Altitude Research Center

Rapid ascent to altitude in susceptible persons may result in severe hypoxemia, pulmonary hypertension, and even pulmonary edema. This life-threatening syndrome affects approximately i% of climbers who rapidly ascend to more than 3000 m (1). The underlying mechanisms for this problem have yet to be determined. We used bubble contrast and Doppler echocardiography on 12 climbers at 4200 m on Mount McKinley. Alaska, to test the hypothesis that a patent foramen ovale may provide an avenue for right-to-left shunting during highaltitude-induced hypoxia and pulmonary hypertension, resulting in disproportionate hypoxemia and contributing to the development of high-altitude pulmonary edema. the right ventricular outflow tract at 35 mm Hg (PPA = 79 -0-45 [acceleration time]) (2). Trieuspid regurgitation was present, with a peak velocity of 3.5 m/s, suggesting a right ventricular systolic pressure of 60 mm Hg (3). Contrast echocardiography with agitated saline revealed prominent right-to-left shunting of microbubbles across the interatrial septum at rest ( .

Consensus on high altitude diseases. High Alt Med Biol 6: [147][148][149][150][151][152][153][154][155][156][157] 2005.-This is an international consensus statement of an ad hoc committee formed by the International Society for Mountain Medicine (ISMM) at the VI World Congress on Mountain Medicine and High Altitude Physiology (Xining, China; and represents the committee's interpretation of the current knowledge with regard to the most common chronic and subacute high altitude diseases. It has been developed by medical and scientific authorities from the committee experienced in the recognition and prevention of high altitude diseases and is based mainly on published, peer-reviewed articles. It is intended to include all legitimate criteria for choosing to use a specific method or procedure to diagnose or manage high altitude diseases. However, the ISMM recognizes that specific patient care decisions depend on the different geographic circumstances involved in the development of each chronic high altitude disease. These guidelines are established to inform the medical services on site who are directed to solve high altitude health problems about the definition, diagnosis, treatment, and prevention of the most common

Abnormal control of ventilation in high-altitude pulmonary edema. J. Appl. Physiol. 64(3): 1268-1272, 1988.-We wished to determine the role of hypoxic chemosensitivity in highaltitude pulmonary edema (HAPE) by studying persons when ill and upon recovery. We studied seven males with HAPE and seventeen controls at 4,400 m on Mt. McKinley.

The efficacy of carbonic anhydrase (CA) inhibitors in amelioration of periodic breathing during sleep at high altitude is not fully understood, Although CA is present in a number oftissues, we hypothesized that selective renal CA inhibition without physiologically important inhibition of other tissue CA, may be sufficient alone by its generation of a mild metabolic acidosis to stimulate ventilation and prevent periodic breathing. We studied benzolamide (3 mg/kg), a selective inhibitor of renal CA, in 4 climbers on ventilation and ventilatory responses at sea level and on arterial 02 saturation (Sao,%) and periodic breathing during sleep at altitude. At sea level, ventilation increased and Pao, rose accompanied by a mild metabolic acidosis. The isocapnic hypoxic ventilatory response was unchanged but the hyperoxic hypercapnic ventilatory response rose 40%. At high altitude (4400 m), daytime Sao,% improved from 81 to 85 and venous plasma HCO; fell from 18.9 to 14.8 raM. During sleep, mean Sao,% rose from 76 to 80 and periodic breathing decreased 75~o. We conclude that metabolic acidosis occurring with all CA inhibitors is one of the major st!mulant actions of these drugs on ~vntilation while awake and during sleep at high altitude. Carbonic anhydrase, selective renal blockade; Control of breathing, high altitude, sleep; High altitude, carbonic anhydrase, periodic breathing; Mammals, human; Sleep, periodic breathing, high altitude Periodic breathing occurs frequently during sleep at high altitude (Powles and Sutton, 1983). The consequences of this phenomenon include poor quality sleep, episodic arterial oxygen desaturation and probably augmentation of existing baseline pulmonary hypertension. This has led quite logically to the use of respiratory stimulants for the amelioration of periodic breathing at high altitude, of which the most commonly used are the carbonic anhydrase (CA) inhibitors such as acetazolamide and methazolamide. In addition to their well established role in reducing the incidence of acute mountain sickness (Larson el ai.; 1982, Wright et al., 1983), acetazolamide also markedly dimin-Correspondence to: E.R. Swenson, Pulmonary/Critical Care Section (IIIB),

Acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE) continue to cause significant morbidity and occasional deaths among mountain recreationists and residents. Descent to lower altitude is still considered the treatment of choice, but an increased role for medical therapy is emerging. Acetazolamide is currently the drug of choice for prevention of AMS, and probably HAPE as well. Numerous studies have demonstrated the drug's effectiveness when it is started 12 to 24 hours before ascent. Suggestions for indications, dosage, and regimen vary with different authors. Lower dosage offers adequate protection with fewer side effects. Acetazolamide has still not been adequately studied for treatment of altitude illness. Oxygen effectively treats HAPE and mild AMS, but is not as useful for cerebral edema. Dexamethasone recently was found effective for treatment of AMS, including early cerebral edema, but not for advanced cerebral edema. Side effects limit its use for prophylaxis, but dexamethasone offers an alternative to acetazolamide for those with sulfa intolerance. [Hackett PH, Roach RC: Medical therapy of altitude illness. Ann Emerg Med September 1987;16:980-986.]

