Assessment of Lung Morphological Changes in Acute Intoxications with Clozapine, Ethanol and Their Combination

Objective:to detect lung morphological changes in acute intoxications with clozapine, ethanol, and their combination 3 and 24 hours after poisoning.

Materials and methods. Experiments were carried out in outbred male rats weighing 270—300 g. Clozapine was given in a dose of 250 mg per kg animal body weight under chloralose anesthesia. Following 3 and 24 hours, the animals were withdrawn from the experiment by decapitation. Lung histological sections from 6 rats that had received oral clozapine 250 mg/kg, 6 rats that had oral ethanol 8.6 ml/kg, and 6 rats that had a combination of ethanol and clozapine orally in the above doses were examined 3 hours after intoxication. Those from 18 rats that had been orally given the similar agents in the above doses and withdrawn from the experiment were also investigated 24 hours after drug administration. The sections were compared with those from 6 rats that had not received the above agents. Nonparametric methods (χ2 test) were used for statistical processing. The investigators assessed the following morphological signs: circulatory disorders (plethora, hemorrhages), interstitial and alveolar edema, damage to the bronchial and alveolar epithelium and to the endothelium, and a cell reaction. The differences were considered significant at p<0.05.

Results. In the control animal group, histological examination did not reveal any circulatory disorders and damage to the bronchial and alveolar epithelium and to the endothelium. Three hours after its administration, the animals that had received clozapine were observed to have acute pulmonary circulatory disorders (plethora in the pulmonary artery system, focal plethora of the capillaries of interalveolar septa and that of veins) that increased 24 hours after its ingestion. If death occurred 3 hours after ethanol intake, there was obvious perivascular edema, plethora, and hemorrhage; some alveoli contained transudate. Moderate venous plethora was seen 24 hours following ethanol administration. The secretory activity of the bronchial mucosa decreased. Three hours after coadminis tration of clozapine and ethanol, there were acute pulmonary circulatory disorders (marked plethora, multiple hemorrhages, and alveolar edema), bronchial epithelial lesion (desquamation), and no staining of endothelial cell nuclei. Lymphocyte accumulation was observed around the veins and arteriovenous anastomoses. Perivascular edema was absent. The lesions increased 24 hours after coadministration of clozapine and ethanol.

Conclusion. The changes found at lung histological examination of the animals receiving clozapine alone and its combination with ethanol in conjunction with the results of forensic chemical analysis may be used to diag nose relevant intoxications and to establish their duration.

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