Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA010

Poster Communications

Can atropine and pralidoxime restore neuroreflex cardiorespiratory function after acute exposure to chlorpyrifos in rats?

I. S. Felippe2,1, C. J. Muller2, A. A. Siqueira2, L. dos Santos3, V. Beijamini2, J. F. Paton1,4, K. N. Sampaio2

1. Physiology, The University of Auckland, Auckland, New Zealand. 2. Pharmaceutical Sciences, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. 3. Physiological Science, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil. 4. Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, United Kingdom.

Previous work from our group showed that acute exposure to chlorpyrifos (CPF), an organophosphorus (OP) compound, impairs chemoreflex and baroreflex function in rats (Cunha et al. 2018). However, whether atropine (ATR) or/and pralidoxime (2-PAM), antidotes frequently used in OP poisoning, are capable of restoring cardiorespiratory function, remains unknown. The study abide by the Brazilian National Council for Animal Experimentation; being approved (number 058/2014) by the University Committee for Animals Ethical Use. Rats (350-400g; n=65) were catheterized under anesthesia (tribromoethanol, 250 mg/kg, i.p.) and, on the next day, injected with CPF (30 mg/Kg, i.p.) or saline (SAL, 0.9%, i.p.). One hour later, animals were split in groups receiving either ATR (10 mg/Kg, i.p.) or 2-PAM (40 mg/Kg, i.p.) separately and in combination. Mean arterial pressure, systolic arterial pressure (SAP), pulse interval (PI) and heart rate (HR) were derived from pulsatile arterial pressure while respiratory parameters were obtained through plethysmography. Recordings were performed in awake rats 24 hours after injections. Time-domain [variance, standard deviation (SD), root mean square of successive inter-beat intervals (RMSSD)] and frequency-domain parameters [normalized low (LF) and high frequency (HF) bands of spectral analysis] were used to estimate heart rate variability derived from undisturbed recordings (software CardioSeries; version 1.2). Spontaneous baroreflex gain (sBRG) was estimated for upward and downward ramps from regular beat-to-beat arterial pulses. Chemoreflex was activated by potassium cyanide injections (KCN; 10, 20, 40, 80µg/rat, i.v.). Data were analyzed by Generalized mixed model and Generalized Estimating Equations. CPF exposure increased SD (P=0.035) and variance (P=0.028) of SAP compared with SAL animals. 2-PAM treatment restored these parameters (P= 0.023). CPF decreased RMSSD (P=0.051), which was corrected by ATR (P=0.033). CPF exposure decreased HF band (P= 0.042) compared with SAL animals, which was not restored by either ATR or 2-PAM treatment. CPF animals exhibited a marginally reduced up-ramps sBRG (P=0.061) when compared with SAL, which was restored by ATR (P=0.014). Reduced hypertensive (P=0.015) and bradycardic (P=0.001) chemoreflex responses were also observed in CPF group. While 2-PAM restored the hypertensive response (P=0.005), ATR treatment recovered the bradycardic responses (P=0.038). CPF impaired the chemoreflex tachypneic response (P=0.02), being restored by ATR (P=0.023). ATR and 2-PAM given together resulted in a summation of the responses when drugs were administered individually. These data indicate that ATR and 2-PAM treatment separately or in combination, are capable of restoring CPF induced cardiorespiratory neuroreflex impairment, having important implications for poisoned patients treatment.

Where applicable, experiments conform with Society ethical requirements