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PubMed2000

Ketamine anesthesia at high altitude.

There is a clinical need for a safe and effective anesthetic technique in high altitude and remote areas. This report presents a series of 11 consecutive cases documenting the use of ketamine anesthesia in a remote hospital at an altitude of 3,900 m, by primary-care physicians without specialist training in anesthesia. The method of administration is fully described. At a low dose of 2.0 mg/kg, ketamine produces a dissociative anesthesia that does not depress the hypoxic drive, or interfere with the pharyngeal or laryngeal reflexes. Although supplemental oxygen is useful in the recovery phase for less acclimatized individuals, it is usually not required as reductions in oxygen saturation can be raised by physical stimulation that encourages the patient to breathe faster and deeper. The common side effect of emergent nightmares was avoided using midazolam as premedication and a quiet recovery area. This study offers the first available evidence that ketamine with midazolam offers a safe and effective means of anaesthesia at very high altitude, without the need for specialist equipment or training, by careful clinicians experienced in basic airway management.

Acclimatization↗
PubMed2000

Physiological effects of intermittent hypoxia.

Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.

Acclimatization↗
PubMed2000

Effects of a 21-day expedition to 6,194 m on human skeletal muscle SR Ca2+-ATPase.

We investigated the effects of a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m) on selected Ca2+ sequestration properties of sarcoplasmic reticulum (SR) calcium pump in vastus lateralis muscle. Muscle samples were obtained by biopsy from 5 male climbers (peak oxygen consumption, VO2peak = 52.3 +/- 2.1 mL.kg(-1).min(-1)) approximately 7 days prior to (PRE) and 4 days following (POST) the expedition. A comparison of PRE versus POST measures of maximal Ca2+-ATPase activities (117 +/- 8.5 vs. 97.6 +/- 5.6 nmol.mg protein(-1).min(-1)) and Ca2+-uptake (204 +/- 15 vs. 161 +/- 11 nmol.mg protein(-1).min(-1)) measured in crude homogenates obtained from pre-exercised muscle, indicated only an effect (p < 0.05) of the expedition on Ca2+-uptake. The reduction in Ca2+-ATPase activity, representing 16.6%, was not significant (p = 0.089). The sarco endoplasmic reticulum calcium (SERCA)-ATPase isoforms, measured using Western blotting techniques, revealed a small reduction (p < 0.05) in SERCA 1 (-4.6 +/- 1.9%), but not in SERCA 2a (+2.0 +/- 1.4%). Prior to the expedition, both Ca2+-ATPase activity and Ca2+-uptake were reduced (p < 0.05) by approximately 34 and 18%, respectively, following 40 min of a two-step continuous cycling task (20 min at 59% VO2peak and 20 min at 74% VO2peak). The exercise-induced reduction in Ca2+-ATPase activity was independent of fiber type. Only in the case of Ca2+-uptake was a lower exercise response (p < 0.05) observed following the expedition, an effect that was due to the lower resting value. It is concluded that acclimatization as experienced during a mountaineering expedition induces changes in the properties of the SR Ca2+-pump, and particularly to Ca2+-sequestering function.

Acclimatization↗
PubMed2000

The quality of sleep and periodic breathing in healthy subjects at an altitude of 3,200 m.

The medical risks of travel and stay at high altitude are well known. Many more people travel for recreation to lower but still significant altitudes. To investigate the quality of sleep and sleep-related breathing disorders (SRBD) at that altitude we performed full polysomnography in nine young volunteers at lowland (760 m above sea level) on the first and sixth night after ascent to 3,200 m. There have been few studies on such populations. The subjects were nonsmoking healthy males aged 20.3 +/- 3.5 years with normal spirometry and arterial blood gas measurements performed at low altitude. Although there was no statistically significant difference in the duration of stages and sleep quality between low altitude night and both nights at high altitude as assessed by percent of sleep spent in stage 1, 2, 3+4 NREM, and REM sleep, total sleep time (TST), and sleep efficiency; the number of arousals and awakenings doubled at high altitude. There was no periodic breathing (PB) during sleep, except in isolated central events of SRBD, at low altitude. PB appeared at altitude mostly during NREM sleep and its intensity remained stable throughout the study period. Individual variations of PB intensity were high, ranging from 0.1 to 24% of TST. There were also some episodes of obstructive apnea and hypopnea during sleep at high altitude (p < 0.001). Mean SaO2 was lower during the study nights at high altitude when compared with low altitude. There were some signs of ventilatory acclimatization as shown by a higher mean SaO2 during the sixth compared with the first night at altitude (p < 0.001). We conclude that the sleep quality at the altitude of 3,200 m remains satisfactory when compared to low altitude. There is high individual variability in intensity of PB at that altitude.

