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Review
. 2021 Jan 14:7:586229.
doi: 10.3389/fmed.2020.586229. eCollection 2020.

Inhaled Gases as Therapies for Post-Cardiac Arrest Syndrome: A Narrative Review of Recent Developments

Kei Hayashida  1   2 , Santiago J Miyara  1   2   3   4   5 , Koichiro Shinozaki  1   2 , Ryosuke Takegawa  1   2 , Tai Yin  1   2 , Daniel M Rolston  2   6   7 , Rishabh C Choudhary  1   2 , Sara Guevara  6 , Ernesto P Molmenti  4   5   7 , Lance B Becker  1   2   7
Affiliations
Review

Inhaled Gases as Therapies for Post-Cardiac Arrest Syndrome: A Narrative Review of Recent Developments

Kei Hayashida et al. Front Med (Lausanne). .

Abstract

Despite recent advances in the management of post-cardiac arrest syndrome (PCAS), the survival rate, without neurologic sequelae after resuscitation, remains very low. Whole-body ischemia, followed by reperfusion after cardiac arrest (CA), contributes to PCAS, for which established pharmaceutical interventions are still lacking. It has been shown that a number of different processes can ultimately lead to neuronal injury and cell death in the pathology of PCAS, including vasoconstriction, protein modification, impaired mitochondrial respiration, cell death signaling, inflammation, and excessive oxidative stress. Recently, the pathophysiological effects of inhaled gases including nitric oxide (NO), molecular hydrogen (H2), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H2, and Xe for treating PCAS. Recent basic and clinical research has shown that these gases have cytoprotective effects against PCAS. Nevertheless, there are likely differences in the mechanisms by which these gases modulate reperfusion injury after CA. Further preclinical and clinical studies examining the combinations of standard post-CA care and inhaled gas treatment to prevent ischemia-reperfusion injury are warranted to improve outcomes in patients who are being failed by our current therapies.

Keywords: PCAS; cardiac arrest; cardiopulmonary resuscitation; ischemia-reperfusion injury; molecular hydrogen (H2); neuroprotection; nitric oxide; xenon.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Potential mechanisms by which inhaled nitric oxide (iNO) improves outcomes in post–cardiac arrest syndrome (PCAS). GC, guanylyl cyclase; GTP, guanosine triphosphate; cGMP, cyclic guanosine monophosphate; SNO, S-nitrosylation.
Figure 2
Figure 2
Outline of nitric oxide metabolism. (A) Cardiac arrest and resuscitation increase the activity of GSNOR. (B) Genetic or pharmacological inhibition of GSNOR increases the tissue levels of protein SNO and NO bioavailability. GC, guanylyl cyclase; cGMP, cyclic guanosine monophosphate; SH, cysteine thiols; GSNO, S-nitrosoglutathione; GSNOR, GSNO reductase; GSSG, glutathione disulfide; NH3, ammonia; NO, nitric oxide; SNO, S-nitrosylation.
Figure 3
Figure 3
Potential mechanisms by which hydrogen (H2) inhalation improves outcomes in post–cardiac arrest syndrome (PCAS). NADPH, nicotinamide adenine dinucleotide phosphate; •O2-, superoxide anion radicals; H2O2, hydrogen peroxide; •OH, hydroxyl radical; ONOO−, peroxynitrite; •NO, nitric oxide; SOD, superoxide dismutase; CAT, catalase.
Figure 4
Figure 4
Potential mechanisms by which xenon (Xe) inhalation improves outcomes in post–cardiac arrest syndrome (PCAS). NMDA; N-methyl-d-aspartate.
See this image and copyright information in PMC

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