Disconnect between hypoxaemia and dyspnoea in severe sustained hypoxia

Minute ventilation (VE) during sustained hypoxia is not constant but begins to decline within 10–25 min in adult humans. The decrease in brain tissue PCO2 may be related to this decline in VE, because hypoxia causes an increase in brain blood flow, thus resulting in enhanced clearance of CO2 from the brain tissue. To examine the validity of this hypothesis, we measured VE and arterial and internal jugular venous blood gases simultaneously and repeatedly in 15 healthy male volunteers during progressive and subsequent sustained isocapnic hypoxia (arterial PO2 = 45 Torr) for 20 min. It was assumed that jugular venous PCO2 was an index of brain tissue PCO2. Mean VE declined significantly from the initial (16.5 l/min) to the final phase (14.1 l/min) of sustained hypoxia (P less than 0.05). Compared with the control (50.9 Torr), jugular venous PCO2 significantly decreased to 47.4 Torr at the initial phase of hypoxia but did not differ among the phases of hypoxia (47.2 Torr for the intermediate phase and 47.7 Torr for the final phase). We classified the subjects into two groups by hypoxic ventilatory response during progressive hypoxia at the mean value. The decrease in VE during sustained hypoxia was significant in the low responders (n = 9) [13.2 (initial phase) to 9.3 l/min (final phase of hypoxia), P less than 0.01], but not in the high responders (n = 6) (20.9–21.3 l/min, NS). This finding could not be explained by the change of arterial or jugular venous gases, which did not significantly change during sustained hypoxia in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

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Reactive oxygen species in the plasticity of respiratory behavior elicited by chronic intermittent hypoxia

Journal of Applied Physiology ◽

10.1152/japplphysiol.00613.2002 ◽

2003 ◽

Vol 94 (6) ◽

pp. 2342-2349 ◽

Cited By ~ 107

Author(s):

Ying-Jie Peng ◽

Nanduri R. Prabhakar

Keyword(s):

Intermittent Hypoxia ◽

Motor Behavior ◽

Motor Output ◽

Chronic Intermittent Hypoxia ◽

Radical Scavenger ◽

Respiratory Behavior ◽

Cumulative Duration ◽

Posthypoxic Period ◽

Long Term Facilitation ◽

Sustained Hypoxia

Long-term facilitation (LTF) of breathing elicited by episodic hypoxia (EH) is an extensively studied example of plasticity of respiratory motor behavior. Previous studies employed the paradigm of EH wherein each episode of hypoxia was 5 min. This paradigm is rarely encountered in nature. Brief episodes of hypoxia are encountered frequently with recurrent apneas, wherein hypoxic episodes last a few seconds only. Recent studies suggest that chronic intermittent hypoxia (CIH) represents a form of oxidative stress involving reactive O2species. The objectives of the present study were to determine 1) whether acute, repeated, brief EH (15 s) elicit LTF in breathing and 2) whether prior conditioning with CIH modulates acute EH-induced LTF of breathing, and if so whether reactive O2 species are involved. Experiments were performed on anesthetized, vagotomized, paralyzed, and mechanically ventilated rats, and efferent phrenic nerve activity was monitored as an index of respiratory motor output. In control animals, acute EH (15-s hypoxia; 10 episodes; n = 9) increased minute neural respiration, which persisted during 60 min of the posthypoxic period, suggesting LTF of breathing. EH-induced LTF of respiration was markedly augmented in CIH-conditioned animals (15-s hypoxia, 9 episodes/h, 8 h/day for 10 days; n = 9). By contrast, conditioning with a comparable, cumulative duration of sustained hypoxia (4-h hypoxia; n = 8) did not augment LTF elicited by acute EH. Systemic administration of manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (5 mg · kg−1 · day−1for 10 days), a potent scavenger of O[Formula: see text]·, prevented CIH-induced potentiation of LTF ( n = 9). These results demonstrate that 1) acute, brief EH elicits LTF in respiratory motor output; 2) prior conditioning with CIH, but not with comparable, cumulative duration of sustained hypoxia, augments LTF elicited by acute EH; and 3) O[Formula: see text]· radical scavenger prevents CIH-induced potentiation of LTF of respiration.

