Abstract
The purpose of our study was to investigate the effects of nebulized adenosine 5'- monophosphate on airflow limitation in healthy cats determined by barometric whole body plethysmography (BWBP), in comparison to the effects of carbachol. Ten healthy 4- to 6-year-old domestic shorthair cats were included in the study. Each cat was placed in a BWBP plexiglass chamber (volume 38 l). Changes in box pressure were measured at baseline and after nebulization of vehicle and increasing concentrations of carbachol and adenosine 5'- monophosphate. Airway responsiveness was monitored as increases in enhanced pause (PENH), a unitless variable derived from dose-response curves estimating airflow limitation. The chosen endpoint was the agonist concentration which increased PENH to 300% of the value obtained after saline nebulization (PCPENH 300). Inter-day repeatability of measurements was assessed by repeated bronchoprovocations with both agonists 2-3 days apart. For carbachol, PCPENH300 was reached in all cats and correlated significantly between days (mean ± SD; 0.54 ± 0.42 mg/ml and 0.64 ± 0.45 mg/ml respectively; r = 0.58, p < 0.05) In contrast, we found no reaction to adenosine 5'- monophosphate even with the highest concentration nebulized during both measurements. At baseline, mean ± SD PENH was 0.47 ± 0.18 and 0.58 ± 0.24 (measurements 1 and 2), whereas PENH after 500 mg/ml adenosine 5'- monophosphate was 0.46 ± 0.20 and 0.71 ± 0.37. All bronchoprovocation tests were well tolerated by the cats. We conclude that healthy airways in cats do not demonstrate airway responsiveness to inhaled adenosine 5'- monophosphate. This is in agreement with observations in humans as well as our previous findings in dogs, where adenosine 5'- monophosphate had no effect on healthy canine airways, but caused significant airflow limitation after induction of acute bronchitis. To define the value of bronchoprovocation testing with adenosine 5'- monophosphate in the feline respiratory tract, further investigation of this agonist in cats with spontaneous lower airway disease will be required.
Highlights
Inhalational aerosol challenge with measurement of airway responsiveness is considered a valuable diagnostic tool for the detection of lower airway disease
The purpose of our study was to investigate the effects of nebulized adenosine 5’monophosphate on airflow limitation in healthy cats determined by barometric whole body plethysmography (BWBP), in comparison to the effects of carbachol
PCPENH300 was reached in all cats and correlated significantly between days In contrast, we found no reaction to adenosine 5’monophosphate even with the highest concentration nebulized during both measurements
Summary
Inhalational aerosol challenge with measurement of airway responsiveness is considered a valuable diagnostic tool for the detection of lower airway disease. A bronchoprovocative agonist commonly used for aerosol challenge in cats is carbachol, which causes airflow limitation by a direct action on the effector cells involved in the reduction of flow, such as airway smooth muscle cells, bronchial vascular endothelial cells and mucus producing cells. 5’- monophosphate (AMP), are thought to be more specific, since they only cause airflow limitation in inflamed airways. Their mechanism of action is based on cells other than the effector cells; these cells subsequently interact with the aforementioned effector cells. Barometric whole body plethysmography (BWBP) is an extremely non-invasive method used for monitoring airway responses to induced bronchoconstriction in rodents, cats or dogs (Chand et al 1993; Hamelmann et al 1997; Hofmann et al 1999; Talavera et al 2004). Breathing pattern is assessed dynamically by analysis of box-pressure signals that increase and decrease with the respiratory cycle (Fig. 1) (Hofmann et al 1999)
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