Dexamethasone Alleviates Meconium‐Induced Airway Hyperresponsiveness and Lung Inflammation in Rabbits

Abstract

The effects of dexamethasone on in vitro airway reactivity associated with lung inflammation were investigated in rabbits with meconium aspiration. Oxygen-ventilated adult rabbits received an intratracheal bolus of 4 ml/kg body weight of saline (Sal, n = 4) or human meconium (25 mg/ml). Thirty minutes later, meconium-instilled animals intravenously received 0.5 mg/kg of dexamethasone (Dexa, n = 6), or were left without treatment (Meco, n = 5). The animals were ventilated for a further 5 hr and then sacrificed. The left lungs were lavaged with saline, and the white blood cell (WBC) count was estimated. Tracheal and right-lung tissue strips were placed into organ chambers with Krebs-Henseleit solution. Cumulative doses of histamine (10(-8)-10(-3) mol/l) and acetylcholine (10(-8)-10(-3) mol/l) were added to the chambers, and recordings of contractions were made after a 30-min loading phase with a tension of 4 grams, and another 30-min adaptation phase with a tension of 2 g. Tracheal smooth muscle in vitro reactivity to histamine was higher in the Meco than in the Sal group, and dexamethasone decreased the reactivity compared to the Meco group (P < 0.05). Lung tissue in vitro reactivity to histamine was slightly higher in the Meco than in the Sal group (P > 0.05), and dexamethasone decreased the reactivity compared to both the Meco and Sal groups (P < 0.05). No between-group differences were observed in tracheal or lung in vitro reactivity to acetylcholine (P > 0.05). In the Meco group, blood WBC (P > 0.05) and neutrophil (P < 0.05) counts were lower than in the Sal and Dexa groups. Lung neutrophils and eosinophils were higher in both the Meco and Dexa groups than in the Sal group (P < 0.01). Dexamethasone decreased neutrophils (P < 0.05) compared to the Meco group. Meconium-induced airway hyperreactivity to histamine and lung inflammation were alleviated by dexamethasone.