Pathophysiologic study of 3-methylindole-induced pulmonary toxicosis in immature cattle.

In 5 Friesian calves given 3-methylindole (3-MI) (100 mg/kg once a week for 8 weeks, except calf 4, given a 50 mg/kg dose on weeks 3 to 8), pulmonary function (PF) values and arterial blood gas tensions (PaO2 and PaCO2) were measured 24 hours after dosing was done and were correlated with clinical, biochemical, and pathologic changes. Three of the calves (No. 1, 2, and 3) showed acute respiratory distress syndrome 24 hours after the first 3-MI treatment, with a large increase in respiratory frequency, minute viscous work, and PaCO2 and a large decrease in tidal volume, dynamic lung compliance, and PaCO2. They died 36, 38, and 84 hours after dosing. Pulmonary function changes were compatible with the severe pulmonary edema and alveolar damage observed at necropsy. The 2 other calves, after they were given the 1st dose, showed only subacute respiratory distress syndrome with less severe changes in PF values recorded at 24 hours. Furthermore, they became progressively more tolerant to the 2nd, 3rd, and 4th weekly treatments, and showed base-line PF values after the 5th weekly treatment. Pathologic changes were not observed in lung biopsy material from these 2 animals at 2 and at 12 weeks after the 8th (or last) 3-MI treatment.

3-methylindole-induced pulmonary toxicosis in ponies.

In unanesthetized ponies, arterial blood gas tensions, pulmonary mechanics, and lung volumes were determined before and 24 to 48 hours after oral administration of 500 ml of corn oil or 100 mg of 3-methylindole (3MI)/kg of body weight in 500 ml of corn oil. In the latter group, variables were also measured after bilateral cervical vagotomy. Respiratory rate and minute ventilation were increased by 3MI treatment and decreased after vagotomy, suggesting that the tachypnea induced by 3MI was vagally mediated. The arterial O2 tension (PaO2) was unaffected but arterial CO2 tension (PaCO2) decreased below base line after 3 MI and vagotomy. Specific respiratory conductance and dynamic compliance wee decreased by 3MI. Specific conductance increased again after vagotomy. Functional residual capacity, which increased after 3MI, was unaffected by vagotomy. Total lung capacity and quasistatic compliance were unaffected by either treatment. Minimal volume was larger in 3MI-treated ponies than in untreated ponies. Decreased dynamic compliance and specific respiratory conductance and increased functional residual capacity and minimal volume are all compatible with small airway obstruction produced by the necrotizing bronchiolitis and bronchiolar obstruction observed histologically in 3MI-treated ponies.