Selected Contribution: Peripheral chemoreflex function in high-altitude natives and patients with chronic mountain sickness

2003 ◽  
Vol 94 (3) ◽  
pp. 1269-1278 ◽  
Author(s):  
Fabiola León-Velarde ◽  
Alfredo Gamboa ◽  
Maria Rivera-Ch ◽  
Jose-Antonio Palacios ◽  
Peter A. Robbins
Keyword(s):  
High Altitude ◽  
Low Dose ◽  
Ventilatory Response ◽  
Chronic Mountain Sickness ◽  
Ventilatory Responses ◽  
High Altitude Natives ◽  
Mountain Sickness ◽  
Group 2 ◽  
End Tidal ◽  
Peripheral Chemoreflex

Peripheral chemoreflex function was studied in high-altitude (HA) natives at HA, in patients with chronic mountain sickness (CMS) at HA, and in sea-level (SL) natives at SL. Results were as follows. 1) Acute ventilatory responses to hypoxia (AHVR) in the HA and CMS groups were approximately one-third of those of the SL group. 2) In CMS patients, some indexes of AHVR were modestly, but significantly, lower than in healthy HA natives. 3) Prior oxygenation increased AHVR in all subject groups. 4) Neither low-dose dopamine nor somatostatin suppressed any component of ventilation that could not be suppressed by acute hyperoxia. 5) In all subject groups, the ventilatory response to hyperoxia was biphasic. Initially, ventilation fell but subsequently rose so that, by 20 min, ventilation was higher in hyperoxia than hypoxia for both HA and CMS subjects. 6) Peripheral chemoreflex stimulation of ventilation was modestly greater in HA and CMS subjects at an end-tidal Po 2= 52.5 Torr than in SL natives at an end-tidal Po 2 = 100 Torr. 7) For the HA and CMS subjects combined, there was a strong correlation between end-tidal Pco 2 and hematocrit, which persisted after controlling for AHVR.

Selected Contribution: Ventilatory response to CO2 in high-altitude natives and patients with chronic mountain sickness

2003 ◽  
Vol 94 (3) ◽  
pp. 1279-1287 ◽  
Author(s):  
Marzieh Fatemian ◽  
Alfredo Gamboa ◽  
Fabiola León-Velarde ◽  
Maria Rivera-Ch ◽  
Jose-Antonio Palacios ◽  
...  
Keyword(s):  
High Altitude ◽  
Binary Sequence ◽  
Chronic Mountain Sickness ◽  
Ventilatory Responses ◽  
Chemoreflex Sensitivity ◽  
High Altitude Natives ◽  
Mountain Sickness ◽  
End Tidal ◽  
Peripheral Chemoreflex ◽  
Ventilatory Response To Co2

The ventilatory responses to CO2 of high-altitude (HA) natives and patients with chronic mountain sickness (CMS) were studied and compared with sea-level (SL) natives living at SL. A multifrequency binary sequence (MFBS) in end-tidal Pco 2 was employed to separate the fast (peripheral) and slow (central) components of the chemoreflex response. MFBS was imposed against a background of both euoxia (end-tidal Po 2 of 100 Torr) and hypoxia (52.5 Torr). Both total and central chemoreflex sensitivity to CO2 in euoxia were higher in HA and CMS subjects compared with SL subjects. Peripheral chemoreflex sensitivity to CO2in euoxia was higher in HA subjects than in SL subjects. Hypoxia induced a greater increase in total chemoreflex sensitivity to CO2 in SL subjects than in HA and CMS subjects, but peripheral chemoreflex sensitivity to CO2 in hypoxia was no greater in SL subjects than in HA and CMS subjects. Values for the slow (central) time constant were significantly greater for HA and CMS subjects than for SL subjects.

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.

Selected Contribution: Acute and sustained ventilatory responses to hypoxia in high-altitude natives living at sea level

2003 ◽  
Vol 94 (3) ◽  
pp. 1255-1262 ◽  
Author(s):  
Alfredo Gamboa ◽  
Fabiola León-Velarde ◽  
Maria Rivera-Ch ◽  
Jose-Antonio Palacios ◽  
Timothy R. Pragnell ◽  
...  
Keyword(s):  
Confidence Interval ◽  
High Altitude ◽  
Sea Level ◽  
Hypoxic Exposure ◽  
Ventilatory Responses ◽  
High Altitude Natives ◽  
Ventilatory Depression ◽  
End Tidal ◽  
Sustained Hypoxia

