{"title":"Preconditioning with Moderate Hypoxia Increases Tolerance to Subsequent Severe Hypoxia in Rats with LPS-Induced Endotoxemia","authors":"Zh. A. Donina","doi":"10.1134/s002209302403027x","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Hyperproduction of mediators of LPS-induced inflammatory process\n(endotoxicosis, sepsis) initiates the development of acute respiratory\nfailure (ARF), impaired gas exchange, progressive hypoxemia and hypercapnia,\nhypotension, respiratory arrest and death. Severe sepsis associated\nwith hypoxemia remains the main cause of death, and therefore the\ndevelopment of methods to increase resistance to acute hypoxia in\nseptic patients is an urgent task. The aim of the work was to study\nthe effectiveness of preconditioning with short-term intermittent\nmoderate hypoxia to increase tolerance to subsequent severe hypoxia\nin rats with LPS-induced endotoxicosis. The experiments were carried\nout on anesthetized and traheostomized male Wistar rats. Endotoxicosis\nwas modeled by administration of a lipopolysaccharide solution (<i>Escherichia coli</i>) in an amount of\n7 mg/kg. To assess resistance to severe hypoxia, the rebreathing\nmethod of (RM) with a gradual decrease in oxygen in the rebreather\nfrom 21% to the onset of apnea was used. Hypoxic preconditioning\n(hypoxic training, HT) was also created by the method of RM in the\nmode of 3 cycles: reduction of the oxygen fraction in the rebreather\nto 12%—3 min, 5 min—normoxia. 3 groups of animals were studied:\nI-control-NaCl, II-LPS, III-LPS+HT. The following parameters were\nrecorded: external respiration, mean arterial pressure (MAP), saturation (SpO<sub>2</sub>),\nfraction of inhaled O<sub>2</sub>, time of onset of\napnea, the amount of spontaneous respiratory recovery (autoresuscitation)\nin the posthypoxic period. It was shown that the administration\nof LPS under normoxic conditions was accompanied by hyperventilation,\nhypoxemia and hypotension. The maximum deterioration in resistance\nto severe hypoxia was observed in rats with LPS, which was manifested\nby a decrease in MAP, SpO<sub>2</sub> and a decrease\nin the possibility of autoresuscitation after hypoxic apnea. The effect\nof HT prevented a decrease in arterial pressure, SpO<sub>2</sub> increased\nby 1.4 times, survival increased by 2 times, which is comparable\nto the level of normoxia before the introduction of LPS. It is assumed\nthat the effectiveness of hypoxic preconditioning is due to the\ninhibition of the inflammatory response.</p>","PeriodicalId":15805,"journal":{"name":"Journal of Evolutionary Biochemistry and Physiology","volume":"355 1","pages":""},"PeriodicalIF":0.6000,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Evolutionary Biochemistry and Physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1134/s002209302403027x","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Hyperproduction of mediators of LPS-induced inflammatory process
(endotoxicosis, sepsis) initiates the development of acute respiratory
failure (ARF), impaired gas exchange, progressive hypoxemia and hypercapnia,
hypotension, respiratory arrest and death. Severe sepsis associated
with hypoxemia remains the main cause of death, and therefore the
development of methods to increase resistance to acute hypoxia in
septic patients is an urgent task. The aim of the work was to study
the effectiveness of preconditioning with short-term intermittent
moderate hypoxia to increase tolerance to subsequent severe hypoxia
in rats with LPS-induced endotoxicosis. The experiments were carried
out on anesthetized and traheostomized male Wistar rats. Endotoxicosis
was modeled by administration of a lipopolysaccharide solution (Escherichia coli) in an amount of
7 mg/kg. To assess resistance to severe hypoxia, the rebreathing
method of (RM) with a gradual decrease in oxygen in the rebreather
from 21% to the onset of apnea was used. Hypoxic preconditioning
(hypoxic training, HT) was also created by the method of RM in the
mode of 3 cycles: reduction of the oxygen fraction in the rebreather
to 12%—3 min, 5 min—normoxia. 3 groups of animals were studied:
I-control-NaCl, II-LPS, III-LPS+HT. The following parameters were
recorded: external respiration, mean arterial pressure (MAP), saturation (SpO2),
fraction of inhaled O2, time of onset of
apnea, the amount of spontaneous respiratory recovery (autoresuscitation)
in the posthypoxic period. It was shown that the administration
of LPS under normoxic conditions was accompanied by hyperventilation,
hypoxemia and hypotension. The maximum deterioration in resistance
to severe hypoxia was observed in rats with LPS, which was manifested
by a decrease in MAP, SpO2 and a decrease
in the possibility of autoresuscitation after hypoxic apnea. The effect
of HT prevented a decrease in arterial pressure, SpO2 increased
by 1.4 times, survival increased by 2 times, which is comparable
to the level of normoxia before the introduction of LPS. It is assumed
that the effectiveness of hypoxic preconditioning is due to the
inhibition of the inflammatory response.
期刊介绍：
Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.
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