Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA004

Poster Communications

In situ evaluation of tonic and reflex cardiorespiratory changes induced by chlorpyrifos-oxon in rats.

C. J. Muller1, I. S. Felippe1,2, A. P. Abdala3, L. M. Passamani1, J. F. Paton3,2, K. N. Sampaio1

1. Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil. 2. Physiology, University of Auckland, Auckland, New Zealand. 3. Physiology, University of Bristol, Bristol, United Kingdom.


Chlorpyrifos-oxon (CPO) is the active metabolite of chlorpyrifos (CPF), an organophosphorus (OP) compound highly associated with poisoning and death worldwide (Eddleston et al. 2005; Munõz-Quezada et al. 2017). With the recent increase in the frequency of nerve agent (acetylcholinesterase inhibitors) attacks on humans it becomes crucial to understand the effects on vital visceral function and to test for effective antidotes. Previous data from our group showed that in vivo exposure to CPF impaired cardiovascular reflexes in rats (Cunha et al. 2018). Recent experiments using an iin situ arterially perfused decerebrate rodent preparation, showed that 24 hours after CPF exposure, a marked reduction in peripheral chemoreflex function and basal respiratory discharge was observed (unpublished data). However, the temporal profile of immediate changes exerted by this compound on cardiorespiratory modulation remains unexplored. The aim of the present study was to evaluate the baseline and reflex cardiorespiratory changes induced by CPO within the first hours after poisoning. An in situ preparation was set up using juvenile rats (92.3 ± 12.7 g; n = 17) perfused with a modified Ringer solution and neuromuscularly blocked (rocuronium bromide, 10 mg/mL), as previously described (Paton 1996). Basal records of phrenic nerve (PNA), recurrent laryngeal nerve (RLN), sympathetic nerve activities (tSNA), heart rate (HR), ECG and perfusion pressure (PP) were compared before and after CPO (15 mg/kg in DMSO 55%) or DMSO (control vehicle), which were added to perfusate. Before and 15 minutes after CPO administration, KCN (0.03%; 50, 75, 100 μL) or phenylephrine (30 mg/mL; 100 μL) were injected through the ascending aorta to stimulate the peripheral chemo- and baro- reflexes, respectively. Data were analysed by generalized estimating equations (GEE) and presented as means ± S.E.M. Within the first minutes of poisoning, CPO increased basal HR and tSNA (p<0.0001) and decreased respiratory frequency (p<0.0001). PP was transiently increased (p <0.0001) after CPO administration. CPO decreased the time to reach inspiratory peak of phrenic nerve discharge (p <0.0001) and increased duration of expiratory phase (p <0.0001). Duration of RLN post-inspiratory activity was increased (p <0.001) while amplitude was decreased (p <0.0001) by CPO. Chemoreflex induced sympatho-excitation (p <0.05) and pressor response (p <0.05) were decreased, while bradycardia (p <0.0001) was increased after CPO administration. No change in chemoreflex tachypneic response was observed. CPO exposure reduced baroreflex mediated sympatho-inhibition (p<0.05). CPO induced marked immediate changes in tonic and reflex cardiorespiratory function, which may have important implications in the treatment of poisoned patients.

Where applicable, experiments conform with Society ethical requirements