Proceedings of The Physiological Society

Kings College London (2005) J Physiol 565P, C169

Communications

Acute inflammation of the carotid body: functional manifestations

Zapata, P ; Fernandez, R ; Reyes, E P; Larrain, C ;

1. Lab. Neurobiology, P. Catholic University of Chile, Santiago, Chile.


Ventilatory responses to hypoxia are mainly mediated by carotid body (CB) chemoreceptor excitation, but no reports have been published on CB function during acute endotoxaemia. Having characterized the early steps of CB inflammation induced by I.V. infusion of lipopolysaccharide (LPS) in cats [Fernandez et al, this meeting], this preparation provided the opportunity to study its functional manifestations. Experiments were performed on 11 cats anaesthetized with sodium pentobarbitone 40 mg/kg I.P. supplemented I.V. as required, breathing spontaneously through a tracheal cannula connected to a pneumotachograph, and whose body temperature was maintained at 38oC by a regulated heating device. LPS was infused I.V. (0.75 mg/kg at 0.35 ml/min along 20 min) and its effects were observed for at least 4 h. LPS administration evoked marked increases in respiratory frequency (to 156.6 ± 12.5% of control, at 210 min; mean ± SEM), heart rate (to 110.7 ± 4.4%, at 90 min) and haematocrit (to 125.2 ± 2.9%, at 210-270 min), accompanied by systemic hypotension (mean arterial pressure reduced to 74.2 ± 5.1% at 150 min). LPS decreased ventilatory responses to 10 s 100% N2 breathing (to 62.5% of control responses, at 210 min). Ventilatory responses to I.V. nicotine were diminished in sensitivity (ED50 displaced from 13.4 to 57.2 μg/kg, at 150 min) and maximal reactivity (65.3% of control, at 210 min). LPS increased basal frequency of carotid nerve chemosensory discharges in normoxia (> 2-fold from 30 min on), but decreased CB chemoreceptor sensitivity to stimulation by I.V. nicotine (LED displaced 20-fold to the right after 210 min), without significant changes in maximal chemoreceptor responses to brief hypoxic exposures. Ventilatory chemosensory drive, evaluated by breathing 100% O2 for 60 s under control conditions (normoxia) and after 1 min hypoxia (10% O2 in N2), was diminished from 90 min after LPS administration. LPS-induced tachypnoea was prevented by bilateral carotid neurotomy. Cats were killed by an overdose of pentobarbitone given I.V. at the end of experiments. Our results suggest that LPS-induced endotoxaemia rapidly increases the basal level of CB chemosensory discharges, but decreases the sensitivity of CB chemoreceptor responses and ventilatory chemosensory drive; LPS also induces tachypnoea but reduces ventilatory chemoreflexes. Results support the idea that many pathophysiological reactions associated with the presence of high levels of LPS in the bloodstream may be originated from the CBs.

Where applicable, experiments conform with Society ethical requirements