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

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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 tracheostomated 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 blood pressure (APm.), 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 APm, SpO2 and a decrease in the possibility of autoresuscitation after hypoxic apnea. The effect of HT prevented a decrease in blood 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.

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About the authors

Zh. A. Donina

Pavlov Institute of Physiology the Russian Academy of Sciences

Author for correspondence.
Email: zdonina@mail.ru
Russian Federation, St. Petersburg

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2. Fig. 1. Average blood pressure in rats with LPS-induced endotoxemia at the point of hypoxic apnea before and after hypoxic training. On the abscissa axis - experimental groups, on the ordinate axis – average blood pressure. ** p < 00.1

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3. Fig. 2. Saturation in rats with LPS-induced endotoxemia at the point of hypoxic apnea before and after hypoxic training. ** p < 0.01.

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4. Fig. 3. Posthypoxic respiration recovery in rats with LPS-induced endotoxemia before and after hypoxic training. On the abscissa axis – experimental groups, on the ordinate axis – recovery in %. ** – p < 0.01.

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