what response would you expect after traveling to high altitude for two weeks?

Introduction

Last decades, the number of people traveling to high altitude is increasing in connexion with economic or recreational purposes (W, 2012). High altitude surround poses many challenges, simply exposure to alveolar hypoxia is the most prominent among them (Burtscher et al., 2018). The ambient hypoxia triggers a number of physiologic responses including hyperventilation, increased resting heart rate and stimulation of erythrocyte product with the goal of maintaining the oxygen content of arterial blood at or to a higher place ocean level values (Due west, 2004). In permanent loftier altitude residents, exposure to chronic hypoxia leads to an increment in erythrocyte numbers and hemoglobin concentration (Leon-Velarde et al., 2000).

A large group of people, such as workers of mining companies, employees of route structure companies or military machine divisions in high-altitude border areas are exposed repetitively to loftier distance over a long time by commuting between high altitude and lowland (Powell and Garcia, 2000; Richalet et al., 2002; West, 2002; Farias et al., 2013). Nonetheless, the effects of the long-term exposure to intermittent hypoxia on hemoglobin concentration have been less well studied. Only few studies accept assessed hematological changes induced by long-term intermittent high altitude exposure. Some studies reported a marked increment in hemoglobin (or hematocrit) levels in response to long-term exposure to intermittent high altitude (Gunga et al., 1996; Heinicke et al., 2003), whereas others did not find a significant consequence (Richalet et al., 2002; Brito et al., 2007, 2018). Therefore, the aim of the current study was to determine the clan of long-term intermittent high altitude exposure with hemoglobin levels as well every bit to explore the nature of this possible relationship.

Materials and Methods

Subjects and Study Design

This is a cross-sectional report of mine employees exposed repetitively to high altitude for long periods of time. All of them work at the aureate mine run by the Kumtor Gold Company (Centerra Gold Inc., Canada). Mine employees are transported to the mine site by motorbus, and the ascent lasts 7 h in total.

Every worker undergoes an annual medical checkup in a specially designated clinic in Bishkek (Kyrgyzstan, 760 g), which includes concrete examination, clinical lab work (consummate blood count, urine assay, and biochemistry), ECG, echocardiography, exercise testing and spirometry. All the male employees of the Kumtor Gold Company, who had medical checkup during October–December 2016, were enrolled into the study. The inclusion criteria were male sexual activity, uninterrupted working at loftier distance in xiv×fourteen shifts (14 days of working at altitude followed by a resting menstruum of 14 days at lowland) and a salubrious status without serious cardiopulmonary comorbidities. The exclusion criteria were chronic obstructive pulmonary illness, moderate or severe hypertension, and coronary heart illness.

In total, 266 salubrious males (aged 45.9 ± 0.6 years) were included into the study. Subjects were truck drivers, gold mill operators, camp and kitchen staff, security personnel, and engineers. All subjects commuted betwixt loftier distance and living place (760 grand or ane,600 m) in a 14×14 shift regimen. The miners slept at 3,800 m and worked a 12-h 24-hour interval shift at 3,800 to 4,000 m, only few subjects (operators of drilling rigs) went to 4,500 k.

Written informed consent was obtained from all participants in accordance with the Declaration of Helsinki. This study was approved by the Research Ideals Committee of the National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan.

Measured Variables

Measures were taken once at low distance in a specially designated clinic in Bishkek during the annual medical bank check-upward. Commonly, the almanac medical cheque-upward is carried out ane calendar week afterward descent. Whatsoever cardiac or pulmonary disorder was excluded based on the results of clinical test, clinical lab piece of work (blood cell count, urine assay, and biochemistry), ECG, echocardiography, and pulmonary function tests.

General Data

Weight and summit measured by means of a digital weight calibration and a stadiometer with each participant barefoot and wearing underwear. Trunk mass index values were calculated equally weight in kilograms divided by height in meters squared and rounded to 1 decimal place.

