Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed a decrease in ventilation. The precise mechanism of this decline in ventilation during sustained hypoxia is unknown. Recent studies hypothesized that the accumulation of dopamine in the central nervous system might have a major role in production of hypoxic respiratory depression. The purpose of this study was to examine whether dopamine has an effect on occurance of central ventilatory depression which is seen in acute hypoxia in peripheral chemoreceptors denervated animals. The experiment were conducted in rabbits anesthetized with Na-pentobarbital (25 mg x kg(-1) i.v.). For intracerebroventricular (i.c.v.) injections of dopamine (1 microg) in each animal, canula was placed in left lateral cerebral ventricle by stereotaxic method. Respiratory frequency (f x min(-1)), tidal volume (V(T)) ventilation minute volume (V(E)) and systemic arterial blood pressure (BP) were recorded during air and 3 minutes hypoxic gas mixture (8%O2-92%N2) breathing. I.c.v. administration of dopamine during normoxia decreased V(T), f, V(E) and BP, significantly. When rabbits were injected with an i.c.v. dopamine on hypoxic gas mixture breathing in control animals, there was depression of hypoxic ventilatory responses. After i.c.v. administration of dopamine antagonists haloperidol (0.1 mg) and domperidone (0.07 mg) in chemodenervated rabbits, the significant increases in V(T), V(E) and BP were observed. On the breathing of hypoxic gas mixture of chemodenervated and i.c.v. dopamine antagonists administrated rabbits, hypoxic depression was completely abolished. These results of this study show that accumulation of dopamine in the brain seems to reduce the response of the central control mechanisms to chemoreceptor impulses during normoxia and hypoxia. In conclusion present study suggests important role played by central dopaminergic pathways in the occurence of acute hypoxic ventilatory depression.

Objective: The present study was undertaken to investigate the ventilatory response due to sustained isocapnic moderate hypoxia and the possible role of adenosine in hypoxic depression in anesthetized cats. Materials and Methods: Cats anesthetized with pentothal sodium (30 mg kg^–1 i.p.) were divided into two groups: treated (n = 11) and control (n = 15). Respiratory frequency (f), tidal volume (V_T), minute volume (v̇E) and systemic arterial blood pressure were recorded during air and 20 min of breathing hypoxic gas mixture (14% O₂-86% N₂). Isocapnia was maintained by adding fractions of 1% CO₂ to the inspired hypoxic gas mixture. The PaO₂ and PaCO₂ were determined. Results: On hypoxic gas mixture breathing, V_T and v̇E values of the control animals increased significantly, at 5 min to 50 ± 6 and 53 ± 6%, respectively, above the prehypoxic air phase value (p < 0.001). After that, the magnitude of increase in V_T and v̇E declined gradually. At 20 min of hypoxia, V_T and v̇E were less than those in prehypoxic air phase (17 ± 7, 16 ± 7%, respectively). In cats injected with an adenosine antagonist (theophylline 13.6 mg kg^–1 i.v.), f, V_T and v̇E increased significantly at 5 min of hypoxia (p < 0.001). At 20 min of hypoxia, f, V_T and v̇E were 8 ± 2, 30 ± 8, and 39 ± 8%, respectively, higher than corresponding values of the prehypoxic stage. In cats injected with theophylline (0.5 mg kg^–1) by cisternal puncture V_T and v̇E increased significantly at 5 min of hypoxia. At 20 min of hypoxia, V_T and v̇E were 27 ± 7 and 31 ± 8% higher than those in the prehypoxic air phase. Conclusion: The results of this study show that accumulation of adenosine in the brain during hypoxia seems to reduce the response of the central mechanisms to chemoreceptor impulses.

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PurposeThe purpose of this study was to investigate the activation of the respiratory centers during insufflation of the larynx with CO2 at different flow rates and concentrations.Materials and MethodsThe experiments were carried out in spontaneous air breathing rabbits, anesthetized with thiopental sodium (25 mg kg-1i.v.). The larynx was separated from the oropharyngeal cavity and the trachea. The tidal volume (VT) and respiratory frequency (f min-1) were recorded from the lower tracheal cannula. The respiratory minute volume (VE) was calculated, the action potentials from the right phrenic nerve were recorded and the inspiratory (TI) and expiratory (TE) periods and the mean inspiratory flow rate (VT/TI) were calculated. The larynx was insufflated at flow rates of 500 mL min-1 and 750 mL min-1, with 7 and 12% CO2-Air by means of a respiratory pump.ResultsInsufflation of the larynx, with both gas mixtures, decreased the f and VT significantly. The TI and TE were found to increase significantly due to the decreasing in f. There was a significant decrease in VT/TI ratio. Following bilateral midcervical vagotomy, on the passing of both gas mixtures, significant decreases were observed in the VT, and the responses of f, TI and TE were abolished. After cutting the superior laryngeal nerve, the responses of the VT to both gas mixtures were abolished.ConclusionIn conclusion, the results of this study purpose that the stimulation of the laryngeal mechanoreceptors by the effect of hypercapnia decreases the activation of the respiratory center.