Ponencia
Carotid chemosensory responses to acute hypoxia are reduced by chronic phenytoin treatment
Autor
Alcayaga-Urbina, Julio Andrés
Oyarce-Moraga, María Paz
Del Río, Rodrigo
Institución
Resumen
Carotid body (CB) chemoafferents are the main peripheral signal that participates in ventilatory control. In the rat, the sensory
neurons that innervate CB receptor cells present a persistent Na+ current (INaP), which blockade reduces both normoxic afferent
activity and increases in frequency discharge induced by acute hypoxia. Because there is no data available on the effects of prolonged
INaP blockade on chemoafferent activity, we recorded carotid nerve discharges and responses to acute hypoxia from animals treated
with phenytoin for two to four weeks. Male Sprague-Dawley rats (204 ± 6 g; n = 18), under isoflurane anesthesia, were implanted
subcutaneously with an osmotic pulp filled with vehicle (control) or with phenytoin (10 mg daily dose); the animals received
antibiotics and anti-inflammatory after surgery. After sixteen to 28 days, the rats were anesthetized with sodium pentobarbitone
(60 mg/Kg) placed in a thermoregulated pad. The neck was opened through the midline, the trachea cannulated, the carotid
bifurcation exposed and the carotid nerve severed at its origin in the glossopharyngeal nerve. The nerve was placed in paired Pt/
Ir electrodes, connected in turn to an AC preamplifier, and covered with mineral oil. The recorded signal was amplified, band-pass
filtered (10-1000 Hz) and digitally counted to assess the chemoafferent discharge (ƒx), in Hz. Basal chemoafferent discharges in
normoxia (fraction of inspired oxygen, FIO2 = 21%) as well as well as the changes in chemoafferent discharges (Δƒx) induced by
30 s changes in FIO2 (0 – 100% range) were recorded. The animals were sacrificed with an anesthetic overdose at the end of the
recording. The basal chemoafferent discharges were not significantly different (P > 0.3; Student´s t-test) between controls (76.5 ±
8.6 Hz; n=10) and phenytoin treated (93.4 ± 14.5 Hz; n= 8) animals. However, responses induced by changing FIO2 were significantly
(P < 0.02; 2 way ANOVA) reduced by phenytoin treatment. Moreover, responses induced by the lowest values of FIO2 in the range,
were significantly lower (P < 0.05; Bonferrroni test after 2 Way ANOVA) in treated animals (FIO2 5 %, Δƒx = 96.5 ± 22.4 Hz; FIO2 0 %,
Δƒx = 92.0 ± 14.4 Hz) than in control ones (FIO2 5 %, Δƒx = 161.2 ± 17.3 Hz; FIO2 0 %, Δƒx = 167.3 ± 20.0 Hz). Thus, afferent discharges
in normoxia are not modified by phenytoin treatment, while responses to short acute hypoxic challenges are significantly reduced
by phenytoin treatment. This reduction in hypoxic sensibility may alter ventilatory responses after chronic phenytoin treatment.