Non-specific cardiovascular depressant effect of methyl isocyanate (MIC) in rats

Methyl isocyanate (MIC) either inhaled (5, 10 mg/lit) or administered by intravenous (5, 10, 28 mg/kg) or subcutaneous (1300, 1500 mg/kg) routes produced a dose dependent fall in blood pressure (BP) and heart rate (HR) in anaesthetised rats. Higher doses (10 mg/lit inhalation, 10 & 28 mg/kg i.v., 1500 mg/kg s.c.) increased the lung body weight index (LBI) and tracheobronchial resistance (TBR) concomitant with gross pulmonary damage and edema. However, lower doses (5 mg/lit inhalation, 5 mg/kg i.v., 1300 mg/kg s.c.) produced the cardiovascular depressant effect without affecting LBI, lung morphology and TBR. The effects of MIC on BP, HR and TBR were not counteracted by muscarinic, histaminic and 5-HT receptor blockers and by vagotomy. Studies with hydrolysis products of MIC showed that relatively large doses of methylamine (MA) and dimethylurea (DMU) (i.v.) produced cardiovascular depressant effects, without affecting the LBI & TBR. The results indicate that the cardiovascular depressant effect of MIC may not be entirely a sequel to its effect on respiratory organs, release of vasoactive substances or its hydrolysis products. A non-specific cardiovascular depressant effect of MIC is suggested.