Abstract—The goal of the present study was to investigate the molecular mechanisms that underlie heart and skeletal muscle damage in male Wistar rats weighing 200–250 g in response to a 3-h exposure to 180 mm Hg (5% O2) in the model of severe hypobaric hypoxia. It has been demonstrated that the level of the cardiac biomarker troponin I in the blood plasma of rats exposed to severe hypobaric hypoxia for 3 h increased significantly compared to the control group, indicating myocardial injury. At the same time, the administration of the HIF-1α transcription factor inhibitor did not affect the plasma level of troponin I. In contrast, the release of the non-specific biomarker myoglobin into the bloodstream did not increase in response to hypoxia compared to the control animals. In addition, 24 h after the exposure to severe hypobaric hypoxia the serum myoglobin level was significantly lower in animals administered with the HIF-1α inhibitor topotecan than in rats that did not receive topotecan. Therefore, it may be assumed that the inhibition of the HIF-1α transcription factor 10 min before exposure to severe hypobaric hypoxia reduces skeletal muscle damage. The mechanisms that affect the adaptation of heart and skeletal muscles to hypoxia are discussed.
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ACKNOWLEDGMENTS
The authors are grateful to Dc. O.V. Vetrovoy for organizing the experiments on animal model of severe hypobaric hypoxia.
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Translated by I. Matiulko
Abbreviations: HIF, hypoxia-inducible factor; NO, nitrogen monoxide.
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Fedorov, D.A., Frolova, M.Y., Krasovskaya, I.E. et al. The Effects of Severe Hypobaric Hypoxia and Inhibition of Hypoxia-Inducible Factor-1 (HIF-1) on Biomarkers of Cardiac and Skeletal Muscle Injury in Rats. BIOPHYSICS 64, 808–811 (2019). https://doi.org/10.1134/S000635091905004X
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DOI: https://doi.org/10.1134/S000635091905004X