Propranolol impairs the closure of pressure ulcers in mice

Abstract

Aims: β-Adrenoceptors modulate acute wound healing; however, few studies have shown the effects of β-adrenoceptor blockade on chronic wounds. Therefore, this study investigated the effect of β1-/β2-adrenoceptor blockade in wound healing of pressure ulcers.

Main methods: Male mice were daily treated with propranolol (β1-/β2-adrenoceptor antagonist) until euthanasia. One day after the beginning of treatment, two cycles of ischemia-reperfusion by external application of two magnetic plates were performed in skin to induce pressure ulcer formation.

Key findings: Propranolol administration reduced keratinocyte migration, transforming growth factor-β protein expression, re-epithelialization, and necrotic tissue loss. Neutrophil number and neutrophil elastase protein expression were increased in propranolol-treated group when compared with control group. Propranolol administration delayed macrophage mobilization and metalloproteinase-12 protein expression and reduced monocyte chemoattractant protein-1 protein expression. Myofibroblastic differentiation, angiogenesis, and wound closure were delayed in the propranolol-treated animals. Propranolol administration increased neo-epidermis thickness, reduced collagen deposition, and enhanced tenascin-C expression resulting in the formation of an immature and disorganized collagenous scar.

Significance: β1-/β2-Adrenoceptor blockade delays wound healing of ischemia-reperfusion skin injury through the impairment of the re-epithelialization and necrotic tissue loss which compromise wound inflammation, dermal reconstruction, and scar formation.

Keywords: Diaminobenzidine (PubChem CID: 7071); Formalin (PubChem CID: 712); Hematoxylin (PubChem CID: 442514); Hydrochloric acid (PubChem CID: 313); Ischemia–reperfusion injury; Ketamine (PubChem CID: 3821); Methanol (PubChem CID: 887); Polyacrylamide (PubChem CID: 6579); Pressure ulcer; Propranolol hydrochloride (PubChem CID: 62882); Skin; Sodium dodecylsulfate (PubChem CID: 3423265); Sodium hydroxide (PubChem CID: 14798); Sulfuric acid (PubChem CID: 1118); Wound healing; Xylazine (PubChem CID: 5707); Xylenol orange (PubChem CID: 16220156); β-Adrenoceptors.