Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression

Swenson, Erik R.

doi:10.1183/09031936.98.12061242

Cited by 131 publications

(140 citation statements)

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“…In the present study, an improvement in mean nocturnal PET,CO 2 , Sa,O 2 and lowest Sa,O 2 , and a decrease of the percentage of time Sa,O 2 v90% was found. The maximal dose of ACET shown not to induce a significant arterial-to-end tidal CO 2 tension gradient gradient was 4 mg?kg -1 in cats (which is equivalent to 250 mg ACET every 8-12 h) [31]. SWENSON [31] also showed that although a higher dose may increase ventilation, an impaired CO 2 transport and ventilation/perfusion mismatch in the lung occurs.…”

Section: Nocturnal Measurementsmentioning

confidence: 99%

“…The maximal dose of ACET shown not to induce a significant arterial-to-end tidal CO 2 tension gradient gradient was 4 mg?kg -1 in cats (which is equivalent to 250 mg ACET every 8-12 h) [31]. SWENSON [31] also showed that although a higher dose may increase ventilation, an impaired CO 2 transport and ventilation/perfusion mismatch in the lung occurs. Furthermore, in the treatment of central apnoea syndrome as well as obstructive sleep apnoea, a low dose of ACET (250 mg?day -1 ) was shown to be sufficient to increase overall tonic output of the respiratory controller, augment breathing and to improve quality of life.…”

Section: Nocturnal Measurementsmentioning

confidence: 99%

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Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

Wagenaar¹,

Vos²,

Heijdra³

et al. 2002

Eur Respir J

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Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients. M. Wagenaar, P. Je Vos, Y.F. Heijdra, L.J. Teppema, H.T.M. Folgering. #ERS Journals Ltd 2002. ABSTRACT: Medroxyprogesterone acetate (MPA) and acetazolamide (ACET) are two ventilatory stimulants which are used in hypoxic and hypercapnic patients with chronic obstructive pulmonary disease (COPD).In a double-blind randomised study, the effects of a 2-week treatment with MPA (30 mg b.i.d.) or ACET (250 mg b.i.d.), followed by a 2-week treatment with a combination of both drugs (MPA/ACET), on daytime and nocturnal ventilatory and blood gas parameters in 17 stable hypercapnic COPD patients were investigated.ACET, MPA and MPA/ACET treatment decreased mean daytime carbon dioxide tension in arterial blood by 0.4, 0.7 and 1.2 kPa, respectively. Minute ventilation was improved only with combined therapy, from 9.3 to 11.2 L?min -1 . With MPA/ACET therapy, the hypercapnic and hypoxic ventilatory responses significantly increased, from 3.7 to 5.8 L?min -1 ?kPa -1 and from -0.13 to -0.40 L?min -1 ?% -1 , respectively. The mouth exclusion pressure response to hypoxia increased during combination therapy, from -0.01 to -0.03 kPa?% -1 . Nocturnal end-tidal carbon dioxide tension decreased with MPA and MPA/ACET treatment, by 0.9 and 1.4 kPa, respectively. MPA/ACET significantly increased mean nocturnal arterial oxygen saturation values, from 85.5 to 90.2%.The authors conclude that short-term combined treatment with medroxyprogesterone acetate and acetazolamide has a more favourable effect on day and night-time blood gas values and chemical drive than single drug treatment.

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Section: Nocturnal Measurementsmentioning

confidence: 99%

Section: Nocturnal Measurementsmentioning

confidence: 99%

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

Wagenaar¹,

Vos²,

Heijdra³

et al. 2002

Eur Respir J

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“…For example, the carbonic anhydrase inhibitors acetazolamide and benzolamide produce a metabolic acidosis without increasing the isocapnic AHR (20,37,38,43). Apart from a substantial acidemia, acetazolamide also causes a substantial drop in arterial PCO 2 induced by a carotid bodymediated rise in ventilation (35,38,41). When the Pa CO 2 is kept at the much higher pre-drug resting value, the AHR after acetazolamide becomes higher than control (43).…”

