Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model

Abstract

INTRODUCTIONOrganophosphate (OP) poisoning produces a cholinergic crisis by blockade of acetylcholinesterase in the central and peripheral nervous systems. Acute effects of poisoning include central apnea [1][2][3][4], seizures [5,6], bronchorrhea, bronchoconstriction, muscle weakness, myosis, urination, and salivation [7][8][9][10]. The morbidity and mortality from acute OP poisoning is attributed to respiratory failure [11] but the relative contributions of the central and peripheral effects in producing collapse of the respiratory system [12] is unclear. The clinical literature emphasizes the peripheral effects contributing to acute pulmonary insufficiency [11,13]. However this does not exclude early mortality in the field due to central apnea [14,15].In this study we used a rodent model to analyze the dynamics of respiratory and cardiovascular collapse during acute OP poisoning. We found that poisoning caused a rapidly lethal central apnea. Central apnea consistently occurred soon after the poisoning but pulmonary insufficiency was more variable in both timing and severity. Mortality was reduced in animals that were sustained solely by artificial ventilation; however most ventilated animals exhibited signs of impaired gas exchange due to pulmonary insufficiency. Our findings support the hypothesis that OP poisoning in this animal model causes a sequential "two hit" insult, with rapid central apnea followed by delayed impairment of pulmonary gas exchange with prominent airway secretions. MATERIALS AND METHODSWe studied 27 male Wistar rats, weighing 275-325 gm (Charles River Laboratories, Wilmington, MA). The University of Massachusetts Medical School Institutional Animal Care and Utilization Committee approved all experimental procedures and protocols. The animal model used in this study is a novel preparation for OP research and the procedures are described in detail below.Corresponding Author: Romolo J Gaspari, MD, MSc, Assistant Professor, Department of Emergency Medicine, University of Massachusetts School of Medicine, 55 Lake Ave North, Worcester, MA 01655, Phone -508-334-7943, Fax -508-421-1490, Gasparir@UMMHC.org, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Surgical ProceduresSurgical procedures were performed under general anesthesia with 1.5 -2.2% isoflurane (Abbott Labs, North Chicago, IL) titrated to achieve a respiratory rate of 50-60 breaths per minute. All surgical procedures were performed under 100% oxygen. The animals were restrained in a supine position with the head extended and limbs abducted. Adequacy of anesthesia was confir...

A rodent model of human organophosphate exposure producing status epilepticus and neuropathology

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Cardiac Effects of Magnesium Sulfate Pretreatment on Acute Dichlorvos-Induced Organophosphate Poisoning: An Experimental Study in Rats

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Bilateral Loculated Pleural Effusion as a Manifestation of Acute Parenteral Organophosphate Intoxication: A Case Report

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