Imidazoline 1 receptor activation preserves respiratory drive in spontaneously breathing newborn rats during dexmedetomidine administration

2017 ◽  
Vol 27 (5) ◽  
pp. 506-515 ◽  
Author(s):  
Nana Sato ◽  
Chikako Saiki ◽  
Junko Tamiya ◽  
Toshio Imai ◽  
Katsuhisa Sunada
2014 ◽  
Vol 24 (12) ◽  
pp. 1245-1251 ◽  
Author(s):  
Junko Tamiya ◽  
Ryoji Ide ◽  
Masayuki Takahashi ◽  
Chikako Saiki

1989 ◽  
Vol 66 (3) ◽  
pp. 1297-1303 ◽  
Author(s):  
S. Iscoe

The role of phrenic afferents in controlling inspiratory duration (TI) at elevated end-expiratory lung volume (EEV) has been studied in pentobarbital-anesthetized, spontaneously breathing cats with intact vagi. Responses to increases in EEV, induced by imposition of an expiratory threshold load (ETL) of 10 cmH2O, were monitored before and after section of cervical dorsal roots C3-C7. The immediate (first-breath) effect of application of ETL was a prolongation of both TI and expiratory duration (TE). After 10 min of breathing against the ETL, average TI returned to control values but TE remained prolonged. Abolishing feedback from the diaphragm did not affect these responses. When steady-state responses to ETL were compared with those elicited by inhalation of 5–6% CO2 in O2, changes in EEV had, on average, no independent effect on respiratory drive (rate of rise of integrated phrenic activity), although phrenic activity increased greatly in some cats despite little or no change in arterial partial pressure of CO2. These data indicate that diaphragmatic receptors do not contribute to either the immediate (first-breath) or steady-state responses of phrenic motoneurons to increases in EEV in intact cats.


1986 ◽  
Vol 61 (6) ◽  
pp. 2122-2128 ◽  
Author(s):  
D. E. Weese-Mayer ◽  
R. T. Brouillette ◽  
L. M. Klemka ◽  
C. E. Hunt

We previously demonstrated dose-dependent increases in both hypoglossal and phrenic electroneurograms after almitrine in anesthetized, paralyzed, and vagotomized cats. We have now investigated the effect of this peripheral chemoreceptor stimulant on diaphragmatic and genioglossal (GG, an upper airway-maintaining muscle) electromyograms in five unanesthetized, chronically instrumented, spontaneously breathing adult cats during slow-wave sleep. In 12 studies almitrine doses of 1.0–6.0 mg/kg increased inspired minute ventilation (VI), frequency (f), and tidal volume (VT) and decreased expiratory time (TE). However, almitrine doses as high as 6.0 mg/kg failed to augment phasic inspiratory GG activity. To determine why almitrine induced phasic inspiratory upper airway activity in anesthetized, vagotomized cats but not in sleeping cats, additional studies were performed. In four dose-response studies in three pentobarbital-anesthetized cats, almitrine, 1.0–6.0 mg/kg, did not produce phasic inspiratory GG activity. Almitrine did induce phasic inspiratory GG activity in two of three studies in three vagotomized, tracheostomized, alpha-chloralose-urethan-anesthetized cats. These results suggest that almitrine would not be useful in obstructive sleep apnea, yet because almitrine markedly increased VI, f, and VT and decreased TE in unanesthetized sleeping cats the drug may be effective in patients who lack normal central neural respiratory drive, such as the preterm infant.


1991 ◽  
Vol 70 (1) ◽  
pp. 251-259 ◽  
Author(s):  
R. A. Darnall ◽  
G. Green ◽  
L. Pinto ◽  
N. Hart

Changes in local brain stem perfusion that alter extracellular fluid Pco2 and/or [H+] near central chemoreceptors may contribute to the decrease in respiration observed during hypoxia after peripheral chemoreceptor denervation and to the delayed decrease observed during hypoxia in the newborn. In this study, we measured the changes in respiration and brain stem blood flow (BBF) during 2–4 min of hypoxic hypoxia in both intact and denervated piglets and calculated the changes in brain stem Pco2 and [H+] that would be expected to occur as a result of the changes in BBF. All animals were anesthetized, spontaneously breathing, and between 2 and 7 days of age. Respiratory and other variables were measured before and during hypoxia in all animals, and BBF (microspheres) was measured in a subgroup of intact and denervated animals at 0, 30, and 260 s and at 0 and 80 s, respectively. During hypoxia, minute ventilation increased and then decreased (biphasic response) in the intact animals but decreased only in the denervated animals. BBF increased in a near linear fashion, and calculated brain stem extracellular fluid Pco2 and [H+] decreased over the first 80 s both before and after denervation. We speculate that a rapid increase in BBF during acute hypoxia decreases brain stem extracellular fluid Pco2 and [H+], which, in turn, negatively modulate the increase in respiratory drive produced by peripheral chemoreceptor input to the central respiratory generator.


1998 ◽  
Vol 84 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Patricia J. Ohtake ◽  
José E. Torres ◽  
Yair M. Gozal ◽  
Gavin R. Graff ◽  
David Gozal

N-methyl-d-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (V˙e) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (Vt) decreased while frequency increased, resulting in a modest reduction inV˙e. Inspiratory time (Ti) decreased, whereas expiratory time remained unchanged. TheV˙e responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (Vt/Ti) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas Vt was unaffected. Sodium cyanide doses associated with significantV˙eincreases were 5 and 50 μg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reducedV˙e during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.


