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Journal articles on the topic 'Intermittent chronic hypoxia'

Author: Grafiati

Published: 2 June 2025

Last updated: 31 July 2025

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1

Martinez, Chloe-Anne, Bernadette Kerr, Charley Jin, Peter Cistulli, and Kristina Cook. "Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells." International Journal of Molecular Sciences 20, no. 2 (2019): 445. http://dx.doi.org/10.3390/ijms20020445.

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Obstructive sleep apnea (OSA) affects a significant proportion of the population and is linked to increased rates of cancer development and a worse cancer outcome. OSA is characterized by nocturnal intermittent hypoxia and animal models of OSA-like intermittent hypoxia show increased tumor growth and metastasis. Advanced tumors typically have regions of chronic hypoxia, activating the transcription factor, HIF-1, which controls the expression of genes involved in cancer progression. Rapid intermittent hypoxia from OSA has been proposed to increase HIF-1 activity and this may occur in tumors. T

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Prabhakar, Nanduri R. "Invited Review: Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms." Journal of Applied Physiology 90, no. 5 (2001): 1986–94. http://dx.doi.org/10.1152/jappl.2001.90.5.1986.

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To the majority of the population, recurrent episodes of hypoxia are more likely encountered in life than sustained hypoxia. Until recently, much of the information on the long-term effects of intermittent hypoxia has come from studies on human subjects experiencing chronic recurrent apneas. Recent development of animal models of intermittent hypoxia and techniques for exposing cell cultures to alternating cycles of hypoxia have led to new information on the effects of episodic hypoxia on oxygen-sensing mechanisms in the carotid body chemoreceptors and regulation of gene expression. The purpos

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Mouradian, Gary C., Satyan Lakshminrusimha, and Girija G. Konduri. "Perinatal Hypoxemia and Oxygen Sensing." Comprehensive Physiology 11, no. 2 (2021): 1653–77. https://doi.org/10.1002/j.2040-4603.2021.tb00155.x.

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AbstractThe development of the control of breathing begins in utero and continues postnatally. Fetal breathing movements are needed for establishing connectivity between the lungs and central mechanisms controlling breathing. Maturation of the control of breathing, including the increase of hypoxia chemosensitivity, continues postnatally. Insufficient oxygenation, or hypoxia, is a major stressor that can manifest for different reasons in the fetus and neonate. Though the fetus and neonate have different hypoxia sensing mechanisms and respond differently to acute hypoxia, both responses prevent

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Ma, Qiang, Renxiao Zhang, Yuliang Wei, Mengqing Liang, and Houguo Xu. "Effects of Intermittent and Chronic Hypoxia on Fish Size and Nutrient Metabolism in Tiger Puffer (Takifugu rubripes)." Animals 14, no. 17 (2024): 2470. http://dx.doi.org/10.3390/ani14172470.

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Intermittent and chronic hypoxia are common stresses to marine fish, but the different responses of fish to intermittent and chronic hypoxia have not been well-known. In this study, tiger puffers were farmed in normoxia conditions (NO, 6.5 ± 0.5 mg/L), intermittent hypoxia (IH, 6.5 ± 0.5 mg/L in the day and 3.5 ± 0.5 mg/L in the night), or choric hypoxia (CH, 3.5 ± 0.5 mg/L) conditions for 4 weeks, after which the growth, nutrient metabolism and three hifα isoforms expression were measured. Both intermittent and chronic hypoxia decreased the fish growth and visceral weight but increased the fe

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Hunyor, Imre, and Kristina M. Cook. "Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 315, no. 4 (2018): R669—R687. http://dx.doi.org/10.1152/ajpregu.00036.2018.

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Obstructive sleep apnea (OSA) is common and linked to a variety of poor health outcomes. A key modulator of this disease is nocturnal intermittent hypoxia. There is striking epidemiological evidence that patients with OSA have higher rates of cancer and cancer mortality. Small-animal models demonstrate an important role for systemic intermittent hypoxia in tumor growth and metastasis, yet the underlying mechanisms are poorly understood. Emerging data indicate that intermittent hypoxia activates the hypoxic response and inflammatory pathways in a manner distinct from chronic hypoxia. However, t

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Usategui-Martín, Ricardo, Álvaro Del Del Real, José A. Sainz-Aja, et al. "Analysis of Bone Histomorphometry in Rat and Guinea Pig Animal Models Subject to Hypoxia." International Journal of Molecular Sciences 23, no. 21 (2022): 12742. http://dx.doi.org/10.3390/ijms232112742.

