Moderate and severe hypoxia elicit divergent effects on cardiovascular function and physiological rhythms

Abstract

Hypoxia is both a consequence and cause of many acute and chronic diseases. Severe hypoxia causes hypertension with cardiovascular sequelae; however, the rare studies using moderate severities of hypoxia indicate that it can be beneficial, suggesting that hypoxia may not always be detrimental. Comparisons between studies are difficult because of the varied classifications of hypoxic severities, methods of delivery and use of anaesthetics. Thus, to investigate the long-term effects of moderate hypoxia on cardiovascular health, radiotelemetry was used to obtain in vivo physiological measurements in unanaesthetized mice during 24 h of either moderate or severe hypoxia, followed by 72 h of normoxic recovery. Systolic blood pressure was decreased during recovery following moderate hypoxia but increased following severe hypoxia. Moderate and severe hypoxia increased haeme oxygenase-1 expression during recovery, suggesting parity in hypoxic stress at the level of the artery. Severe but not moderate hypoxia increased the low/high frequency ratio of heart rate variability 72 h post-hypoxia, indicating a shift in sympathovagal balance. Moderate hypoxia dampened the amplitude of circadian rhythm, whereas severe disrupted rhythm during the entire insult, with perturbations persisting throughout normoxic recovery. Thus, hypoxic severity differentially regulates circadian blood pressure.

Disruption of Physiological Rhythms Persist Following Cessation of Cigarette Smoke Exposure in Mice

“…Cigarette smoke increases blood carboxyhemoglobin levels (CoHb, carbon monoxide and Hb) (Watson et al, 1987), resulting in hypoxia (Fricker et al, 2018). Our findings agree with previous work (Steiner et al, 2000;Allwood et al, 2018) on hypoxia-induced anapyrexia (i.e., a decrease in thermoneutral body temperature), bradycardia, and hypotension in mice. While we observed a greater decrease in SBP in response to cigarette exposure compared to traditional hypoxic hypoxia, it is likely due to the combined hypoxia and confounding effects of the thousands of chemicals in cigarette smoke.…”

“…Telemetry surgeries were completed as previously described (Allwood et al, 2018). Briefly, mice were implanted with transmitters (HD-X11, Data Science International, St. Paul, MN, United States) equipped to measure body temperature, heart rate, SBP, and activity.…”

“…Hourly means were obtained by averaging raw data between all animals and organizing into 24 h periods (Excel 2016, Microsoft Corp., Redmond, WA, United States). Cosine wave characteristics, including mesor (i.e., an estimation of the mean statistic of circadian rhythms), acrophase (i.e., time at the cycle's peak), and amplitude (i.e., the difference between the peak/trough and mean statistic) were evaluated using cosinor analysis as previously described (Allwood et al, 2018). R 2 , an index of goodness-of-fit, was also calculated using GraphPad Prism Software, version 6 (GraphPad Inc., La Jolla, CA, United States).…”

Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes

“…We induced normobaric hypoxia in adult (6–8 weeks old) C57BL/6 female mice using a hypoxia chamber where animals were acclimated over 20 min from 20.9% to 10% oxygen as described previously [ 92 , 93 ]. This percentage of oxygen is consistent severe hypoxia in humans [ 94 ] and mice [ 95 ]. Mice were exposed to hypoxia for 1w and monitored daily without opening the chamber so the hypoxic exposure was unaffected.…”

Antihypoxic activity of the VMA-10-18 derivate under hypobaric hypoxia in mice

“…This problem plays an important role in various fields of human activities: military, sports, space, etc. [2,3]. In people who are often exposed to hypoxia, disturbances in ion channel conductance, acid-base homeostasis are observed.…”