Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

APPLICATION OF MOLECULAR HYDROGEN IN THE CARDIAC SURGERY ASSOCIATED ACUTE KIDNEY INJURY

J. Vlkovicova 1 , D. Snurikova 1 , N. Vrbjar 1 , B. Kura 1 , J. Slezak 1 , V. Hudec 2 , M. Ondrusek 2 , I. Gasparovic 2 , R. Sramaty 2 , J. Luptak 2 , M. Hulman 2 , B. Kalocayova 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, Bratislava, Slovakia Cardiac surgery-associated acute kidney injury (CS-AKI) is a major complication associated with increased morbidity and mortality. It is assumed that oxidative stress may be involved in the mechanisms that influence CS-AKI. To protect injured tissues and prevent further damage of organs during cardiac surgery, the administration of antioxidant reagents for scavenging ROS has been widely applied. Molecular hydrogen (H 2 ) is a novel agent that has been previously shown to scavenge ROS. We evaluated the potential effect of H 2 application on the kidney in an in vivo model of simulated heart transplantation. Prestice Black-Pied pigs were used for the simulation of heart transplantation by occluding venae cavae and pulmonary veins, cross-clamping of ascending aorta, and connection to extracorporeal circulation (ECC). Cold crystalloid cardioplegia was administered for 3 hours. After the time of cold arrest, the coronary arteries were rinsed with Plasmalyte solution and the aortic clamp was released. This was followed by rewarming the heart. After 60 minutes of reperfusion, the pigs were detached from ECC and the experiment was terminated. We used 2 experimental groups: T - pigs after transplantation, TH - pigs after transplantation treated with H 2 that was applied in gaseous form (3% H 2 ) during inhalation of anesthesia, as well as during oxygenation of blood in ECC. H 2 present in the arterial blood of pigs was measured using a needle-type Hydrogen Sensor. In this experiment, levels of creatinine, urea, and phosphorus in the plasma were detected. We focused also on the renal Na,K-ATPase activity, a key enzyme in maintaining intracellular sodium homeostasis. By methods of enzyme kinetics, depending on increasing concentrations of the energy substrate ATP and cofactor Na+ we have gained new insights into the functional properties of this enzyme in CS-AKI, as well as the potential effect of H 2 in these conditions. When activating the Na,K-ATPase with increasing concentrations of ATP, and/or cofactor Na+, its activity was lower in the whole concentration range in TH group vs. T. Evaluation of kinetic parameters revealed a significant decrease of the maximum velocity (Vmax) in TH group in comparison to T group (by 23,3% for ATP kinetic and by 19,7% for Na + kinetic) suggesting decreased sodium reabsorption. Unchanged Km values in both kinetics indicate that the cofactor affinity as well as the energy utilization by renal Na,K-ATPase remained unaffected after H 2 administration. This experiment showed that the administration of H 2 had a protective effect on the kidneys of pigs after CS-AKI, especially in terms of normalization of urea, phosphate, and creatinine to control levels before cardiac surgery.

Keywords: molecular hydrogen, kidney, Na,K-ATPase, simulated heart transplantation

Funding: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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