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Hypoxia may be associated with alterations in bone remodeling, but the published results are contradictory. The aim of this study was to characterize the bone morphometry changes subject to hypoxia for a better understanding of the bone response to hypoxia and its possible clinical consequences on the bone metabolism. This study analyzed the bone morphometry parameters by micro-computed tomography (μCT) in rat and guinea pig normobaric hypoxia models. Adult male and female Wistar rats were exposed to chronic hypoxia for 7 and 15 days. Additionally, adult male guinea pigs were exposed to chroni

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Carreres, Lydie, Marion Mercey-Ressejac, Keerthi Kurma, et al. "Chronic Intermittent Hypoxia Increases Cell Proliferation in Hepatocellular Carcinoma." Cells 11, no. 13 (2022): 2051. http://dx.doi.org/10.3390/cells11132051.

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Obstructive sleep apnea (OSA) syndrome is characterized by chronic intermittent hypoxia and is associated with an increased risk of all-cause mortality, including cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by increasing incidence and high mortality. However, the link between HCC and OSA-related chronic intermittent hypoxia remains unclear. Herein, we used a diethylnitrosamine (DEN)-induced HCC model to investigate whether OSA-related chronic intermittent hypoxia has an impact on HCC progression. To elucidate the associated mechanisms

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Wu, Ming-Jane, Stéphane Vinit, Chun-Lin Chen, and Kun-Ze Lee. "5-HT7 Receptor Inhibition Transiently Improves Respiratory Function Following Daily Acute Intermittent Hypercapnic-Hypoxia in Rats With Chronic Midcervical Spinal Cord Contusion." Neurorehabilitation and Neural Repair 34, no. 4 (2020): 333–43. http://dx.doi.org/10.1177/1545968320905806.

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Background. Intermittent hypoxia can induce respiratory neuroplasticity to enhance respiratory motor outputs following hypoxic treatment. This type of respiratory neuroplasticity is primarily mediated by the activation of Gq-protein-coupled 5-HT2 receptors and constrained by Gs-protein-coupled 5-HT7 receptors. Objective. The present study hypothesized that the blockade of 5-HT7 receptors can potentiate the effect of intermittent hypercapnic-hypoxia on respiratory function after cervical spinal cord contusion injury. Methods. The ventilatory behaviors of unanesthetized rats with midcervical spi

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Savransky, Vladimir, Ashika Nanayakkara, Jianguo Li, et al. "Chronic Intermittent Hypoxia Induces Atherosclerosis." American Journal of Respiratory and Critical Care Medicine 175, no. 12 (2007): 1290–97. http://dx.doi.org/10.1164/rccm.200612-1771oc.

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Makarenko, Vladislav V., Ying-Jie Peng, Shakil A. Khan, Jayasri Nanduri, Aaron P. Fox, and Nanduri R. Prabhakar. "Long-term facilitation of catecholamine secretion from adrenal chromaffin cells of neonatal rats by chronic intermittent hypoxia." Journal of Neurophysiology 122, no. 5 (2019): 1874–83. http://dx.doi.org/10.1152/jn.00435.2019.

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In neonates, catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMC) is an important mechanism for maintaining homeostasis during hypoxia. Nearly 90% of premature infants experience chronic intermittent hypoxia (IH) because of high incidence of apnea of prematurity, which is characterized by periodic stoppage of breathing. The present study examined the effects of repetitive hypoxia, designed to mimic apnea of prematurity, on CA release from AMC of neonatal rats. Neonatal rats were exposed to either control conditions or chronic intermittent hypoxia (IH) from ages postnatal

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Neubauer, Judith A. "Invited Review: Physiological and pathophysiological responses to intermittent hypoxia." Journal of Applied Physiology 90, no. 4 (2001): 1593–99. http://dx.doi.org/10.1152/jappl.2001.90.4.1593.

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This mini-review summarizes the physiological adaptations to and pathophysiological consequences of intermittent hypoxia with special emphasis given to the pathophysiology associated with obstructive sleep apnea. Intermittent hypoxia is an effective stimulus for evoking the respiratory, cardiovascular, and metabolic adaptations normally associated with continuous chronic hypoxia. These adaptations are thought by some to be beneficial in that they may provide protection against disease as well as improve exercise performance in athletes. The long-term consequences of chronic intermittent hypoxi

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Douglas, Robert M., Naoyuki Miyasaka, Kan Takahashi, Adrianna Latuszek-Barrantes, Gabriel G. Haddad, and Hoby P. Hetherington. "Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 3 (2007): R1254—R1259. http://dx.doi.org/10.1152/ajpregu.00404.2006.

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Chronic constant hypoxia (CCH) and chronic intermittent hypoxia (CIH) are known to have deleterious effects on the central nervous system. Because of the difference in the pattern of hypoxic exposure, it is possible that the pathological outcome would vary. The N-acetyl aspartate/creatine (NAA/Cr) ratio is a reliable marker of neuronal integrity, and this can be noninvasively measured by proton nuclear magnetic resonance spectroscopy. P2 CD1 mouse pups with their dams were exposed to either CCH, where the FiO2 was maintained at 11% continuously or to CIH, where the FiO2 was varied between 21 a

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Peng, Ying-Jie, and Nanduri R. Prabhakar. "Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity." Journal of Applied Physiology 96, no. 3 (2004): 1236–42. http://dx.doi.org/10.1152/japplphysiol.00820.2003.

