Respiratory recovery following organophosphate poisoning in a rat model is suppressed by isolated hypoxia at the point of apnea

Normal respiratory activity (eupnea) and gasping represent different types of respiratory activity, one of which is supported by oxygen (eupnea) and the other suppressed by oxygen (gasping). There is a loss of respiratory activity post-organophosphate (OP) poisoning that returns following treatment. It is not clear if post-OP respiratory activity represents eupnea or gasping. Depending on the type of respiratory activity, oxygenation during recovery from OP poisoning may have the potential to either support or suppress respiratory activity. We hypothesize that respiratory recovery following OP-induced central apnea represents a resumption of eupnea and is supported by oxygenation. We used an animal model of acute OP poisoning with detailed physiologic recordings. Animals were poisoned with dichlorvos and allowed to recover during a period of mechanical ventilation. Two experimental models were analyzed: (1) animals supported with 100% oxygen and (2) animals supported with a normoxic gas mixture titrated to a PaO2 of 115 mmHg. Rats in this study demonstrated breathing that resumes spontaneously following OP-induced apnea with characteristics of both eupnea and gasping. The post-OP respiratory activity was suppressed by hypoxia, a characteristic of eupneic respiration and not gasping respiration. However, the respiratory rate during post-apneic breathing corresponded more closely to gasping. Analysis of phrenic nerve discharge activity was distinct from both eupnea and gasping, with peak inspiratory and post-inspiratory discharge activities significantly reduced compared to both eupnea and gasping. In summary, in this animal model post-apneic breathing distinct from eupnea and gasping that emerges following prolonged OP-induced central apnea is suppressed by hypoxia.

► Respiratory recovery returns following organophosphate induced central apnea.
► Return of respiratory activity post organophosphate-induced apnea is distinct from both normal respiration and gasping.
► Respiratory activity that emerges post organophosphate-induced apnea is suppressed by hypoxia at the point of apnea.
► Respiratory activity that emerges post organophosphate-induced apnea is supported by oxygenation during the recovery period.