Isoflurane does not depress the hypoxic response of rabbit carotid body chemoreceptors.

UNLABELLED: Whether volatile anesthetics have an effect on the peripheral chemoreceptors is controversial, possibly because of differences in end-tidal CO(2) concentrations. We studied the effect of isoflurane on the hypoxic chemosensitivity of carotid body chemoreceptors at three different PaCO(2) levels before and during the administration of 1.0% isoflurane (0.5 minimum alveolar anesthetic concentration) in six normothermic New Zealand white rabbits anesthetized with thiopental. The response of the chemoreceptors was fitted to the equation: Frequency (Hz) = a + b x PaCO(2) + c x (1/PaO(2)) + Dx (1/PaO(2))(2). Mean values for the coefficients a, b, c and d for the control state were -4.5, 0.13, 771, and 6332, respectively. This relationship was not changed by addition of isoflurane at 1.0% end-tidal concentration (P = 0.40, analysis of variance). We conclude that isoflurane at 1.0% end-tidal concentration does not depress the hypoxic response of rabbit carotid body chemoreceptors during either hypo-, normo-, or hypercapnia. IMPLICATIONS: By measuring single-fiber chemoreceptor activity in anesthetized rabbits, we showed that isoflurane at 1.0% end-tidal concentration does not depress the hypoxic chemosensitivity of peripheral chemoreceptors during either hypo-, normo-, or hypercapnia in this species.

Carotid body chemoreceptor response to prolonged hypoxia in the rabbit: effects of domperidone and propranolol.

1. The discharge of single afferent chemoreceptor fibres was recorded from the cut sinus nerve over periods of 60 or 90 min of constant, isocapnic hypoxia (arterial O2 pressure, Pa,O2, 3.13-5.25 kPa), in twenty anaesthetized rabbits, after dividing the sympathetic supply to the carotid body. 2. Under control conditions, discharge after 60 min of hypoxia adapted to a mean (S.E.M.) of 71.95 (2.75)% of that attained at 5 min of hypoxia in twenty-three hypoxic experiments. This adaptation was more pronounced when Pa,O2 was lower than 4 kPa (30 Torr). 3. Domperidone (1 mg kg-1 bolus + 1 mg kg-1 h-1 infusion I.V.), increased normoxic afferent discharge by a mean of 142%. In ten experiments, discharge after 60 min of hypoxia adapted to a mean (S.E.M.) of 56.22 (+/- 3.40)% of that attained at 5 min of hypoxia which was significantly different from control hypoxic runs (P = 0.006). 4. In seven experiments propranolol (1 mg kg-1 bolus + 1 mg kg-1 h-1 infusion I.V.) did not affect the normoxic discharge. The mean adaptation of discharge after 60 min of hypoxia was to 77.43 (3.97)% of discharge attained at 5 min of hypoxia, which was not significantly different from control hypoxic runs (P = 0.34). 5. Under control conditions plasma [K+] increased steadily during 60 min of hypoxia, in fourteen experiments, from a mean of 2.76 (0.14) to 2.85 (0.12) mmol l-1 but this was not significant (P = 0.21). Domperidone (n = 6) did not affect plasma [K+] at any time, but after propranolol (n = 6) it increased by a mean (S.E.M.) of 0.39 (0.09) mmol l-1 (P = 0.01) in normoxia and by a further 0.62 (0.28) mmol l-1 (P = 0.08) at 60 min of hypoxia. 6. The results suggest that the adaptation of chemoreceptor discharge to hypoxia in the rabbit is not mediated by changes in plasma [K+]; in addition, endogenous dopamine, but not noradrenaline, contributes to the maintenance of chemoreceptor discharge in prolonged hypoxia.

Studies on the regenerated carotid sinus nerve of the rabbit.

