Reduction of adhesion formation by intraperitoneal administration of various anti-inflammatory agents

Adhesion formation is a major source of postoperative morbidity and mortality. Therefore, the reduction of postoperative adhesion formation would be of clinical benefit. Various modalities have been shown to reduce adhesion formation, including fibrinolytic enzymes, nonsteroidal anti-inflammatory drugs, and barriers that reduce the apposition of sites of potential adhesion formation. In this report, the ability of three compounds with different mechanisms of action, all-trans-retinoic acid, quinacrine, and dipyridamole, to reduce the formation of intraperitoneal adhesions was examined in two rabbit models. In the sidewall model, the medicaments were administered via an Alzet miniosmotic pump for the entire postoperative interval. With all three agents, there was a reduction in the area of the sidewall injury that was involved in adhesions to the cecum and the bowel at both doses tested. In the same model, quinacrine also reduced the area of the sidewall injury that was involved in adhesions to the cecum and the bowel. At the higher concentrations of quinacrine, there was a deposition and walling off of the quinacrine at the site of delivery. In the double uterine horn model (DUH), the medicaments were administered via an Alzet miniosmotic pump to the area of injury for either 1, 2, 3, or 7 days. Administration of all three compounds for as little as 24 h after surgery significantly reduced the extent of adhesion formation. However, there was a further reduction in the amount of adhesion when the retinoic acid or dipyridamole was administered for 72 h postoperatively. However, when the quinacrine was administered for longer times postoperatively, the amount of adhesion reduction observed was less. These studies demonstrate that postoperative administration of retinoic acid, quinacrine, or dipyridamole to the site of injury reduced the formation of postoperative adhesions in two animal models.