The effectiveness of prolonged hypothermic preservation of isolated rat hearts using oxygen, medical nitrous oxide and carbon monoxide gas mixtures

Abstract

The possibility of using an oxygen-nitrous oxide mixture for prolonged hypothermic preservation of rat heart for 24 h was investigated. A comparative analysis of restoration of functional activity of hearts in the groups of 24-h preservation at +4 °C with different gases (O₂, N₂) and gas mixtures (CO + O₂, N₂O + O₂, N₂+O₂, N₂O + N₂) was carried out. It was shown that the presence of oxygen in the gas mixture was the key factor for heart preservation. No stable heart preservation was observed in oxygen-free mixtures. At the same time, preservation in pure oxygen showed a significantly lower level of cardiac recovery compared to preservation in gas mixtures O₂+CO (6.5 atm.) and O₂+N₂O (6.5 atm.). LVDP (left ventricular developed pressure) values were 30 ± 19 mmHg and 46 ± 9 mmHg, respectively, with no significant differences found. The decrease in LDVP after 24 h of storage was 26–40 % of the intact control. The results obtained indicate the presence of pronounced synergistic effects of both gases during 24-h heart preservation, which is confirmed by data of marker genes Nfe2l2, Nox1, Prdx1, Hif1a, Nos2, Slc2a4, Ucp-1, Jun, Casp3 expression analysis and myocardial infarction damage level data. The more frequent occurrence of arrhythmias was observed in the oxygen-nitrous oxide group compared with the CO group, and the mechanism of this phenomenon is unclear. Nevertheless, the already medically approved N₂O + O₂ gas mixture could serve as a balanced choice for future improvements, offering a shorter duration of cardiac preservation compared to the CO + O₂ mixture, while ensuring safety in its use.