Hematological Measurements

Consummate blood count was performed past an automatic hematology analyser Mindray BC-2300 (Guangzhou Shihai Medical Equipment Co., Ltd., Mainland china) using 15 μm of EDTA whole venous blood according to the manufacturer's instructions. Hematocrit, concentration of hemoglobin, erythrocytes, leukocytes, and platelets were measured. The analyser uses electrical impedance method for prison cell counting and cyanide gratuitous method for hemoglobin detection. Red blood cell indices included hemoglobin concentration and hateful corpuscular book.

Data Analysis

Statistical assay was performed using SPSS version 23.0 for Windows (IBM, Chicago, IL, U.s.a.). Data are expressed as mean ± standard error. The Kolmogorov–Smirnov test was used to appraise the normality of distribution of quantitative variables. All quantitative variables were distributed normally. Linearity was assessed through examination of diverse bivariate scatterplots. Linear regression (univariate and multivariable) assay was used to cheque the association betwixt hemoglobin levels and other parameters. Differences betwixt unlike BMI categories were assessed by one-way ANOVA followed by Tukey's multiple comparisons postal service hoc test. For comparing proportions, we used chi-squared test. For linear trend in quantitative variables we used 1-way ANOVA linear contrast method. The values P < 0.05 were considered as statistically significant. Statistical power assay was performed using G^∗Power 3.1.

Results

Characteristics describing the subjects are provided in Tabular array one. One hundred and eighty-iv workers were residents of moderate altitude (1,600 m); the remaining 82 men were residents of depression altitude (760 m). The duration of exposure to intermittent loftier distance ranged from 0 to 21 years. The average tape of service was 10.1 years. The bulk of subjects were ethnic Kyrgyz (92%), but in that location were some Caucasians as well (8%). Prevalence of obesity in the sample was 16.1 ± 2.4%. The mean hemoglobin level in workers was sixteen.two ± 0.11 chiliad/dL (Table ane). Table ii shows higher hemoglobin levels, as well as age and BMI, in subjects with longer duration of loftier altitude exposure. It is clear that hemoglobin levels are higher when the duration of exposure is longer (p < 0.001). Notably, the differences in age and BMI were also statistically significant; therefore, we cannot ascribe the differences in hemoglobin levels to the effects of loftier distance lone. Indeed, hemoglobin values were significantly higher in obese subjects compared to those with normal weight (Figure 1).

Table 1. Anthropometric hematological characteristics of the subjects (n = 266).

TABLE 2. Distribution of the hemoglobin levels, historic period, trunk mass index, and residence place of the subjects according to the years of high altitude exposure.

Figure 1. Hemoglobin (Hb) levels in subjects according to their trunk mass index (BMI) category: normal weight (<25), overweight (25–30), and obese (≥xxx). ^∗ P < 0.05 for differences between normal weight and obese subjects. Data presented as mean ± SEM. Statistical analysis was carried out using one-way ANOVA followed past Tukey's multiple comparison test.

Univariate linear regression revealed an association of the hemoglobin levels with the years of exposure (Figure 2). In a univariate regression model, every consecutive year was associated with an increment in hemoglobin of 0.068 thousand/dL [95% CI: 0.037 to 0.099, p < 0.001].

Figure 2. Scatter plot of correlation between the hemoglobin (Hb) levels and the years of exposure to intermittent loftier altitude. The all-time-fit line is shown, and the shaded area represents the 95% conviction intervals (n = 266).

Further, afterwards adjusting for other variables (historic period, living at low or moderate distance, BMI, and occupation) using multivariable regression analysis, the magnitude of hemoglobin level changes decreased, but remained statistically significant: 0.046 yard/dL [95% CI: 0.005 to 0.086, p < 0.05]. Despite a significant association of the hemoglobin levels with age by univariate regression analysis, information technology failed to show the significance after adjusting for the rest variables (BMI, years of exposure, altitude of residence (0.006 g/dL [95% CI -0.024 to -0.035]) (Table 3). However, BMI and elapsing of exposure retained to have a weak just significant relationship with hemoglobin levels (0.065 1000/dL [95% CI: 0.006 to 0.124] and 0.046 g/dL [95% CI: 0.005 to 0.086], respectively) (Table 3).

