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Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380 m), where 84 participants with a hematocrit (HCT) >= 65% and CMS score > 6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N-acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO2, PaCO2, CMS score, and serum and urine cobalt concentrations. The mean ( SD) hematocrit, CMS score and serum cobalt concentrations were 69 +/- 4%, 9.8 +/- 2.4 and 0.24 +/- 0.15 mu g/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p = 0.048) and the CMS score fell by 34.9% vs. 14.8% (p = 0.014) compared to placebo, while the reduction in PaCO2 was 10.5% vs. an increase of 0.6% = 0.003), with a relative increase in PaO2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p = 0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures.

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the prevention and treatment of acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations for their roles in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to the prevention and management of each disorder that incorporate these recommendations.

High-altitude illnesses have profound consequences on the health of many unsuspecting and otherwise healthy individuals who sojourn to high altitude for recreation and work. The clinical manifestations of high-altitude illnesses are secondary to the extravasation of fluid from the intravascular to extravascular space, especially in the brain and lungs. The most common of these illnesses, which can present as low as 2,000 m, is acute mountain sickness, which is usually self-limited but can progress to the more severe and potentially fatal entities of high-altitude cerebral edema and high-altitude pulmonary edema. This article will briefly review normal adaptation to high altitude and then more extensive reviews of the clinical presentations, prevention, and treatments of these potentially fatal conditions. Research on the mechanisms of these conditions will also be reviewed. A better understanding of these disorders by practitioners will lead to improved prevention and rational treatment for the increasing number of people visiting high-altitude areas around the globe. There will not be space for writing about high-altitude residents, medical conditions in low-altitude residents going to high altitude, or training for athletes at high altitude. These topics deserve another article.

High-altitude athletes and adventurers face a number of environmental and medical risks. Clinicians often advise participants or guiding agencies before or during these experiences. Preparticipation evaluation (PPE) has the potential to reduce risk of high-altitude illnesses in athletes and adventurers. Specific conditions susceptible to high-altitude exacerbation also important to evaluate include cardiovascular and lung diseases. Recommendations by which to counsel individuals before participation in altitude sports and adventures are few and of limited focus. We reviewed the literature, collected expert opinion, and augmented principles of a traditional sport PPE to accommodate the high-altitude wilderness athlete/adventurer. We present our findings with specific recommendations on risk stratification during a PPE for the high-altitude athlete/adventurer.

The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude.

This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function. Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise. The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.

This paper asks how the decline in maximal O(2) uptake rate (VO(2),max) with age is related to the properties of a key muscle group involved in physical activity - the quadriceps muscles. Maximal oxygen consumption on a cycle ergometer was examined in nine adult (mean age 38.8 years) and 39 elderly subjects (mean age 68.8 years) and compared with the oxidative capacity and volume of the quadriceps. VO(2),max declined with age between 25 and 80 years and the increment in oxygen consumption from unloaded cycling to VO(2),max (delta VO(2)) in the elderly was 45 % of the adult value. The cross-sectional areas of the primary muscles involved in cycling - the hamstrings, gluteus maximus and quadriceps - were all lower in the elderly group. The quadriceps volume was reduced in the elderly to 67 % of the adult value. Oxidative capacity per quadriceps volume was reduced to 53 % of the adult value. The product of oxidative capacity and muscle volume - the quadriceps oxidative capacity - was 36 % of the adult value in the elderly. Quadriceps oxidative capacity was linearly correlated with delta VO(2) among the subjects with the slope indicating that the quadriceps represented 36 % of the VO(2) increase during cycling. The decline in quadriceps oxidative capacity with age resulted from reductions in both muscle volume and oxidative capacity per volume in the elderly and appears to be an important determinant of the age-related reduction in delta VO(2) and VO(2),max found in this study.

Ventilatory acclimatization to high altitude has been discussed in a chronologic fashion, i.e. the acute, prolonged, and chronic or lifelong phases, and the integration of exercise ventilation as it relates to each of these phases has been outlined. Unanswered questions in each of these areas have been posed as fertile grounds for future investigation.

Much of the clinical impact of acute altitude illnesses stems from fluid accumulation in interstitial spaces and nowhere is this more apparent than in the lungs as the edema escapes into the alveoli to cause life-threatening hypoxemia. This chapter will update our knowledge of HAPE over the past decade about the vasculature, alveolar epithelium, innervation, immune response, and genetics of the lung in hypoxia, as well as prophylactic and therapeutic strategies to reduce the toll of this most common alpine life-threatening illness.