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Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250–300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15sof5%O2 + 5 min of 21% O2, 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per

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Prabhakar, Nanduri R., R. Douglas Fields, Tracy Baker, and Eugene C. Fletcher. "Intermittent hypoxia: cell to system." American Journal of Physiology-Lung Cellular and Molecular Physiology 281, no. 3 (2001): L524—L528. http://dx.doi.org/10.1152/ajplung.2001.281.3.l524.

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This symposium was organized to present research dealing with the effects of intermittent hypoxia on cardiorespiratory systems and cellular mechanisms. The pattern of neural impulse activity has been shown to be critical in the induction of genes in neuronal cells and involves distinct signaling pathways. Mechanisms associated with different patterns of intermittent hypoxia might share similar mechanisms. Chronic intermittent hypoxia selectively augments carotid body sensitivity to hypoxia and causes long-lasting activation of sensory discharge. Intermittent hypoxia also activates hypoxia-indu

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Arriaza, Karem, Julio Brito, Patricia Siques, et al. "Effects of Zinc on the Right Cardiovascular Circuit in Long-Term Hypobaric Hypoxia in Wistar Rats." International Journal of Molecular Sciences 24, no. 11 (2023): 9567. http://dx.doi.org/10.3390/ijms24119567.

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Hypobaric hypoxia under chromic conditions triggers hypoxic pulmonary vasoconstriction (HPV) and right ventricular hypertrophy (RVH). The role of zinc (Zn) under hypoxia is controversial and remains unclear. We evaluated the effect of Zn supplementation in prolonged hypobaric hypoxia on HIF2α/MTF-1/MT/ZIP12/PKCε pathway in the lung and RVH. Wistar rats were exposed to hypobaric hypoxia for 30 days and randomly allocated into three groups: chronic hypoxia (CH); intermittent hypoxia (2 days hypoxia/2 days normoxia; CIH); and normoxia (sea level control; NX). Each group was subdivided (n = 8) to

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Sheel, Andrew William, and Meaghan Joelle MacNutt. "Control of ventilation in humans following intermittent hypoxia." Applied Physiology, Nutrition, and Metabolism 33, no. 3 (2008): 573–81. http://dx.doi.org/10.1139/h08-008.

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Exposure to chronic or intermittent hypoxia produces alterations in the ventilatory response to hypoxia. These adaptations can differ depending on the severity of the hypoxic stimulus, its duration, its pattern, and the presence or absence of other chemical stimuli. As such, there are significant differences between the responses to intermittent versus continuous hypoxia. Intermittent hypoxia (IH) has been shown to elicit significant changes in the peripheral chemoresponse, but the functional implications of these changes for resting and exercise ventilation are not clear. We summarize the imp

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Siques, Patricia, Ángel Luis López de Pablo, Julio Brito, et al. "Nitric Oxide and Superoxide Anion Balance in Rats Exposed to Chronic and Long Term Intermittent Hypoxia." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/610474.

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Work at high altitude in shifts exposes humans to a new form of chronic intermittent hypoxia, with still unknown health consequences. We have established a rat model resembling this situation, which develops a milder form of right ventricular hypertrophy and pulmonary artery remodelling compared to continuous chronic exposure. We aimed to compare the alterations in pulmonary artery nitric oxide (NO) availability induced by these forms of hypoxia and the mechanisms implicated. Rats were exposed for 46 days to normoxia or hypobaric hypoxia, either continuous (CH) or intermittent (2 day shifts, C

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Aragón-Vela, Jerónimo, Jacob Bejder, Jesús R Huertas, Julio Plaza-Diaz, and Nikolai B. Nordsborg. "Does intermittent exposure to high altitude increase the risk of cardiovascular disease in workers? A systematic narrative review." BMJ Open 10, no. 11 (2020): e041532. http://dx.doi.org/10.1136/bmjopen-2020-041532.

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ObjectiveSeveral working groups (eg, miners, flight crews and soldiers) are subjected to chronic intermittent hypoxic exposure. The cardiovascular implications have been studied but not systematically reviewed with focus on possible negative health implications. The aim of the present review was to systematically evaluate the hypothesis that intermittent hypoxic exposure causes cardiovascular stress detrimental to health in workers.DesignSystematic review.Data sourcesElectronic database search of PubMed, Scopus and Web of Science up to April 2020.Eligibility criteriaStudies of workers ≥18 year

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Xu, J., E. Geng, L. Brake, et al. "0237 Effect of Chronic Intermittent Hypoxia on Spatial Performance in Rats." Sleep 43, Supplement_1 (2020): A91. http://dx.doi.org/10.1093/sleep/zsaa056.235.

