Topical Mithramycin-A Modulates Submucosal Collagen Deposition after Esophageal Burn Injury in Rats

Abstract

Objective. To evaluate efficacy of a drug-eluting, dissolvable esophageal (DEDE) stent for the prevention of submucosal collagen deposition in a rat model of acute esophageal injury. Setting. University laboratory. Study Design. Interventional randomized controlled trial. Subjects and Methods. Forty two adult, male, age-matched Sprague Dawley rats were randomized to undergo either sham esophageal surgery, esophageal burn injury, or esophageal burn injury and placement of a DEDE stent. All animals underwent open gastrotomy under anesthesia. In group 1, a cautery device was inserted through the gastrotomy into the distal esophagus and removed without creating an injury. In group 2, the cautery was placed in the distal esophagus and a circumferential thermal burn injury was created. In group 3, an identical burn injury was created and a DEDE stent was placed at the site of injury and secured. On postoperative day 28, animals were sacrificed, and the distal esophagi were harvested and processed for histology. Submucosal collagen area was quantified histologically and compared across the 3 experimental groups. Results. After the investigators controlled for luminal circumference and multiple measurements, submucosal collagen area was increased in group 2 (burn) compared with group 1 (sham) ( P = .012). Submucosal collagen area was decreased in group 3 (DEDE stent) compared with group 2 ( P = .042). No statistically significant difference in submucosal collagen area was observed between animals in group 1 and group 3 ( P = .800). Conclusions.Topical application of mithramycin-A via a DEDE stent modulates collagen deposition after acute thermal injury in the rat esophagus.