Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine

Cole, Alexis R.; Perry, Dorothy A.; Raza, Ali; Nedder, Arthur; Pollack, Elizabeth; Regan, William; Bosch, Sarah J. van den; Polizzotti, Brian D.; Yang, Edward; Dávila, Daniel Lovera; Afacan, Onur; Warfield, Simon K.; Ou, Yangming; Sefton, Brenda A.; Lidov, Hart G.W.; Mayer, John E.; Kheir, John N.

doi:10.1016/j.jacbts.2018.11.006

Cited by 18 publications

(18 citation statements)

References 44 publications

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“…In swine, inhalation of 4% H 2 improved myocardial stunning, and reduced myocardial infarct size [104,176]. Similarly, inhalation of 2.4% H 2 gas during and for 24 h after cardiopulmonary bypass in swine significantly attenuated the neurological and renal injury induced by the ischemic assault [177].…”

Section: Potential Usage Of H2 Against Diseasesmentioning

confidence: 99%

A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress

et al. 2019

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Cardiovascular diseases are the most common causes of morbidity and mortality worldwide. Redox dysregulation and a dyshomeostasis of inflammation arise from, and result in, cellular aberrations and pathological conditions, which lead to cardiovascular diseases. Despite years of intensive research, there is still no safe and effective method for their prevention and treatment. Recently, molecular hydrogen has been investigated in preclinical and clinical studies on various diseases associated with oxidative and inflammatory stress such as radiation-induced heart disease, ischemia-reperfusion injury, myocardial and brain infarction, storage of the heart, heart transplantation, etc. Hydrogen is primarily administered via inhalation, drinking hydrogen-rich water, or injection of hydrogen-rich saline. It favorably modulates signal transduction and gene expression resulting in suppression of proinflammatory cytokines, excess ROS production, and in the activation of the Nrf2 antioxidant transcription factor. Although H2 appears to be an important biological molecule with anti-oxidant, anti-inflammatory, and anti-apoptotic effects, the exact mechanisms of action remain elusive. There is no reported clinical toxicity; however, some data suggests that H2 has a mild hormetic-like effect, which likely mediate some of its benefits. The mechanistic data, coupled with the pre-clinical and clinical studies, suggest that H2 may be useful for ROS/inflammation-induced cardiotoxicity and other conditions.

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Section: Potential Usage Of H2 Against Diseasesmentioning

confidence: 99%

A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress

et al. 2019

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“…(15,22) Further, the neuroprotective effects of perioperatively inhaled H 2 gas were reported using a large animal porcine model of cardiopulmonary bypass. (23) Recently, we also clinically translated the H 2 gas inhalation method for humans with PCAS. (24) Although reported in animal studies, the effect of H 2 on oxidative stress and inflammatory cytokines in human PCAS has not been studied.…”

mentioning

confidence: 99%

Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome

Tamura

Suzuki

Hayashida

et al. 2020

J. Clin. Biochem. Nutr.

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Oxidative stress plays a key role in the pathophysiology of post cardiac arrest syndrome. Molecular hydrogen reduces oxidative stress and exerts anti inflammatory effects in an animal model of cardiac arrest. However, its effect on human post cardiac arrest syndrome is unclear. We consecutively enrolled five comatose post cardiac arrest patients (three males; mean age, 65 ± 15 years; four cardiogenic, one septic cardiac arrest) and evaluated temporal changes in oxidative stress markers and cytokines with inhaled hydrogen. All patients were treated with target temperature management. Hydrogen gas inhalation (2% hydrogen with titrated oxygen) was initiated upon admission for 18 h. Blood hydrogen concentrations, plasma and urine oxidative stress markers (derivatives of reactive oxygen metabolites, biological antioxidant potential, 8 hydroxy 2' deoxyguanosine, N ε hexanoyl lysine, lipid hydroperoxide), and cytokines (interleukin 6 and tumor necrosis factor α) were measured before and 3, 9, 18, and 24 h after hydrogen gas inhalation. Arterial hydrogen concentration was measurable and it was equilibrated with inhaled hydrogen. Oxidative stress was reduced and cytokine levels were unchanged in cardiogenic patients, whereas oxidative stress was unchanged and cytokine levels were diminished in the septic patient. The effect of inhaled hydrogen on oxidative stress and cytokines in comatose post cardiac arrest patients remains indefinite because of methodological weaknesses.

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“…Administration of H 2 has been reported to produce protective and anti-inflammatory effects in multiple experimental injury settings, including cardiac ischemia, organ transplantation, sepsis, and 1-methl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neuronal loss (Ohta, 2014). Inhalation of 2% H 2 gas reduced infarction in rats after tMCAO (Ohsawa et al, 2007) and brain injury in swine after TGI (Cole et al, 2019). Besides radical scavenging, indirect mechanisms, e.g., activation of transcription factor Nrf2, have been suggested to contribute to protective effects (Kawamura et al, 2013).…”

Section: Blocking Excitotoxicity In the Ischemic Human Brainmentioning

confidence: 99%

“…Besides radical scavenging, indirect mechanisms, e.g., activation of transcription factor Nrf2, have been suggested to contribute to protective effects (Kawamura et al, 2013). A small randomized controlled trial of H 2 gas inhalation in stroke patients reported good safety and a hint of benefit (Cole et al, 2019). My colleagues at Stony Brook University have initiated a pilot therapeutic trial of H 2 in patients with acute ischemic stroke in combination with a 5 days course of minocycline (H2M treatment -ClinicalTrials.gov Identifier NCT03320018).…”

Section: Blocking Excitotoxicity In the Ischemic Human Brainmentioning

confidence: 99%

Excitotoxicity: Still Hammering the Ischemic Brain in 2020

2020

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Interest in excitotoxicity expanded following its implication in the pathogenesis of ischemic brain injury in the 1980s, but waned subsequent to the failure of N-methyl-D-aspartate (NMDA) antagonists in high profile clinical stroke trials. Nonetheless there has been steady progress in elucidating underlying mechanisms. This review will outline the historical path to current understandings of excitotoxicity in the ischemic brain, and suggest that this knowledge should be leveraged now to develop neuroprotective treatments for stroke.

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Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine

Abstract: Visual Abstract

Cited by 18 publications

References 44 publications

A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress

A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress

Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome

Excitotoxicity: Still Hammering the Ischemic Brain in 2020

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