Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain

Wang, Kang; Smith, Zachary M.; Buxton, Richard B.; Swenson, Erik R.; Dubowitz, David J.

doi:10.1152/japplphysiol.00117.2015

Cited by 19 publications

(12 citation statements)

References 47 publications

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“…2,42,48 Another recent report showed that acetazolamide, a carbonic anhydrase inhibitor, abolished the CMRO 2 effect by hypoxia. 56 Since carbonic anhydrase inhibitor has a similar effect as hypercapnia in terms of lowering blood pH, this finding appears to be consistent with the observations of the present study.…”

Section: 34supporting

confidence: 92%

Searching for a truly “iso-metabolic” gas challenge in physiological MRI

Peng

Ravi

Sheng

et al. 2016

J Cereb Blood Flow Metab

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Hypercapnia challenge (e.g. inhalation of CO 2 ) has been used in calibrated fMRI as well as in the mapping of vascular reactivity in cerebrovascular diseases. An important assumption underlying these measurements is that CO 2 is a pure vascular challenge but does not alter neural activity. However, recent reports have suggested that CO 2 inhalation may suppress neural activity and brain metabolic rate. Therefore, the goal of this study is to propose and test a gas challenge that is truly ''iso-metabolic,'' by adding a hypoxic component to the hypercapnic challenge, since hypoxia has been shown to enhance cerebral metabolic rate of oxygen (CMRO 2 ). Measurement of global CMRO 2 under various gas challenge conditions revealed that, while hypercapnia (P ¼ 0.002) and hypoxia (P ¼ 0.002) individually altered CMRO 2 (by À7.6 AE 1.7% and 16.7 AE 4.1%, respectively), inhalation of hypercapnic-hypoxia gas (5% CO 2 /13% O 2 ) did not change brain metabolism (CMRO 2 change: 1.5 AE 3.9%, P ¼ 0.92). Moreover, cerebral blood flow response to the hypercapnichypoxia challenge (in terms of % change per mmHg CO 2 change) was even greater than that to hypercapnia alone (P ¼ 0.007). Findings in this study suggest that hypercapnic-hypoxia gas challenge may be a useful maneuver in physiological MRI as it preserves vasodilatory response yet does not alter brain metabolism.

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Section: 34supporting

confidence: 92%

Searching for a truly “iso-metabolic” gas challenge in physiological MRI

Peng

Ravi

Sheng

et al. 2016

J Cereb Blood Flow Metab

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“…This finding is corroborated by the finding that an increase in CMRO 2 following 6 h of normobaric hypoxia is removed with acetazolamide (Wang et al . ).…”

Section: Discussionmentioning

confidence: 97%

Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia

Bain

Ainslie

Hoiland

et al. 2016

The Journal of Physiology

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Key points The present study describes the cerebral oxidative and non‐oxidative metabolism in man during a prolonged apnoea (ranging from 3 min 36 s to 7 min 26 s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide. The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radial artery‐jugular venous oxygen content difference, was reduced by ∼29% at the termination of apnoea, although there was no change in the non‐oxidative metabolism. A subset study with mild and severe hypercapnic breathing at the same level of hypoxia suggests that hypercapnia can partly explain the cerebral metabolic reduction near the apnoea breakpoint. A hypercapnia‐induced oxygen‐conserving response may protect the brain against severe oxygen deprivation associated with prolonged apnoea. Abstract Prolonged apnoea in humans is reflected in progressive hypoxaemia and hypercapnia. In the present study, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnoea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO2) will be reduced near the termination of apnoea, attributed in part to the hypercapnia. Fourteen elite apnoea‐divers performed a maximal apnoea (range 3 min 36 s to 7 min 26 s) under dry laboratory conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, against the background of similar hypoxia. In both studies, the CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery‐internal jugular venous oxygen content difference. Non‐oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO2 was reduced by ∼29% (P < 0.01, Cohen's d = 1.18) near the termination of apnoea compared to baseline, although non‐oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O2 tension: ∼38.4 mmHg), severe hypercapnia (arterial CO2 tension: ∼58.7 mmHg), but not mild‐hypercapnia (arterial CO2 tension: ∼46.3 mmHg), depressed the CMRO2 (∼17%, P = 0.04, Cohen's d = 0.87). Similarly to the apnoea, there was no change in the non‐oxidative metabolism. These data indicate that hypercapnia can partly explain the reduction in CMRO2 near the apnoea breakpoint. This hypercapnic‐induced oxygen conservation may protect the brain against severe hypoxaemia associated with prolonged apnoea.