2006 ◽  
Vol 101 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Rurong Wang ◽  
Fadi Xu

Apnea and respiratory failure often occur in infants with pulmonary disease. Bronchopulmonary C-fiber (PCF)-mediated apnea is an important component of respiratory dysfunction. This study was undertaken to define the postnatal development of PCF-mediated apnea. The experiments were conducted in five groups of anesthetized, tracheotomized, and spontaneously breathing rats with ages at postnatal days P1–3, P7–9, P14–16, P21–23, and P56–58. Right atrial bolus injection of three doses of capsaicin (Cap), equivalent to 2, 4, and 8 μg/kg used previously in 450-g rats, was applied to stimulate PCFs. We found that 1) Cap-induced apneic response [percent change from the baseline expiratory duration (Te) values (ΔTe%)] and the sensitivity of this response (ΔTe%·μg−1) were significantly greater in the rats <P10 than those >P10; 2) the Cap-induced apneas were vagally dependent in all rats tested; and 3) bivagotomy-induced prolongation of Te was much greater in the rats <P10 than those >P10. From these findings we concluded that, compared with the older rats (>P10), the newborn rats have a stronger PCF-mediated respiratory inhibition that may contribute to infants' vulnerability to respiratory failure.


2011 ◽  
Vol 140 ◽  
pp. 191-194
Author(s):  
Kang Xin Tan ◽  
Dong Xiao Lu ◽  
Yuan Ming Luo

Assessment of neural respiratory drive is useful for diagnosis and management of breathing difficulty. The diaphragm is the most important muscle of respiration, therefore its electrical activity during spontaneously breathing could be used to reflect neural respiratory drive. In this study a catheter which was composed of 10 electrodes and two balloons was developed and was used to assess neural respiratory drive during CO2rebreathing in six healthy subjects. There was a good linear relationship between diaphragm EMG and end-tidal CO2(r = 0.98±0.01) during CO2rebreathing. Transdiaphragmatic pressure was also well correlated with end-tidal CO2during CO2rebreathing. We concluded that the combined catheter developed in this study can be used to assess neural respiratory drive.


2007 ◽  
Vol 293 (4) ◽  
pp. R1728-R1735 ◽  
Author(s):  
Lachlan M. McDowall ◽  
Jouji Horiuchi ◽  
Roger A. L. Dampney

Neurons within the dorsomedial hypothalamus (DMH) play a critical role in subserving the cardiovascular and neuroendocrine response to psychological stress. An increase in respiratory activity is also a characteristic feature of the physiological response to psychological stress, but there have been few studies of the role of DMH neurons in regulating respiratory activity. In this study we determined the effects of activation of DMH neurons on respiratory activity (assessed by measuring phrenic nerve activity, PNA) and the relationship between evoked changes in respiratory activity and changes in sympathetic vasomotor activity in spontaneously breathing urethane-anesthetized rats. Microinjections of bicuculline (4–40 pmol in 20 nl) into the DMH evoked dose-dependent increases in PNA burst frequency and amplitude. These were accompanied by dose-dependent decreases in mean tracheal CO2 levels, indicative of hyperventilation. In control experiments, microinjections of bicuculline into sites adjacent to the DMH evoked much smaller or no changes in PNA. In experiments where renal sympathetic nerve activity (RSNA) was also measured, cycle-triggered averaging revealed that RSNA under resting conditions was partly correlated with the PNA, but in response to DMH disinhibition there was no consistent change in the amplitude of the respiratory-related variations in RSNA. The results indicate that DMH neurons can exert a powerful stimulatory effect on respiratory activity, causing hyperventilation. This is not associated with an increase in the degree of coupling between PNA and RSNA, indicating that the DMH-evoked increase in RSNA is not a consequence of increased central respiratory drive.


1994 ◽  
Vol 76 (1) ◽  
pp. 242-252 ◽  
Author(s):  
A. De Troyer ◽  
M. Cappello ◽  
J. F. Brichant

To assess the respiratory function of the scalene and sternomastoid muscles in the dog, we studied the effect of graded increases in inspiratory airflow resistance and single-breath airway occlusion on the electrical activity of these muscles in 18 supine anesthetized spontaneously breathing animals. The sternomastoids never showed any activity, and the scalenes showed some inspiratory activity during occlusion in only two animals. The adoption of the prone position and bilateral cervical vagotomy did not affect this pattern. Hypercapnia also did not elicit any sternomastoid activity and induced scalene inspiratory activity during occlusion in only four of nine animals. On microscopic examination, however, both muscles were found to contain large numbers of spindles, suggesting that they have the capacity to respond to stretch. In addition, with increases in inspiratory resistance, both the sternum and ribs were displaced in the caudal direction. As a result, the scalenes demonstrated a gradual inspiratory lengthening and the normal inspiratory lengthening of the sternomastoids was accentuated. Additional studies in three unanesthetized animals showed consistent activity in the scalene and sternomastoid muscles during movements of the trunk and neck but no activity during breathing, including occluded breathing. These observations thus indicate that the alpha-motoneurons of the scalene and sternomastoid muscles in the dog have very small central respiratory drive potentials with respect to their critical firing threshold. In this animal, these muscles do not have a significant respiratory function.


Anaesthesia ◽  
2002 ◽  
Vol 57 (6) ◽  
pp. 540-543 ◽  
Author(s):  
G. Conti ◽  
S. Pierdominici ◽  
G. Ferro ◽  
M. G. Bocci ◽  
M. Antonelli ◽  
...  

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