Pulmonary Toxicity of Monocrotaline Differs in Neonatal, Young and Adult Rats

Abstract

We hypothesized that the toxic effect of a single monocrotaline (M)injection(60mg/kg)would result in pulmonary vascular abnormalities of different severity in neonatal-3day(N),infant-8day(I) and adult-8 week(A)rats and might affect lung growth. Mixed Sprague-Dawley litters and A rats were used:½ injected with M, and ½ with saline-controls(C).Two and 4 weeks after injection,rats were killed,right and left ventricles(RV,LV)weighed and lungs injected and fixed inflated for lung volumes(Vol),and morphometric analysis of alveoli/mm2,arteries per 100 alveoli(A:100a),medial wall thickness of muscular arteries(%WT) and extension of muscle into peripheral arteries(%Ext). NM rats died 2-3 wks post injection.Pulmonary vascular changes and lung Vol. were similar to IM rats but alveolar multiplication was impaired(alv/mm2=129±24 vs 198±29 in NC,p<0.05) IM rats had normal lung growth,vascular changes at 2 wks similar to AM rats but at 4 wks 'adapted' ie.medial hypertrophy did not occur, and %Ext and RV:LV were less.Thus young lungs may respond to toxic agents more adversely during early critical periods of growth,more adaptively later.

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