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Sustained hypoxia enhances chondrocyte matrix synthesis

Journal of Orthopaedic Research® ◽

10.1002/jor.20816 ◽

2009 ◽

Vol 27 (6) ◽

pp. 793-799 ◽

Cited By ~ 48

Author(s):

Christian H. Coyle ◽

Nicholas J. Izzo ◽

Constance R. Chu

Keyword(s):

Matrix Synthesis ◽

Sustained Hypoxia

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Visceral White Adipose Tissue after Chronic Intermittent and Sustained Hypoxia in Mice

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/rcmb.2016-0243oc ◽

2017 ◽

Vol 56 (4) ◽

pp. 477-487 ◽

Cited By ~ 32

Author(s):

David Gozal ◽

Alex Gileles-Hillel ◽

Rene Cortese ◽

Yan Li ◽

Isaac Almendros ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Sustained Hypoxia

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Spinal protein phosphatase 1 constrains respiratory plasticity after sustained hypoxia (1091.2)

The FASEB Journal ◽

10.1096/fasebj.28.1_supplement.1091.2 ◽

2014 ◽

Vol 28 (S1) ◽

Author(s):

Adrianne Huxtable ◽

Timothy Peterson ◽

Elizabeth Kopp ◽

Gordon Mitchell

Keyword(s):

Protein Phosphatase ◽

Protein Phosphatase 1 ◽

Respiratory Plasticity ◽

Sustained Hypoxia

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Chronic Caffeine Intake in Adult Rat Inhibits Carotid Body Sensitization Produced by Chronic Sustained Hypoxia but Maintains Intact Chemoreflex Output

Molecular Pharmacology ◽

10.1124/mol.112.081216 ◽

2012 ◽

Vol 82 (6) ◽

pp. 1056-1065 ◽

Cited By ~ 12

Author(s):

Silvia V. Conde ◽

Maria J. Ribeiro ◽

Ana Obeso ◽

Ricardo Rigual ◽

Emilia C. Monteiro ◽

...

Keyword(s):

Carotid Body ◽

Caffeine Intake ◽

Adult Rat ◽

Chronic Caffeine ◽

Sustained Hypoxia

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Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype

SLEEP ◽

10.1093/sleep/zsab290 ◽

2021 ◽

Author(s):

Xin Zhen ◽

Esteban A Moya ◽

Mary Gautane ◽

Huayi Zhao ◽

Elijah S Lawrence ◽

...

Keyword(s):

Blood Pressure ◽

Intermittent Hypoxia ◽

Systolic Pressure ◽

Metabolic Effects ◽

Metabolic Phenotype ◽

Glucose Disposal ◽

Chronic Obstructive ◽

Ventricular Systolic Pressure ◽

Obstructive Sleep ◽

Sustained Hypoxia

Abstract Study objectives Chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome is associated with excess mortality, and outcomes are related to the degree of hypoxemia. People at high altitude are susceptible to periodic breathing, and hypoxia at altitude is associated with cardio-metabolic dysfunction. Hypoxemia in these scenarios may be described as superimposed sustained plus intermittent hypoxia, or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice. Methods C57BL/6J mice were subjected to either sustained hypoxia (SH, FiO2=0.10), intermittent hypoxia (IH, FiO2=0.21 for 12 hours, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 hours), OH (FiO2=0.13 for 12 hours, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 hours), or room air (RA), n=8/group. Blood pressure and intraperitoneal glucose tolerance test were measured serially, and right ventricular systolic pressure (RVSP) was assessed. Results Systolic blood pressure transiently increased in IH and OH relative to SH and RA. RVSP did not increase in IH, but increased in SH and OH by 52% (p<0.001) and 20% (p=0.001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum LDL and VLDL increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH. Conclusions Overlap hypoxia may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of sustained hypoxia.

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