Exploring Iodide and Hydrogen Sulfide as ROS Scavengers to Delay Acute Rejection in MHC-Defined Vascularized...

Area of Science:

• Transplantation immunology
• Vascularized composite allografts (VCAs)
• Ischemia-reperfusion injury

Background:

• Vascularized composite allografts (VCAs) are susceptible to ischemia-reperfusion (I/R) injury due to limited availability and delayed reperfusion.
• Oxidative stress and immune reactions during reperfusion exacerbate I/R injuries and contribute to graft rejection.
• Scavenger molecules offer a potential strategy to mitigate I/R injuries and subsequent immune responses in VCA transplantation.

Purpose of the Study:

• To evaluate the efficacy of two scavenger molecules, sodium iodide (NaI) and hydrogen sulfide (H2S), in mitigating ischemia-reperfusion injuries in a myocutaneous flap VCA model.
• To assess the impact of these scavengers on graft survival in both matched and mismatched transplantation scenarios without immunosuppression.

Main Methods:

• A myocutaneous flap VCA model was established in 18 MHC-defined miniature swine, divided into MATCH (minor antigen mismatch) and MISMATCH (full mismatch) groups.
• Grafts were pretreated with saline, NaI, or H2S, stored for 3 hours at 4°C, and then transplanted.
• Flap survival was monitored until clinical rejection, and rhabdomyolysis markers were assessed.

Main Results:

• In the MATCH group, flap survival was not significantly different between saline and H2S treatments (p=0.483) but was significantly reduced with NaI treatment (p=0.007).
• Similarly, in the MISMATCH group, survival was similar for saline and H2S (p=0.483) but decreased with NaI (p=0.007).
• Rhabdomyolysis markers were lower, though not significantly, in H2S and NaI subgroups compared to saline in both groups.

Conclusions:

• Hydrogen sulfide (H2S) demonstrates potential as a protective agent against ischemia-reperfusion injury in vascularized composite allografts (VCAs).
• Sodium iodide (NaI) appears detrimental to VCA graft survival, irrespective of the degree of Major histocompatibility complex (MHC) mismatch.
• Antioxidant-based strategies, particularly using H2S, warrant further investigation for improving VCA transplantation outcomes by mitigating rejection.