An improved porcine model of stable methacholine-induced bronchospasm

OBJECTIVE: To validate an animal model replicating the pathophysiological characteristics of severe induced bronchospasm observed in humans, with a high level of stability permitting measurements such as the assessment of ventilation-perfusion relationships with the multiple inert gas elimination technique. DESIGN AND SETTING: Experimental study in an animal research laboratory. SUBJECTS: 13 piglets (age 3-4 months) were studied and 7 underwent the complete protocol INTERVENTIONS: The animals were anesthetized and paralyzed. Mechanical ventilation was initiated in a volume-controlled mode. Ventilatory parameters were adjusted to obtain normocapnia and were maintained constant during the bronchospasm. Methacholine was administered via a synchronized nebulizer and progressively adjusted to obtain a stable twofold increase in peak inspiratory pressure. MEASUREMENTS AND RESULTS: Cardiopulmonary physiological data including assessment of lung mechanics and measurement of ventilation-perfusion relationships were obtained before and during the bronchospasm. Peak inspiratory pressure increased from 19.7+/-2.9 to 44.4+/-7.1 cmH(2)O during the bronchospasm. The latter remained stable over 2 h. Respiratory mechanics, gas exchange, and ventilation-perfusion distribution changes typical of those observed in severe bronchospasm in humans were observed in all animals. CONCLUSIONS: The present experimental model replicates some of the physiopathological characteristics of severe human bronchospasm, and its stability should facilitate studies of the effects of different ventilatory modes in the setting of acute severe asthma.