Hackett, Peter H., and Robert C. Roach. High altitude cerebral edema. High Alt. Med. Biol. 5:136-146, 2004.-This review focuses on the epidemiology, clinical description, pathophysiology, treatment, and prevention of high altitude cerebral edema (HACE). HACE is an uncommon and sometimes fatal complication of traveling too high, too fast to high altitudes. HACE is distinguished by disturbances of consciousness that may progress to deep coma, psychiatric changes of varying degree, confusion, and ataxia of gait. It is most often a complication of acute mountain sickness or high altitude pulmonary edema. The current leading theory of its pathophysiology is that HACE is a vasogenic edema; that is, a disruption of the blood-brain barrier, and we review possible mechanisms to explain this. Treatment and prevention of HACE are similar to those for the other altitude illnesses, but with greater emphasis on descent and steroids. We conclude the review with several case histories to illustrate key clinical features of the disorder.

At the dawn of the 21st century, we are poised to make great new discoveries about how humans respond to hypoxia. These discoveries will probably include fundamentally new information about the molecular mechanisms of our physiological responses to short-and long-term hypoxia and about the functional consequences of these responses. In this review, we explore acute mountain sickness (AMS) in detail to illustrate the exciting near future in this field.

We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure ϭ 429 Torr, ϳ4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (V E), pulmonary function, arterial oxygen saturation (Sa O 2), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 Ϯ 1.0 and 1.3 Ϯ 0.4 in Ex and Sed, respectively (P Ͻ 0.01); but resting V E and Sa O 2 were not different between trials. However, Sa O 2 during the exercise bouts in Ex was at 76.3 Ϯ 1.7%, lower than during either Sed or at rest in Ex (81.4 Ϯ 1.8 and 82.2 Ϯ 2.6%, respectively, P Ͻ 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P ϭ 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors. fluid balance; edema; oxygen saturation; pathophysiology

Regional limb blood flow has been measured with dilution techniques (cardio-green or thermodilution) and ultrasound Doppler. When applied to the femoral artery and vein at rest and during dynamical exercise these methods give similar reproducible results. The blood flow in the femoral artery is $0.3 L min A1 at rest and increases linearly with dynamical knee-extensor exercise as a function of the power output to 6±10 L min A1 (Q 1.94 + 0.07 load). Considering the size of the knee-extensor muscles, perfusion during peak effort may amount to 2±3 L kg A1 min A1 , i.e. $100-fold elevation from rest. The onset of hyperaemia is very fast at the start of exercise with T of 2±10 s related to the power output with the muscle pump bringing about the very ®rst increase in blood¯ow. A steady level is reached within $10±150 s of exercise. At all exercise intensities the blood¯ow¯uctuates primarily due to the variation in intramuscular pressure, resulting in a phase shift with the pulse pressure as a superimposed minor in¯uence. Among the many vasoactive compounds likely to contribute to the vasodilation after the ®rst contraction adenosine is a primary candidate as it can be demonstrated to (1) cause a change in limb blood¯ow when infused i.a., that is similar in time and magnitude as observed in exercise, and (2) become elevated in the interstitial space (microdialysis technique) during exercise to levels inducing vasodilation. NO appears less likely since NOS blockade with L-NMMA causing a reduced blood¯ow at rest and during recovery, it has no effect during exercise. Muscle contraction causes with some delay (60 s) an elevation in muscle sympathetic nerve activity (MSNA), related to the exercise intensity. The compounds produced in the contracting muscle activating the group III±IV sensory nerves (the muscle re¯ex) are unknown. In small muscle group exercise an elevation in MSNA may not cause vasoconstriction (functional sympatholysis). The mechanism for functional sympatholysis is still unknown. However, when engaging a large fraction of the muscle mass more intensely during exercise, the MSNA has an important functional role in maintaining blood pressure by limiting blood¯ow also to exercising muscles.

