Abstract 232: Delayed Inhaled Carbon Monoxide Improves Diabetic Wound Healing
Background Nonhealing wounds are a major source of morbidity in diabetic patients. These wounds persist due to a persistent inflammatory state and poor resistance to infection. Carbon monoxide (CO) is a naturally occurring byproduct of heme degradation that possesses both anti-inflammatory and pro-angiogenic properties. Thus, we hypothesize that inhaled CO will improve cutaneous wound healing in the setting of diabetes.
Methods Excisional wounds (1.5 x 1.5 cm) were created in db/db mice. The mice were treated with inhaled CO at 250 ppm for 1 hr daily starting immediately after wounding or starting on day 8. Control mice remained in room air. Wounds were measured by planimetry. At day 20, mice were sacrificed and the residual wounds were collected for immunohistochemistry.
Results Inhaled CO initiated immediately after wounding did not improve healing with less granulation tissue formation. However, when CO treatment was delayed until day 8, wound healing was greatly improved compared to controls (residual wounds measuring 27.2 ± 5.3% of original vs 52.2 ± 5.8% on day 20; N=10-14 per group; p < 0.005). CD31 staining showed increased angiogenesis in the delayed CO treated animals (Figure 1).
Conclusions Early inhaled CO was detrimental to wound healing while delaying CO treatment accelerated healing, potentially through increased angiogenesis. Early administration of CO likely inhibits inflammatory responses and cellular recruitment essential for wound healing. Delayed CO may inhibit the persistent inflammation that leads to chronic non-healing wounds, allowing for improved wound healing in diabetes.
- © 2013 by American Heart Association, Inc.