The Reflex Effects on the Respiratory Regulation of the CO2 at the Different Flow Rate and Concentration

Purpose: The 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 Methods: The experiments were carried out in spontaneous air breathing rabbits, anesthetized with thiopental sodium (25 mg kg(-1) i.v.). The larynx was separated from the oropharyngeal cavity and the trachea. The tidal volume (V-T) and respiratory frequency (f min(-1)) were recorded from the lower tracheal cannula. The respiratory minute volume (V-E) was calculated, the action potentials from the right phrenic nerve were recorded and the inspiratory (T-I) and expiratory (T-E) periods and the mean inspiratory flow rate (V-T/T-I) 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. Results: Insufflation of the larynx, with both gas mixtures, decreased the f and VT significantly. The T, and TE were found to increase significantly due to the decreasing in f. There was a significant decrease in V-T/T-I ratio. Following bilateral midcervical vagotomy, on the passing of both gas mixtures, significant decreases were observed in the VT, and the responses of f, T, and TE were abolished. After cutting the superior laryngeal nerve, the responses of the VT to both gas mixtures were abolished. Conclusion: In 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

The role of gamma-aminobutyric acid and glutamate for hypoxic ventilatory response in anesthetized rabbits

Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed by a decrease in ventilation. Hypoxia causes changes in brain neurotransmitters depending on its severity and durations. The purpose of this study was to investigate the role of gamma-aminobutyric acid (GABA) and glutamate for hypoxic ventilatory response in rabbits. The experiments were performed in peripheral chemoreceptors intact and denervated rabbits anesthetized with Na-pentobarbitate. For intracerebroventricular (ICV) injections of reagents in each animal, cannula was placed in left lateral cerebral ventricle by stereotaxic method. After ICV injection of GABA (0.48 mg/kg), air breathing in both groups caused a depression of respiratory activity. On the other hand, after ICV injection of GABA, breathing of hypoxic gas mixture (8% O-2-92% N-2) in both groups produced the hypoxic hyperventilation. After ICV injection of GABA, blockade of GABA(A) receptors with bicuculline (0.2 mg/kg) did not prevent the hypoxic hyperventilation. In contrast, after ICV GABA injection, blockade of glutamate NMDA receptors with MK-801 (0.09 mg/kg) completely abolished the hypoxic hyperventilation observed while the animals were breathing hypoxic gas mixture. Our findings suggest that ICV injection of GABA causes respiratory depression in normoxic conditions, and that it increases ventilation in hypoxic conditions with or without peripheral chemoreceptor impulses by increasing,glutamate. (C) 2004 Tohoku University Medical Press

The effects of vagal stimulation on laryngeal vascular resistance and intraluminal pressure in the dog

In anaesthetized dogs (sodium pentobarbitone 30 mg/kg, i.v.) laryngeal vascular resistance was measured by unilateral perfusion at constant flow of the branch of the cranial superior thyroid artery that supplies the larynx. Arterial perfusion was at constant flow and inflow pressure was divided by flow to give laryngeal vascular resistance (R-LV). Intraluminal laryngeal pressure (P-L) and systemic arterial blood pressure (BP) were also measured. Stimulation (20 V, 20 Hz, 0.2 milliseconds) of the central end of cervical vagus caused an increase in R-LV (+22.9+/-6.1%) and a decrease in P-L (-12.1+/-4.4%). Stimulation (10 V, 10 Hz, 0.2 milliseconds) of the central end of the recurrent laryngeal nerve (RLN) reduced R-LV (-3.4+/-0.8%) and P-L (-7.5+/-4.1%). Stimulation of the peripheral end of the RLN decreased RLV (-7.1+/-1.9%) and increased P-L (+21.6+/-7.7%). Stimulation of the central end of the superior laryngeal nerve (SLN) increased R-LV (+17.9+/-3.2%) and P-L (+59.8+/-2.7%), whereas stimulation of the peripheral end of the SLN decreased R-LV (-4.8+/-1.6%) and P-L (-4.1+/-2.4%). After treatment with alpha-adrenoreceptor antagonist phentolamine (0.5 mg/kg, Lv.), stimulation of the central end of cervical vagus nerve reduced R-LV by 25% and decreased BP. Phentolamine caused a decrease in BP and reduced the magnitude of increase in R-LV in response to stimulation of central end of SLN. After atropine sulphate (0.5-2.0 mg/kg, i.v.), the stimulation of both central and peripheral ends of RLN reduced RLV. The decrease in R-LV during stimulation of peripheral end of SLN was reduced by atropine. Thereafter, pancuronium bromide (0.06-0.1 mg/kg, i.v.) was given and dogs were artifically ventilated. After paralyzed, stimulation of the central end of the SLN decreased R-LV (+26.0+/-4.5%) but produced no change in P-L. It is concluded that parasympathetic motor fibers in the RLN and SLN are effective for the laryngeal vascularity and non-adrenergic system may be responsible for laryngeal vasoconstriction

Hypoxic initiation of pulmonary hypertension is mediated by serotonin secretion from neuroepithelial bodies in chemodenervated dogs

The purpose of this study was to investigate the stimulatory effect of hypoxia on the secretion of serotonin by neuroepithelial bodies (NEB) as well as to determine the relation between its level and changes in pulmonary arterial pressure (PAP) and also to determinate the effect of serotonin antagonists (pizotifen and methysergide) on the responses of pulmonary and systemic arterial pressures. The experiments were carried out in peripheral chemoreceptor-denervated dogs anesthetized with Na penthabarbital (30 mg/kg i.v.). On the breathing of normoxic and hypoxic (7% O-2-93% N-2) gas mixtures and on the injection of KCN (80 mug/kg i.v.), PAP, systemic arterial blood pressure (BP), tidal volume (V-T), respiratory frequency (f/min), ventilation minute volume (V-E) were determined. Also PAP and BP were recorded before and after the injection of pizotifen (0.5 mg/kg i.v.) and methysergide (1 mg/kg i.v.) during normoxic or hypoxic gas mixture breathing. At the end of each experimantal phase, serotonin level, PaO2, PaCO2 and pH(a) values in blood samples obtained from left ventricle and femoral artery were determined. On the breathing of the hypoxic gas mixture of the chemodenervated dogs, VT, VE and BP significantly decreased (P<0.001, P<0.001, P<0.01). The mean value of PAP and serotonin levels (ventricular and femoral) were found significantly increased when compared with the corresponding normoxic values (P<0.001, P<0.05). On the other hand, injection of KCN produced no significant changes in PAP, serotonin levels, BP and respiratory parameters. After the injection of pizotifen, PAP was significantly increased in hypoxia (P<0.01). After the injection of methysergide, the response of PAP was completely abolished during the breathing of hypoxic gas mixture. The finding of the abolition of response of PAP to hypoxia after the injection of methysergide indicates that serotonin release from NEB may be responsible for the elevation of PAP in hypoxic hypoxia