TABLE 3. Associations between hemoglobin levels and other variables past univariate and multivariable analysis.

Discussion

To our best knowledge, this is the get-go study performed on a large population of Kyrgyz workers intermittently exposed to high distance for a very long menstruum up to 21 years. We showed that there is a statistically significant correlation between the hemoglobin levels and the years of exposure. Using multivariable regression analysis, we showed that hemoglobin levels increase by an boilerplate of 0.046 g/dL for every consecutive yr of intermittent loftier altitude exposure, later on adjusting for other variables (age, living at low or moderate altitude, BMI, and occupation). Interestingly, the residence at low or moderate altitudes did not bear on the hemoglobin levels. This may be due to the relatively pocket-size difference in the altitude of residence (less than 900 grand).

Chronic high altitude hypoxia leads to an increase in cherry cell numbers and hemoglobin concentration. Previous studies take shown that permanent loftier altitude residents possess elevated hemoglobin levels and hematocrit values (Leon-Velarde et al., 2000). In sea-level residents, hematocrit and hemoglobin concentration were elevated after exposure to 3,550-m altitude for 8 months; however, none of the parameters reached pathological values (Siques et al., 2007). Only few studies take assessed hematological changes induced by long-term intermittent high altitude exposure in a comprehensive mode. An earlier study in Chilean workers exposed to intermittent loftier altitude for >v years revealed hemoglobin values that were comparable to those reported in the literature for loftier altitude populations (Gunga et al., 1996). Similarly, increased hemoglobin concentration and hematocrit values (15.8 ± 1.2 thousand/dL and 46.2 ± 3.viii%, respectively) were shown in Chilean army officers exposed to intermittent hypoxia for about 22 years later three days following descent to sea level (Heinicke et al., 2003). Remarkably, hemoglobin concentration and hematocrit values (16.5 ± 0.9 g/dL and 48.1 ± 2.9%, respectively) measured at high altitude were comparable to those establish in permanent loftier altitude residents (Heinicke et al., 2003). Another written report conducted in a group of Chilean army officers exposed to intermittent high distance for at least 12 years (50% had been >25 years at altitude) reported a smaller increment in hemoglobin concentration and hematocrit values (fifteen.1 ± 1.0 thou/dL and 45.02 ± ii.vii%, respectively) measured on twenty-four hours 1 following descent to sea level (Brito et al., 2007). Similarly, a period of ii.5-year exposure to intermittent hypoxia induced a pregnant hematocrit increment in Chilean miners, which was, however, lower than what is observed in permanent high distance residents (Richalet et al., 2002). A recent cross-sectional written report in healthy Chilean male miners working at an altitude of iv,400 or 4,800 m for, on boilerplate, fourteen years reported mean hematocrit and hemoglobin values of 47.6 ± 0.3% and xvi.2 ± 0.1 chiliad/dL, respectively, with none of the subjects having pathological values (Brito et al., 2018). In our study, hemoglobin concentration and hematocrit values in shift workers were higher than those observed in sea level residents, but were lower than values reported in Aymara native residents at iii,800–4,065 m (Beall et al., 1998).

Various factors may be responsible for the discrepancy. A meta-analysis and a Monte Carlo simulation on the extracted data showed that red cell volume expansion for a given duration of exposure is dependent on the distance (Rasmussen et al., 2013). The authors suggested that, at altitudes above 4,000 m, exposure fourth dimension must exceed 2 weeks to exert a significant effect and that the magnitude of the erythropoietic response depends on the initial blood-red cell volume (Rasmussen et al., 2013). In add-on, hemoglobin mass returns to baseline sea level values in 2–3 weeks following descent to sea level (Wachsmuth et al., 2013). Moreover, the mining companies and military divisions in different countries implement various commuting patterns complicating the estimation of the hematological changes induced by the long-term intermittent high altitude exposure. The almost mutual shift patterns range from four×three days to 28×28 days (Gunga et al., 1996; Richalet et al., 2002; Heinicke et al., 2003; Sarybaev et al., 2003; Brito et al., 2007; Vinnikov et al., 2011). Furthermore, ethnic differences take been shown in hematological responses in loftier distance residents (Beall, 2006). If ethnicity affects hematological responses to chronic intermittent high altitude exposure is not known.

