in volumes equivalent to 2.5%, 5%, and 10% of the measured circulating blood volume. The 2.5% and 5% infusions had no effect on the parameters measured; infusion of the 10% volume produced transient hemodynamic, coagulation, and gas exchange abnormalities. Hyaluronic acid solutions are efficacious in the prevention of pericardial adhesions in this model, and they appear safe in doses five times the amount needed to prevent adhesions. Further studies investigating the mechanism by which these solutions prevent adhesions, their optimal dose and method of application, and documentation of their safe use in humans are warranted.