Chronic intermittent hypoxia increases sympathetic  responsiveness to hypoxia and hypercapnia

Greenberg, Harly; Sica, Anthony L.; Batson, Deirdre; Scharf, Steven M.

doi:10.1152/jappl.1999.86.1.298

Cited by 194 publications

(159 citation statements)

References 30 publications

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“…Irrespective of the consciousness state of the rats, response to HR either decreases 14 or does not change in response to CO 2 inhalation ranging from mild (3-6%) to severe (12%) hypercapnic levels under general room conditions (Walker 1987;Greenberg et al 1999;Hirakawa and Hayashida 2002;Krohn et al 2003). In contrast to these findings, we induced an increase in the HR of anesthetized rats during water immersion.…”

Section: Discussionmentioning

confidence: 69%

Spinal cord transection inhibits HR reduction in anesthetized rats immersed in an artificial CO2-hot spring bath

Yamamoto

Hashimoto

2006

Int J Biometeorol

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Like humans, the heart rate (HR) of anesthetized rats immersed in CO 2 -water is lower than that when immersed in tap water at the same temperature. To investigate the afferent signal pathway in the mechanism of HR reduction, Wistar rats were anesthetized with urethane and then the spinal cord was transected between T 4 and T 5 . The animals were immersed up to the axilla in a bathtub of tap-water (CO 2 contents:10-20 mg·L -1 ) or of CO 2 -water (965-1400 mg·L -1 ) at 35°C while recording HR, arterial blood pressure, and arterial blood gas parameters (PaCO 2 , PaO 2 , pH). Arterial blood gas parameters did not change during immersion irrespective of CO 2 concentration of the bath water, whereas the HR was reduced in the CO 2 -water bath. The inhalation of CO 2 -mixed gas (5 % CO 2 , 20% O 2 , 75 % N 2 ) resulted in increased levels of blood gases and an increased HR during immersion in all types of water tested. The HR reduction observed in sham transected control animals immersed in CO 2 -water disappeared after subsequent spinal cord transection. These results show that the dominant afferent signal pathway to the brain, which is involved in inducing the reduced HR during immersion in CO 2 -water, is located in the neuronal route and not in the bloodstream.

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Section: Discussionmentioning

confidence: 69%

Spinal cord transection inhibits HR reduction in anesthetized rats immersed in an artificial CO2-hot spring bath

Yamamoto

Hashimoto

2006

Int J Biometeorol

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“…1) [3,6]. Intermittent hypoxia causes increased sympathetic nervous system stimulation, angiotensin II production and altered vasoconstrictor activity [12,13]. Increased vasoconstrictor activity leads to hypertension [12,13].…”

Section: Obstructive Sleep Apnea Associated With Endothelial Functionmentioning

confidence: 99%

“…Intermittent hypoxia causes increased sympathetic nervous system stimulation, angiotensin II production and altered vasoconstrictor activity [12,13]. Increased vasoconstrictor activity leads to hypertension [12,13]. Intermittent hypoxia leads to endothelin-1 production which is associated with endothelial dysfunction and vasoconstriction [6].…”

Section: Obstructive Sleep Apnea Associated With Endothelial Functionmentioning

confidence: 99%

Mechanism of development of pre-eclampsia linking breathing disorders to endothelial dysfunction

