Abstract
Acute High Altitude Climbing Reduces Lung Diffusing Capacity
Agostoni et al (2013) measured lung CO diffusing capacity (DLCO) and alveolar volume (VA) in 43 healthy subjects at sea level and 1 and 3 days after a challenging climb of about 1400 m to 4559 m. DLCO was 6% lower on day 1 and 8.5% lower on day 3. Membrane diffusion (DM) fell 10.7% on day 1 and 14.5% on day 3. Capillary volume (VC) rose 58% on day 1, remaining up 58% on day 3. Regardless of treatment, lung comets increased from 0 to 7.2. Plasma surfactant derived protein B (SPB) and receptor of advanced glycation end-products (RAGE), markers of alveolar-capillary membrane damage, were unchanged. Agostoni et al had found increased DLCO after 2 weeks resting at Everest base camp (5400 m) in a previous report (JAP 2011;110:1564). They believe the climbing effort is not responsible for the fall because tests of injury were negative. Perhaps the reduced DLCO resulted from injury not detectable by these tests. The lung comets support some kind of injury.
Increased Lung Diffusing Capacity (DLCO) in High Altitude Newcomers
Martinot et al (2013) measured DLCO and in 25 lowlanders at sea level and at 4300 m after 2–3 days and 7–8 days. They found DLCO increased 24% on day 2–3 and returned to control on day 7–8. Both DmCO and Vc increased on day 2–3. Alveolar volume increased by 16% on day 2–3 and normalized on 7–8. The two studies differed mainly because these subjects were partially acclimatized at 3000 m altitude (Tarma, Peru) and reached 4300 m passively by car (Cerro de Pasco). I conclude that strenuous climbing was responsible for the difference.
Cognitive Performance Unimpaired in Climbers up to 6265 m
To investigate whether high altitude climbing leads to cognitive impairment, Merz et al (2013) used neuropsychological tests and measurements of eye movement (EM) performance during different stimulus conditions in 32 mountaineers participating in an expedition to Muztagh Ata (7546 m). Neuropsychological tests were figural fluency, line bisection, letter and number cancellation, and a modified pegboard task. Saccadic eye movements were evaluated under three stimulus conditions with varying degrees of cortical involvement: visually guided pro- and anti-saccades, and visuo-visual interaction. Measurements were taken at a baseline level of 440 m and at altitudes of 4497, 5533, 6265, and again at 440 m. All subjects reached 5533 m, and 28 reached 6265 m. The neuropsychological test results did not reveal any cognitive impairment. Complete eye movement recordings for all stimulus conditions were obtained in 24 subjects at baseline and at least two altitudes and in 10 subjects at baseline and all altitudes. Measurements of saccade performances were well within normal limits.
Effects of Altitude and Acute Mountain Sickness (AMS) on Retinal Function
Electroretinography (ERG), SaO2, heart rate and AM) were studied in 14 subjects at low and high altitude (4559 m) (Schatz et al., 2013). At altitude the maximum response of the scotopic sensitivity function, the implicit times of the a- and b-wave of the combined rod-cone responses and implicit times of the photopic negative responses (PhNR) were significantly altered and a-wave slopes and i-waves were significantly decreased at high altitude. PhNR correlated with SpO2 (r=0.68; p<0.05). Photopic b-wave implicit time (10 cd.s.m−2) was significantly correlated with AMS score (r=0.57; p<0.05). ERG data show that retinal function of inner, outer and ganglion cell layer is altered by high altitude hypoxia. The most affected ERG parameters were those related to combined rod-cone responses, which indicate that phototransduction and visual processing, especially under conditions of rod-cone interaction, are primarily affected at high altitude.
Store-Operated Channels (SOC) in Hypoxic Pulmonary Vasoconstriction
Parrau et al (2013) investigated the role of store-operated channels (SOC) in pulmonary artery responses to acute and chronic hypoxia in high and low altitude gestated neonatal lambs. In acute hypoxia, SOC blockade by 2-aminoethyldiphenylborinate (2-APB) reduced pulmonary vascular resistance more in high altitude lambs, but had no effect in normoxia. Isolated pulmonary arteries of altitude lambs showed a greater relaxation and sensitivity to SOC blockers. The pulmonary expression of two SOC-forming subunits, TRPC4 and STIM1, was up-regulated in the altitude lambs. The authors suggest that SOC contributes to the development of neonatal pulmonary hypertension so blockade might treat neonatal pulmonary hypertension.
Genetic Evidence of Paleolithic Colonization and Neolithic Expansion of Modern Humans on the Tibetan Plateau
To reconstruct the prehistoric colonization and demographic history of modern humans on the Tibetan Plateau, Qi et al (2013) analyzed phylogeographic patterns of samples from 6109 Tibetan individuals from 41 geographic populations. Data show two distinct, major prehistoric migrations of modern humans dated to around 30,000 and 7000–10,000 years ago, before and after the last ice age. The recent settlers shared Y chromosome and mitochondrial DNA haplotypes between Tibetans and Han Chinese.
VEGFA SNPs Associated With Mountain Sickness (MS) in Han and Tibetan Chinese on the Qinghai-Tibetan Plateau
Buroker et al (2013) compared genetic analyses of seven single nucleotide polymorphisms (SNPs) in the promoter region of VEGFA gene in lowland (Han) and highland (Tibetan) Chinese 64 patients with acute and 48 with chronic mountain sickness (MS) with equivalent healthy controls. SaO2 was found to be significantly associated with rs699947, rs34357231, rs13207351, and rs1570360 SNPs in Han patients with AMS. The rs2010963 SNP was significantly associated with healthy Tibetans. The Han and Tibetan control groups were found to diverge significantly for the rs28357093 and rs2010963 SNPs. MS was found to be significantly associated with these SNPs indicating that these nucleotide substitutions result in transcriptional factor binding site changes.
