Intermittent hypoxia: cell to system

2001 ◽  
Vol 281 (3) ◽  
pp. L524-L528 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
R. Douglas Fields ◽  
Tracy Baker ◽  
Eugene C. Fletcher
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Chronic Intermittent Hypoxia ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Arterial Blood ◽  
Long Term Facilitation

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-inducible factor-1. Reactive oxygen species are critical in altering carotid body function and hypoxia-inducible factor-1 activation caused by intermittent hypoxia. Blockade of serotonin function in the spinal cord prevents long-term facilitation in respiratory motor output elicited by episodic hypoxia and requires de novo protein synthesis. Chronic intermittent hypoxia leads to sustained elevation in arterial blood pressure and is associated with upregulation of catecholaminergic and renin-angiotensin systems and downregulation of nitric oxide synthases.

Selected Contribution: Chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats

2003 ◽  
Vol 95 (6) ◽  
pp. 2614-2623 ◽  
Author(s):  
A. G. Zabka ◽  
G. S. Mitchell ◽  
E. B. Olson ◽  
M. Behan
Keyword(s):  
Intermittent Hypoxia ◽  
Young Female ◽  
Time Dependent ◽  
Female Rats ◽  
Chronic Intermittent Hypoxia ◽  
Middle Aged ◽  
Short Term ◽  
Hypoxic Response ◽  
Long Term Facilitation

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 Sprague-Dawley rats and in a group of geriatric rats exposed to 1 wk of nocturnal CIH (11 vs. 21% O2 at 5-min intervals, 12 h/night). In anesthetized, paralyzed, vagotomized, and ventilated rats, time-dependent hypoxic phrenic and XII responses were assessed. The short-term hypoxic response was measured during the first of three 5-min episodes of isocapnic hypoxia (arterial Po2 35-45 Torr). LTF was assessed 15, 30, and 60 min postepisodic hypoxia. Phrenic and XII short-term hypoxic response was not different among groups, regardless of CIH treatment ( P > 0.05). LTF in geriatric female rats was smaller than previously reported for middle-aged rats but comparable to that in young female rats. CIH augmented phrenic and XII LTF to levels similar to those of middle-aged female rats without CIH ( P < 0.05). The magnitude of phrenic and XII LTF in all groups was inversely related to the ratio of progesterone to estradiol serum levels ( P < 0.05). Thus CIH and sex hormones influence the magnitude of LTF in geriatric female rats.

scholarly journals Chronic Intermittent Hypoxia Induces the Long-Term Facilitation of Genioglossus Corticomotor Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zou ◽  
Wei Wang ◽  
Xinshi Nie ◽  
Jian Kang
Keyword(s):  
Obstructive Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Magnetic Stimulation ◽  
Upper Airway ◽  
Emg Activity ◽  
Chronic Intermittent Hypoxia ◽  
Experimental Conditions ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Obstructive sleep apnea (OSA) is characterized by the repetitive collapse of the upper airway and chronic intermittent hypoxia (CIH) during sleep. It has been reported that CIH can increase the EMG activity of genioglossus in rats, which may be related to the neuromuscular compensation of OSA patients. This study aimed to explore whether CIH could induce the long-term facilitation (LTF) of genioglossus corticomotor activity. 16 rats were divided into the air group (n=8) and the CIH group (n=8). The CIH group was exposed to hypoxia for 4 weeks; the air group was subjected to air under identical experimental conditions in parallel. Transcranial magnetic stimulation (TMS) was applied every ten minutes and lasted for 1 h/day on the 1st, 3rd, 7th, 14th, 21st, and 28th days of air/CIH exposure. Genioglossus EMG was also recorded at the same time. Compared with the air group, the CIH group showed decreased TMS latency from 10 to 60 minutes on the 7th, 14th, 21st, and 28th days. The increased TMS amplitude lasting for 60 minutes was only observed on the 21st day. Genioglossus EMG activity increased only on the 28th day of CIH. We concluded that CIH could induce LTF of genioglossus corticomotor activity in rats.

scholarly journals Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas

2003 ◽  
Vol 100 (17) ◽  
pp. 10073-10078 ◽  
Author(s):  
Y.-J. Peng ◽  
J. L. Overholt ◽  
D. Kline ◽  
G. K. Kumar ◽  
N. R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Long Term Facilitation

scholarly journals Episode Frequency Determines the Impact of Chronic Intermittent Hypoxia on Phrenic Long Term Facilitation

2017 ◽  
Vol 31 (S1) ◽  
Author(s):  
Elisa Janine Gonzalez‐Rothi ◽  
Raphael Rodrigues Perim ◽  
Arash Tadjalli ◽  
Alec K Simon ◽  
Marissa Ciesla ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Episode Frequency ◽  
Long Term Facilitation ◽  
The Impact

scholarly journals Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia

2008 ◽  
Vol 104 (5) ◽  
pp. 1287-1294 ◽  
Author(s):  
Anita Pawar ◽  
Ying-Jie Peng ◽  
Frank J. Jacono ◽  
Nanduri R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Ex Vivo ◽  
Adult Life ◽  
Sensory Response ◽  
Chronic Intermittent Hypoxia ◽  
Adult Rats ◽  
Adult Rat ◽  
Carotid Bodies

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1–10 days) and adult (6–8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.

