Dexamethasone alleviates meconium-induced airway hyperresponsiveness and lung inflammation in rabbits.
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.
Mokry
Juraj
J
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. mokry@jfmed.uniba.sk
Mokra
Daniela
D
Antosova
Martina
M
Bulikova
Janka
J
Calkovska
Andrea
A
Nosalova
Gabriela
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008470:Meconium / Q000737:chemistry*; D008471:Meconium Aspiration Syndrome / Q000503:physiopathology; D009130:Muscle, Smooth / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy*; D011817:Rabbits; D014132:Trachea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone