Effects of haloperidol on ventilation during isocapnic hypoxia in humans

1997 ◽  
Vol 83 (4) ◽  
pp. 1110-1115 ◽  
Author(s):  
Michala E. F. Pedersen ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Dopamine Receptor ◽  
Analysis Of Variance ◽  
Similar Pattern ◽  
Ventilatory Response ◽  
Placebo Control ◽  
Hypoxic Ventilatory Response ◽  
Abrupt Increase ◽  
Receptor Antagonism ◽  
Ventilatory Responses ◽  
End Tidal

Pedersen, Michala E. F., Keith L. Dorrington, and Peter A. Robbins. Effects of haloperidol on ventilation during isocapnic hypoxia in humans. J. Appl. Physiol.83(4): 1110–1115, 1997.—Exposure to isocapnic hypoxia produces an abrupt increase in ventilation [acute hypoxic ventilatory response (AHVR)], which is followed by a subsequent decline [hypoxic ventilatory depression or decline (HVD)]. In cats, both anesthetized and awake, haloperidol has been reported to increase AHVR and almost entirely abolish HVD. To investigate whether this occurs in humans, the ventilatory responses of 15 healthy young volunteers to 20 min of isocapnic hypoxia (end-tidal [Formula: see text] = 50 Torr) were assessed at 1, 2, and 4.5 h after placebo (control) and after oral haloperidol (Seranace, 0.05 mg/kg) on different days. Three subjects were unable to complete the study because of akathisia. AHVR was significantly greater with haloperidol compared with control ( P < 0.01, analysis of variance). However, no significant change in HVD was found [control HVD = 9.3 ± 1.6 (SD) l/min, haloperidol HVD = 9.9 ± 2.1 l/min; P = not significant, analysis of variance]. We conclude that combined central and peripheral dopamine-receptor antagonism in humans with haloperidol produces a similar pattern of change to that reported previously with the peripheral antagonist domperidone. We have been unable to show in humans a decrease in HVD by the centrally acting drug as observed in cats.

Time course of augmentation and depression of hypoxic ventilatory responses at altitude

1994 ◽  
Vol 77 (1) ◽  
pp. 313-316 ◽  
Author(s):  
M. Sato ◽  
J. W. Severinghaus ◽  
P. Bickler
Keyword(s):  
Pulse Oximetry ◽  
Sea Level ◽  
Time Course ◽  
Ventilatory Response ◽  
Barometric Pressure ◽  
Hypoxic Ventilatory Response ◽  
Set Point ◽  
Ventilatory Responses ◽  
End Tidal ◽  
Arterial O2 Saturation

Hypoxic ventilatory response (HVR) and hypoxic ventilatory depression (HVD) were measured in six subjects before, during, and after 12 days at 3,810-m altitude (barometric pressure approximately 488 Torr) with and without 15 min of preoxygenation. HVR was tested by 5-min isocapnic steps to 75% arterial O2 saturation measured by pulse oximetry (Spo2) at an isocapnic PCO2 (P*CO2) chosen to set hyperoxic resting ventilation to 140 ml.kg-1.min-1. Hypercapnic ventilatory response (HCVR, 1.min-1.Torr-1) was tested at ambient and high SPO2 6–8 min after a 6- to 10-Torr step increase of end-tidal PCO2 (PETCO2) above P*CO2. HCVR was independent of preoxygenation and was not significantly increased at altitude (when corrected to delta logPCO2). Preoxygenated HVR rose from -1.13 +/- 0.23 (SE) l.min-1.%SPO2(-1) at sea level to -2.17 +/- 0.13 by altitude day 12, without reaching a plateau, and returned to control after return to sea level for 4 days. Ambient HVR was measured at P*CO2 by step reduction of SPO2 from its ambient value (86–91%) to approximately 75%. Ambient HVR slope was not significantly less, but ventilation at equal levels of SPO2 and PCO2 was lower by 13.3 +/- 2.4 l/min on day 2 (SPO2 = 86.2 +/- 2.3) and by 5.9 +/- 3.5 l/min on day 12 (SPO2 = 91.0 +/- 1.5; P < 0.05). This lower ventilation was estimated (from HCVR) to be equivalent to an elevation of the central chemoreceptor PCO2 set point of 9.2 +/- 2.1 Torr on day 2 and 4.5 +/- 1.3 on day 12.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory responses to hypercapnia and hypoxia during continuous aspirin ingestion

1977 ◽  
Vol 43 (6) ◽  
pp. 971-976 ◽  
Author(s):  
D. J. Riley ◽  
B. A. Legawiec ◽  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Normal Subjects ◽  
Carbon Dioxide Tension ◽  
Base Line ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
Hypercapnic Ventilatory Response ◽  
The Central Nervous System ◽  
End Tidal

Hypercapnic and hypoxic ventilatory responses were serially measured in nine normal subjects given 3.9 g aspirin (ASA) per day for 9 days. Minute ventilation (VE), end-tidal carbon dioxide tension (PETCO2), venous bicarbonate concentration [HCO3-], oxygen consumption (VO2), hypercapnic ventilatory response (deltaVE/deltaPCO2), and isocapnic hypoxic ventilatory response (A) were determined before, 2 h after the first dose, and at 72-h intervals during the next 14 days. Serum salicylate levels averaged 18.6 +/- 2.0 mg/dl. VE increased (P less than 0.05, PETCO2 decreased (P less than 0.05), and [HCO3-] did not change significantly during drug ingestion. deltaVE/deltaPCO2 increased gradually to a value 37% greater than control by day 3 and remained constant (P less 0.01). A increased by 251% and VO2 by 18% within 2 h and remained constant for the remainder of the ASA period (P less than 0.01). All values returned to base line within 24 h following cessation of ASA. We conclude that during continuous ASA ingestion there is a gradual increase of hypercapnic ventilatory response. This may reflect slow entrance of ASA into the central nervous system. In contrast, there is a rapid rise in hypoxic ventilatory response which may be mechanically linked to changes in metabolic rate.

Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes

2002 ◽  
Vol 93 (4) ◽  
pp. 1498-1505 ◽  
Author(s):  
Nathan E. Townsend ◽  
Christopher J. Gore ◽  
Allan G. Hahn ◽  
Michael J. McKenna ◽  
Robert J. Aughey ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Endurance Athletes ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Hypoxic Ventilatory Response ◽  
Ambient Conditions ◽  
Altitude Exposure ◽  
End Tidal

This study determined whether “living high-training low” (LHTL)-simulated altitude exposure increased the hypoxic ventilatory response (HVR) in well-trained endurance athletes. Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20 nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11). LHTLc and LHTLi slept 8–10 h/day overnight in normobaric hypoxia (∼2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR (ΔV˙e/ΔSpO2 , whereV˙e is minute ventilation and SpO2 is blood O2 saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15 nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the exposure night 20 (Post). Before each HVR test, end-tidal Pco 2(Pet CO2 ) and V˙e were measured during room air breathing at rest. HVR (l · min−1 · %−1) was higher ( P < 0.05) in LHTLc than in Con at N1 (0.56 ± 0.32 vs. 0.28 ± 0.16), N3 (0.69 ± 0.30 vs. 0.36 ± 0.24), N10 (0.79 ± 0.36 vs. 0.34 ± 0.14), N15 (1.00 ± 0.38 vs. 0.36 ± 0.23), and Post (0.79 ± 0.37 vs. 0.36 ± 0.26). HVR at N15 was higher ( P < 0.05) in LHTLi (0.67 ± 0.33) than in Con and in LHTLc than in LHTLi. Pet CO2 was depressed in LHTLc and LHTLi compared with Con at all points after hypoxia ( P < 0.05). No significant differences were observed for V˙e at any point. We conclude that LHTL increases HVR in endurance athletes in a time-dependent manner and decreases Pet CO2 in normoxia, without change inV˙e. Thus endurance athletes sleeping in mild hypoxia may experience changes to the respiratory control system.

Ventilatory response to 8 h of isocapnic and poikilocapnic hypoxia in humans

1995 ◽  
Vol 78 (3) ◽  
pp. 1092-1097 ◽  
Author(s):  
L. S. Howard ◽  
P. A. Robbins
Keyword(s):  
Analysis Of Variance ◽  
Ventilatory Response ◽  
Progressive Increase ◽  
Nasal Catheter ◽  
Partial Pressures ◽  
End Tidal ◽  
Almost All ◽  
And Control