Another caption could be the diverse duration of stay at high distance and the meridian accomplished in different studies Therefore, a term "hypoxic dose" has recently been introduced as a new metric incorporating both altitude and total exposure time to measure an increase in hemoglobin mass because of intermittent hypoxic training or intermittent hypoxic exposure (Garvican-Lewis et al., 2016a). The models advise that hypoxic exposure in backlog of 250 km h is sufficient to produce an increase in hemoglobin mass (Garvican-Lewis et al., 2016b). In our study, the workers were exposed to the hypoxic dose of nearly one,300 km h, which is considered to be sufficient to induce an increase in hemoglobin levels.

Univariate assay showed a relationship of hemoglobin levels with aging; yet, after adjusting for other variables, the value ceased to be significant. These results are in line with the findings from other studies. Thus, no meaning hematocrit modify over 11.6 years was demonstrated in a recent prospective study (Carallo et al., 2011). In another study, while fibrinogen, another claret viscosity parameter, increased with age, the hemoglobin level on the contrary slightly decreased in the elderly subjects (Coppola et al., 2000). Notably, we revealed a meaning relation of hemoglobin levels with the BMI in workers exposed to intermittent high altitude for a long period. It is in accordance with other studies that demonstrated a positive association between hemoglobin and BMI in lowland populations (Micozzi et al., 1989; Skjelbakken et al., 2010). In dissimilarity, no correlation between hemoglobin levels and BMI was reported by others (Ghadiri-Anari et al., 2014). Nevertheless, in a recent prospective study of high-altitude mine workers in Peru, male gender, elapsing of the intermittent high altitude exposure and BMI were independent predictors of hemoglobin level changes (Mejia et al., 2017). The underlying mechanisms remain poorly understood. Still, a negative event of BMI on oxygen saturation was demonstrated in Chinese Han young males during loftier altitude acclimatization (Peng et al., 2013). Interestingly, a negative association betwixt BMI and claret oxygenation was also found in healthy high distance residents in Peru (Pereira-Victorio et al., 2014; Miele et al., 2016). These information suggest that shift workers with higher BMI will have a greater increase in hemoglobin during chronic intermittent high distance exposure.

It has been shown that borderline polycythemia (hematocrit above 50%) was associated with increased mortality from coronary heart disease (Kunnas et al., 2009). However, the connection betwixt hemoglobin and cardiovascular diseases is complex and is still not clear (Brown et al., 2001; Frackiewicz et al., 2018). We have to admit that prolonged intermittent high altitude hypoxia can provoke cardiovascular events in patients with clinical or subclinical coronary atherosclerosis considering of blood rheology changes. Interestingly, accumulating evidence demonstrates that short-term daily sessions of hypoxia alternating with equal durations of normoxia for 2–3 weeks exert beneficial effects on diverse cardiovascular diseases (Serebrovskaya and Xi, 2016), thus potentially opposing deleterious effects of polycythemia. At the aforementioned time, the increase in hemoglobin levels due to chronic intermittent high altitude exposure should not lead to increased probability of cardiovascular events per se.

Although the literature on the relation between changes in hemoglobin concentration and cardiovascular disorders in subjects exposed to long-term intermittent high distance hypoxia is very deficient, nosotros believe that such a small, though statistically significant, increase in hemoglobin concentration represents an adaptive response rather than a take chances factor for cardiovascular diseases. An annual increase in hemoglobin level by 0.046 m/dL ways that for every 10 years of work at intermittent high altitude hypoxia hemoglobin levels will rise, on average, less than 0.5 g/dL. Indeed, in nigh of the subjects chronically exposed to intermittent high altitude, hemoglobin concentration and hematocrit reach intermediate values that are higher than those in sea level residents only lower than those in healthy loftier altitude dwellers (Richalet et al., 2002; Brito et al., 2007). It is unlikely that this rather small increase in hemoglobin levels would take whatever meaning pathological effects (Burtscher, 2014; Corante et al., 2018).