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Abstract Introduction Cognitive and spatial dysfunction is common among patients with obstructive sleep apnea (OSA). The cause of these abnormalities may be related to the effects of hypoxic damage in the brain during sleep. Here we report a rodent model for chronic intermittent hypoxia (CIH) that examines spatial performance tasks via a Barnes Maze paradigm. We hypothesized that increased severity of CIH yields decreased cognitive and spatial performance. Methods Three groups of rats were subject to varying levels of hypoxia conditions: sham (21% oxygen; n = 19), moderate (11% oxygen; n = 14)

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Saxena and Jolly. "Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression." Biomolecules 9, no. 8 (2019): 339. http://dx.doi.org/10.3390/biom9080339.

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Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called intermittent hypoxia or IH). Cyclic hypoxia is mimicked in vitro and in vivo by periodic exposure to cycles of hypoxia and reoxygenation (H–R cycles). Compared to chronic hypoxia, cyclic hypoxia has been shown to augment various hallmarks of cancer to a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling hypoxia has also been shown to be the major contributing factor in inc

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Beaudin, Andrew E., Sara E. Hartmann, Matiram Pun, and Marc J. Poulin. "Human cerebral blood flow control during hypoxia: focus on chronic pulmonary obstructive disease and obstructive sleep apnea." Journal of Applied Physiology 123, no. 5 (2017): 1350–61. http://dx.doi.org/10.1152/japplphysiol.00352.2017.

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The brain is a vital organ that relies on a constant and adequate blood flow to match oxygen and glucose delivery with the local metabolic demands of active neurons. Thus exquisite regulation of cerebral blood flow (CBF) is particularly important under hypoxic conditions to prevent a detrimental decrease in the partial pressure of oxygen within the brain tissues. Cerebrovascular sensitivity to hypoxia, assessed as the change in CBF during a hypoxic challenge, represents the capacity of cerebral vessels to respond to, and compensate for, a reduced oxygen supply, and has been shown to be impaire

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Marciante, Alexandria B., Lei A. Wang, Joel T. Little, and J. Thomas Cunningham. "Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats." American Journal of Physiology-Heart and Circulatory Physiology 318, no. 1 (2020): H34—H48. http://dx.doi.org/10.1152/ajpheart.00350.2019.

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Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hy

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Milano, Giuseppina, Antonio F. Corno, Silvio Lippa, Ludwig K. von Segesser, and Michele Samaja. "Chronic and Intermittent Hypoxia Induce Different Degrees of Myocardial Tolerance to Hypoxia-Induced Dysfunction." Experimental Biology and Medicine 227, no. 6 (2002): 389–97. http://dx.doi.org/10.1177/153537020222700604.

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Chronic hypoxia (CH) is believed to induce myocardial protection, but this is in contrast with clinical evidence. Here, we test the hypothesis that repeated brief reoxygenation episodes during prolonged CH improve myocardial tolerance to hypoxia-induced dysfunction. Male 5-week-old Sprague-Dawley rats (n = 7–9/group) were exposed for 2 weeks to CH (F1O2 = 0.10), intermittent hypoxia (IH, same as CH, but 1 hr/day exposure to room air), or normoxia (N, F1O2 = 0.21). Hearts were isolated, Langendorff perfused for 30 min with hypoxic medium (Krebs-Henseleit, PO2 = 67 mmHg), and exposed to hyperoxi

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Fletcher, Eugene C. "Invited Review: Physiological consequences of intermittent hypoxia: systemic blood pressure." Journal of Applied Physiology 90, no. 4 (2001): 1600–1605. http://dx.doi.org/10.1152/jappl.2001.90.4.1600.

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One of the major manifestations of obstructive sleep apnea is profound and repeated hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn increases sympathetic outflow, acutely increasing blood pressure. The chronic effect of these repeated episodic or intermittent periods of hypoxia in humans is difficult to study because chronic cardiovascular changes may take many years to manifest. Rodents have been a tremendous source of information in short- and long-term studies of hypertension and other cardiovascular diseases. Recurrent short cycles o

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Shameem, Mohammed, Alexa Sen, Rajeev Vikram, Chenchen Xia, and Ahmad Alshehri. "Hypoxia-induced cardioprotection: A review." Arhiv za farmaciju 74, no. 5 (2024): 658–78. http://dx.doi.org/10.5937/arhfarm74-53114.