Acclimatization↗
PubMed2001

Reascent following resolution of high altitude pulmonary edema (HAPE).

There is an absence of information in the literature regarding reascent to high altitude following resolution of HAPE (high altitude pulmonary edema). This report presents three cases of HAPE that are notable for later reascent to a high summit (up to 8,850 m) within the time course of each expedition. These cases illustrate that careful, gradual reascent following recovery and acclimatization after an episode of HAPE precipitated by rapid ascent may be considered. The pathophysiology of HAPE is reviewed with a focus on the evidence for rapid reversibility of pulmonary vascular injury. The evidence for protective pulmonary vascular remodeling is discussed to further support such a recommendation for cases of uncomplicated HAPE.

Acclimatization↗
PubMed2002

Potential use of oxygen enrichment of room air in mountain resorts.

Oxygen enrichment of room air has proved to be valuable for people who need to work at altitudes of 4000 m and above. In the present study the feasibility of using the same technique in ski and other mountain resorts at the lower altitudes of 2500 to 4000 m is considered. Although many people find these altitudes invigorating, some are distressed by the hypoxia, especially at night. The analysis shows that all resorts up to an altitude of 3250 m (10,600 ft) can have the equivalent altitude reduced to 1000 m (3280 ft) by oxygen enrichment without incurring a fire hazard. (The equivalent altitude is that which provides the same inspired P(O2) during air breathing.) Even resorts or laboratories as high as 4250 m can have the equivalent altitude safely reduced to 1500 m, that is, lower than the altitude of Denver, Colorado. This application of oxygen enrichment is likely to be most valuable for improving sleep and assisting in the initial acclimatization process.

Acclimatization↗
PubMed2003

Persistence of the lactate paradox over 8 weeks at 3,800 m.

The arterial blood lactate [La] response to exercise increases in acute hypoxia, but returns to near the normoxic (sea level, SL) response after 2 to 5 weeks of altitude acclimatization. Recently, it has been suggested that this gradual return to the SL response in [La], known as the lactate paradox (LP), unexpectedly disappears after 8 to 9 weeks at altitude. We tested this idea by recording the [La] response to exercise every 2 weeks over 8 weeks at altitude. Five normal, fit SL-residents were studied at SL and 3,800 m (Pbar = 485 torr) in both normoxia (PIO2 = 150 torr) and hypoxia (PIO2 = 91 torr approximately air at 3,800 m). Arterial [La] and blood gas values were determined at rest and during cycle exercise at the same absolute workloads (0, 25, 50, 75, 90, and 100% of initial SL-VO2Max) and exercise duration (4, 4, 4, 2, 1.5, and 0.75 min, respectively) at each time point. [La] curves were elevated in acute hypoxia at SL (p < 0.01) and at 3,800 m fell progressively toward the SL-normoxic curve (p < 0.01). On the same days, [La] responses in acute normoxia showed essentially no changes over time and were similar to initial SL normoxic responses. We also measured arterial catecholamine levels at each load and found a close relationship to [La] over time, supporting a role for adrenergic influence on [La]. In summary, extending the time at this altitude to 8 weeks produced no evidence for reversal of the LP, consistent with prior data obtained over shorter periods of altitude residence.

Acclimatization↗
PubMed2004

Absence of work efficiency differences during cycle ergometry exercise in Bolivian Aymara.

