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Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.

Cancado JE, Mendes ES, Arana J, Horvath G, Monzon ME, Salathe M, Wanner A - BMC Pharmacol Toxicol (2015)

Bottom Line: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation).The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation.These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. educancado@uol.com.br.

ABSTRACT

Background: In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway.

Methods: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed.

Results: Mean ± SE EBC pH (units) and ΔQ̇aw (μl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing).

Conclusions: Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH.

Trial registration: Registered at clinicaltrials.gov: NCT01216748 .

No MeSH data available.


Related in: MedlinePlus

Relative albuterol-induced changes in airway blood flow (ΔQ̇aw) during four breathing maneuvers. Values are mean ± SE. *p < 0.01 and ** p < 0.02 vs quiet breathing and eucapnic hyperventilation.
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Fig1: Relative albuterol-induced changes in airway blood flow (ΔQ̇aw) during four breathing maneuvers. Values are mean ± SE. *p < 0.01 and ** p < 0.02 vs quiet breathing and eucapnic hyperventilation.

Mentions: Baseline mean Q̇aw values were similar before the four breathing maneuvers and remained unchanged during the subsequent breathing maneuvers as reflected by the pre-albuterol values (Table 3). All subjects had similar albuterol response to the different breathing maneuvers. Albuterol increased mean Q̇aw significantly, by 46.2 and 33.8% 15 min post drug inhalation during quiet breathing and eucapnic hyperventilation, respectively (Table 3, Figure 1). In contrast, albuterol had no effect on mean Q̇aw during hypercapnic hyperventilation (4.9%) or hypocapnic hyperventilation (-1.3%) maneuvers, which were associated with a decrease or increase in EBC pH.Table 3


Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.

Cancado JE, Mendes ES, Arana J, Horvath G, Monzon ME, Salathe M, Wanner A - BMC Pharmacol Toxicol (2015)

Relative albuterol-induced changes in airway blood flow (ΔQ̇aw) during four breathing maneuvers. Values are mean ± SE. *p < 0.01 and ** p < 0.02 vs quiet breathing and eucapnic hyperventilation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4384333&req=5

Fig1: Relative albuterol-induced changes in airway blood flow (ΔQ̇aw) during four breathing maneuvers. Values are mean ± SE. *p < 0.01 and ** p < 0.02 vs quiet breathing and eucapnic hyperventilation.
Mentions: Baseline mean Q̇aw values were similar before the four breathing maneuvers and remained unchanged during the subsequent breathing maneuvers as reflected by the pre-albuterol values (Table 3). All subjects had similar albuterol response to the different breathing maneuvers. Albuterol increased mean Q̇aw significantly, by 46.2 and 33.8% 15 min post drug inhalation during quiet breathing and eucapnic hyperventilation, respectively (Table 3, Figure 1). In contrast, albuterol had no effect on mean Q̇aw during hypercapnic hyperventilation (4.9%) or hypocapnic hyperventilation (-1.3%) maneuvers, which were associated with a decrease or increase in EBC pH.Table 3

Bottom Line: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation).The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation.These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. educancado@uol.com.br.

ABSTRACT

Background: In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway.

Methods: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed.

Results: Mean ± SE EBC pH (units) and ΔQ̇aw (μl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing).

Conclusions: Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH.

Trial registration: Registered at clinicaltrials.gov: NCT01216748 .

No MeSH data available.


Related in: MedlinePlus