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Hypoxia, a state of reduced oxygen availability, exerts complex and often paradoxical effects on the heart. While chronic hypoxia is detrimental and leads to adverse cardiac remodeling and dysfunction, short-term or intermittent hypoxia can contribute towards protective adaptations that enhances the heart's ability to protect itself from ischemic injury. This protective adaptation, also known as hypoxic preconditioning, drives the activation of several essential signaling pathways, including the hypoxia-inducible factor (HIF) signaling, reactive oxygen species (ROS) signaling, nitric oxide (NO

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Shameem, Mohammed, Alexa Sen, Rajeev Vikram, Chenchen Xia, and Ahmad Alshehri. "Hypoxia-induced cardioprotection: A review." Arhiv za farmaciju 74, no. 5 (2024): 658–78. http://dx.doi.org/10.5937/arhfarm72-53114.

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Hypoxia, a state of reduced oxygen availability, exerts complex and often paradoxical effects on the heart. While chronic hypoxia is detrimental and leads to adverse cardiac remodeling and dysfunction, short-term or intermittent hypoxia can contribute towards protective adaptations that enhances the heart's ability to protect itself from ischemic injury. This protective adaptation, also known as hypoxic preconditioning, drives the activation of several essential signaling pathways, including the hypoxia-inducible factor (HIF) signaling, reactive oxygen species (ROS) signaling, nitric oxide (NO

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Song, Jihyun, Krishna M. Sundar, John Hoidal, and Josef T. Prchal. "Hematological Changes in Chronic Sustained Hypoxia and Chronic Intermittent Hypoxia in a Mouse Model." Blood 134, Supplement_1 (2019): 3525. http://dx.doi.org/10.1182/blood-2019-131309.

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Hypoxia alters cellular metabolism and chemosensory endocrine regulation. Hypoxia increases production of erythrocytes in order to improve oxygen delivery to tissues. Organisms respond differentially to duration and patterns of hypoxia. Acute hypoxia stabilizes transcription factors' a-subunits of hypoxia inducible factors (HIFs; HIF-1a and HIF-2a) while in chronic hypoxia HIF-2a continues to be augmented, but HIF-1a decreases (1, 2). There are two clinical patterns of hypoxia: chronic sustained hypoxia (CSH) and chronic intermittent hypoxia (CIH). CSH is present in people living at high altit

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Sunderram, Jag, John Semmlow, Pranav Patel, et al. "Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic intermittent hypoxia in mice." Journal of Applied Physiology 121, no. 4 (2016): 944–52. http://dx.doi.org/10.1152/japplphysiol.00036.2016.

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Chronic intermittent hypoxia (CIH) increases sympathetic tone and respiratory instability. Our previous work showed that chronic hypoxia induces the oxygen-sensing enzyme heme oxygenase-1 (HO-1) within the C1 sympathoexcitatory region and the pre-Bötzinger complex (pre-BötC). We therefore examined the effect of CIH on time course of induced expression of HO-1 within these regions and determined whether the induction of HO-1 correlated with changes in respiratory, sigh frequency, and sympathetic responses (spectral analysis of heart rate) to acute hypoxia (10% O2) during 10 days of exposure to

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Neckář, Jan, Irena Marková, František Novák та ін. "Increased expression and altered subcellular distribution of PKC-δ in chronically hypoxic rat myocardium: involvement in cardioprotection". American Journal of Physiology-Heart and Circulatory Physiology 288, № 4 (2005): H1566—H1572. http://dx.doi.org/10.1152/ajpheart.00586.2004.

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We examined the role of protein kinase C (PKC) in the cardioprotective mechanism induced by long-term adaptation to chronic intermittent hypoxia. Adult male Wistar rats were exposed to hypobaric hypoxia of 7,000 m for 8 h/day, 5 days/wk; the total number of exposures was 24–32. A control group was kept under normoxic conditions. Western blot analysis of PKC isoforms-δ and -ε was performed in the cytosol and three particulate fractions of left ventricular myocardium. Infarct size was determined in open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion. The PKC inhi

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Waskova-Arnostova, Petra, Barbara Elsnicova, Dita Kasparova, et al. "Cardioprotective adaptation of rats to intermittent hypobaric hypoxia is accompanied by the increased association of hexokinase with mitochondria." Journal of Applied Physiology 119, no. 12 (2015): 1487–93. http://dx.doi.org/10.1152/japplphysiol.01035.2014.

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Chronic hypoxia increases the myocardial resistance to acute ischemia-reperfusion injury by affecting the mitochondrial redox balance. Hexokinase (HK) bears a high potential to suppress the excessive formation of reactive oxygen species because of its increased association with mitochondria, thereby inhibiting the membrane permeability transition pore opening and preventing cell death. The purpose of this study was to determine the effect of severe intermittent hypobaric hypoxia (7,000 m, 8 h/day, 5 wk) on the function and colocalization of HK isoforms with mitochondria in the left (LV) and ri

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Marciante, Alexandria B., Brent Shell, George E. Farmer, and J. Thomas Cunningham. "Role of angiotensin II in chronic intermittent hypoxia-induced hypertension and cognitive decline." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 320, no. 4 (2021): R519—R525. http://dx.doi.org/10.1152/ajpregu.00222.2020.

