MAKETA 5/2 po

More documents

Recommendations

Info

$(Tabu\276ky_VV\212_2007- JLF UK v Martine.xls) - Jesseniova ...$

18 A C T A M E D I C A M A R T I N I A N A 2 0 0 5 5/2 and those originated in esophagus in patients with GERD and subsequent convergence of these afferent inputs in the nucleus of the solitary tract (nTs) could be responsible for cough in this group of patients, although the pathological process is localized outside the respiratory tract area, from which the cough could be clearly elicited (11). The simplest hypothesis explaining the cough enhancement by reflux is that the intense activation of sensory nerves in esophagus either directly triggers cough and/or sensitizes the cough reflex. These changes would result in the inappropriately active cough reflex leading to chronic coughing. In our previous study we approached this hypothesis in the guinea pig cough models. Citric acid–induced cough was elicited during stimulation of the esophageal afferent nerves in the intact esophagus or esophagus with injured mucosa. We found that in either model the transient introduction of the nociceptive sensory nerve activator capsaicin into the esophagus did not trigger cough or affected cough induced by citric acid. Our results suggest that acute localized stimulation of esophageal mucosal nerves is not sufficient to trigger and/or enhance cough in guinea pigs. There is also suggestion that stimulation of afferent nerve endings in injured esophageal mucosa is able to change the cough sensitivity only in patients with some subclinical pathological changes in the airways (12). For that reason we decided to assess the effect of intraesophageal administration of capsaicin in supramaximal concentration on citric- acid induced cough in guinea pigs with experimentally induced allergic disorder of the respiratory system. Aim: The aim of the study was to assess the effect of intraesophageal administration of capsaicin (noxious stimulus activating nerve endings of C – fibres and subpopulation of Aδ nerve fibres) on citric acid induced cough in animals with experimental allergic rhinitis after passive sensitisation with ovalbumin and repeated sequence of active sensitisations with intranasal ovalbumin challenges, as well. METHODS Animals: All experiments were approved by Jessenius Faculty of Medicine Ethical Committee and followed the criteria of welfare of experimental animals, as well. Animals (guinea pigs n = 16) (body weight 350-450 g) were housed in an approved animal house, maintained at room temperature 21-22 O C, humidity 60-70%, ventilation, 12-h light-dark cycle and free access to water and standard animal food. Male TRIK strain guinea pigs were obtained from the Department of Experimental Pharmacology, Slovak Academy of Science (Dobra Voda, Slovak Republic) and used after at least 1week adaptation period in the animal house. Guinea pigs were adapted to experimental conditions two times, by inhalation of nebulized saline in the plethysmographic box. Ovalbumin sensitization: All animals (n = 16) were passively sensitized with ovalbumin (OA) (10 μg, Sigma) administered intraperitoneally together with aluminum hydroxide (100 mg) in saline (1 ml i.p) (13). Twenty-one days after successful sensitization was confirmed by skin prick test (intradermal injection of ovalbumin 25 μl of 200 μg.ml -1 ) on the skin of the back. Only sensitised animals with marked erythema and oedema were involved in the study. Animals were used for experiments 7 days later. Model of allergic rhinitis: Sensitized animals were used to develop a model of allergic rhinitis by repeated intranasal instillation of 0.015 ml of 0.5% OA into both nares via a thin catheter. These animals were repeatedly intranasally challenged with OA at 7-day intervals for 6 weeks. These challenges of antigen were followed by allergic nasal response (sneezing, nasal discharge and worsening of nasal breathing) and so this model of experimental allergic rhinitis was taken as confirmed. Intraesophageal administration of stimulating substances: Animals (n=16) were placed into a plastic cylinder (a part of the body chamber of the plethysmographic box equipment (double chamber plethysmograph type 855, Hugo Sachs Elektronik, Germany). This allowed immobilization of animals.
A C T A M E D I C A M A R T I N I A N A 2 0 0 5 5/2 19 After that, using a mouth opener device, thin portex catheter (external diameter 0.3 cm) with conducting wire was introduced into the esophagus of the animal. The catheter was tipped with cotton tampon and its end was positioned in the middle part of esophagus. Capsaicin (Sigma, 1000 μM, 0.2 ml) was applied into the catheter in a manner that allowed absorption of the solutions used into the cotton tampon. Conducting wire was then introduced into the catheter and cotton tampon was disengaged from its tip by means of careful moving of the conducting wire. Then the catheter was pulled out from esophagus and mouth. Induction of coughing: Awake guinea pigs were placed into the plastic cylinder (a part of plethysmographic box equipment) allowing immobilization of the animal. Then the animals were placed individually in a bodyplethysmograph (type 855, Hugo Sachs Electronic, Germany) (Fig.1) consisting of a head chamber and a body chamber. The opening between the head chamber and body chamber was equipped with a plastic collar lining around animal neck to prevent communication between the chambers. Appropriate collar size was chosen for each animal to prevent neck compression, which could cause airway obstruction and/or mechanical stimulation of the upper trachea and larynx. Fig. 1: Double chamber bodyplethysmograph (type 855, Hugo Sachs Elektronik, Germany) which is used in our department for induction of cough by administration of tussive aerosols into the front chamber of the plethysmograph. To expose an animal to aerosol, the head chamber was connected to a nebulizer (Pari Provokation Test I, Menzel, Germany, manufacturer’s specification: output 5 l.min -1 , particle mass median aerodynamic diameter 1.2 μm). A suction device adjusted to the same input 5 l. min -1 was connected to the head chamber to maintain constant airflow through the chamber during aerosol administration. Respiratory changes in the airflow were measured using pneumotachograph (Godart, Germany) with Fleisch head (No. 1, Gould Godart Statham BV) connected to the head chamber and recorded directly with pen recorder (Multiscriptor Hellige, Germany). Respiratory sounds including cough and sneezing were recorded with a microphone placed in the roof of the head chamber and connected to a preamplifier and loudspeaker. Pneumotachograph and tape recorder outputs were simultaneously recorded on a PC for off- line analysis. Cough challenge was performed using inhalation of citric acid (CA) (Lachema, 0.3 M) for 1 minute. Cough was detected from the expiratory change of airflow interrupting basic respiratory pattern accompanied by a cough sound during 1 min exposure to CA and subsequent 2 minutes period. Statistical analysis: Data for number of the cough efforts are expressed as a median and interquartil range. Statistical analysis of the samples was performed using a Kruskal – Wallis test. A probability value of P< 0.05 was considered as significant.
Page 1 and 2: ISSN 1335-8421 Acta Med Mart 2005,
Page 3 and 4: A C T A M E D I C A M A R T I N I A
Page 17: A C T A M E D I C A M A R T I N I A
Page 35: A C T A M E D I C A M A R T I N I A

MAKETA 5/2 po

Create successful ePaper yourself

Delete template?

Save as template?