Additionally, another effect related to hemoglobin levels at loftier-altitude is the change in skeletal musculus mass, since muscles are the chief consumer of oxygen in the body. While some studies indicated some decrease in skeletal muscle mass at loftier-distance exposure (Hoppeler et al., 1990; MacDougall et al., 1991; Mizuno et al., 2008), the others were not able to show significant loss of muscle mass (Lundby et al., 2004; D'Hulst et al., 2016; Jacobs et al., 2016). Differences in the hypoxic doses may account for this discrepancy. Thus, information technology has been suggested that a minimum hypoxic exposure of 5,000 km h is required for hypoxia-induced musculus cloudburst to develop (D'Hulst and Deldicque, 2017). Although, nosotros have non measured the skeletal muscle fiber cross exclusive area changes in the workers, it seems unlikely that the relatively depression hypoxic dose in our written report tin can significantly touch the skeletal muscle.

Some other kind of intermittent hypoxia which deserves further commentary is obstructive sleep apnea syndrome (OSAS). OSAS is a pathological condition characterized by recurrent or cyclic short periods of isobaric hypoxia and asphyxia during sleep (coupled with oxygen desaturation), oftentimes more than sixty times per hour (Neubauer, 2001). Such frequent fluctuations of oxygen saturation pb to sympathetic overactivity, increased oxidative stress, and activation of inflammatory response pathways (Mansukhani et al., 2014; Passali et al., 2015; de Lima et al., 2016). In addition to hypoxemia, these events are associated with significant hypercapnia. Consequently, OSAS is an contained and well-known major gamble gene for various cardiovascular diseases, including hypertension, stroke, myocardial infarction, and congestive heart failure (Kendzerska et al., 2014; Drager et al., 2015; Bauters et al., 2016). In contrast, chronic intermittent hypoxic exposure in miners involves prolonged cycles of hypobaric hypoxia alternating with normobaric normoxia. The frequency of high altitude intermittent hypoxia is commonly 1 to four times a calendar month, which does not accept such unfavorable effects on the body. Thus, equally previously pointed out (Richalet et al., 2002), OSAS is quite different from the chronic intermittent hypoxic exposure in miners.

One of the limitations of this report is its cross-sectional nature. Further, well-nigh of the subjects were permanent residents of a moderate distance, so the deviation in altitude between the residence place and working altitude was relatively small. Still, the strengths of our study include high number of subjects, which provided the high statistical power, and larger duration of intermittent loftier altitude exposure than in nigh other studies.

Decision

In summary, this study adds to the growing body of knowledge apropos the physiology of long-term intermittent high altitude exposure. We defined for the first time hemoglobin levels in Kyrgyz shift workers commuting between high altitude and lowland. Further, our report provides prove that hemoglobin levels take a linear relationship with years of intermittent high altitude exposure and BMI. Apparently, in chronic intermittent hypoxia exposure even over longer periods, excessive erythrocytosis does not represent a major problem for healthy shift workers. Our findings might accept important implications for occupational medical surveillance to monitor health status of the workers exposed to chronic intermittent loftier distance. We hope that our study would encourage further research to explore the long-term consequences of this unique biological condition.

Author Contributions

AA, AbS, and ApS conceived and designed the written report, drafted the manuscript, and provided overall supervision. AA, AbS, TT, and Advertizement performed the information acquisition, analysis, or interpretation. AA, AbS, TT, Ad, and ApS critically revised important intellectual content in the manuscript and canonical the final version of the manuscript.

Funding

This work was supported by Ministry of Education and Science of the Kyrgyzstan (Grant No. 0005823).

Conflict of Involvement Statement

TT and AD were employed by the Kumtor Gold Company.

The remaining authors declare that the research was conducted in the absenteeism of whatsoever commercial or financial relationships that could exist construed as a potential conflict of involvement.

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Source: https://www.frontiersin.org/articles/10.3389/fphys.2018.01552/full

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