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Peer-reviewedCC BYJPRAS open

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

  1. 1Istanbul Medeniyet University, Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Turkey
  2. 2Istanbul Aydın University, Department of Histology and Embryology, Faculty of Medicine, Turkey
  3. 3Experimental Animal Application and Research Center, Maltepe University, Turkey

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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BibTeX
@article{onal2026sodium,
  title = {{Sodium hydrogen sulfide enhances microcirculation and survival in random-pattern skin flaps: An experimental rat study}},
  author = {Mustafa Onal and Aysun Ozbay Onal and Mehmet Goktug Esmer and Oguz Kaan Tombul and Merdan Serin},
  journal = {JPRAS open},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jpra.2026.10.005},
  url = {https://europepmc.org/article/PMC/PMC13721927},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Sodium hydrogen sulfide enhances microcirculation and survival in random-pattern skin flaps: An experimental rat study
AU  - Mustafa Onal
AU  - Aysun Ozbay Onal
AU  - Mehmet Goktug Esmer
AU  - Oguz Kaan Tombul
AU  - Merdan Serin
PY  - 2026
DA  - 2026/10/22
JO  - JPRAS open
DO  - 10.1016/j.jpra.2026.10.005
UR  - https://europepmc.org/article/PMC/PMC13721927
AB  - Objectives: 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.  Methods: 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.  Results: 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).  Conclusions: 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.
SN  - 2352-5878
ER  -