Almost all studies of the effects of prolonged hypoxia on ventilation (VE) in humans have been performed with the end-tidal PCO2 (PETCO2) left uncontrolled. The purpose of this study was to compare the effects of 8 h of hypoxia with PETCO2 held constant with 8 h of hypoxia with PETCO2 left uncontrolled. Ten subjects completed the study. Each was seated inside a chamber in which the inspired gas could be controlled so as to maintain the desired partial pressures of end-tidal gases (sampled via nasal catheter) constant (see L.S.G.E. Howard et al. J. Appl. Physiol. 78:1088–1091, 1995.). Three 8-h protocols were employed: 1) isocapnic hypoxia, at an end-tidal PO2 of 55 Torr with PETCO2 held at the subject's resting value; 2) poikilocapnic hypoxia, at the same end-tidal PO2; and 3) control, where the inspired gas was air. VE was measured (over 3 min) at 0 and 20 min and at hourly intervals between 1.5 and 7.5 h. There was a rise in VE during isocapnic hypoxia [from an initial VE of 16.2 +/- 1.3 (SE) l/min to a final VE of 24.8 +/- 1.6 l/min], which was significant compared with poikilocapnic hypoxia and control values (P < 0.001, analysis of variance). There was no significant progressive rise in VE during poikilocapnic hypoxia compared with control values. These results show that isocapnic hypoxia produces a progressive increase in VE when sustained over an 8-h period. The onset of this response is faster than has been noted in studies of the progressive rise in VE associated with the poikilocapnic hypoxia of altitude.

Ventilatory responses to carbon dioxide at low and high levels of oxygen are elevated after episodic hypoxia in men compared with women

2004 ◽  
Vol 97 (5) ◽  
pp. 1673-1680 ◽  
Author(s):  
Chris Morelli ◽  
M. Safwan Badr ◽  
Jason H. Mateika
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
High Oxygen ◽  
Set Point ◽  
Ventilatory Responses ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Oxygen Gas ◽  
End Tidal

We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 ± 0.82 vs. women, 4.70 ± 0.77 l·min−1·Torr−1; 150 Torr: men, 4.33 ± 1.15 vs. women, 3.21 ± 0.58 l·min−1·Torr−1). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 ± 1.40 vs. women, 5.97 ± 0.71 l·min−1·Torr−1; 150 Torr: men, 5.73 ± 0.81 vs. women, 3.83 ± 0.56 l·min−1·Torr−1). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.

Effect of elastic loading on ventilatory response to hypoxia in conscious man

1975 ◽  
Vol 39 (4) ◽  
pp. 548-551 ◽  
Author(s):  
A. S. Rebuck ◽  
M. Betts ◽  
N. A. Saunders
Keyword(s):  
Ventilatory Response ◽  
Variable Speed ◽  
Ventilatory Responses ◽  
Elastic Load ◽  
Resistive Loading ◽  
Elastic Loading ◽  
Progressive Hypoxia ◽  
End Tidal ◽  
Linear Regressions ◽  
Ventilatory Response To Hypoxia

Ventilatory responses to isocapnic hypoxia, with and without an inspiratory elastic load (12.1 cmH2O/l), were measured in seven healthy subjects using a rebreathing technique. During each experiment, the end-tidal PCO2 was held constant using a variable-speed pump to draw gas from the rebreathing bag through a CO2 absorbing bypass. Studies with and without the load were performed in a formally randomized order for each subject. Linear regressions for rise in ventilation against fall in SaO2 were calculated. The range of unloaded responses was 0.74–1.38 1/min per 1% fall in SaO2 and loaded responses 0.71–1.56 1/min per 1% fall in SaO2. Elastic loading did not significantly alter the ventilatory response to progressive hypoxia (P greater than 0.2). In all subjects there was, however, a change in breathing pattern during loading, whereby increments in ventilation were attained by smaller tidal volumes and higher frequencies than in the control experiments. These results support the hypothesis previously proposed in our studies of resistive loading during progressive hypoxia, that a similar control pathway appears to be involved in response to the application of loads to breathing, whether ventilation is stimulated by hypoxia or hypercapnia.

Effects of dopamine and domperidone on ventilatory sensitivity to hypoxia after 8 h of isocapnic hypoxia

1999 ◽  
Vol 86 (1) ◽  
pp. 222-229 ◽  
Author(s):  
Michala E. F. Pedersen ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Confidence Interval ◽  
Lower Limit ◽  
Analysis Of Variance ◽  
Significant Interaction ◽  
Low Dose ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Dopaminergic Activity ◽  
Sustained Hypoxia

Acclimatization to altitude involves an increase in the acute hypoxic ventilatory response (AHVR). Because low-dose dopamine decreases AHVR and domperidone increases AHVR, the increase in AHVR at altitude may be generated by a decrease in peripheral dopaminergic activity. The AHVR of nine subjects was determined with and without a prior period of 8 h of isocapnic hypoxia under each of three pharmacological conditions: 1) control, with no drug administered; 2) dopamine (3 μg ⋅ min−1 ⋅ kg−1); and 3) domperidone (Motilin, 40 mg). AHVR increased after hypoxia ( P ≤ 0.001). Dopamine decreased ( P ≤ 0.01), and domperidone increased ( P ≤ 0.005) AHVR. The effect of both drugs on AHVR appeared larger after hypoxia, an observation supported by a significant interaction between prior hypoxia and drug in the analysis of variance ( P ≤ 0.05). Although the increased effect of domperidone after hypoxia of 0.40 l ⋅ min−1 ⋅ %saturation−1[95% confidence interval (CI) −0.11 to 0.92 l ⋅ min−1 ⋅ %−1] did not reach significance, the lower limit for this confidence interval suggests that little of the increase in AHVR after sustained hypoxia was brought about by a decrease in peripheral dopaminergic inhibition.