Study objectives Inflammation may contribute to the pathogenesis of high-altitude pulmonary edema (HAPE). This study was designed to determine whether a marker of inflammation, urinary leukotriene E4 (LTE4), is elevated in patients with HAPE. Design We conducted a case-control study to collect clinical data and urine samples from HAPE patients and healthy control subjects at moderate altitude (≥2727 m), and follow-up urine samples from HAPE patients following their return to low altitude (≤1,600 m). Setting Five medical clinics in Summit County, Colorado. Patients Questionnaire data were evaluated in 71 HAPE patients and 36 control subjects. Urinary LTE4 levels were determined from a random subset of 38 HAPE patients and 10 control subjects presenting at moderate altitude, and on 5 HAPE patients who had returned to low altitude. Measurements and Results Using an enzyme immunoassay technique, urinary LTE4 levels were found to be significantly higher in HAPE patients (123 [16 to 468] pg/mg creatinine, geometric mean [range]) than in control subjects (69 [38 to 135]), p=0.02. Following return to low altitude, urinary LTE4 levels fell significantly from 122 (41.8 to 309) to 53.6 (27.6 to 104) pg/mg creatinine (p=0.05). Urinary LTE4 levels were not related to age, sex, time at altitude, physical condition or habitual exercise, recent use of alcohol or nonsteroidal anti-inflammatory drugs (NSAIDs), or oxygen saturation. Clinical factors associated with HAPE included male sex, regular exercise, and recent use of NSAIDs. Conclusions We conclude that urinary LTE4 levels are elevated in patients with HAPE, supporting the view that HAPE involves inflammatory mechanisms.

We performed a prospective cohort analysis to determine the rate and extent of improvement in pulmonary function abnormalities and self-perceived health for 1 yr after surviving an episode of the acute respiratory distress syndrome (ARDS). We also examined the effect of ARDS severity and etiology, age, and sex on functional recovery. Patients were recruited from the intensive care units of one hospital and followed at regular time intervals from extubation to 1 yr. Fifty-two of 82 eligible adult survivors (63%) consented to participate; 37 of 82 (45%) had at least two examinations, and 20 (24%) had complete follow-up. Risk factors for ARDS included sepsis (n = 12), trauma (n = 15), and other (n = 10). Pulmonary function and self-perceived health scores improved considerably in the first 3 mo after extubation, with only slight additional improvement at 6 mo. No further changes were evident at 1 yr. Patients with more severe ARDS had significantly lower pulmonary function tests than did other survivors throughout follow-up. These observations should be useful for clinical follow-up of ARDS survivors and provide specific information concerning the expected rate of functional recovery in these patients.

To explore the association of end-title partial pressure (Petco(2)) and oxygen saturation (Spo(2)) with the development of AMS in travelers rapidly ascending to Cusco, Peru (3326 m).Using the 715 TIDAL WAVE Sp handheld, portable capnometer/oximeter, we measured Spo(2) and Petco(2) in 175 subjects upon ascent to Cusco, Peru (3326 m) from Lima (sea level) (a mean time of 3.9 hours.) Symptoms of AMS were recorded at the same initial time on arrival to altitude and 24 hours later using the Environmental Symptoms Questionnaire (ESQ).This study showed that no subjects with the lowest Petco(2) of 23 to 30 mm Hg had AMS (P.044). The data also demonstrate that subjects with a higher Petco(2) (36-40 mm Hg) and lower Sao(2) (72%-86%) have a higher incidence of AMS.The most important finding of this study is that Petco(2) upon ascent was found to have a more significant effect than Spo(2) on a subject's ultimate ESQ score. This study demonstrates that those individuals with a brisk ventilatory response upon ascent to moderate altitude, as measured by Petco(2), did not develop AMS, whereas a blunted ventilatory response, as reflected in the highest Petco(2), was related to the subsequent development of AMS.

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 anumber of tissues, 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 O 2 saturation (Sa O 2 %) and periodic breathing during sleep at altitude. At sea level, ventilation increased and Pa O 2 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 Sa O 2 % improved from 81 to 85 and venous plasma HCO 3 fell from 18.9 to 14.8 mM. During sleep, mean Sa O 2 % rose from 76 to 80 and periodic breathing decreased 75%. We conclude that metabolic acidosis occurring with all CA inhibitors is one of the major stimulant actions of these drugs on ventilation while awake and during sleep at high altitude.