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Sleep apnea is characterized by momentary interruptions in normal respiration and leads to periods of decreased oxygen, or intermittent hypoxia. Chronic intermittent hypoxia is a model of the hypoxemia associated with sleep apnea and results in a sustained hypertension that is maintained during normoxia. Adaptations of the carotid body and activation of the renin-angiotensin system may contribute to the development of hypertension associated with chronic intermittent hypoxia. The subsequent activation of the brain renin-angiotensin system may produce changes in sympathetic regulatory neural ne

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Zhang, Jing, Xu Guo, Yanwei Shi, Jing Ma, and Guangfa Wang. "Intermittent hypoxia with or without hypercapnia is associated with tumorigenesis by decreasing the expression of brain derived neurotrophic factor and miR-34a in rats." Chinese Medical Journal 127, no. 1 (2014): 43–47. http://dx.doi.org/10.3760/cma.j.issn.0366-6999.20131683.

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Background Very recent studies revealed that obstructive sleep apnoea (OSA) is a contributor of the increased incidence and mortality of cancer in humans, but mechanisms of how OSA promotes tumorigenesis remains largely unknown. We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis. Methods First, Sprague-Dawley (SD) male rats (12 weeks old) were subjected to different hypoxia exposures: intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air. The systemic application of chronic fast rate hypoxia with o

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Nanduri, Jayasri, Gregg L. Semenza, and Nanduri R. Prabhakar. "Epigenetic changes by DNA methylation in chronic and intermittent hypoxia." American Journal of Physiology-Lung Cellular and Molecular Physiology 313, no. 6 (2017): L1096—L1100. http://dx.doi.org/10.1152/ajplung.00325.2017.

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DNA methylation of cytosine residues is a well-studied epigenetic change, which regulates gene transcription by altering accessibility for transcription factors. Hypoxia is a pervasive stimulus that affects many physiological processes. The circulatory and respiratory systems adapt to chronic sustained hypoxia, such as that encountered during a high-altitude sojourn. Many people living at sea level experience chronic intermittent hypoxia (IH) due to sleep apnea, which leads to cardiovascular and respiratory maladaptation. This article presents a brief update on emerging evidence suggesting tha

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Morgan, Barbara J., Russell Adrian, Zun-yi Wang, Melissa L. Bates, and John M. Dopp. "Chronic intermittent hypoxia alters ventilatory and metabolic responses to acute hypoxia in rats." Journal of Applied Physiology 120, no. 10 (2016): 1186–95. http://dx.doi.org/10.1152/japplphysiol.00015.2016.

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We determined the effects of chronic exposure to intermittent hypoxia (CIH) on chemoreflex control of ventilation in conscious animals. Adult male Sprague-Dawley rats were exposed to CIH [nadir oxygen saturation (SpO2), 75%; 15 events/h; 10 h/day] or normoxia (NORM) for 21 days. We assessed the following responses to acute, graded hypoxia before and after exposures: ventilation (V̇e, via barometric plethysmography), V̇o2 and V̇co2 (analysis of expired air), heart rate (HR), and SpO2 (pulse oximetry via neck collar). We quantified hypoxia-induced chemoreceptor sensitivity by calculating the sti

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Kang, Jing, Yuanyuan Li, Ke Hu, et al. "Chronic intermittent hypoxia versus continuous hypoxia: Same effects on hemorheology?" Clinical Hemorheology and Microcirculation 63, no. 3 (2016): 245–55. http://dx.doi.org/10.3233/ch-151973.

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Greenberg, Harly E., Anthony Sica, Deirdre Batson, and Steven M. Scharf. "Chronic intermittent hypoxia increases sympathetic responsiveness to hypoxia and hypercapnia." Journal of Applied Physiology 86, no. 1 (1999): 298–305. http://dx.doi.org/10.1152/jappl.1999.86.1.298.

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We sought to determine whether chronic exposure to intermittent hypoxia (CIH) increases sympathetic responsiveness to subsequent chemoreflex stimulation. Sprague-Dawley rats were exposed to 30 days of CIH: exposure chamber %O2 [fractional concentration of chamber O2([Formula: see text])] nadir 6.5–7% with return to 21% each minute for 8 h/day during the diurnal sleep period (Exp group). Sham controls (SC group) were similarly handled but kept at 21%[Formula: see text] and compared with unhandled controls (UC group). Rats were then anesthetized with urethan, and preganglionic cervical sympathet

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Prabhakar, Nanduri R., Ganesh K. Kumar, and Ying-Jie Peng. "Sympatho-adrenal activation by chronic intermittent hypoxia." Journal of Applied Physiology 113, no. 8 (2012): 1304–10. http://dx.doi.org/10.1152/japplphysiol.00444.2012.