This study tested the hypothesis that Andean natives are adapted to high altitude (HA) via high work efficiency during exercise in hypoxia. A total of 186 young males and females were tested in Bolivia, comprising eight different subject groups. Groups were identified based on gender, ancestry (Aymara vs. European), altitude of birth (highlands vs. lowlands), and the altitude where tested (420, 3600, 3850 m). This design allows partitioning of ancestral (i.e., genetic) and developmental effects. To minimize measurement error, subjects were given two submaximal exercise tests on a cycle ergometer (on separate days). Each test consisted of four 5-min work bouts (levels), each separated by a 5-min rest period. For all groups, the oxygen consumption (V(O2))-work rate relationship was not different from the sea-level reference. Gross and net efficiencies (GE and NE) were not different between groups at any work level, with the exception of European men born in the lowlands and acclimatized and tested at 3600 m. These men showed slightly lower V(O2) at high work output, but this may be due to a nonsteady-state V(O2) kinetic, rather than to an altered steady-state V(O2)-work rate relationship per se. There were no significant group differences in delta efficiency (DE). In sum, these results provide no support for the hypothesis of energetic advantage during submaximal work in Andean HA natives. A review and analysis of the literature suggest that the same is true for HA natives in the Himalayas.

Acclimatization↗
PubMed2005

Cellular and molecular mechanisms associated with carotid body adaptations to chronic hypoxia.

Chronic hypoxia leads to adaptations in the respiratory system manifested as a persistent increase in resting ventilation, termed ventilatory acclimatization to hypoxia (VAH). Increased afferent nerve activity from carotid bodies and the ensuing reflex activation of ventilation are critical for eliciting VAH. In this review we highlight recent information on the cellular and molecular mechanisms associated with chronic hypoxia-induced functional and structural changes in the carotid body. Chronic hypoxia leads to hypersensitivity of the carotid bodies and induces morphological changes, including enlargement of the organ, hyperplasia of glomus cells, and neovascularization. Enhanced hypoxic sensitivity is due to alterations in ion current densities, as well as changes in neurotransmitter dynamics and recruitment of additional neuromodulators (endothelin- 1, ET-1) in glomus cells. Morphological alterations are in part due to upregulation of growth factors (e.g., VEGF). VAH is markedly attenuated in mice partially deficient in HIF-1 transcription factor, which regulates several downstream genes, including VEGF, ET-1, and Ca(2+) channels. The finding that VAH is also blunted in mice deficient in the fosB gene led to the suggestion that the magnitude and time course of VAH depend on complex interactions between more than one transcription factor, resulting in coordinated regulation of several downstream genes and their protein products.

Acclimatization↗
PubMed2005

Statistical models of acute mountain sickness.

Acute mountain sickness (AMS) is caused by exposure to altitudes exceeding 2500 m and often resolves by acclimatization without further ascent. Statistical models of AMS score and the probability of an AMS diagnosis were developed to allow the combination of dissimilar exposures for simultaneous analysis. The study population was 302 trekkers from a previous investigation who provided self-reported symptoms upon arrival at 3840 m during hikes through altitudes of 1500 to 6200 m. AMS score (Hackett scale) was estimated by linear regression and the probability of an AMS diagnosis (Lake Louise criteria) by logistic regression. AMS score or probability was significantly associated with exposure day and altitude. Increased altitude over the prior 3 days resulted in higher estimated AMS score or probability and decreased altitude in lower score or probability. The odds ratio (OR) of AMS was 3.6 if not on acetazolamide. Females appeared slightly more susceptible than males (1.5 OR). The approach offers the advantages of (1) improved statistical power by combining exposures, (2) insight into the dose-response relationship of altitude exposure and AMS risk, (3) quantitative tests for the significance of factors that might affect AMS susceptibility, and (4) practical tools to track individual climbers and plan operational ascents.

Acclimatization↗
PubMed2006

Respiratory control in residents at high altitude: physiology and pathophysiology.

