Preconditioning with Moderate Hypoxia Increases Tolerance to Subsequent Severe Hypoxia in Rats with LPS-Induced Endotoxemia

Hyperproduction of mediators of LPS-induced inflammatory process(endotoxicosis, sepsis) initiates the development of acute respiratoryfailure (ARF), impaired gas exchange, progressive hypoxemia and hypercapnia,hypotension, respiratory arrest and death. Severe sepsis associatedwith hypoxemia remains the main cause of death, and therefore thedevelopment of methods to increase resistance to acute hypoxia inseptic patients is an urgent task. The aim of the work was to studythe effectiveness of preconditioning with short-term intermittentmoderate hypoxia to increase tolerance to subsequent severe hypoxiain rats with LPS-induced endotoxicosis. The experiments were carriedout on anesthetized and traheostomized male Wistar rats. Endotoxicosiswas modeled by administration of a lipopolysaccharide solution (Escherichia coli) in an amount of7 mg/kg. To assess resistance to severe hypoxia, the rebreathingmethod of (RM) with a gradual decrease in oxygen in the rebreatherfrom 21% to the onset of apnea was used. Hypoxic preconditioning(hypoxic training, HT) was also created by the method of RM in themode of 3 cycles: reduction of the oxygen fraction in the rebreatherto 12%—3 min, 5 min—normoxia. 3 groups of animals were studied:I-control-NaCl, II-LPS, III-LPS+HT. The following parameters wererecorded: external respiration, mean arterial pressure (MAP), saturation (SpO₂),fraction of inhaled O₂, time of onset ofapnea, the amount of spontaneous respiratory recovery (autoresuscitation)in the posthypoxic period. It was shown that the administrationof LPS under normoxic conditions was accompanied by hyperventilation,hypoxemia and hypotension. The maximum deterioration in resistanceto severe hypoxia was observed in rats with LPS, which was manifestedby a decrease in MAP, SpO₂ and a decreasein the possibility of autoresuscitation after hypoxic apnea. The effectof HT prevented a decrease in arterial pressure, SpO₂ increasedby 1.4 times, survival increased by 2 times, which is comparableto the level of normoxia before the introduction of LPS. It is assumedthat the effectiveness of hypoxic preconditioning is due to theinhibition of the inflammatory response.