DIABETES-IMPAIRED HEALING AND REDUCED WOUND NITRIC-OXIDE SYNTHESIS - A POSSIBLE PATHOPHYSIOLOGIC CORRELATION

Background. Nitric oxide (NO) is synthesized in wounds, but its role i n the healing process is not fully understood. The inhibition of NO pr oduction during wound healing is accompanied by decreased wound repara tive collagen deposition. To further define the role of NO in reparati ve collagen accumulation, we studied its production during diabetes-in duced wound healing impairment. Methods. Male Sprague-Dawley rats (290 to 310 gm) were rendered diabetic by intraperitoneal streptozotocin a dministration. Seven days after induction of diabetes (blood glucose g reater than 300 mg/dl), the mts underwent dorsal skin incision and sub cutaneous implantation of polyvinyl alcohol sponges. Beginning art the day of wounding, 21 diabetic animals were treated with 3 units/day in sulin via intraperitoneally implanted miniosmotic pumps. Ten days afte r injury, wound nd breaking strength was determined, and wound collage n accumulation and types I and III collagen gene expression were measu red in subcutaneously implanted polyvinyl alcohol sponges. NO synthesi s, as measured by nitrite/nitrate accumulation, was determined in woun d fluid and in supernatants of wound cell cultures. Results, Streptozo tocin-induced diabetes markedly impaired wound breaking strength and c ollagen deposition. A parallel decrease occurred in wound NO synthesis as reflected by decreased nitrite/nitrate concentration in wound flui d and in diminished ex vivo NO production by wound cells. Insulin trea tment partially but significantly improved wound mechanical strength ( p < 0.01) and collagen accumulation (p < 0.001). Decreased wound NO ac cumulation, and ex vivo NO production by wound cells were also partial ly restored by insulin treatment. Conclusions. Impaired diabetic wound healing is paralleled by decreased wound NO synthesis, supporting the hypothesis that NO plays a significant role in wound reparative colla gen accumulation.