Highland population (HA) from the Andes, living above 3000 m, have a blunted ventilatory response to increasing hypoxia, breathe less compared to acclimatized newcomers, but more, compared to sea-level natives at sea level. Subjects with chronic mountain sickness (CMS) breathe like sea-level natives and have excessive erythrocytosis (EE). The respiratory stimulation that arises through the peripheral chemoreflex is modestly less in the CMS group when compared with the HA group at the same P(ET(O2)). With regard to CO(2) sensitivity, CMS subjects seem to have reset their central CO(2) chemoreceptors to operate around the sea-level resting P(ET(CO2)). Acetazolamide, an acidifying drug that increases the chemosensitivity of regions in the brain stem that contain CO(2)/H(+) sensitive neurons, partially reverses this phenomenon, thus, providing CMS subjects with the possibility to have high CO(2) changes, despite small changes in ventilation. However, the same type of adjustments of the breathing pattern established for Andeans has not been found necessarily in Asian humans and/or domestic animals nor in the various high altitude species studied. The differing time frames of exposure to hypoxia among the populations, as well as the reversibility of the different components of the respiratory process at sea level, provide key concepts concerning the importance of time at high altitude in the evolution of an appropriate breathing pattern.

Acclimatization↗
PubMed2006

Chronic mountain sickness, optimal hemoglobin, and heart disease.

For the male inhabitants of La Paz, Bolivia (3200-4100 m), and other high altitude regions in America and Asia, chronic mountain sickness (CMS) is a major health problem. Since CMS was first described by Carlos Monge in the Peruvian Andes in 1925, numerous research papers have been devoted to this topic, but many unanswered questions still exist with respect to the beginning of the disease and its cause(s). The experience with CMS has shown that an excessively high hemoglobin concentration is not favorable for high altitude acclimatization, and the hypothesis of theoretically "optimal" hematocrit and "optimal" hemoglobin has been made. The calculated optimal hemoglobin concentration of 14.7 g/dL for resting men in the Andes is discussed as theoretical and not applicable in real life. The most frequent congenital and acquired heart diseases are discussed, such as patent ductus, atrial septum defect, ventricle septum defect among congenital heart diseases and the still very frequent rheumatic valve cardiopathies and Chagas disease as acquired cardiopathies. Among the typical acquired heart diseases of the high altitude dweller, special attention is given to chronic cor pulmonale as a consequence of severe CMS with pulmonary hypertension.

Acclimatization↗
PubMed2006

Conditions leading to high CO2 (>5 kPa) in waterlogged-flooded soils and possible effects on root growth and metabolism.

AIMS: Soil waterlogging impedes gas exchange with the atmosphere, resulting in low P(O2) and often high P(CO2). Conditions conducive to development of high P(CO2) (5-70 kPa) during soil waterlogging and flooding are discussed. The scant information on responses of roots to high P(CO2) in terms of growth and metabolism is reviewed. SCOPE: P(CO2) at 15-70 kPa has been reported for flooded paddy-field soils; however, even 15 kPa P(CO2) may not always be reached, e.g. when soil pH is above 7. Increases of P(CO2) in soils following waterlogging will develop much more slowly than decreases in P(O2); in soil from rice paddies in pots without plants, maxima in P(CO2) were reached after 2-3 weeks. There are no reliable data on P(CO2) in roots when in waterlogged or flooded soils. In rhizomes and internodes, P(CO2) sometimes reached 10 kPa, inferring even higher partial pressures in the roots, as a CO2 diffusion gradient will exist from the roots to the rhizomes and shoots. Preliminary modelling predicts that when P(CO2) is higher in a soil than in roots, P(CO2) in the roots would remain well below the P(CO2) in the soil, particularly when there is ventilation via a well-developed gas-space continuum from the roots to the atmosphere. The few available results on the effects of P(CO2) at > 5 kPa on growth have nearly all involved sudden increases to 10-100 kPa P(CO2); consequently, the results cannot be extrapolated with certainty to the much more gradual increases of P(CO2) in waterlogged soils. Nevertheless, rice in an anaerobic nutrient solution was tolerant to 50 kPa CO2 being suddenly imposed. By contrast, P(CO2) at 25 kPa retarded germination of some maize genotypes by 50%. With regard to metabolism, assuming that the usual pH of the cytoplasm of 7.5 was maintained, every increase of 10 kPa CO2 would result in an increase of 75-90 mM HCO3(-) in the cytoplasm. pH maintenance would depend on the biochemical and biophysical pH stats (i.e. regulatory systems). Furthermore, there are indications that metabolism is adversely affected when HCO3(-) in the cytoplasm rises above 50 mM, or even lower; succinic dehydrogenase and cytochrome oxidase are inhibited by HCO3(-) as low as 10 mM. Such effects could be mitigated by a decrease in the set point for the pH of the cytoplasm, thus lowering levels of HCO3(-) at the prevailing P(CO2) in the roots. CONCLUSIONS: Measurements are needed on P(CO2) in a range of soil types and in roots of diverse species, during waterlogging and flooding. Species well adapted to high P(CO2) in the root zone, such as rice and other wetland plants, thrive even when P(CO2) is well over 10 kPa; mechanisms of adaptation, or acclimatization, by these species need exploration.