High-altitude (HA) natives have blunted ventilatory responses to hypoxia (HVR), but studies differ as to whether this blunting is lost when HA natives migrate to live at sea level (SL), possibly because HVR has been assessed with different durations of hypoxic exposure (acute vs. sustained). To investigate this, 50 HA natives (>3,500 m, for >20 yr) now resident at SL were compared with 50 SL natives as controls. Isocapnic HVR was assessed by using two protocols: protocol 1, progressive stepwise induction of hypoxia over 5–6 min; and protocol 2, sustained (20-min) hypoxia (end-tidal Po 2 = 50 Torr). Acute HVR was assessed from both protocols, and sustained HVR from protocol 2. For HA natives, acute HVR was 79% [95% confidence interval (CI): 52–106%, P = not significant] of SL controls for protocol 1 and 74% (95% CI: 52–96%, P < 0.05) for protocol 2. By contrast, sustained HVR after 20-min hypoxia was only 30% (95% CI: −7–67%, P < 0.001) of SL control values. The persistent blunting of HVR of HA natives resident at SL is substantially less to acute than to sustained hypoxia, when hypoxic ventilatory depression can develop.

scholarly journals High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men

2009 ◽  
Vol 296 (6) ◽  
pp. E1319-E1325 ◽  
Author(s):  
Gustavo F. Gonzales ◽  
Manuel Gasco ◽  
Vilma Tapia ◽  
Cynthia Gonzales-Castañeda
Keyword(s):  
Thyroid Hormones ◽  
High Altitude ◽  
Serum Testosterone ◽  
High Serum ◽  
Chronic Mountain Sickness ◽  
Testosterone Levels ◽  
High Altitude Natives ◽  
Mountain Sickness ◽  
Low Altitude ◽  
Cerro De Pasco

Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis (EE) secondary to hypoventilation. Erythropoietin (Epo) and testosterone regulate erythrocyte production. Low thyroid hormone levels are also associated to hypoventilation. Hence, these hormones can play a role in etiopathogeny of EE. The purpose of this study was to elucidate the effect of sexual and thyroid hormones and Epo in residents from Lima (150 m) and Cerro de Pasco (4,340 m), Peru, and the response to human chorionic gonadotrophin stimulation (hCG). Three groups, one at low altitude and two at high altitude [1 with hemoglobin values >16–21 g/dl and the second with Hb ≥21 g/dl (EE)], were studied. hCG was administered intramuscularly in a single dose (1,000 IU), and blood samples were obtained at 0, 6, 12, 24, 48, and 72 h after injection. High-altitude natives present similar levels of gonadotropins and thyroid hormones but lower dehydroepiandrosterone sulphate (DHEAS) levels ( P < 0.01) and greater Epo ( P < 0.01), 17α-hydroxyprogesterone ( P < 0.01), and testosterone levels ( P < 0.01) than those at 150 m. Serum testosterone levels (524.13 ± 55.91 μg/dl vs. 328.14 ± 53.23 ng/dl, means ± SE; P < 0.05) and testosterone/DHEAS ratios are higher (7.98 ± 1.1 vs. 3.65 ± 1.1; P < 0.01) and DHEAS levels lower in the EE group (83.85 ± 14.60 μg/dl vs. 148.95 ± 19.11 ug/dl; P < 0.05), whereas Epo was not further affected. Testosterone levels were highest and DHEAS levels lowest in the EE group at all times after hCG stimulation. In conclusion, high androgen activity could be involved in the etiopathogeny of CMS. This evidence provides an opportunity to develop new therapeutic strategies.

Influences of Subanesthetic Isoflurane on Ventilatory Control in Humans

1995 ◽  
Vol 83 (3) ◽  
pp. 478-490. ◽  
Author(s):  
Maarten van den Elsen ◽  
Albert Dahan ◽  
Jacob DeGoede ◽  
Aad Berkenbosch ◽  
Jack van Kleef
Keyword(s):  
Carbon Dioxide ◽  
Healthy Volunteers ◽  
Ventilatory Response ◽  
Carbon Dioxide Tension ◽  
Central Component ◽  
Ventilatory Control ◽  
Ventilatory Responses ◽  
End Tidal ◽  
Peripheral Chemoreflex ◽  
Ventilatory Response To Hypoxia

Background The purpose of this study was to quantify in humans the effects of subanesthetic isoflurane on the ventilatory control system, in particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isoflurane wash-in upon sustained hypoxic steady-state ventilation, and the ventilatory response at the onset of 20 min of isocapnic hypoxia. Methods Study 1: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set (apneic threshold). Study 2: The ventilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min after the induction of isocapnic hypoxia, were studied in 11 healthy volunteers. Study 3: The ventilatory responses to a step decrease in end-tidal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 breaths; duration of hypoxia 20 min) were assessed in eight healthy volunteers at 0, 0.1, and 0.2 MAC isoflurane. Results Values are reported as means +/- SF. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 l.min-1.mmHg-1 (isoflurane; P &lt; 0.01). The central carbon dioxide sensitivities (control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 l.min-1.mmHg-1) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0.2 mmHg) did not differ between treatments. Study 2: Within 30 s of exposure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 l.min-1 (hypoxia, isoflurane). Study 3: At the initiation of hypoxia ventilation increased by 7.7 +/- 1.4 (control), 4.1 +/- 0.8 (0.1 MAC; P &lt; 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P &lt; 0.05 vs. control) l.min-1. The subsequent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0.5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P &lt; 0.05 vs. control) l.min-1. There was a good correlation between the acute hypoxic response and the hypoxic ventilatory decrease (r = 0.9; P &lt; 0.001). Conclusions The results of all three studies indicate a selective and profound effect of subanesthetic isoflurane on the peripheral chemoreflex loop at the site of the peripheral chemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.