2009

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s u m m a r yHigh blood pressure is an important component of pre-eclampsia. The underlying mechanism of development of hypertension in pre-eclampsia is complicated and still remains obscure. Several theories have been advanced including endothelial dysfunction, uteroplacental insufficiency leading to generalized vasoconstriction, increased cardiac output, and sympathetic hyperactivity. Increased blood flow and pressure are thought to lead to capillary dilatation, which damages end-organ sites, leading to hypertension, proteinuria and edema. Additional theories have been put forward based on epidemiological research, implicating immunological and genetic factors. None of these theories have been substantiated. Based on a review of literature this paper postulates that the initiating event for the development of preeclampsia is intermittent hypoxia associated with irregular breathing during sleep, hypoapnea, apnea, inadequate respiratory excursions during the waking hours and inadequate cardiopulmonary synchronization (abnormal sympatho-vagal balance).Ó 2009 Elsevier Ltd. All rights reserved. BackgroundDespite being one of leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanism responsible for the pathogenesis of pre-eclampsia remains unclear [1,2]. Evidence shows that inadequate oxygenation from various causes leads to the initiation of an abnormal autonomic response. Several studies show a strong association between obstructive sleep apnea (OSA) and hypertension in the non-pregnant state [3,4]. Few studies in pregnancy corroborate this finding [5,6]. Nocturnal hypertension is observed significantly more in patients who have pre-eclampsia than those with gestational hypertension or chronic hypertension [5]. Also in OSA there is relative increase of the sympathetic activity associated with vasospasm, endothelial dysfunction, and increased angiotensin II levels, findings that are also implicated in the pathogenesis of pre-eclampsia [7,8].Incidence of snoring, hypoapnea and sleep apnea in the nonpregnant state, pregnancy and pre-eclampsiaThe incidence of snoring, hypoapnea, and sleep apnea is 9% in non-pregnant females and 14% in pregnant women [9][10][11]. By the third trimester, 24% of women were reported to have a snoring problem (symptom of sleep apnea). Habitual snorers had a higher frequency of pregnancy-induced hypertension (14%) compared to 6% of non-habitual snorers. The intrauterine growth retardation incidence was 7% in habitual snorers compared to 2.6% in nonsnorers [10]. In this study it was noted that all subjects who habitually snored and developed pre-eclampsia started to snore before hypertension or proteinuria was present. Abnormalities of breathing such as inspiratory flow limitation are observed more frequently in patients with pre-eclampsia (31 ± 8%) as compared to normal pregnant women (15.5 ± 2.3%), and non-pregnant females (<5%) [9]. The autonomic imbalance associated with this abnormal breathing was found to be associated with high systoli...

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“…However, there may be shortcomings that limit or constrain the potential of CIH as a therapeutic tool. For example, certain CIH protocols elicit pathophysiology such as systemic hypertension (Fletcher et al, 1992), altered sympathetic chemoreflexes (Greenberg et al, 1999), and hippocampal apoptosis (Gozal et al, 2001). These pathophysiological effects probably depend on the duration and severity of hypoxia.…”

Section: Significancementioning

confidence: 99%

Synaptic Pathways to Phrenic Motoneurons Are Enhanced by Chronic Intermittent Hypoxia after Cervical Spinal Cord Injury

Fuller¹,

Johnson²,

et al. 2003

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Spinal hemisection at C2 reveals caudal synaptic pathways that cross the spinal midline (crossed phrenic pathways) and can restore inspiratory activity in ipsilateral phrenic motoneurons. Intermittent hypoxia induces plasticity in the cervical spinal cord, resulting in enhanced inspiratory phrenic motor output. We hypothesized that chronic intermittent hypoxia (CIH) (alternating 11% O 2 and air; 5 min periods; 12 hr per night; 7 nights) would strengthen crossed phrenic pathways. Experiments were performed on anesthetized, vagotomized, paralyzed, ventilated, and spinally injured (C2 hemisection) rats that were exposed to either normoxia or CIH before acute injury (preconditioning) or after chronic injury (postconditioning). Spontaneous inspiratory bursts or compound action potentials evoked via stimulation of the ventrolateral funiculus (contralateral to injury) were recorded in both phrenic nerves. Spontaneous or evoked activity in crossed phrenic pathways were minimal or absent in all acutely injured rats regardless of preconditioning. In rats postconditioned with normoxia, crossed phrenic inspiratory bursts were observed occasionally during baseline conditions and always during chemoreceptor stimulation (hypoxia and hypercapnia). However, CIH postconditioned rats had substantially larger crossed phrenic inspiratory bursts during baseline, hypoxia, and hypercapnia (all p Ͻ 0.05 vs normoxic group). Short-latency (0.7 msec) evoked crossed phrenic potentials were also enhanced by CIH conditioning in chronically injured rats ( p Ͻ 0.05). We conclude that CIH induced spinal cord plasticityenhanced phrenic motor output. This plasticity required preconditions established by chronic spinal injury.

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Chronic intermittent hypoxia increases sympathetic responsiveness to hypoxia and hypercapnia

Cited by 194 publications

References 30 publications

Spinal cord transection inhibits HR reduction in anesthetized rats immersed in an artificial CO2-hot spring bath

Spinal cord transection inhibits HR reduction in anesthetized rats immersed in an artificial CO2-hot spring bath

Mechanism of development of pre-eclampsia linking breathing disorders to endothelial dysfunction

Synaptic Pathways to Phrenic Motoneurons Are Enhanced by Chronic Intermittent Hypoxia after Cervical Spinal Cord Injury

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