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

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.

The ventilatory responses to CO(2) 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 CO(2) in euoxia were higher in HA and CMS subjects compared with SL subjects. Peripheral chemoreflex sensitivity to CO(2) in euoxia was higher in HA subjects than in SL subjects. Hypoxia induced a greater increase in total chemoreflex sensitivity to CO(2) in SL subjects than in HA and CMS subjects, but peripheral chemoreflex sensitivity to CO(2) 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.     

Autonomic cardiovascular regulation in subjects with acute mountain sickness

The aims of this study were 1) to evaluate whether subjects suffering from acute mountain sickness (AMS) during exposure to high altitude have signs of autonomic dysfunction and 2) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS. Forty-one mountaineers were studied at 4,559-m altitude. AMS was diagnosed using the Lake Louise score, and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure (BP) variability on 10-min resting recordings. Seventeen subjects (41%) had AMS. Subjects with AMS were older than those without AMS (P < 0.01). At high altitude, the low-frequency (LF) component of systolic BP variability (LF(SBP)) was higher (P = 0.02) and the LF component of R-R variability in normalized units (LF(RR)NU) was lower (P = 0.001) in subjects with AMS. After 3 mo, 21 subjects (43% with AMS) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture. LF(RR)NU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude (P < 0.001) and did not change between low and high altitude in subjects with AMS. Conversely, LF(SBP) increased significantly during short-term hypoxia only in subjects with AMS, who also had higher resting BP (P < 0.05) than those without AMS. Autonomic cardiovascular dysfunction accompanies AMS. Marked LF(SBP) response to short-term hypoxia identifies AMS-prone subjects, supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS.     

Blood rheology in acute mountain sickness and high-altitude pulmonary edema.

The role of blood rheology in the pathogenesis of acute mountain sickness and high-altitude pulmonary edema was investigated. Twenty-three volunteers, 12 with a history of high-altitude pulmonary edema, were studied at low altitude (490 m) and at 2 h and 18 h after arrival at 4,559 m. Eight subjects remained healthy, seven developed acute mountain sickness, and eight developed high-altitude pulmonary edema. Hematocrit, whole blood viscosity, plasma viscosity, erythrocyte aggregation, and erythrocyte deformability (filtration) were measured. Plasma viscosity and erythrocyte deformability remained unaffected. The hematocrit level was lower 2 h after the arrival at high altitude and higher after 18 h compared with low altitude. The whole blood viscosity changed accordingly. The erythrocyte aggregation was about doubled 18 h after the arrival compared with low-altitude values, which reflects the acute phase reaction. There were, however, no significant differences in any rheological parameters between healthy individuals and subjects with acute mountain sickness or high-altitude pulmonary edema, either before or during the illness. We conclude that rheological abnormalities can be excluded as an initiating event in the development of acute mountain sickness and high-altitude pulmonary edema.     

Sleep of Andean high altitude natives.

The structure of sleep in lowland visitors to altitudes greater than 4000 m is grossly disturbed. There are no data on sleep in long-term residents of high altitudes. This paper describes an electroencephalographic study of sleep in high altitude dwellers who were born in and are permanent residents of Cerro de Pasco in the Peruvian Andes, situated at 4330 m. Eight healthy male volunteers aged between 18 and 69 years were studied. Sleep was measured on three consecutive nights for each subject. Electroencephalographs, submental electromyographs and electro-oculograms were recorded. Only data from the third night were used in the analysis. The sleep patterns of these subjects resembled the normal sleep patterns described by others in lowlanders at sea level. There were significant amounts of slow wave sleep in the younger subjects and rapid eye movement sleep seemed unimpaired.     

