ABSTRACT
A new method has been developed to measure airway functions in unanaesthetized, unrestrained guinea-pigs. The technique utilizes a specially designed pneumotachograph that is placed inside the trachea, and a saline-filled balloon, placed inside the pleural cavity. The pneumotachograph consists of a stainless steel cylinder with coaxial and perpendicular tubes attached to it, measuring the total pressure and the lateral pressure in the trachea, respectively. Via air-filled silicon conducting tubes, subcutaneously driven and permanently attached to the neck of the animal, the pressures are fed into a differential pressure transducer, yielding a pressure difference proportional to the airflow in the trachea. Via a saline-filled tubing, the pleural balloon is similarly attached to the neck of the animal, and pleural pressure (Ppl) is measured using a second pressure transducer. These data permit calculation of airway functions in conscious, unstressed animals. Control values for airway resistance (RAW), Ppl, tidal volume and respiratory frequency are all in the range of results reported previously for this species. A very significant correlation between RAW and Ppl (P < 0.001) was observed, indicating that sole Ppl-measurement can be used as a relatively simple and sensitive method to assess bronchial obstructive reactions in unrestrained guinea-pigs. Using a specially designed provocation cage, which allowed the animals to remain in a stress-free, unrestrained condition, the method has been successfully applied for the assessment of the dose-dependent bronchoconstrictor sensitivity to histamine as well as to allergen-induced early and late phase airway reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Bronchial Provocation Tests/instrumentation , Pulmonary Ventilation , Airway Resistance , Animals , Equipment Design , Female , Guinea Pigs , Male , TransducersABSTRACT
Removal of the epithelial layer of rat tracheal tissue did not affect the methacholine-induced contraction of the tracheal smooth muscle, but attenuated the (-)-isoprenaline induced relaxation (expressed as percentage of the methacholine contraction). In this way the epithelial layer seemed to play a role in the maintenance of an autonomic balance between sympathetic and parasympathetic receptor responses. Incubation of rat tracheal tissue with cumene hydroperoxide (3 x 10(-5)-10(-3) M) resulted in a dose-dependent destruction and (partial) removal of the epithelial layer. Cumene hydroperoxide diminished muscarinic receptor responses of the rat trachea. Moreover, the autonomic balance between muscarinic and beta-adrenoceptor responses was affected. The effects of cumene hydroperoxide on receptor responses were more pronounced after epithelium removal. The protective role of the epithelial layer of pulmonary tissue against oxidative stress has therefore been emphasized.
Subject(s)
Benzene Derivatives/toxicity , Isoproterenol/toxicity , Methacholine Chloride/toxicity , Muscle, Smooth/drug effects , Receptors, Adrenergic, beta/drug effects , Receptors, Muscarinic/drug effects , Trachea/drug effects , Animals , Epithelium/physiology , Male , Muscle Contraction/drug effects , Rats , Rats, Inbred Strains , Trachea/pathologyABSTRACT
Chronic exposure to several types of mineral dust particles induces an inflammatory reaction in the lung. Dust particles activate alveolar macrophages and prime leukocytes (neutrophils, eosinophils, and basophils), leading to an enhanced release of reactive oxygen species. Sometimes mineral dust particles also contain radicals. Reactive oxygen species (superoxide anion radical, hydrogen peroxide, hydroxyl radical, and singlet oxygen) may lead to tissue damage. These are able to break DNA strands, to destroy proteins, and to induce the process of lipid peroxidation. The effects of oxygen radicals on the beta-adrenergic and muscarinic receptor response of the guinea pig and rat tracheal strip are described. The beta-adrenergic receptor response appeared to be more susceptible to oxidative stress than the muscarinic receptor response. This may lead to an autonomic imbalance on exposure to oxygen radicals. The lipid peroxidation product 4-hydroxy-2,3-trans-nonenal diminished the beta-adrenergic responsiveness in guinea pig tracheal preparations. Histologic examinations indicated that at low concentrations of cumene hydroperoxide (10(-4) M) the epithelial layer of rat trachea was already destroyed, whereas no effect on the muscarinic response was found. Oxygen radical-mediated damage in lung tissue may lead to lung emphysema, hyperresponsiveness, and hypersensitivity. Pharmacotherapeutic interventions that prevent initiation or propagation of these free radical reactions may have a beneficial effect in mineral dust-associated lung disease.
