Medical Gases: A Novel Strategy for Attenuating Ischemia—Reperfusion Injury in Organ Transplantation?

Abstract

Ischemia reperfusion injury (IRI) is an inevitable clinical consequence in organ transplantation. It can lead to early graft nonfunction and contribute to acute and chronic graft rejection. Advanced molecular biology has revealed the highly complex nature of this phenomenon and few definitive therapies exist. This paper reviews factors involved in the pathophysiology of IRI and potential ways to attenuate it. In recent years, inhaled nitric oxide, carbon monoxide, and hydrogen sulfide have been increasingly explored as plausible novel medical gases that can attenuate IRI via multiple mechanisms, including microvascular vasorelaxation, reduced inflammation, and mitochondrial modulation. Here, we review recent advances in research utilizing inhaled nitric oxide, carbon monoxide, and hydrogen sulfide in animal and human studies of IRI and postulate on its future applications specific to solid organ transplantation.

Hydrogen sulfide chemical biology: Pathophysiological roles and detection

“…Likewise, the effect of peroxynitrite can be neutralized by H 2 S in brain endothelial cells during oxidative stress and in liver, heart and lung during I/R injury [11; 176], possibly through chemical mechanisms discussed above. Along this line, it has been suggested that a combination of NO and H 2 S therapy may be a better option for treatment of I/R injury after organ transplantation to effectively balance the impact of each molecule on ROS toxicity [177]. However, additional studies are needed to more comprehensively examine the effect of H 2 S on ROS formation and associated defense pathways, as it is likely that both are affected.…”

Ischemia-Reperfusion Injury in Stroke

“…Additionally, in an animal model of cerebral ischemia, the inhalation of hydrogen gas proved to serve as a neuroprotectant through its role in reducing oxidative stress under conditions where reperfusion injury was shown to lead to apoptotic cell death [92,93]. Other gases used therapeutically across tissue models of ischemia-reperfusion include nitric oxide, hydrogen sulfide and carbon monoxide [29,94,95,96]. …”

Ischemia–reperfusion injury

“…Preventive therapies might include ischemic conditioning involving short, nonlethal episodes of ischemia [1], several metabolic intervention options [2,3], therapeutic gas application [4], modulation of nucleotide signaling [5,6 && ] or microRNA application [7]. Targeting innate and adaptive immune activation by inhibiting Toll-like receptor (TLR) signaling [8], complement activation [9] or inducing the recruitment of regulatory T cells [10] might promote the therapeutic effects against IRI.…”