Program and book of abstracts 1st conference

1 st Conference of European Academy for Molecular Hydrogen Research in Biomedicine “Hydrogen for Biomedicine“

INTRODUCTION: Although heart transplantation becomes a routine method of treatment, ischemic reperfusion damage to the heart after cold ischemic storage and subsequent reperfusion is the most critical part in restoring heart function as a pump. After the cold-induced ischemic asystole and cold storage, the initial reperfusion with warm oxygenated blood, increases reactive oxygen species (ROS) including highly toxic nitrosyl and the •OH radicals. Anesthetics and hyperoxia used during anesthesia, has also been shown to be involved in ROS formation and may represent an independent mortality risk factor. Moreover, often needed defibrillations cause cellular destruction in the ventricular myocardium and oxidative stress producing lipid peroxides and other oxidative stress products can complicate success of transplantation. MATERIALS AND METHODS: Two main pig groups were established: a group with simulated heart transplantation, and a group with heart transplantation with hydrogen rich air (4% of hydrogen, >40% of oxygen) in anesthesia administered during the whole experiment, Markers measured from plasma included the 3rd experimental group (control) and this is represented by blood samples collected before hydrogen administration. Markers of inflammation and tissue damage, markers of oxidative stress damage, protein expression levels of total connexin 43, activity of matrix metalloproteinases 2 and 9, and histochemistry of hypoxic/ischemic injury sensitive enzymes were analyzed and electron microscopy of cardiac tissue was evaluated. RESULTS: Hydrogen-treated swine exhibited significantly less severe ventricular fibrillation than controls, and improved histopathology findings. Addition of 4% inhaled hydrogen gas to inspiratory gases before the heart is taken from the donor, its cold storage, and after its implantation and subsequent warming up during its reperfusion, significantly decreased oxidative stress, markers of ischemia, inflammation, and peroxidation. CONCLUSION: Administration of hydrogen gas may mitigate the injury by selectively reducing the hydroxyl radicals, decrease lipid peroxidation, inflammation, decrease activity of native antioxidant enzymes, and improve resumption of pumping activity of 3 hours cold ischemia stored and implanted pig heart. With proper precautions, hydrogen may be administered safely through conventional ventilators, in ECC oxygenators andmay represent a complementary therapy that can be easily incorporated into current transplantation technique. Funding: This research was funded by grants from Slovak Research and Development Agency (APVV 0241-11, APVV-15-0376, APVV-19-0317), grant from the Slovak Academy of Sciences (VEGA 2/0092/22 and 2/0063/18), grant from European Union Structural funds (ITMS 26230120009), grant (2018/7838:1-26C0), and grant fromMinistry of Health of The Slovak Republic (2019-CEMSAV-1).

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