慢性高原病血清血管生成因子的变化

目的：慢性高原病（CMS）以红细胞过度增生、肺动脉高压和低氧血症为特征,但对该病的发病机制尚未完全阐明。本研究以CMS患者和高原世居藏族健康人为研究对象,探讨血管生成相关因子在CMS发生、发展过程中的作用。方法：以海拔4380m地区的CMS患者35例（CMS组）和高原世居藏族健康人13名（世居组）为研究对象,西宁地区（海拔2260m）世居健康人17名为对照组,采用固相双抗体夹心ELISA方法测定血清碱性成纤维生长因子（bFGF）、血管内皮生长因子（VEGF）和血小板源生长因子（PDGF）浓度,同时测定血红蛋白（Hb）浓度、红细胞比积（Hct）和动脉血氧饱和度（SaO2）。结果：血清bFGF浓度CMS组（107．26±7．86）ng／L与世居组（37．01±9．16）ng／L和对照组（40．58±5．34）ng／L比较,有显著差异（P〈0．01）;血清PDGF浓度CMS组（630．18±9．89）ng／L与世居组（292．16±6．88）ng／L和对照组（287．68±8．33）ng／L比较,有显著差异（P〈0．01）;血清VEGF浓度CMS组（543．74±6．76）ng／L与世居组（125．51±7．26）ng／L和对照组（76．26±4．60）ng／L比较,有显著差异（P〈0．01）,世居组与对照组比较,也有显著差异（P〈0．01）。CMS患者血红蛋白（Hb）浓度与其血清bFGF、PDGF和VEGF水平均呈正相关（P〈0．01）。血清bFGF、PDGF、VEGF之间亦呈正相关（P〈0．01）。结论：CMS患者血清bFGF、PDGF和VEGF水平显著高于居住在同一个海拔高度的健康人和居住在西宁地区的健康人,提示CMS患者血管生成因子过度表达,血管新生可能是CMS病理生理的重要方面;血清VEGF水平高原健康人高于西宁地区健康人,提示VEGF高表达可能是高原健康人对高原环境适应机制的组成部分;CMS患者Hb浓度与其血清bFGF、PDGF和VEGF水平均呈正相关,提示在CMS患者中,bFGF、PDGF和VEGF可能与红细胞生成有?     

Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia

Desplanches, D., H. Hoppeler, L. Tüscher, M. H. Mayet,H. Spielvogel, G. Ferretti, B. Kayser, M. Leuenberger, A. Grünenfelder, and R. Favier. Muscle tissue adaptations ofhigh-altitude natives to training in chronic hypoxia or acute normoxia.J. Appl. Physiol. 81(5):1946-1951, 1996.Twenty healthy high-altitude natives, residentsof La Paz, Bolivia (3,600 m), participated in 6 wk of enduranceexercise training on bicycle ergometers, 5 times/wk, 30 min/session, aspreviously described in normoxia-trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl.Physiol. 59: 320-327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometricpressure = 500 mmHg; inspired O₂fraction = 0.209); a second group of 10 subjects was trained in acutenormoxia (NT; barometric pressure = 500 mmHg; inspired O₂ fraction = 0.314). Theworkloads were adjusted to ~70% of peak O₂ consumption(O_{2 peak}) measuredeither in hypoxia for the HT group or in normoxia for the NT group.O_{2 peak} determination and biopsies of the vastus lateralis muscle were taken before and afterthe training program.O_{2 peak} in the HTgroup was increased (14%) in a way similar to that in NT sea-levelnatives with the same protocol. Moreover,O_{2 peak} in the NTgroup was not further increased by additionalO₂ delivery during the training session. HT or NT induced similar increases in musclecapillary-to-fiber ratio (26%) and capillary density (19%) as well asin the volume density of total mitochondria and citrate synthaseactivity (45%). It is concluded that high-altitude natives have areduced capillarity and muscle tissue oxidative capacity; however,their training response is similar to that of sea-level residents,independent of whether training is carried out in hypobaric hypoxia orhypobaric normoxia.