An assessment of nasal functions in control of breathing

1988 ◽  
Vol 65 (4) ◽  
pp. 1520-1524 ◽  
Author(s):  
Y. Tanaka ◽  
T. Morikawa ◽  
Y. Honda
Keyword(s):  
Steady State ◽  
Dead Space ◽  
Airway Resistance ◽  
Breathing Pattern ◽  
Ventilatory Response ◽  
Control Of Breathing ◽  
Mouth Breathing ◽  
Occlusion Pressure ◽  
Ventilatory Responses ◽  
End Tidal

Breathing pattern and steady-state CO2 ventilatory response during mouth breathing were compared with those during nose breathing in nine healthy adults. In addition, the effect of warming and humidification of the inspired air on the ventilatory response was observed during breathing through a mouthpiece. We found the following. 1) Dead space and airway resistance were significantly greater during nose than during mouth breathing. 2) The slope of CO2 ventilatory responses did not differ appreciably during the two types of breathing, but CO2 occlusion pressure response was significantly enhanced during nose breathing. 3) Inhalation of warm and humid air through a mouthpiece significantly depressed CO2 ventilation and occlusion pressure responses. These results fit our observation that end-tidal PCO2 was significantly higher during nose than during mouth breathing. It is suggested that a loss of nasal functions, such as during nasal obstruction, may result in lowering of CO2, fostering apneic spells during sleep.

Respiratory control in humans after 8 h of lowered arterial Po 2, hemodilution, or carboxyhemoglobinemia

2001 ◽  
Vol 90 (4) ◽  
pp. 1189-1195 ◽  
Author(s):  
Xiaohui Ren ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Oxygen Content ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Venous Blood ◽  
Respiratory Control ◽  
Progressive Increase ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Arterial Oxygen Content ◽  
End Tidal

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial Po 2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal Po 2 was held at 55 Torr and end-tidal Pco 2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH ( P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial Po 2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.

Sevoflurane-induced Reduction of Hypoxic Drive Is Sex-independent 

1999 ◽  
Vol 90 (5) ◽  
pp. 1288-1293 ◽  
Author(s):  
Elise Sarton ◽  
Minke van der Wal ◽  
Diederik Nieuwenhuijs ◽  
Luc Teppema ◽  
James L. Robotham ◽  
...  
Keyword(s):  
Bispectral Index ◽  
Low Dose ◽  
Ventilatory Response ◽  
Carbon Dioxide Tension ◽  
Opioid Agonist ◽  
Men And Women ◽  
Ventilatory Responses ◽  
Inhalational Anesthetic ◽  
Ventilatory Effects ◽  
End Tidal

Background Although the mu-opioid agonist morphine affects ventilatory control in men and women in different ways, no data exist regarding the influence of sex on the ventilatory effects of inhalational anesthetics. The authors compared the effect of sevoflurane on the ventilatory response to isocapnic hypoxia in healthy young men and women. Methods Breath-to-breath ventilatory responses to hypoxic steps (number of hypoxic steps, four-six; duration, 3 min; end-tidal oxygen tension, approximately 50 mmHg; end-tidal carbon dioxide tension clamped at approximately 4 mmHg above resting values) were assessed in nine men and nine women without and with low-dose sevoflurane (end-tidal concentration, 0.25%). The bispectral index of the electroencephalogram was measured concomitantly. Results Sevoflurane reduced the hypoxic ventilatory sensitivity significantly in both sexes (men: control, 0.62 +/- 0.17 vs. sevoflurane, 0.38 +/- 0.19 l x min(-1) x %(-1); women: control, 0.52 +/- 0.30 vs. sevoflurane, 0.34 +/- 0.15 l x min(-1) x %(-1)). Sevoflurane-induced reductions of the hypoxic responses were not different in the men and women. During sevoflurane inhalation, the bispectral index values decreased equally in men and women. Conclusion In contrast to morphine, the influence of a low dose of the inhalational anesthetic sevoflurane on the ventilatory response to hypoxia is independent of sex.

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