Mechanism of action of atracurium on airways

Histamine-releasing drugs may produce significant effects on airways in high-risk populations. To determine if clinically relevant doses of atracurium produce adverse effects on airways, we measured changes in airway resistance in the lung periphery of anesthetized Basenji-Greyhound dogs before and after intravenous (iv) administration of atracurium. A wedged bronchoscope technique was used to measure collateral system resistance (Rcs). After a stable baseline was obtained, atracurium (1.2 or 0.5 mg/kg) or histamine (200 micrograms) were administered as an iv bolus, and percent increase in Rcs was calculated. On separate days dogs were pretreated with the histamine 1 receptor antagonist, chlorpheniramine (0.2 mg/kg iv), with or without atropine (0.2 mg/kg iv) and ranitidine (0.75 mg/kg iv) and the experiment repeated. Histamine (200 micrograms) increased Rcs 97 +/- 24% at 30 s (8 sublobar segments), whereas a second dose increased Rcs 77 +/- 15%. Pretreatment with chlorpheniramine (0.2 mg/kg iv) totally prevented increases in Rcs (9 sublobar segments). Atracurium (1.2 mg/kg) increased Rcs to 174 +/- 35% at 3 min (14 sublobar segments), whereas 0.5 mg/kg had little effect (10 sublobar segments). A second bolus of atracurium (1.2 mg/kg) increased Rcs to only 54 +/- 14% (P less than 0.01). Chlorpheniramine pretreatment (0.2 mg/kg iv) reduced the response to the initial dose of atracurium to only 26 +/- 14% (10 sublobar segments). Pretreatment with a combination of atropine and chlorpheniramine (4 sublobar segments), or ranitidine and chlorpheniramine (5 sublobar segments), did not attenuate the increase in Rcs significantly more than chlorpheniramine pretreatment alone.(ABSTRACT TRUNCATED AT 250 WORDS)