Protective effects of penehyclidine hydrochloride on acute lung injury caused by severe dichlorvos poisoning in swine.

BACKGROUND: Organophosphate poisoning is an important health problem in developing countries which causes death mainly by inducing acute lung injury. In this study, we examined the effects of penehyclidine hydrochloride (PHC), a selective M-receptor inhibitor, on dichlorvos-induced acute lung injury in swine.

METHODS: Twenty-two female swines were randomly divided into control (n = 5), dichlorvos (n = 6), atropine (n = 6), and PHC (n = 5) groups. Hemodynamic data, extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) were monitored; blood gas analysis and acetylcholinesterase (AchE) levels were measured. PaO2/FiO2, cardiac index (CI), and pulmonary vascular resistance indices (PVRI) were calculated. At termination of the study, pulmonary tissue was collected for ATPase activity determination and wet to dry weight ratio (W/D) testing 6 hours post-poisoning. TUNEL assay, and Bax, Bcl-2, and caspase-3 expression were applied to pulmonary tissue, and histopathology was observed.

RESULTS: After poisoning, PHC markedly decreased PVRI, increased CI more effectively than atropine. Anticholinergic treatment reduced W/D, apoptosis index (AI), and mitigated injury to the structure of lung; however, PHC reduced AI and caspase-3 expression and improved Bcl-2/Bax more effectively than atropine. Atropine and PHC improved ATPase activities; a significant difference between groups was observed in Ca(2+)-ATPase activity, but not Na(+)-K(+)-ATPase activity.

CONCLUSIONS: The PHC group showed mild impairment in pathology, less apoptotic cells, and little impact on cardiac function compared with the atropine group in dichlorvos-induced acute lung injury.