Acclimatization↗
PubMed1998

Selection for longevity confers resistance to low-temperature stress in Drosophila melanogaster.

One theory of the evolution of longevity says that improvement in life span is dependent on an increased ability to resist environmental stresses of all kind. Selective breeding of Drosophila melanogaster populations for longevity has demonstrably increased life span and also altered a number of other traits, such as resistance to starvation, desiccation, and ethanol fumes, and the ability to sustain longer flight. While the exact physiologic basis of some of these traits is not yet fully understood, at least some are known to derive from the properties of metabolic substrates of glycolysis. Improvement in those characters can depend partially, therefore, on altered stores of metabolites created from glycogen. Based on the known general relationship of some traits and the suspected basis in metabolism of others, we examine the possibility here that increased life span is accompanied by other traits that also confer physiologic resistance to stress. Specifically, we test the prediction that long-lived populations of fruit flies should be more resistant to low (prefreezing) and freezing temperature extremes. Both selected and control populations were found to be susceptible to prefreezing (1.5 degrees C) and freezing temperatures (0 degree C) here, but adults and pupae of the long-lived populations generally survived better in both situations, and at all durations of exposure. The resistance of individuals improved with acclimatization, but was superior in the long-lived populations whether thermal decline was rapid or stepwise. Cold resistant, long-lived populations also had significantly higher in vitro levels of glycerol, a cryoprotectant metabolite produced from glycogen. However, while adults and pupae of long-lived stocks were more resistant to cold, larvae of those stocks were more sensitive and survived relatively poorly at every length of exposure and acclimation. This surprising result implies that larvae maintain lower levels of cryoprotectant substances. Upon becoming pupae, however, stage-specific capabilities for environmental resistance and long life emerge. This conclusion agrees with a prior study of these stocks indicating that the uptake and use of nutrients in developing larvae are restricted in long-lived populations.

Acclimatization↗
PubMed2003

Relative humidity is a key factor in the acclimation of the stomatal response to CO(2).

Previous work has shown that stomata of growth chamber-grown Vicia faba leaves have an enhanced CO2 response when compared with stomata of greenhouse-grown plants. This guard cell response to CO2 acclimatizes to the environmental conditions on the transfer of plants between the two environments. In the present study, air relative humidity is identified as a key environmental factor mediating the changes in stomatal sensitivity to CO2. In the greenhouse environment, elevation of relative humidity to growth chamber levels resulted in an enhanced CO2 response, whereas a reduction in the light level to that comparable to growth chamber conditions had no effect on stomatal CO2 sensitivity. The transfer of plants between humidified and normal greenhouse conditions resulted in an acclimation response with a time-course matching that previously obtained in transfers of plants between greenhouse and growth chamber environments. The high stomatal sensitivity to CO2 of growth chamber-grown plants could be reduced by lowering growth chamber relative humidity and then restored with its characteristic acclimation time-course by an elevation of relative humidity. Leaf temperature was unchanged during this restoration, eliminating it as a primary factor in the acclimation response. Humidity regulation of stomatal CO2 sensitivity could function as a signal for leaves inside dense foliage canopies, promoting stomatal opening under low light, low CO2 conditions.

