Molecular hydrogen potentiates beneficial anti-infarct effect of hypoxic postconditioning in isolated rat hearts: a novel cardioprotective intervention

Abstract

Keyword:Ischemia-reperfusion injury, ischemic postconditioning, hypoxic postconditioning, molecular hydrogen, antioxidants https://mc06.manuscriptcentral.com/cjpp-pubs AbstractGeneration of free radicals through incomplete reduction of oxygen during ischemia/ reperfusion is well-described. On the other hand, molecular hydrogen (H 2 ) reduces oxidative stress due to its ability to react with strong oxidants and easily penetrate cells by diffusion, without disturbing metabolic redox reactions. This study was designed to explore cardioprotective potential of hypoxic postconditioning (HpostC) against ischemia/reperfusion (30-min global I/120-min R) in isolated rat hearts using oxygen-free Krebs-Henseleit buffer (KHB). Furthermore, the possibility to potentiate the effect of HpostC by H 2 using oxygenfree KHB saturated with H 2 (H2+HpostC) was tested. HPostC was induced by 4 cycles of 1-min perfusion with oxygen-free KHB intercepted by 1-min perfusion with normal KHB, at the onset of reperfusion. H 2 +HPostC was applied in a similar manner using H 2 enriched oxygen-free KHB. Cardioprotective effects were evaluated on the basis of infarct size (IS, in % of area at risk, AR) reduction, post-I/R recovery of heart function and occurrence of reperfusion arrhythmias. HPostC significantly reduced IS/AR compared to non-conditioned controls. H 2 present in KHB during HPostC further decreased IS/AR compared to the effect of HPostC, attenuated severe arrhythmias, and significantly restored heart function (vs. controls). Cardioprotection by hypoxic postconditioning can be augmented by molecular hydrogen infusion.

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

“…For example, the lipid peroxidation product, 4-hydroxy-2-nonenal, in cardiomyocytes mediates the Nrf2-dependent upregulation of uncoupling protein 3 (UCP3) [135]. This effect might be particularly important in mediating the protective effects of pre-conditioning, which induces mild oxidative stress and subsequent upregulation of various proteins including cytokines, heat-shock proteins, NF-κB, and Nrf2 [8,136,137,138]. This process of a stress being mildly toxic followed by increased cellular protection is referred to as hormesis [139].…”

Effect of molecular hydrogen on coenzyme Q in plasma, myocardial tissue and mitochondria of rats

“…The role of H 2 was found in hypoxic postconditioning, radiation-induced heart injury, mediastinal irradiation in rats, acute cardiac injury, radiation-induced heart disease and changes in microRNA-1, -15b and -21 levels in irradiated rat hearts. [17][18][19][20][21][22] Beneficial effect of H 2 in clinical medicine was found in various diseases, such as cardiovascular diseases, type 2 diabetes, dyslipidemia, obesity and metabolic syndrome, in vascular health. [23][24][25] Molecular hydrogen water improved the progression of Parkinson´s disease.…”

“…27 H 2 protects antioxidant enzyme -superoxide dismutase. 22 Molecular hydrogen effect on other antioxidant -coenzyme Q (CoQ) -is not known up to now.…”

The transfer of hydrogen from inert gas to therapeutic gas

“… 52 A research in 2017 demonstrated that compared with hypoxic postconditioning (HpostC) alone, the combined cardioprotective effect of hydrogen and HpostC could be better brought into play, which showed up as the reduction of infarct size, the attenuation of severe arrhythmias, and the improvement of heart function. 53 Another study showed that hydrogen inhalation during percutaneous coronary intervention was feasible and could also promote left ventricular reverse remodeling at 6 months after ST-elevated myocardial infarction, which was the first clinical research of hydrogen on percutaneous coronary intervention surgery for myocardial infarction. 54 However, the limited subjects could not determine the therapeutic effect of this method for sure, which need to be further confirmed.…”