Decreased MRI Cerebral Apparent Diffusion Coefficient (ADC) in Acute Mountain Sickness (AMS)
Hunt et al (2013) show that reduced MRI diffusion apparent diffusion coefficient (ADC) correlated with symptoms of acute mountain sickness in 7 AMS+ but not in 7 AMS- subjects after 2 days at 3,800 m altitude. ADC increased in asymptomatic subjects, and as symptoms abated with acclimatization. The pattern was similar in basal ganglia, white matter, and gray matter. Corpus callosum behaved differently; restricted diffusion was absent (or rapidly reversed) in the splenium, and was sustained in the genu. T2 changes did not correlate with AMS symptoms. The authors claim in the abstract that this method “predicted” AMS, but ADC was only measured after AMS had developed in susceptible subjects. Prediction will require serial testing before AMS occurs, needing to do the testing near the MRI at sea level using normobaric hypoxia.
A Useful Experimental Animal Model of High Altitude Cerebral Edema (HACE)
Guo et al (2013) developed an acute hypobaric rat model of HACE using exhaustive exercise. Procedure: 2 days of normoxic treadmill adaptation, 2 days at 4000 m with exhaustive exercise, and 8000 m resting for 3 days. Compared with controls, the test group had greater (p<0.01) brain water content and Evans blue staining. Hippocampus was seriously damaged, the number of pyramidal cells decreased, brain structure was loosened with leakage of lanthanum nitrate particles from brain microvessels into the surrounding tissue through widened tight junctions. Some neurons and glial cell organelles were swollen and some nerve fibers were demyelinated.
VEGF Contributes to Hypoxic Vascular Remodeling in Fetal Ovine Carotid Artery Contractile Proteins
Vascular endothelial growth factor (VEGF) may modulate smooth muscle phenotype and alter the composition and function of arteries upstream from the microcirculation, where angiogenesis occurs. Pregnant ewes were acclimatized at sea level or at altitude (3820 m) for the final 110 days of gestation (Adeoye et al., 2013). Endothelium-denuded carotid arteries from full-term fetuses were used fresh or after 24 h of organ culture in a physiological concentration (3 ng/ml) of VEGF. After 110 days, hypoxia had no effect on VEGF abundance but markedly increased abundance of the Flk-1 (171%) and Flt-1 (786%) VEGF receptors. Hypoxia decreased myosin light chain (MLC) kinase (MLCK) and increased 20-kDa regulatory MLC (MLC(20)), increased MLCK-SMalphaA, MLC(20)-SMalphaA, and MLCK-MLC(20) colocalization. Organ culture with VEGF produced the same pattern of changes in contractile protein abundance and colocalization. Effects of VEGF on colocalization were blocked by the VEGF receptor antagonists vatalanib (240 nM) and dasatinib (6.3 nM). The authors conclude that, by increasing VEGF receptor density, VEGF helps mediate remodeling of fetal arteries upstream from the microcirculation through changes in abundance, organization, and function of contractile proteins.
Chronic Hypoxia Inhibits Pregnancy-Induced Upregulation of SKCa Channel Expression and Function in Uterine Arteries
Small-conductance Ca++-activated K+ (SKCa) channels are crucial in regulating vascular tone and blood pressure. Zhu et al (2013) isolated uterine arteries from nonpregnant and near-term pregnant sheep maintained at sea level ( approximately 300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. The expression of type 2 (SK2) and type 3 (SK3) channels was significantly increased during normoxic pregnancy but was inhibited by chronic hypoxia. In normoxic animals, both SKCa channel opener NS309 and a large-conductance (BKCa) channel opener NS1619 relaxed norepinephrine-contracted uterine arteries in pregnant but not nonpregnant sheep. These relaxations were inhibited by selective SKCa and BKCa channel blockers, respectively. NS309-induced relaxation was largely endothelium-independent. In high-altitude hypoxic animals, neither NS1691 nor NS309 produced significant relaxation of uterine arteries in either nonpregnant or pregnant sheep. The ability of SKCa channels to regulate myogenic reactivity of uterine arteries and arterial myocytes in pregnant animals was blocked by chronic hypoxia causing maladaptation of uteroplacental circulation during gestation.
High Temperature Coefficient of Blood Oxygen Affinity of Bar-headed Geese
In flying over the Himalaya, bar headed geese must work hard due to thin air, and must ventilate more of air at ∼1/3 ATA, and temperature <-20C. Blood cooled in passing the lung is rewarmed by muscle work. Meir and Milsom (2013) suggest that a steep temperature gradient of blood O2 affinity would help load O2 into the cooled lung capillary blood. They confirm that such a high temperature coefficient does exist in this species compared with other birds and mammals.
A Strategy For in-Flight Measurements of Physiology of Pilots of High-Performance Fighter Aircraft
Pilots have reported brief confusion or functional ability in high G, rapid altitude change or other sudden events. In order to obtain some physiologic data about pilot safety in these very powerful planes, John West (2013a) describes a plan for measuring the inspired and expired PO2 and PCO2 in the pilot's mask, inspiratory flow rate, and pressure in the mask, using commercially available small light weight apparatus.
Denis Jourdanet (1815–1892) Recognizes Hypoxia at High Altitude
West and Richalet (2013) remind readers that Denis Jourdanet in Mexico has been poorly credited as the first to show the relation of altitude to hypoxia illnesses.
Torricelli and the Ocean of Air: The First Measurement of Barometric Pressure
The recognition of barometric pressure was a critical step in the development of environmental physiology (West, 2013b). In 1644, Evangelista Torricelli described the first mercury barometer in a letter that contained the phrase, “We live submerged at the bottom of an ocean of the element air, which…is known to have weight.”