Acclimatization↗
PubMed1997

Improving eggshell quality at high temperatures with dietary sodium bicarbonate.

Two experiments were conducted that confirmed the hypothesis that a dietary bicarbonate supplement will improve eggshell quality in hens at high temperatures as long as feed is consumed during the period of eggshell formation. End-of-lay hens were maintained on continuous light at temperatures of 30 and 35 C. Individual egg weights and shell quality measures for each hen were calculated as a proportion of the initial values determined during an acclimatization period at 25 C. Improvements in shell breaking strength in both experiments were observed as a result of supplementing control diets with 1% sodium bicarbonate (NaHCO3). This response to NaHCO3 was not a reflection of a reduced rate of lay or egg mass output, as these were similar or inferior on the control diets. Similar feed intakes on the control and NaHCO3 diets indicated that the response was not related to differences in calcium intakes. Supplements of zinc methionine and ascorbic acid proved to be inferior to NaHCO3. Improvements in egg weight were associated with the introduction of continuous lighting.

Acclimatization↗
PubMed1998

Research notes: Effect of environmental temperature on broiler chickens subjected to growth restriction at an early age.

An experiment was carried out to evaluate the effect of early growth restriction (EGR) induced by feed restriction on the ability of male broiler chickens to withstand exposure to high environmental temperatures. A 2 x 4 factorial arrangement of treatments was employed to determine whether such an exposure affects the beneficial effect of EGR on performance and carcass quality. Chicks consumed feed ad libitum or were feed-restricted from 6 to 12 d of age (to achieve 60% growth of the ad libitum birds). From 4 to 8 wk of age, the chickens were kept in temperature-controlled chambers at 25, 30, 35 C and a diurnal cyclic temperature of 25:35 C. Weight gain, feed intake, and feed efficiency from 6 to 8 wk of age (after acclimatization to the various temperatures) and BW at 8 wk of age were significantly (P < or = 0.05) depressed by the high temperatures (35 and 25:35 C) compared with values observed at 25 and 30 C. Early growth restriction did not affect these variables. Relative heart, liver, and breast meat weights at 8 wk of age were decreased significantly with increasing temperature. Relative liver weight was also decreased significantly in the EGR chicks, whereas breast yield was increased significantly in these birds. Relative abdominal fat pad size was not affected by increasing the temperature from 25 to 35 C, but it was significantly lower in chickens kept at 25:35 C than in those kept at 25 and 35 C. Early growth restriction significantly reduced the size of abdominal fat. Because no significant interactions between EGR and ambient temperature on the above mentioned variables were observed during 4 to 8 wk of age, it is concluded that EGR can not alleviate the adverse effect of high ambient temperature on performance, nor can high ambient temperature obliterate the beneficial effect of EGR in improving feed efficiency and reducing fattening.

Acclimatization↗
PubMed1993

The effects of continuous operation in a chemical protective ensemble on the performance of medical tasks in trauma management.

Treating casualties in a chemically hazardous environment constitutes a unique problem. Physical protection of the medical personnel may impair their performance and potentially affect patients' prognoses. The present study examined the effect of prolonged physical protection on the accomplishment of medical tasks related to trauma management. Sixty one emergency medical technicians, acclimatized to operating in protective gear, underwent four rounds of testing during eight hours of continuously wearing either a chemical protective suit or regular fatigues. The quality of the designated medical tasks, including sterility, was maintained throughout the study. A significant reduction in speed of performance was noted (approximately 30% slowing, p < 0.0001 in multivariate analysis) because of protective clothing. There was no additional decrement in performance following a prolonged stay in the protective gear. We conclude that in a chemically contaminated area, fully protected medical personnel are capable of treating trauma patients reasonably well, and for a relatively long period of time. The importance of pretraining and proper instruction is emphasized.

Acclimatization↗