Objective: To investigate the association of optic nerve sheath diameter (ONSD), as a correlate of intracranial pressure (ICP), with acute mountain sickness (AMS). Design: Longitudinal cohort study of mountaineers from sea level to 6400 m. Setting: Mount Everest (North side). Participants: 13 mountaineers (10 men, 3 women; aged 23-52 years) on a British expedition to climb Mount Everest. Interventions: ONSD was measured ultrasonically, 3 mm behind the globe using B scans recorded with an OTI-Scan 3D scanner (Ophthalmic Technologies, Canada). Serial binocular scans were recorded at sea level, and 2000, 3700, 5200 and 6400 m. All ONSDs were measured by a blinded observer. Main outcome measures: ONSD, AMS score (using the Lake Louise scoring system), heart rate, and oxygen saturation levels. Results: All results were analysed by regression analysis with adjustment. ONSD was positively associated with increasing altitude above sea level (0.10 mm increase in ONSD per 1000 m, 95% CI 0.05 to 0.14 mm) and AMS score (0.12 mm per score, 95% CI 0.06 to 0.18 mm); further associations were found with resting heart rate (0.29 mm per 20 beats/min, 95% CI 0.17 to 0.41 mm) and oxygen saturations (0.20 mm per 10% decrease, 95% CI 0.11 to 0.29 mm). Conclusions: ONSD increases at high altitude, and this increase is associated with more severe symptoms of AMS. Given the linkage between ONSD and ICP, these results strongly suggest that intracranial pressure plays an important role in the pathophysiology of AMS.

To estimate the separate and combined effects of reduced P B and O 2 levels on body fluid balance and regulating hormones, measurements were made during reduced P B (altitude, ALT; P B ϭ 432 mm Hg, F I O 2 ϭ 0.207), reduced inspired O 2 concentration (normobaric hypoxia, HYX; P B ϭ 614 mm Hg, F I O 2 ϭ 0.142), and lowered ambient pressure without hypoxia (normoxic hypobaria HYB; P B ϭ 434 mm Hg, F I O 2 ϭ 0.296). Nine fit and healthy young men were exposed to these conditions for 10 h in a decompression chamber. Lake Louise AMS scores, urine collections, and blood samples were obtained every 3 h, with recovery measurements 2 h after exposure. AMS was significantly greater during ALT than HYX, as previously reported (J. Appl. Physiol. 81:1908-1910. 1996), because the combination of reduced P B and PO 2 over the 10 h favored fluid retention by reducing urine volume, while plasma volume (PV) remained higher than during HYX. At ALT the plasma Na ϩ fell significantly at 6 h, probably from dilution of extracellular fluid, and antidiuretic hormone (ADH) was highest (p ϭ 0.006 versus HYB). The PV, urine flow, free water clearance, and plasma renin activity (PRA) rose significantly during recovery from ALT as AMS symptoms subsided, suggesting increased intravascular fluid and reduced adrenergic tone. During HYB, the plasma aldosterone (ALDO) and K ϩ levels were significantly elevated, and PRA was highest and ADH lowest, without fluid retention. During HYX, fluid balance was similar to HYB, but PV and ALDO were significantly lower, and ALDO increased significantly in recovery from HYX. The fluid retention at ALT in AMS-susceptible subjects appears related to a synergistic interaction involving reduced P B and ADH and ALDO.

We investigated the effect of acute hypoxia (AH) on dynamic cerebral autoregulation (CA) using two independent assessment techniques to clarify previous, conflicting reports. Twelve healthy volunteers (6 men, 6 women) performed six classic leg cuff tests, three breathing normoxic (FiO2 = 0.21) and three breathing hypoxic (FiO2 = 0.12) gas, using a single blinded, Latin squares design with 5-min washout between trials. Continuous measurements of middle cerebral artery blood flow velocity (CBFv; DWL MultiDop X2) and radial artery blood pressure (ABP; Colin 7000) were recorded in the supine position during a single experimental session. Autoregulation index (ARI) scores were calculated using the model of Tiecks et al. (Tiecks FP, Lam AM, Aaslid R, Newell DW. Stroke 26: 1014–1019, 1995) from ABP and CBFv changes following rapid cuff deflation (cuff ARI) and from ABP to CBFv transfer function, impulse, and step responses (TFA ARI) obtained during a 4-min period prior to cuff inflation. A...

The volume of red blood cells (VRBC) is used routinely in the diagnostic workup of polycythemia, in assessing the efficacy of erythropoietin administration, and to study factors affecting oxygen transport. However, errors of various methods of measurement of VRBC and related parameters are not well characterized. We meta-analyzed 346 estimates of error of measurement of VRBC for techniques based on Evans blue (VRBC,Evans), 51chromium-labeled red blood cells (VRBC,51Cr), and carbon monoxide (CO) rebreathing (VRBC,CO), as well as hemoglobin mass with the carbon-monoxide method (MHb,CO), in athletes and active and inactive subjects undergoing various experimental and control treatments lasting minutes to months. Subject characteristics and experimental treatments had little effect on error of measurement, but measures with the smallest error showed some increase in error with increasing time between trials. Adjusted to 1 day between trials and expressed as coefficients of variation, me...