Breathing pattern in response to maximal exercise was examined in four subjects during a 7-day acclimatisation to a simulated altitude of 4247 m (barometric pressure, PB = 59.5 kPa). Graded exercise tests to exhaustion were performed during normoxia (day 0), and on days 2 and 7 of hypoxia, respectively. Ventilation was significantly augmented in the hypoxic environment, as were both the mean inspiratory flow (VT/TI) and inspiratory duty cycle (TI/TTOT) components of it. VI/TI was increased due to a significant increase in tidal volume (VT) and a corresponding decrease in inspiratory time duration (TI). Throughout a range of exercise ventilation, TI/TTOT was increased due to an apparently greater decrease in expiratory time duration (TE) with respect to TI. In all cases, the relation between VT and TI displayed a typical range 2 behaviour, with evidence of a range 3 occurring at very high ventilatory rates. There was essentially no difference observed in the VT-TI relation during exercise between the normoxic and hypoxic conditions. No significant changes were observed in the breathing pattern in response to exercise within the exposure period (from day 2 to day 7), although there was a discernible tendency to a higher stage 3 plateau by day 7 of altitude exposure.

Under most conditions, the lungs compensate for the stresses of illness to ensure adequate acquisition of oxygen. Even with exposure to high altitude, the lungs' adaptations ensure that this process takes place. This process is challenged by global hypoxia, especially if there is impairment in the three processes needed for adequate tissue oxygenation: (1) intact ventilatory drive to breathe; (2) sufficient increase in alveolar ventilation, which is stimulated by that drive; and (3) intact gas exchange at the alveolar-capillary interface. This article reviews the mechanisms that make the study of high altitude relevant to patients who have heart or lung disease at low altitude.

During the last decade, major advances in the understanding of the mechanism of high altitude pulmonary edema (HAPE) have supplemented the landmark work done in the previous 30 years. A brief review of the earlier studies will be described, which will then be followed by a more complete treatise on the subsequent research, which has elucidated the role of accentuated pulmonary hypertension in the development of HAPE. Vasoactive mediators, such as nitric oxide (NO) and endothelin-1, have played a major role in this understanding and have led to preventive and therapeutic interventions. Additionally, the role of the alveolar epithelium and the Na–K ATPase pump in alveolar fluid clearance has also more recently been understood. Direction for future work will be given as well.

Objective: To determine if a physician-administered physical examination and screening questionnaire accurately detects exercise-induced bronchoconstriction (EIB) in adolescent athletes. Study design: Cross-sectional study of 256 adolescents participating in organized sports from 3 suburban high schools. The number of persons screened positive for EIB by physical examination and questionnaire was compared with the number of persons with EIB diagnosed by a "gold standard" test that consisted of a 7-minute exercise challenge followed by serial spirometry. Results: We diagnosed EIB in 9.4% of adolescent athletes. The screening history identified persons with symptoms or a previous diagnosis suggestive of EIB in 39.5% of the participants, but only 12.9% of these persons actually had EIB. Among adolescents with a negative review of symptoms of asthma or EIB, 7.8% had EIB. Among adolescents with no previous diagnosis of asthma, allergic rhinitis, or EIB, 7.2% had EIB diagnosed by exercise challenge. Persons who screened negative on all questions about symptoms or history of asthma, EIB, and allergic rhinitis accounted for 45.8% of the adolescents with EIB. Conclusions: EIB occurs frequently in adolescent athletes, and screening by physical examination and medical history does not accurately detect it. (J Pediatr 2002;141:343-9)