1. The central end of the distally cut left carotid sinus nerve was sutured to the tunica media of the external carotid artery, 1 cm cranial to the carotid bifurcation, in nineteen rabbits. The carotid body was removed in fourteen of these rabbits but left in situ in the remaining five. After 56-165 days of recovery a neuroma was identified at the site of the suture. Ventilatory reflexes mediated by both sinus nerves were tested and afferent activity recorded from the regenerated nerve. 2. Ventilatory reflex responses to hypoxia and sodium cyanide were abolished on sectioning the right sinus nerve, whilst the hypercapnic response was maintained. 3. Electrical stimulation of the regenerated sinus nerve caused hypotension and hyperventilation. These responses were attenuated compared to stimulation of the right sinus nerve. 4. A level of afferent activity equivalent to that found in non-regeneration experiments was recorded from all regenerated sinus nerves. Whole-nerve afferent activity was modulated by changes in carotid sinus blood pressure but not by changes in Pa,O2, Pa,CO2 (arterial O2 and CO2 pressures) or intracarotid injection of sodium cyanide. 5. A minimum of thirty single afferent fibres was identified in each experiment, the vast majority of which were mechanoreceptors. In only nine experiments were chemoreceptor fibres found and only twelve chemoreceptor fibres (1.7% of total) were identified in these nine experiments. In ten experiments no chemoreceptor fibres could be found. Leaving the carotid body in situ increased the incidence of chemoreceptive preparations. A small number of fibres unresponsive to mechanical stimulation and asphyxia was also identified. 6. The responses of regenerated chemoreceptor fibres to physiological and pharmacological stimuli were generally similar to those found in control carotid body preparations. Fibres unresponsive to mechanical stimulation and asphyxia did not respond to sodium cyanide, dopamine or isoprenaline; some of these fibres were excited by nicotine. 7. The receptive fields of mechanosensitive fibres were localized on or up to 2 cm away from the neuroma. Surface application of 20-40 microliters sodium cyanide (200 micrograms ml-1) was used to localize the receptive fields of seven of the twelve chemoreceptor fibres. All seven were localized to the site of the carotid body. 8. The neuroma and site of the carotid body were examined under light and electron microscopy. Glomus tissue was absent from the neuroma but was found at the site of the carotid body. 9. In conclusion, recovery of chemoreceptor function after carotid sinus nerve section appears to be associated with reinnervation of glomus tissue.

Interactions between hypoxia, acetylcholine and dopamine in the carotid body of rabbit and cat.

1. Acetylcholine (ACh) and dopamine (DA) were either infused into the carotid artery or applied directly to the surface of the carotid body of twenty-six rabbits and fifteen cats. Afferent discharge of single chemoreceptor units was recorded at a range of Pa,O2 (arterial O2 pressure) values during drug administration. 2. There were no observable systemic effects of either drug when applied to the surface of the carotid body. 3. Acetylcholine tended to depress afferent discharge when applied to the surface of the rabbit carotid body or when infused into the carotid sinus. In the cat, intracarotid and surface application of ACh had mild and inconsistent effects. DA consistently depressed discharge in both species independent of the route of administration. Antagonists of ACh and DA failed to abolish the chemoreceptor response to hypoxia. 4. The changes in afferent discharge elicited by all drugs were small compared with the range of discharge rates attained with physiological stimuli. The effects of ACh and DA were more marked in hyperoxia than in hypoxia for both routes of administration, disappearing at Pa,O2 values close to 20 Torr (7.5 Torr = 1 kPa). 5. A role for DA in the maintenance of the hypoxic response was investigated in six rabbits. After 15 min of hypoxia (Pa,O2 = 21.8 +/- 1.1 Torr; mean +/- S.E.M.) the discharge of single chemoreceptor fibres adapted moderately (to 79.3 +/- 5.2% of maximum discharge). Following administration of domperidone or haloperidol (1.0-5.3 mg kg-1, I.V.) the same fibres responded with equal magnitude to the onset of the hypoxic stimulus but showed a significantly larger adaptation (to 48.5 +/- 4.4%). 6. It is concluded that endogenous ACh and DA are unlikely to mediate the transduction process of the carotid body, but DA may play a role in preventing adaptation to a prolonged hypoxic stimulus.

Effect of halothane, enflurane and isoflurane on carotid body chemoreceptor activity in the rabbit and the cat.

The response of the carotid body chemoreceptors to administration of halothane, enflurane and isoflurane was tested in the rabbit and cat. In the steady-state all three volatile anaesthetics, in doses up to 1%, were mildly chemodepressant. The oxygen response curves were shifted downwards, but hypoxic stimuli below 5.3 kPa overcame this chemodepression. Two-point carbon dioxide response curves were also shifted downwards, but with no change in slope. Possible mechanisms involved in the chemoreceptor response to transient and steady-state anaesthetic administration are discussed.

Effect of thiopentone, etomidate and propofol on carotid body chemoreceptor activity in the rabbit and the cat.

The response of the carotid body chemoreceptors to intracarotid administration of thiopentone, etomidate and propofol was tested in the rabbit and cat. Thiopentone 3-6 mg min-1 and etomidate 300-600 micrograms min-1 were mildly excitatory, shifting the oxygen and carbon dioxide response curves upwards. Propofol 1.5-3.0 mg min-1 was a potent chemodepressant and abolished discharge at PaO2 values greater than 8 kPa. Prolonged infusion of propofol at higher rates (6 mg min-1) abolished the response to hypoxia completely. The significance of these results is discussed in relation to the known ventilatory effects of the three anaesthetics.