scholarly journals Importance of Testosterone on Adaptation at High Altitude

2018 ◽  
Vol 2 (4) ◽  
pp. 689-697 ◽  
Author(s):  
Gustavo Gonzales
Keyword(s):  
Androgen Receptor ◽  
High Altitude ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Serum Testosterone ◽  
Arterial Oxygen ◽  
High Altitudes ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness ◽  
Ventilatory Response To Hypoxia

Adaptation or natural acclimatization results from the interaction between genetic variations and acclimatization resulting in individuals with ability to live and reproduce without problems at high altitudes. Testosterone is a hormone that increases erythropoiesis and inhibits ventilation. It could therefore, be associated to the adaptation to high altitudes. Excessive erythrocytosis, which in turn will develop chronic mountain sickness is caused by low arterial oxygen saturation and ventilatory inefficiency and blunted ventilatory response to hypoxia. Testosterone is elevated in natives at high altitude with excessive erythrocytosis (>21 g /dl hemoglobin in men and >19 g/dl in women). Natives from the Peruvian central Andes with chronic mountain sickness express gene SENP1 that enhances the activity of the androgen receptor. Results of the current investigations suggest that increase in serum testosterone and hemoglobin is not adequate for adaptation to high altitude.

scholarly journals Ventilatory responses to acute hypoxia and hypercapnia in humans with a patent foramen ovale

2019 ◽  
Vol 126 (3) ◽  
pp. 730-738 ◽  
Author(s):  
James T. Davis ◽  
Lindsey M. Boulet ◽  
Alyssa M. Hardin ◽  
Alex J. Chang ◽  
Andrew T. Lovering ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
High Altitude ◽  
Patent Foramen Ovale ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Acute Exposure ◽  
Foramen Ovale ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
Peripheral Chemoreflex

Subjects with a patent foramen ovale (PFO) have blunted ventilatory acclimatization to high altitude compared with subjects without PFO. The blunted response observed could be because of differences in central and/or peripheral respiratory chemoreflexes. We hypothesized that compared with subjects without a PFO (PFO−), subjects with a PFO (PFO+) would have blunted ventilatory responses to acute hypoxia and hypercapnia. Sixteen PFO+ subjects (9 female) and 15 PFO− subjects (8 female) completed four 20-min trials on the same day: 1) normoxic hypercapnia (NH), 2) hyperoxic hypercapnia (HH), 3) isocapnic hypoxia (IH), and 4) poikilocapnic hypoxia (PH). Hypercapnic trials were completed before the hypoxic trials, the order of the hypercapnic (NH & HH) and hypoxic (IH & PH) trials were randomized, and trials were separated by ≥40 min. During the NH trials but not the HH trials subjects who were PFO+ had a blunted hypercapnic ventilatory response compared with subjects who were PFO− (1.41 ± 0.46 l·min−1·mmHg−1 vs. 1.98 ± 0.71 l·min−1·mmHg−1, P = 0.02). There were no differences between the PFO+ and PFO− subjects with respect to the acute hypoxic ventilatory response during IH and PH trials. Hypoxic ventilatory depression was similar between subjects who were PFO+ and PFO− during IH. These data suggest that compared with subjects who were PFO−, subjects who were PFO+ have normal ventilatory chemosensitivity to acute hypoxia but blunted ventilatory chemosensitivity to carbon dioxide, possibly because of reduced carbon dioxide sensitivity of either the central and/or the peripheral chemoreceptors. NEW & NOTEWORTHY Patent foramen ovale (PFO) is found in ~25%–40% of the population. The presence of a PFO appears to be associated with blunted ventilatory responses during acute exposure to normoxic hypercapnia. The reason for this blunted ventilatory response during acute exposure to normoxic hypercapnia is unknown but may suggest differences in either central and/or peripheral chemoreflex contribution to hypercapnia.

scholarly journals Chemoreflex mediated arrhythmia during apnea at 5,050 m in low- but not high-altitude natives

