LACK OF CARDIAC OR BRONCHODILATOR TACHYPHYLAXIS TO ISOPRENALINE IN THE DOG

1. Tachyphylaxis to heart rate and bronchodilator effects of (plus or minus)-isoprenaline was studied in anaesthetized open-chest dogs by 5 procedures. 2. Heart rate responses to a series of intravenous injections of isoprenaline were essentially unchanged before and after a 15 min infusion of isoprenaline (at 3 doses). 3. Heart rate and bronchodilator responses in the same animal to an intravenous injection of isoprenaline were not significantly different before and after a 30 min infusion of isoprenaline (at 2 doses). 4. Heart rate responses were relatively constant to an isoprenaline injection given every 30 min during a 4 h infusion of isoprenaline (at 3 doses), but the magnitude of the response was smallest for the largest infusion dose (highest background heart rate) and greatest for the smallest infusion dose (lowest background heart rate). 5. Heart rate and bronchodilator responses in the same animal to isoprenaline were relatively constant during a 5 h infusion of isoprenaline (at 2 doses). 6. Bronchodilator responses to intratracheally administered isoprenaline aerosol were essentially unchanged during a 4-5 h period using various doses and procedures. 7. Tachyphylaxis to the heart rate of bronchodilator effects of isoprenaline was not observed. The present data give no support to the hypothesis that tachyphylaxis to isoprenaline aerosols is an important mechanism in asthma mortality.