     

Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness

Colice, Gene L., Nicholas Hill, Yan-Jie Lee, Hongkai Du,James Klinger, James C. Leiter, and Lo-Chang Ou. Exaggerated pulmonary hypertension with monocrotaline in rats susceptible tochronic mountain sickness. J. Appl.Physiol. 83(1): 25-31, 1997.Hilltop (H) strainSprague-Dawley rats are more susceptible to chronic mountain sicknessthan are the Madison (M) strain rats. It is unclear what role pulmonaryvascular remodeling, polycythemia, and hypoxia-induced vasoconstrictionplay in mediating the more severe pulmonary hypertension that developsin the H rats during chronic hypoxia. It is also unclear whether theincreased sensitivity of the H rats to chronic mountain sickness isspecific for a hypoxia effect or, instead, reflects a generalpropensity toward the development of pulmonary hypertension.Monocrotaline (MCT) causes pulmonary vascular remodeling and pulmonaryhypertension. We hypothesized that the difference in the pulmonaryvascular response to chronic hypoxia between H and M rats reflects anincreased sensitivity of the H rats to any pulmonary hypertensivestimuli. Consequently, we expected the two strains to also differ intheir susceptibility to MCT-induced pulmonary hypertension. Pulmonaryarterial pressures in conscious H and M rats were measured 3 wk after asingle dose of MCT, exposure to a simulated high altitude of 18,000 ft(barometric pressure = 380 mmHg), and administration of a single doseof saline as a placebo. The H rats had significantlyhigher pulmonary arterial pressures and right ventricular weights afterMCT and chronic hypoxia than did the M rats. The H rats also had morepulmonary vascular remodeling, i.e., greater wall thickness as apercentage of vessel diameter, after MCT and chronic hypoxia than didthe M rats. The H rats had significantly lower arterialPO₂ than did the M rats after MCT,but the degree of hypoxemia was mild [arterialPO₂ of 72.5 ± 0.8 (SE) Torr for Hrats vs. 77.4 ± 0.8 Torr for M rats after MCT]. The H ratshad lower arterial PCO₂ and largerminute ventilation values than did the M rats after MCT. Theseventilatory differences suggest that MCT caused more severe pulmonaryvascular damage in the H rats than in the M rats. These data supportthe hypothesis that the H rats have a general propensity to developpulmonary hypertension and suggest that differences in pulmonaryvascular remodeling account for the increased susceptibility of H rats,compared with M rats, to both MCT and chronic hypoxia-induced pulmonaryhypertension.

     

Pulmonary gas exchange in Andean natives with excessive polycythemia--effect of hemodilution

Pulmonary gas exchange in Andean natives (n = 8) with excessive high-altitude (3,600-4,200 m) polycythemia (hematocrit 65.1 +/- 6.6%) and hypoxemia (arterial PO2 45.6 +/- 5.6 Torr) in the absence of pulmonary or cardiovascular disease was investigated both before and after isovolemic hemodilution by use of the inert gas elimination technique. The investigations were carried out in La Paz, Bolivia (3,650 m, 500 mmHg barometric pressure). Before hemodilution, a low ventilation-perfusion (VA/Q) mode (VA/Q less than 0.1) without true shunt accounted for 11.6 +/- 5.5% of the total blood flow and was mainly responsible for the hypoxemia. The hypoventilation with a low mixed venous PO2 value may have contributed to the observed hypoxemia in the absence of an impairment in alveolar capillary diffusion. After hemodilution, cardiac output and ventilation increased from 5.5 +/- 1.2 to 6.9 +/- 1.2 l/min and from 8.5 +/- 1.4 to 9.6 +/- 1.3 l/min, respectively, although arterial and venous PO2 remained constant. VA/Q mismatching fell slightly but significantly. The hypoxemia observed in subjects suffering from high-altitude excessive polycythemia was attributed to an increased in blood flow perfusing poorly ventilated areas, but without true intra- or extrapulmonary shunt. Hypoventilation as well as a low mixed venous PO2 value may also have contributed to the observed hypoxemia.