2018 ◽  
Vol 124 (4) ◽  
pp. 930-937 ◽  
Author(s):  
Stephen A. Busch ◽  
Hannah Davies ◽  
Sean van Diepen ◽  
Lydia L. Simpson ◽  
Frances Sobierajski ◽  
...  
Keyword(s):  
High Altitude ◽  
Chronic Hypoxia ◽  
Ventilatory Response ◽  
Supplemental Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Junctional Rhythm ◽  
High Altitude Natives ◽  
Peripheral Chemoreflex ◽  
Hypoxic State ◽  
Voluntary Apnea

Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic drive under chronic hypoxia may evoke bradyarrhythmias during apneic periods. We determined whether 1) voluntary apnea unmasks arrhythmia at low (344 m) and high (5,050 m) altitude, 2) high-altitude natives (Nepalese Sherpa) exhibit similar cardiovagal responses at altitude, and 3) bradyarrhythmias at altitude are partially chemoreflex mediated. Participants were grouped as Lowlanders ( n = 14; age = 27 ± 6 yr) and Nepalese Sherpa ( n = 8; age = 32 ± 11 yr). Lowlanders were assessed at 344 and 5,050 m, whereas Sherpa were assessed at 5,050 m. Heart rate (HR) and rhythm (lead II ECG) were recorded during rest and voluntary end-expiratory apnea. Peripheral chemoreflex contributions were assessed in Lowlanders ( n = 7) at altitude after 100% oxygen. Lowlanders had higher resting HR at altitude (70 ± 15 vs. 61 ± 15 beats/min; P < 0.01) that was similar to Sherpa (71 ± 5 beats/min; P = 0.94). High-altitude apnea caused arrhythmias in 11 of 14 Lowlanders [junctional rhythm ( n = 4), 3° atrioventricular block ( n = 3), sinus pause ( n = 4)] not present at low altitude and larger marked bradycardia (nadir −39 ± 18 beats/min; P < 0.001). Sherpa exhibited a reduced bradycardia response during apnea compared with Lowlanders ( P < 0.001) and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir −10 ± 14 beats/min; P < 0.001 compared with hypoxic state) and reduced arrhythmia incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias ( P < 0.05). Our data demonstrate apnea-induced bradyarrhythmias in Lowlanders at altitude but not in Sherpa (potentially through cardioprotective phenotypes). The chemoreflex is an important mechanism in genesis of bradyarrhythmias, and the HVR may be predictive for identifying individual susceptibility to events at altitude. NEW & NOTEWORTHY The peripheral chemoreflex increases both parasympathetic and sympathetic drive under chronic hypoxia. We found that this evoked bradyarrhythmias when combined with apneic periods in Lowlanders at altitude, which become relieved through supplemental oxygen. In contrast, high-altitude residents (Nepalese Sherpa) do not exhibit bradyarrhythmias during apnea at altitude through potential cardioprotective adaptations. The degree of bradycardia and bradyarrhythmias was related to the hypoxic ventilatory response, demonstrating that the chemoreflex plays an important role in these findings.

Ventilatory sensitivity to CO2 in hyperoxia and hypoxia in older aged humans

1993 ◽  
Vol 75 (5) ◽  
pp. 2209-2216 ◽  
Author(s):  
M. J. Poulin ◽  
D. A. Cunningham ◽  
D. H. Paterson ◽  
J. M. Kowalchuk ◽  
W. D. Smith
Keyword(s):  
Linear Equation ◽  
Response Curve ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Ventilatory Responses ◽  
Co2 Sensitivity ◽  
End Tidal ◽  
Effects Of Aging ◽  
Peripheral Chemoreflex ◽  
Ventilatory Response To Co2

Findings from studies of the effects of aging on the human respiratory controller are equivocal. This study assessed the ventilatory response to CO2 in hyperoxia and hypoxia in groups of younger (YS) and older (OS) humans. Two protocols were used. In the first, end-tidal PCO2 (PETCO2) was clamped at 1–2 Torr above rest (eucapnia), and, in the second, PETCO2 was clamped at 7–8 torr above resting PETCO2 (moderate hypercapnia). End-tidal PO2 was clamped at 100 Torr throughout except for two 2-min periods at 500 and 50 Torr. The ventilatory responses for each subject at each PO2 were fitted to the linear equation, VE = S(PETCO2 - B), where VE is minute ventilation, S is the response curve slope, and B is the response curve threshold. In eucapnia, there were no differences in hypoxic and hyperoxic VE between YS and OS. In hypercapnia, hypoxic VE was 24% lower in OS [39.93 +/- 2.71 (SE) l/min] than in YS (52.16 +/- 3.17 l/min). In hypoxia, S was significantly lower in OS (3.25 +/- 0.38 l.min-1.Torr-1) than in YS (4.76 +/- 0.37 l.min-1.Torr-1). We conclude that, in older humans, VE is lower in hypoxia during moderate hypercapnia, resulting mainly from a decreased peripheral chemoreflex CO2 sensitivity.

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