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Recurrent apnea with chronic intermittent hypoxia (CIH) is a major clinical problem in adult humans and infants born preterm. Patients with recurrent apnea exhibit heightened sympathetic activity as well as elevated plasma catecholamine levels, and these phenotypes are effectively recapitulated in rodent models of CIH. This article summarizes findings from studies addressing sympathetic activation in recurrent apnea patients and rodent models of CIH and the underlying cellular and molecular mechanisms. Available evidence suggests that augmented chemoreflex and attenuated baroreflex contribute

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Savransky, Vladimir, Ashika Nanayakkara, Angelica Vivero, et al. "Chronic intermittent hypoxia predisposes to liver injury." Hepatology 45, no. 4 (2007): 1007–13. http://dx.doi.org/10.1002/hep.21593.

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Torres, Marta, Mauricio Rojas, Noelia Campillo, et al. "Parabiotic model for differentiating local and systemic effects of continuous and intermittent hypoxia." Journal of Applied Physiology 118, no. 1 (2015): 42–47. http://dx.doi.org/10.1152/japplphysiol.00858.2014.

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Hypoxia can be damaging either because cells are directly sensitive to low oxygen pressure in their local microenvironment and/or because they are exposed to circulating factors systemically secreted in response to hypoxia. The conventional hypoxia model, breathing hypoxic air, does not allow one to distinguish between these local and systemic effects. Here we propose and validate a model for differentially applying local and systemic hypoxic challenges in an animal. We used parabiosis, two mice sharing circulation by surgical union through the skin, and tested the hypothesis that when one of

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Martins, Fátima O., Joana F. Sacramento, Elena Olea, et al. "Chronic Intermittent Hypoxia Induces Early-Stage Metabolic Dysfunction Independently of Adipose Tissue Deregulation." Antioxidants 10, no. 8 (2021): 1233. http://dx.doi.org/10.3390/antiox10081233.

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Several studies demonstrated a link between obstructive sleep apnea (OSA) and the development of insulin resistance. However, the main event triggering insulin resistance in OSA remains to be clarified. Herein, we investigated the effect of mild and severe chronic intermittent hypoxia (CIH) on whole-body metabolic deregulation and visceral adipose tissue dysfunction. Moreover, we studied the contribution of obesity to CIH-induced dysmetabolic states. Experiments were performed in male Wistar rats submitted to a control and high-fat (HF) diet. Two CIH protocols were tested: A mild CIH paradigm

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Shin, Mi-Kyung, Qiaoling Yao, Jonathan C. Jun, et al. "Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia." Journal of Applied Physiology 117, no. 7 (2014): 765–76. http://dx.doi.org/10.1152/japplphysiol.01133.2013.

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Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of insp

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Bader, Samuel B., Mark W. Dewhirst, and Ester M. Hammond. "Cyclic Hypoxia: An Update on Its Characteristics, Methods to Measure It and Biological Implications in Cancer." Cancers 13, no. 1 (2020): 23. http://dx.doi.org/10.3390/cancers13010023.

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Regions of hypoxia occur in most if not all solid cancers. Although the presence of tumor hypoxia is a common occurrence, the levels of hypoxia and proportion of the tumor that are hypoxic vary significantly. Importantly, even within tumors, oxygen levels fluctuate due to changes in red blood cell flux, vascular remodeling and thermoregulation. Together, this leads to cyclic or intermittent hypoxia. Tumor hypoxia predicts for poor patient outcome, in part due to increased resistance to all standard therapies. However, it is less clear how cyclic hypoxia impacts therapy response. Here, we discu

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Xu, J., E. Geng, L. Brake, et al. "0424 Effect of Chronic Intermittent Hypoxia on Global Cerebral Metabolic Rate of Oxygen Consumption in Rats." Sleep 43, Supplement_1 (2020): A162—A163. http://dx.doi.org/10.1093/sleep/zsaa056.421.

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Abstract Introduction Patients with obstructive sleep apnea (OSA) commonly exhibit grey and white matter loss, which may be related to hypoxic damage in the brain during sleep. Our preliminary data demonstrated lower values of cerebral metabolic rate of oxygen (CMRO2) consumption in apneics versus controls. As such, reduced CMRO2 may be an important contributor to the neurologic consequences of OSA. Here we report a rodent model for chronic intermittent hypoxia (CIH) to quantify effects on CMRO2 consumption. We hypothesized that increased severity of CIH results in decreased CMRO2 levels. Meth

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Moreno-Indias, Isabel, Marta Torres, Josep M. Montserrat, et al. "Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea." European Respiratory Journal 45, no. 4 (2014): 1055–65. http://dx.doi.org/10.1183/09031936.00184314.

