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Hydrogen Sulfide Modulation of Microvascular Flow to Optimize Tissue Flap Viability
Neekita Jikaria
*1, Paul Armatowicz
2, Ji Ho Park
1, MohammadHossein Asgardoon
2, Mary Landmesser
2, Lacy Alexander
3, Urara Hasegawa
3, Dino Ravnic
11Department of Surgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA; 2Penn State College of Medicine, Hershey, PA; 3Penn State University, University Park, PA
Introduction: Flaps are central to reconstructive surgery. But they are subject to microvascular hypoperfusion and resultant tissue necrosis. Pharmacologic approaches, such as nitroglycerin, have been utilized in an attempt to improve flap perfusion with variable efficacy. Hydrogen sulfide (H
2S) is a gaseous transmitter that plays a role in blood flow regulation and may represent a therapeutic alternative. We hypothesize that intradermal injection of H
2S will result in a dose dependent increase in flap perfusion.
Methods: 10x2 cm random-pattern skin flaps were created on the rat dorsum. Flaps were marked into three zones - proximal, middle and distal. The base of the flap was intradermally injected with either 50, 100, 200 μM of H
2S or PBS (control) following elevation. Perfusion was assessed prior to injection and 1 hour as well as 1, 4 and 7 days following injection using laser doppler. On Day 7, skin was photographed for gross analyses and excised for histology. Hypoxia-inducible factor 1α (HIF-1α) expression, a surrogate for hypoperfusion, was measured by immunofluorescence. One-way ANOVA was performed; p<0.05 was considered significant.
Results: H
2S injection when compared to PBS control
(Fig. 1A-C) appeared to increase proximal flap perfusion with the 200 υM H
2S dose appearing the most potent. The increase in proximal flap microvascular flow appeared to correlate with diminished tissue necrosis. At day 7, approximately 49% (50 μM), 51% (100 μM), 27% (200 μM) and 54% (PBS) of the flaps demonstrated gross injury/necrosis
(Fig. 1D-G). Furthermore, the expression of HIF-1α across all flap zones was lowest in the 200 μM H
2S group when compared to lower doses of H
2S or the PBS control
(Fig. 1H-J).
Conclusion: H
2S injection at the time of flap elevation appears to modulate microvascular flow and resultant flap viability. It seems that higher doses of H
2S are more potent. However, additional studies are needed to further validate these observations. Nevertheless, H
2S appears to be an innovative alternative pharmacologic in challenging flap reconstructions.

Models adjusted for BMI, tissue expander size, and axillary irradiation. OR > 1 indicates higher odds with early exchange.
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