Time-dependent modulation of carotid body afferent activity during and after intermittent hypoxia

2005 ◽  
Vol 288 (6) ◽  
pp. R1571-R1580 ◽  
Author(s):  
Kevin J. Cummings ◽  
Richard J. A. Wilson
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Current Data ◽  
Time Dependent ◽  
Severe Hypoxia ◽  
Afferent Activity ◽  
Direct Role ◽  
Long Term Facilitation

The ventilatory response to several minutes of hypoxia consists of various time-dependent phenomena, some of which occur during hypoxia (e.g., short-term depression), whereas others appear on return to normoxia (e.g., posthypoxic frequency decline). Additional phenomena can be elicited by acute, intermittent hypoxia (e.g., progressive augmentation, long-term facilitation). Current data suggest that these phenomena originate centrally. We tested the hypothesis that carotid body afferent activity undergoes time-dependent modulation, consistent with a direct role in these ventilatory phenomena. Using an in vitro rat carotid body preparation, we found that 1) afferent activity declined during the first 5 min of severe (40 Torr Po2), moderate (60 Torr Po2), or mild (80 Torr Po2) hypoxia; 2) after return to normoxia (100 Torr Po2) and after several minutes of moderate or severe hypoxia, afferent activity was transiently reduced compared with prehypoxic levels; and 3) with successive 5-min bouts of mild, moderate, or severe hypoxia, afferent activity during bouts increased progressively. We call these phenomena sensory hypoxic decline, sensory posthypoxic decline, and sensory progressive augmentation, respectively. These phenomena were stimulus specific: similar phenomena were not seen with 5-min bouts of normoxic hypercapnia (100 Torr Po2 and 50–60 Torr Pco2) or hypoxic hypocapnia (60 Torr Po2 and 30 Torr Pco2). However, bouts of either normoxic hypercapnia or hypocapnic hypoxia resulted in sensory long-term facilitation. We suggest time-dependent carotid body activity acts in parallel with central mechanisms to shape the dynamics of ventilatory responses to respiratory chemostimuli.

Chronic intermittent hypoxia reduces ventilatory long-term facilitation and enhances apnea frequency in newborn rats

2008 ◽  
Vol 294 (4) ◽  
pp. R1356-R1366 ◽  
Author(s):  
Cécile Julien ◽  
Aida Bairam ◽  
Vincent Joseph
Keyword(s):  
Intermittent Hypoxia ◽  
Gradual Increase ◽  
Minute Ventilation ◽  
Whole Body ◽  
Male Rat ◽  
Chronic Intermittent Hypoxia ◽  
Protective Mechanism ◽  
Rat Pups ◽  
Long Term Facilitation

Ventilatory long-term facilitation (LTF; defined as gradual increase of minute ventilation following repeated hypoxic exposures) is well described in adult mammals and is hypothesized to be a protective mechanism against apnea. In newborns, LTF is absent during the first postnatal days, but its precise developmental pattern is unknown. Accordingly, this study describes this pattern of postnatal development. Additionally, we tested the hypothesis that chronic intermittent hypoxia (CIH) from birth alters this development. LTF was estimated in vivo using whole body plethysmography by exposing rat pups at postnatal days 1, 4, and 10 (P1, P4, and P10) to 10 brief hypoxic cycles (nadir 5% O2) and respiratory recordings during the following 2 h (recovery, 21% O2). Under these conditions, ventilatory LTF (gradual increase of minute ventilation during recovery) was clearly expressed in P10 rats but not in P1 and P4. In a second series of experiments, rat pups were exposed to CIH during the first 10 postnatal days (6 brief cyclic exposures at 5% O2 every 6 min followed by 1 h under normoxia, 24 h a day). Compared with P10 control rats, CIH enhanced hypoxic ventilatory response (estimated during the hypoxic cycles) specifically in male rat pups. Ventilatory LTF was drastically reduced in P10 rats exposed to CIH, which was associated with higher apnea frequency during recovery. We conclude that CIH from birth enhances hypoxic chemoreflex and disrupts LTF development, thus likely contributing to increase apnea frequency.

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