Low-Dose Propranolol Improves Cutaneous Wound Healing of Burn-Injured Rats

Abstract

Severe burns stimulate a hypermetabolic response that causes systemic complications. Propranolol, a nonselective beta-blocker, reduces this response and increases survival. Nevertheless, few studies have shown the effects of propranolol on healing of severe burns. This study evaluated macroscopically and microscopically the effects of the administration of propranolol (low-dose) on cutaneous wound healing of burn-injured rats. A third-degree burn (10 percent total body surface area) was created in female Wistar rats. Beginning 1 week after burning, animals were treated daily with propranolol (n = 5) (6 mg/kg) dissolved in water until they were euthanized, whereas rats in the control group (n = 5) received only water. Wound area was measured weekly and animals were euthanized 63 days after burning. Lesions and adjacent skin were fixed in formalin and embedded in paraffin. Sections were stained with hematoxylin and eosin, Sirius red, and toluidine blue, and immunostained for CD68, alpha-smooth muscle actin, and proliferating cell nuclear antigen. The wound area was greater in the control group than in the propranolol-treated group 21, 53, and 63 days after burning. All propranolol-treated animals presented more than 70 percent of reepithelialized wound area 63 days after burning, whereas control animals did not. The number of inflammatory cells and blood vessel density were greater in the control group than in the propranolol-treated group 63 days after burning. Cellular proliferation, myofibroblast density, collagen deposition, and active matrix metalloproteinase-2 levels were reduced in the control group compared with the propranolol-treated group 63 days after burning. Administration of (low-dose) propranolol improves healing of burned rats, reducing the local inflammatory response and improving subsequent healing phases.