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.

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: 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.

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.

Global REACH 2018: Volume regulation in high-altitude Andeans with and without chronic mountain sickness

2021 ◽  
Author(s):  
Andrew R. Steele ◽  
Michael M. Tymko ◽  
Victoria L. Meah ◽  
Lydia L Simpson ◽  
Christopher Gasho ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Plasma Renin Activity ◽  
High Altitude ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Plasma Renin ◽  
Renin Activity ◽  
Chronic Mountain Sickness ◽  
Plasma Aldosterone Concentration ◽  
Mountain Sickness

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed N-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP), in Andean males without (n=14; age=39±11) and with (n=10; age=40±12) CMS at 4330 meters (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8±7.9 vs. CMS: 8.7±5.4 ng/ml; p=0.025) and plasma aldosterone concentration (non-CMS: 77.5±35.5 vs. CMS: 54.2±28.9 pg/ml; p=0.018) were lower in highlanders with CMS compared to non-CMS, while NT pro-BNP was not different between groups (non-CMS: 1394.9±214.3 vs. CMS: 1451.1±327.8 pg/ml; p=0.15). Highlanders had similar total blood volume (non-CMS: 90±15 vs. CMS: 103±18 ml • kg-1; p=0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46±10 vs. CMS 66±14 ml • kg-1; p<0.01) and smaller plasma volume (non-CMS 43±7 vs. CMS 35±5 ml • kg-1; p=0.03) compared to non-CMS. There were no differences in ePASP between groups (non-CMS 32±9 vs. CMS 31±8 mmHg; p=0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r=-0.66; p<0.01; non-CMS: r=-0.60; p=0.022; CMS: r=-0.63; p=0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high-altitude, causing potentially greater polycythemia and clinical symptoms.

Role of sex hormones in development of chronic mountain sickness in rats

1994 ◽  
Vol 77 (1) ◽  
pp. 427-433 ◽  
Author(s):  
L. C. Ou ◽  
G. L. Sardella ◽  
J. C. Leiter ◽  
T. Brinck-Johnsen ◽  
R. P. Smith
Keyword(s):  
Gender Differences ◽  
Pulmonary Hypertension ◽  
High Altitude ◽  
Sex Hormones ◽  
Systolic Pressure ◽  
Female Rats ◽  
Hypoxic Exposure ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness

After chronic exposure to hypoxia, Hilltop Sprague-Dawley rats developed excessive polycythemia and severe pulmonary hypertension and right ventricular (RV) hypertrophy, signs consistent with human chronic mountain sickness; however, there were gender differences in the magnitude of the polycythemia and susceptibility to the fatal consequence of chronic mountain sickness. Orchiectomy and ovariectomy were performed to evaluate the role of sex hormones in the gender differences in these hypoxic responses. After 40 days of exposure to simulated high altitude (5,500 m; barometric pressure of 370 Torr and inspired Po2 of 73 Torr), both sham-gonadectomized male and female rats developed polycythemia and had increased RV peak systolic pressure and RV hypertrophy. The hematocrit was slightly but significantly higher in males than in females. Orchiectomy did not affect these hypoxic responses, although total ventricular weight was less in the castrated high-altitude rats. At high altitude, the mortality rates were 67% in the sham-operated male rats and 50% in the castrated animals. In contrast, ovariectomy aggravated the high-altitude-associated polycythemia and increased RV peak systolic pressure and RV weight compared with the sham-operated high-altitude female rats. Both sham-operated control and ovariectomized females suffered negligible mortality at high altitude. The present study demonstrated that 1) the male sex hormones play no role in the development of the excessive polycythemia, pulmonary hypertension, and RV hypertrophy during chronic hypoxic exposure or in the associated high mortality and 2) the female sex hormones suppressed both the polycythemic and cardiopulmonary responses in vivo during chronic hypoxic exposure.

The Ventilatory Effects of Doxapram in Normal Man

1983 ◽  
Vol 65 (1) ◽  
pp. 65-69 ◽  
Author(s):  
P. M. A. Calverley ◽  
R. H. Robson ◽  
P. K. Wraith ◽  
L. F. Prescott ◽  
D. C. Flenley
Keyword(s):  
Oxygen Uptake ◽  
Ventilatory Response ◽  
Co2 Production ◽  
Central Action ◽  
Ventilatory Responses ◽  
Ventilatory Effects ◽  
Normal Man ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Ventilatory Response To Co2

1. To determine the mode of action of doxapram in man we have measured ventilation, oxygen uptake, CO2 production, hypoxic and hypercapnic ventilatory responses in six healthy men before and during intravenous infusion to maintain a constant plasma level. 2. Doxapram changed neither resting oxygen uptake nor CO2 production but produced a substantial increase in resting ventilation at both levels of end-tidal CO2 studied. 3. Doxapram increased the ventilatory response to isocapnic hypoxia from − 0.8 ± 0.4 litre min−1 (%Sao2)−1 to −1.63 ± 0.9 litres min−1 (%Sao2)−1. This was similar to the increase in hypoxic sensitivity which resulted from raising the end-tidal CO2 by 0.5 kPa without adding doxapram. 4. The slope of the ventilatory response to rebreathing CO2 rose from 11.6 ± 5.3 litres min−1 kPa−1 to 20,4 ± 9.8 litres min−1 kPa−1 during doxapram infusion. 5. The marked increase in the ventilatory response to CO2 implies that doxapram has a central action, but the potentiation of the hypoxic drive also suggests that the drug acts on peripheral chemoreceptors, or upon their central connections, at therapeutic concentrations in normal unanaesthetized subjects.

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