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“…In addition to altering the neurovascular coupling response, the cerebral metabolic rate of oxygen (CMR O 2 ) does not change during isocapnic hypoxia , with MRI-based evidence indicating that increased neural excitability (and subsequent CMR O 2 ) during PH is a consequence of hypoxic ventilatory response-induced hypocapnia (Smith et al, 2012;Vestergaard et al, 2015). This increase in CMR O 2 has been shown to be mitigated during hypoxia with the administration of acetazolamide (Wang, Smith, Buxton, Swenson, & Dubowitz, 2015), which indicates an important role of hypocapnia and alkalosis in cerebral metabolism during acute hypoxia.…”

Section: Cerebral Haemodynamics and Cognitive Functionmentioning

confidence: 99%

Isolating the independent effects of hypoxia and hyperventilation‐induced hypocapnia on cerebral haemodynamics and cognitive function

Friend

Balanos

Lucas

2019

Experimental Physiology

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New Findings What is the central question of this study?What are the independent effects of hypoxia and hypocapnia on cerebral haemodynamics and cognitive function? What is the main finding and its importance?Exposure to hyperventilation‐induced hypocapnia causes cognitive impairment in both normoxia and hypoxia. In addition, supplementation of carbon dioxide during hypoxia alleviates the cognitive impairment and reverses hypocapnia‐induced vasoconstriction of the cerebrovasculature. These data provide new evidence for the independent effect of hypocapnia on the cognitive impairment associated with hypoxia. Abstract Hypoxia, which is accompanied by hypocapnia at altitude, is associated with cognitive impairment. This study examined the independent effects of hypoxia and hypocapnia on cognitive function and assessed how changes in cerebral haemodynamics may underpin cognitive performance outcomes. Single reaction time (SRT), five‐choice reaction time (CRT) and spatial working memory (SWM) tasks were completed in 20 participants at rest and after 1 h of isocapnic hypoxia (IH, end‐tidal oxygen partial pressure (P ET O2) = 45 mmHg, end‐tidal carbon dioxide partial pressure (P ETC O2) clamped at normal) and poikilocapnic hypoxia (PH, P ET O2 = 45 mmHg, P ETC O2 not clamped). A subgroup of 10 participants were also exposed to euoxic hypocapnia (EH, P ET O2 = 100 mmHg, P ETC O2 clamped 8 mmHg below normal). Middle cerebral artery velocity (MCAv) and prefrontal cerebral haemodynamics were measured with transcranial Doppler and near infrared spectroscopy, respectively. IH did not affect SRT and CRT performance from rest (566 ± 50 and 594 ± 70 ms), whereas PH (721 ± 51 and 765 ± 48 ms) and EH (718 ± 55 and 755 ± 34 ms) slowed response times (P < 0.001 vs. IH). Performance on the SWM task was not altered by condition. MCAv increased during IH compared to PH (P < 0.05), which was unchanged from rest. EH caused a significant fall in MCAv and prefrontal cerebral oxygenation (P < 0.05 vs. baseline). MCAv was moderately correlated to cognitive performance (R2 = 0.266–0.289), whereas prefrontal cerebral tissue perfusion and saturation were not (P > 0.05). These findings reveal a role of hyperventilation‐induced hypocapnia per se on the development of cognitive impairment during normoxic and hypoxic exposures.

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Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain

Cited by 19 publications

References 47 publications

Searching for a truly “iso-metabolic” gas challenge in physiological MRI

Searching for a truly “iso-metabolic” gas challenge in physiological MRI

Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia

Isolating the independent effects of hypoxia and hyperventilation‐induced hypocapnia on cerebral haemodynamics and cognitive function

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