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We assessed whether intermittent hypoxia, which emulates one of the hallmarks of obstructive sleep apnoea (OSA), leads to altered faecal microbiome in a murine model.In vivo partial pressure of oxygen was measured in colonic faeces during intermittent hypoxia in four anesthetised mice. 10 mice were subjected to a pattern of chronic intermittent hypoxia (20 s at 5% O2 and 40 s at room air for 6 h·day−1) for 6 weeks and 10 mice served as normoxic controls. Faecal samples were obtained and microbiome composition was determined by 16S rRNA pyrosequencing and bioinformatic analysis by Quantitative

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Pai, Peiying, Ching Jung Lai, Ching-Yuang Lin, Yi-Fan Liou, Chih-Yang Huang, and Shin-Da Lee. "Effect of superoxide anion scavenger on rat hearts with chronic intermittent hypoxia." Journal of Applied Physiology 120, no. 8 (2016): 982–90. http://dx.doi.org/10.1152/japplphysiol.01109.2014.

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Only very limited information regarding the protective effects of the superoxide anion scavenger on chronic intermittent hypoxia-induced cardiac apoptosis is available. The purpose of this study is to evaluate the effects of the superoxide anion scavenger on cardiac apoptotic and prosurvival pathways in rats with sleep apnea. Forty-two Sprague-Dawley rats were divided into three groups, rats with normoxic exposure (Control, 21% O2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O2 vs. 21% O2 per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide

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Brito, Julio, Patricia Siques, Silvia M. Arribas, et al. "Adventitial Alterations Are the Main Features in Pulmonary Artery Remodeling due to Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats." BioMed Research International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/169841.

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Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH,n=9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia,n=10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX,n=10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was a

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Zabka, A. G., G. S. Mitchell, E. B. Olson, and M. Behan. "Selected Contribution: Chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats." Journal of Applied Physiology 95, no. 6 (2003): 2614–23. http://dx.doi.org/10.1152/japplphysiol.00476.2003.

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Age and the estrus cycle affect time-dependent respiratory responses to episodic hypoxia in female rats. Respiratory long-term facilitation (LTF) is enhanced in middle-aged vs. young female rats ( 72 ). We tested the hypothesis that phrenic and hypoglossal (XII) LTF are diminished in acyclic geriatric rats when fluctuating sex hormone levels no longer establish conditions that enhance LTF. Chronic intermittent hypoxia (CIH) enhances LTF ( 41 ); thus we further predicted that CIH would restore LTF in geriatric female rats. LTF was measured in young (3-4 mo) and geriatric (20-22 mo) female Sasco

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Navarrete-Opazo, Angela, and Gordon S. Mitchell. "Therapeutic potential of intermittent hypoxia: a matter of dose." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 307, no. 10 (2014): R1181—R1197. http://dx.doi.org/10.1152/ajpregu.00208.2014.

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Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we review the extensive literature concerning IH and its impact on the respiratory, cardiovascular, immune, metabolic, bone, and nervous systems. One major goal is to define relevant IH characteristics leading to safe, protective, and/or therapeutic effects vs. pathogenesis. To understand the impact of IH, it is essential to define critical characteristics of the IH protocol under investigat

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Kong, Weiwei, Yixin Liao, Liang Zhao, et al. "Kidney Renin Release under Hypoxia and Its Potential Link with Nitric Oxide: A Narrative Review." Biomedicines 11, no. 11 (2023): 2984. http://dx.doi.org/10.3390/biomedicines11112984.

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The renin–angiotensin system (RAS) and hypoxia have a complex interaction: RAS is activated under hypoxia and activated RAS aggravates hypoxia in reverse. Renin is an aspartyl protease that catalyzes the first step of RAS and tightly regulates RAS activation. Here, we outline kidney renin expression and release under hypoxia and discuss the putative mechanisms involved. It is important that renin generally increases in response to acute hypoxemic hypoxia and intermittent hypoxemic hypoxia, but not under chronic hypoxemic hypoxia. The increase in renin activity can also be observed in anemic hy

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Katayama, Keisho, Curtis A. Smith, Kathleen S. Henderson, and Jerome A. Dempsey. "Chronic intermittent hypoxia increases the CO2 reserve in sleeping dogs." Journal of Applied Physiology 103, no. 6 (2007): 1942–49. http://dx.doi.org/10.1152/japplphysiol.00735.2007.

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We hypothesized that chronic intermittent hypoxia (CIH) would induce a predisposition to apnea in response to induced hypocapnia. To test this, we used pressure support ventilation to quantify the difference in end-tidal partial pressure of CO2 (PetCO2) between eupnea and the apneic threshold (“CO2 reserve”) as an index of the propensity for apnea and unstable breathing during sleep, both before and following up to 3-wk exposure to chronic intermittent hypoxia in dogs. CIH consisted of 25 s of PetO2 = 35–40 Torr followed by 35 s of normoxia, and this pattern was repeated 60 times/h, 7–8 h/day

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