Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

BENEFICIAL EFFECT OF HYDROGEN GAS ON THE HEART THAT HAS UNDERGONE SIMULATED HEART TRANSPLANTATION. POSSIBLE NEW THERAPEUTIC AGENT? B. Kura 1 , B. Kalocayova 1 , B. Szeiffova Bacova 1 , M. Sykora 1 , N. Tribulova 1 , V. Hudec 2 , M. Ondrusek 2 , I. Gasparovic 2 , R. Sramaty 2 , M. Hulman 2 , J. Slezak 1 1 Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia; 2 Department of Cardiac Surgery, Faculty of Medicine, National Institute of Cardiovascular Diseases, Comenius University, Bratislava, Slovakia Background: Acute or chronic heart failure patients often have to undergo a heart replacement from a donor to save their lives. The surgeons must connect the patient to the extracorporeal circulation (ECC), stop the heart activity, and resume the heart activity after replacing it with a new heart. During this procedure, ischemia/reperfusion and the overproduction of reactive oxygen species occur despite the progress in heart preservation and improved surgical techniques. Molecular hydrogen (H 2 ) is a novel substance with significant antioxidant and anti-inflammation capacity used in many experimental models and clinical trials on various diseases. Methods: The main goal of this study was to examine the effect of molecular hydrogen on the heart allograft of pigs (female Přeštice black -mottled pig, 4 months old). The simulation of heart transplantation consisted of occluding venae cavae and pulmonary veins, cross-clamping of ascending aorta, and connection to ECC. Cold crystalloid cardioplegia (Custadiol) was administered for three hours. After the time of cold arrest, the coronary arteries were flushed with Plasmalyte solution and the aortic clamp was released. This was followed by rewarming the heart. After 60 minutes of reperfusion, the pig was detached from ECC and the experiment was terminated. H 2 was administered in gas form during oxygenation of blood and anesthesia (50% O 2 , 3% H 2 ). In this study, levels and activities of oxidative disbalance markers, levels of inflammation, and expression of microRNAs (miRNAs) were measured from blood plasma and left ventricle tissues colorimetrically, by Western blot, and by qPCR methods. Results: According to the results from this study, simulated heart transplantation significantly increases activities and amounts of endogenic antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and molecules of oxidative stress damage (uric acid, malondialdehyde, lactate dehydrogenase, 8-hydroxy-2-deoxyguanosine). Opposite of this, the application of H 2 gas significantly modulates all selected parameters almost up to control pigs. The positive effect of H 2 gas was observed in markers of inflammation damage like tumor necrosis factor alpha and nuclear factor-kappa B. The transplantation causes significant changes also in the levels of selected miRNAs where the H 2 treatment had normalization effects either. Conclusion: We can conclude that the addition of H 2 during heart transplantation could be a new potential therapeutic strategy for minimalizing the negative effect of schemia/reperfusion injury, leading to better recovery of patients.

Keywords: heart transplantation, inflammation, miRNA, molecular hydrogen, oxidative stress

Funding: Grants: APVV-15-0376, APVV-19-0317), European Union Structural funds (ITMS 26230120009), 2018/7838:1-26C0, Ministry of Health of The Slovak Republic (2019/4-CEMSAV 1), and Slovak Academy of Sciences grants (VEGA 2/0063/18, 2/0092/22, and 2/0148/22).

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