Faculty Opinions recommendation of Effect of acetazolamide on ventilatory response in subjects with chronic mountain sickness.

Author(s):  
Robert Schoene
2016 ◽  
Vol 311 (5) ◽  
pp. R940-R947
Author(s):  
Sofien Laouafa ◽  
Elizabeth Elliot-Portal ◽  
Susana Revollo ◽  
Edith M. Schneider Gasser ◽  
Vincent Joseph ◽  
...  

The impact of cerebral erythropoietin (Epo) in the regulation of the hypercapnic ventilatory response (HcVR) is controversial. While we reported that cerebral Epo does not affect the central chemosensitivity in C57Bl6 mice receiving an intracisternal injection of sEpoR (the endogenous antagonist of Epo), a recent study in transgenic mice with constitutive high levels of human Epo in brain and circulation (Tg6) and in brain only (Tg21), showed that Epo blunts the HcVR, maybe by interacting with central and peripheral chemoreceptors. High Epo serum levels in Tg6 mice lead to excessive erythrocytosis (hematocrit ~80–90%), the main symptom of chronic mountain sickness (CMS). These latter results support the hypothesis that reduced central chemosensitivity accounts for the hypoventilation observed in CMS patients. To solve this intriguing divergence, we reevaluate HcVR in Tg6 and Tg21 mouse lines, by assessing the metabolic rate [O consumption (V̇) and CO production (V̇)], a key factor modulating ventilation, the effect of which was not considered in the previous study. Our results showed that the decreased HcVR observed in Tg6 mice (~70% reduction; < 0.01) was due to a significant decrease in the metabolism (~40%; < 0.0001) rather than Epo’s effect on CO chemosensitivity. Additional analysis in Tg21 mice did not reveal differences of HcVR or metabolism. We concluded that cerebral Epo does not modulate the central chemosensitivity system, and that a metabolic effect upon CO inhalation is responsible for decreased HcVR observed in Tg6 animals. As CMS patients also show decreased HcVR, our findings might help to better understand respiratory disorders at high altitude.


2018 ◽  
Vol 2 (4) ◽  
pp. 689-697 ◽  
Author(s):  
Gustavo Gonzales

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.


2003 ◽  
Vol 94 (3) ◽  
pp. 1269-1278 ◽  
Author(s):  
Fabiola León-Velarde ◽  
Alfredo Gamboa ◽  
Maria Rivera-Ch ◽  
Jose-Antonio Palacios ◽  
Peter A. Robbins

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.


2008 ◽  
Vol 162 (3) ◽  
pp. 184-189 ◽  
Author(s):  
Maria Rivera-Ch ◽  
Luis Huicho ◽  
Patrick Bouchet ◽  
Jean Paul Richalet ◽  
Fabiola León-Velarde

Author(s):  
Andrew R. Steele ◽  
Michael M. Tymko ◽  
Victoria L. Meah ◽  
Lydia L Simpson ◽  
Christopher Gasho ◽  
...  

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.


Author(s):  
Ingrid Asmussen ◽  
Luciano Bernardi ◽  
Peter Bärtsch ◽  
Tom Hornbein ◽  
Fabiola Leon-Velarde ◽  
...  

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Daniela Bermudez ◽  
Cecilia Anza‐Ramirez ◽  
Miguel Ángel Orrego‐Solano ◽  
Cristina Guerra‐Giraldez ◽  
Francisco C. Villafuerte

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