Acute induction of tracheo-bronchoconstriction in morphine/chloralose anesthetized dogs: Physiological approach and principles of therapy

The respiratory system serves as a functional gas exchanger and as a defense against perturbing antigens that cause a reflex tracheo-bronchoconstriction which affects homeostasis. In concert with the cardiovascular system, the pulmonary system continually adapts and responds to the demands for oxygen by tissues throughout the body, and pathological abnormalities profoundly deteriorate this function. Airways act reflexively to limit the intrusion of irritating air pollutants that trigger smooth muscle reactivity as in many pulmonary diseases. Tracheo-bronchoconstriction is a common sign in respiratory diseases and can be simulated experimentally in animal models in order to study the underlying mechanisms and to find the proper therapeutic approach. Since airways innervation plays a major role in the mechanism of smooth muscle hyperreactivity, this study was designed to evoke tracheo-bronchoconstriction by different stimuli that alter the autonomic nervous control of the respiratory system. In addition, the respiratory and hemodynamic effects of different classes of known bronchodilators were compared by using induced-bronchoconstriction in anesthetized dogs.; Tracheo-bronchoconstriction in morphine/chloralose anesthetized dogs was induced by hypercapnia (5% CO2), hypoxia (10% O2), or intravenous injection of 0.5 mg/kg bethanechol. After a 15 min period of baseline, each one of 8 dogs was exposed to both gas mixtures and bethanechol for 10 min each with 15 min recovery periods between exposures and then monitored for 30 min after bethanechol. Respiratory and hemodynamic parameters were recorded after each period of stimulus or recovery and they included tracheal (Tp), airway (Paw), bronchial (Brp), pulmonary artery (Pap), left ventricular end-diastolic (LVEDP) pressures, and heart rate (HR).; In conclusion, compared to gas mixtures, bethanechol has the most impressive and prolonged respiratory and hemodynamic effects that resemble acute clinical signs of respiratory diseases such as asthma and COPD. Because the PDE inhibitor and the beta2 agonist could not antagonize the bethanechol-induced bronchoconstriction, it may be concluded that tonic control of large airways is cholinergic. With some limitations such as anesthetic use and differences among species, this model might be of benefit in evaluating the mechanism of other bronchodilators that alter autonomic nervous control. In the future, particular interest should be directed to new M3-selective antimuscarinics that relax airway smooth muscle and decrease mucus secretion with few or no cardiovascular side effects. (Abstract shortened by UMI.)...