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confidence: 99%

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Teppema

Dörp

Dahan

2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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ϩ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic Ϫ normoxic) ventilation over (hypoxic Ϫ normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic Ϫ normoxic) ventilation over (logPa O 2 hypoxia Ϫ logPa O 2 normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal PO2 to ϳ50 Torr lasting 5 min each at three different constant end-tidal PCO2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa CO 2 , and a parallel leftward shift of the ventilatory CO 2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O 2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arteriala without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H ϩ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H ϩ ]a response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated. hypoxic sensitivity; O2-CO2 interaction; hydrogen ions; CO2 THE HYPOXIC VENTILATORY RESPONSE in humans is biphasic and consists of an initial rise in ventilation initiated by the carotid bodies followed by a secondary roll-off, usually designated as hypoxic ventilatory decline (HVD) (8,13,16,25). The magnitude of this decline is proportionally related to the initial rise in ventilation in response to acute hypoxia and thus also to the intensity of the hypoxic stimulus (8,18,25). Measurement of the ventilatory response to hypoxia without the "confounding" influence of HVD is possible by exposing subjects to brief step-wise changes in end-tidal PO 2 lasting 3-5 min, a period too short for HVD to develop. Consequently, the ventilatory response to such an acute hypoxic challenge (the acute hypoxic response, AHR) is attributed to the peripheral chemoreceptors in the carotid bodies. The magnitude of the AHR can be influenced by many factors such as the background arterial PCO 2 . A rise in Pa CO 2 augments the AHR, and this is known as multiplicative O 2 -CO 2 interaction (6, 7, 10). This phenomenon is thought to reside in the carotid bodies (15,22,26), but its mechanism at the molecular level in oxygen-sensitive type I cells remains to be elucidated (29). A rise in Pa CO 2 not only leads to extracellular acidosis (acidemia) but also to increases in ...

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“…Physiological responses and the progress of acclimatization may also have been influenced by the use of small doses of acetazolamide on day 1 in Putre, when leaving Copiapó, and the night before climbing Ojos. Acetazolamide is a well-known potent carbonic anhydrase inhibitor that causes diuresis and renal bicarbonate loss, increases minute ventilation and oxygenation, and improves sleep quality thereby hastening acclimatization (Swenson, 1998). This may probably also be the reason why the less acclimatized subjects who took acetazolamide only the night before climbing Ojos did not suffer from more severe AMS.…”

Section: Resultsmentioning

confidence: 99%

Effects of Pre-acclimatization Applying the ‘‘Climb High and Sleep Low’’ Maxim: An Example of Rapid but Safe Ascent to Extreme Altitude

Burtscher¹,

Koch²

2016

Journal of Human Performance in Extreme Environments

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Pre-acclimatization at a convenient high-altitude location may represent an appropriate method before climbing a more hostile target mountain. The aim of the present field report was to demonstrate the effectiveness of such pre-acclimatizing applying the ''climb high sleep low'' maxim for a subsequent rapid ascent to almost 7000 m. After some pre-acclimatization in the Alps the authors flew to Chile for further pre-acclimatization in the Aymara village of Putre (3650 m). From there they undertook sojourns up to altitudes of 5700 m within 3 days. Subsequently they went back to Arica (sea level) and climbed Ojos del Salado (6893 m) within 5 days without any health problems. Measurements of heart rate and arterial oxygen saturation and of cerebral oxygenation by near infrared spectroscopy at rest and during exercise indicated adequate acclimatization status. This field report demonstrates highly effective pre-acclimatization by the ''climb high and sleep low'' strategy supporting anecdotal reports. The up and down strategy may likely have induced hypoxia (pre)conditioning and subsequently allowed rapid ascent to extreme altitudes without any complications. The duration of the carry-over effect after pre-acclimatization has to be evaluated and proposed physiological mechanisms have to be proved by controlled studies in larger samples.

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Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression

Cited by 131 publications

References 64 publications

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Effects of Pre-acclimatization Applying the ‘‘Climb High and Sleep Low’’ Maxim: An Example of Rapid but Safe Ascent to Extreme Altitude

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Carbonic anhydrase inhibitors and ventilation: a complex interplay of stimulation and suppression

Cited by 131 publications

References 64 publications

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

Effects of Pre-acclimatization Applying the ‘‘Climb High and Sleep Low’’ Maxim: An Example of Rapid but Safe Ascent to Extreme Altitude

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Arterial [H⁺] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis