[Nonspecific inhalative provocation in the sheep as an asthma model--correlation of respiratory and cardiovascular...

Respiratory responses after inhalative challenge tests using methacholine (MCH) are intensively investigated and described in the literature. There is however a considerable lack of knowledge about the correlation of bronchoconstrictory responses to cardiovascular changes like pulmonary arterial pressure or blood gas tensions after unspecific challenges with methacholine or with specific allergens. Ten yearling sheep inhaled MCH-aerosols in increasing concentrations of 0.5, 1.0, 2.0, 5.0 and 10% for one minute respectively in 15 minutes intervals. Airway resistance (RI), dynamic elastance (Edyn) were measured along with systemic and pulmonary artery pressure. Transcutaneously measured oxygen partial pressure (PtcO2) was recorded and correlated to arterial blood gas samples. Mean threshold concentrations of MCH for changes in RI and Edyn were found at 0.9% and for PC100 of 2.2% MCH. Bronchoconstriction was detected with a latency of 30-40 s. Maximum responses occurred after 2-5 min (p < 0.0005) after onset of the challenge. Within 15 minutes, baseline values were almost reached. While mean inspiratory air-flow remained almost unaltered, increased airway resistance and work of breathing was compensated by an increased transpulmonary pressure. A decrease in tidal volume and a rise in respiratory frequency left ventilation almost unaltered. MCH-challenge results in insignificant changes in systemic arterial pressure, while pulmonary arterial pressure increased by more than 50% of the basic value. Arterial PO2 decreased by more than 20 mmHg and was closely correlated to transcutaneously measured O2-pressure (e = 0.93). However, PaCO2 did not increase significantly. (ABSTRACT TRUNCATED AT 250 WORDS)