Hydrogen Sulfide Therapy Versus the Transplant Surgeon’s Inexorable Enemy

Cold ischemia-reperfusion injury (IRI) is an inevitable and unresolved problem that is considered the transplant surgeon’s enemy. It poses a great challenge in solid organ transplantation (SOT), and represents a major factor that increases acute tubular necrosis, decreases graft survival, and delays graft function. This complicates graft quality, post-transplant patient care and organ transplantation outcomes, and therefore undermines the success of SOT. This chapter presents recent advances in research regarding novel pharmacological strategies involving the use of different donor molecules of hydrogen sulfide (H2S), the third established member of the gasotransmitter family, against cold IRI in different experimental models of SOT (kidney, heart, lung, liver, pancreas and intestine). In addition, the author also discusses the molecular mechanisms underlying the effects of these H2S donor molecules in SOT, and suggestions for clinical translation. The findings in this chapter showed that storage of donor organs in H2S-supplemented preservation solution or administration of H2S to organ donor prior to organ procurement and to recipient at the start and during reperfusion is a novel, simple and cost-effective pharmacological approach to minimize cold IRI, limit post-transplant complications and improve transplantation outcomes. In conclusion, experimental evidence demonstrate that H2S donors can significantly mitigate cold IRI during SOT through inhibition of a complex cascade of interconnected cellular and molecular events involving microcirculatory disturbance and microvascular dysfunction, mitochondrial injury, inflammatory responses, cell damage and cell death, and other damaging molecular pathways while promoting protective pathways. Translating these promising findings from bench to bedside will lay the foundation for the use of H2S donor molecules in clinical SOT in the future.