Sodium hydrogen sulfide enhances microcirculation and survival in random-pattern skin flaps: An experimental rat study

Random-pattern skin flaps remain vulnerable to distal ischemia and partial necrosis despite surgical refinements. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter with cytoprotective and proangiogenic properties. This study evaluated the effects of sodium hydrogen sulfide (NaHS) on flap viability, microvascular perfusion, and histological outcomes in a rat dorsal random-pattern skin flap model.

Twenty-one male Sprague-Dawley rats were randomized into control, sham, and NaHS groups (n = 7 each). NaHS (200 µg/kg/day) was administered intraperitoneally for 15 days prior to flap elevation. A 9 × 3 cm caudally based dorsal flap was created using the McFarlane model. On postoperative day 7, perfusion was objectively assessed using indocyanine green fluorescence angiography. Inflammation, re-epithelialization, vascularization, and collagen organization were assessed using semi-quantitative scoring, whereas the apoptotic index was determined quantitatively based on TUNEL-positive cell counts.

NaHS significantly increased viable flap area and reduced distal necrosis compared with control and sham groups. Fluorescence imaging demonstrated enhanced distal perfusion and a denser microvascular network in the NaHS group. Histologically, NaHS promoted complete re-epithelialization, organized collagen structure, and markedly increased vascularization (p < 0.01), while significantly decreasing inflammation and apoptosis (p < 0.001).

Sodium hydrogen sulfide improved random-pattern skin flap viability by enhancing microvascular perfusion and attenuating ischemia-induced inflammation and apoptosis. These findings suggest that H₂S donors may represent a potential pharmacologic approach to improve ischemic flap survival in reconstructive surgery.