Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome

Zwillich, Clifford W.; Sutton, Frank D.; Pierson, David J.; Creagh, Edward; Weil, John V.

doi:10.1016/0002-9343(75)90392-7

Cited by 241 publications

(97 citation statements)

References 20 publications

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“…Indeed, an impairment of ventilatory response to hypercapnia and hypoxaemia has been demonstrated in patients with OHS, with this defect being able to play a role in the development of chronic hypercapnia. 25,26 The role of SDB in the development of diurnal hypercapnia in obesity is rather controversial. Although we found that oxygen desaturation during sleep (ie TST SaO2o90% ) plays a major role in the development of daytime hypercapnia in obese women, the mechanism responsible for the relationship between nocturnal hypoxaemia and the daytime level of PaCO 2 is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Diurnal PaCO2 tension in obese women: relationship with sleep disordered breathing

et al. 2003

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OBJECTIVE: Several obese subjects show a wide array of respiratory disturbances during sleep due to an increased upper-airway resistance. The aim of the present study was to evaluate diurnal PaCO 2 tension in nonsmoking obese women and the possible relationship of this parameter with the presence of sleep disordered breathing (SDB). DESIGN: Cross-sectional study of PaCO 2 tension in obese women. PATIENTS AND METHODS: A total of 91 nonsmoking obese women (BMI Z30 kg/m 2 , aged 42.8715.7 y) were recruited and evaluated for general and anthropometric parameters, respiratory function, sleep-related symptoms, and sleep disorders of breathing. RESULTS: A total of 10 subjects (10.9%) had diurnal hypercapnia (PaCO 2 Z43 mmHg). Age, BMI, neck circumference, apnoea/ hypopnoea index, and nocturnal desaturation (expressed as TST SaO 2o90% ; TST SaO 2o90% ¼ percentage of total sleep time with oxyhaemoglobin saturation o90%) were significantly higher in obese patients with diurnal hypercapnia, compared to normocapnic women. Moreover, hypercapnic patients had reduced forced expiratory volume in 1 s compared to normocapnic individuals. By using multiple regression analysis, the best fitting model (r ¼ 0.62, Po0.001) for predicting diurnal PaCO 2 tension in the study population showed that 24.23% of the variance may be explained by TST SaO 2o90% , according to the equation: PaCO 2 ¼ 0.09 age+0.07 TST SaO 2o90% +33.00. CONCLUSIONS: This study suggests that severity of SDB is the most important factor in determining diurnal PaCO 2 tension in apparently healthy nonsmoking obese women.

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Section: Discussionmentioning

confidence: 99%

Diurnal PaCO2 tension in obese women: relationship with sleep disordered breathing

et al. 2003

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“…However, individuals with OHS fail to compensate their respiratory drive in response to the added load created by excess weight, thus permitting a gradual increase in PCO 2 [32,45,46]. Central ventilatory responsiveness to both hypoxia and hypercapnia are attenuated in OHS compared to non-obese and eucapnic obese patients with or without OSA [47,48]. The decreased ventilatory response is attributed secondary to the blunted neural response to hypercapnia [46,47], which in turn has been shown to improve within days or weeks after initiating PAP therapy, in the absence of significant change in weight [49][50][51][52].…”

Section: Central Respiratory Drivementioning

confidence: 99%

Obesity Hypoventilation Syndrome

2010

IJPM

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Obesity hypoventilation syndrome is a respiratory consequence of morbid obesity that is characterized by alveolar hypoventilation during sleep and wakefulness. The disorder involves a complex interaction between impaired respiratory mechanics, ventilatory drive and sleepdisordered breathing. Early diagnosis and treatment is important, because delay in treatment is associated with significant mortality and morbidity. Available treatment options include noninvasive positive airway pressure (PAP) therapies and weight loss. There is limited long-term data regarding the effectiveness of such therapies. This review outlines the current concepts of clinical presentation, diagnostic and management strategies to help identify and treat patients with obesityhypoventilation syndromes.

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“…8,9 The development of OHS is insidious and is often overlooked because patients are typically free of respiratory complaints. Since altered NMDA receptor mediated mechanisms partially contribute to a ventilatory response to hypoxia during early phase of hypoxic exposure and to a blunted neural respiratory drive during hypoxic exposure in obese Z rats, it is possible that altered NMDA receptor-mediated activity may represent a neural component of OHS in morbidly obese humans.…”

Section: Signi®cancementioning

confidence: 99%

“…1,4 ± 7 The underlying mechanisms responsible for the blunted ventilatory responses in obesity are unknown, but thought to represent part of pathogenesis of obesity hypoventilation syndrome (OHS) in obese humans. 8,9 The ventilatory response to sustained hypoxia in humans and in some animals is characterized by an initial increase in ventilation (early phase), followed by a gradual decline in ventilation (late phase). 10,11 The increase in ventilation during hypoxia is closely related to the release of excitatory neurotransmitters, in particular glutamate, 11 ± 15 acting on Nmethyl-D-aspartate (NMDA) receptors located in brainstem respiratory motor neurons.…”

Section: Introductionmentioning

confidence: 99%

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

2001

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BACKGROUND: Ventilation in response to hypoxia is reduced in some obese humans and is believed to represent part of the pathogenesis of obesity hypoventilation syndrome (OHS). Ventilation in response to hypoxic exposure is closely related to the release of excitatory neurotransmitters, in particular glutamate, acting speci®cally on N-methyl-D-aspartate (NMDA) receptors. OBJECTIVES: The aim of the present study was to investigate whether NMDA receptor-mediated mechanisms are responsible for the altered ventilatory response to sustained hypoxia observed in obese Zucker (Z) rats. SUBJECTS: Seven lean and seven 15-week-old obese male Z rats were studied. MEASUREMENTS: Ventilation (V Ç E ) at rest and during 30 min sustained hypoxic (10% O 2 ) exposure was measured by the barometric method. V Ç E was assessed following the blinded-random administration of equal volumes of either saline (vehicle) or dextromethorphan (DM, 10 mgakg), a non-competitive glutamate NMDA receptor antagonist. RESULTS: DM had no effects on resting V Ç E in both lean and obese rats during room air breathing. Lean rats treated with DM exhibited a signi®cant (P`0.05) depression in V Ç E , V T , and V T aT I during either the early (5 min) or the late phase (30 min) of ventilatory response to sustained hypoxia. In contrast, DM administration in obese rats did not change V Ç E , V T , or V T aT I during the early phase of ventilatory response to hypoxia. During the late phase of ventilatory response to hypoxia. obese rats treated with DM exhibited a similar depression in V Ç E and V T as observed in lean rats, but had no signi®cant change in V T aT I during the 30 min hypoxic exposure. CONCLUSION: Our ®ndings indicate that altered glutamatergic mechanisms acting on NMDA receptors are partially responsible for a blunted early phase of ventilatory response to hypoxia noted in obese rats and also contribute to their reduced neural respiratory drive.

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Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome

Cited by 241 publications

References 20 publications

Diurnal PaCO2 tension in obese women: relationship with sleep disordered breathing

Diurnal PaCO2 tension in obese women: relationship with sleep disordered breathing

Obesity Hypoventilation Syndrome

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

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