The lungs are a delicate interface between the atmosphere and our bodies across which oxygen diffuses from the air we breathe to the blood which carries oxygen to the cells and mitochondria. In healthy lungs at sea level where there is a surfeit of oxygen, this process occurs easily, whereas, in lungs with disease it becomes a task which may not be fully successful and hypoxemia may ensue or worsen. At high altitude where the barometric pressure (Pb) and thus the supply of oxygen is lower, the job of getting oxygen to the blood, even in the healthy lung is more difficult, and in the diseased lung it may be impossible. This presentation will review the lungs’ responses to high altitude, with emphasis on the abnormal. Both acute and chronic responses of patients with pre-existing lung disease will be reviewed. Pulmonary diseases encountered at high altitude in previously healthy people, such as high altitude pulmonary edema and chronic mountain sickness will be touched on only as they pertain to other patients. Pre-existing lung disease (with and without hypoxemia at sea level) such as obstructive lung diseases (asthma, COPD, emphysema), and restrictive lung diseases (sarcoid, asbestosis, interstitial pulmonary fibrosis) will be discussed in terms of gas exchange, lung mechanics, and treatment at high altitude. Disorders of ventilatory control; e.g., obesity-hypoventilation syndrome and sleep apnea, may present formidable problems, and guidelines for their treatment will be discussed. Infectious lung diseases; e.g., pneumonia, cystic fibrosis, and pulmonary vascular disorders such as chronic mountain sickness, primary pulmonary hypertension, and congenital absence of the pulmonary artery are important disorders that require special attention because of the accentuated hypoxic pulmonary vascular response encountered at high altitude. The purpose therefore, is to provide the medical practitioner with the insight into prevention, recognition, and treatment of pulmonary problems encountered specifically at high altitude, as well as guidance on how best to advise patients with lung disease who want to fly in airplanes and/or ascend to high altitude for work or pleasure.

The extreme thinness of the pulmonary blood-gas barrier results in high mechanical stresses in the capillary wall when the capillary pressure rises during exercise. We have previously shown that, in elite cyclists, 6–8 min of maximal exercise increase blood-gas barrier permeability and result in higher concentrations of red blood cells, total protein, and leukotriene B4 in bronchoalveolar lavage (BAL) fluid compared with results in sedentary controls. To test the hypothesis that stress failure of the barrier only occurs at the highest level of exercise, we performed BAL in six healthy athletes after 1 h of exercise at 77% of maximal O2 consumption. Controls were eight normal nonathletes who did not exercise before BAL. In contrast with our previous study, we did not find higher concentrations of red blood cells, total protein, and leukotriene B4 in the exercising athletes compared with control subjects. However, higher concentrations of surfactant apoprotein A and a higher surfactant apoprotein A-to-phospholipid ratio were observed in the athletes performing prolonged exercise, compared with both the controls and the athletes from our previous study. These results suggest that, in elite athletes, the integrity of the blood-gas barrier is altered only at extreme levels of exercise.

Objectives To characterize spirometry and to document the incidence of exercise-induced bronchospasm (EIB) during competition in elite track and field athletes. Design Spirometry was performed in 120 men and 69 women athletes before competition and peak expiratory flows in 50 men and 23 women athletes before and after competition. Setting The 1991 (Randalls Island, NY, U.S.A.) and the 1993 (Eugene, OR, U.S.A.) National Track and Field Championships (World Championship team-qualifying meet). Participants American track and field athletes who met World Championship qualifying standards. Measurements Spirometry (Cybermedic, Inc. Boulder, CO, U.S.A.) and peak expiratory flows (Personal Best, Health-scan Products, Cedar Grove, NJ, U.S.A.) Measurements the best of three reproducible efforts. Results Male sprinters had lower vital capacities than other track athletes, whereas both male and female field (throwing) athletes had larger vital capacities than both runners and other field athletes. Decreases of 10|X% peak expiratory flows were found in 10|X% of men and 26|X% of women track athletes within 15 min after competition. The incidence was higher in longer-distance events. Most participants did not have a history of asthma. Conclusions A higher-than-expected prevalence of EIB was found in high-level track athletes. The results suggest that spirometry and/or peak flows should be measured in track athletes because small decreases in airflow may impair training or performance, a condition that is easily treated.

Study objectives We evaluated the safety and efficacy of treating high-aititude pulmonary edema (HAPE) by bed rest and supplemental oxygen at moderate altitudes. We also characterized clinical parameters in HAPE before and after treatment. Design Case series. Setting Two primary care centers at about 9200 feet (2800 meters) above sea level. Type of participants All patients aged 16–69 years who had been diagnosed with HAPE and were treated with bed rest and supplemental oxygen. Patients were seen on a follow-up visit. Interventions Selected patients were treated with bed rest and supplemental oxygen rather than hospital admission or descent. Main outcome measure Patients were considered improved on follow-up if room air arterial oxygen saturation was increased by 10 percentage points or if their symptoms had improved. Results Of 58 patients with confirmed HAPE, 25 (43%) were treated by bed rest and supplemental oxygen and were seen on return visits to the clinic. All of the treated patients improved at the return visit. Systolic blood pressure, heart rate, respiratory rate, and temperature decreased significantly between the first visit and the return visit. Oxygen saturation improved between visits. Conclusion Some patients with HAPE at moderate altitudes where medical facilities are available can be safely treated with bed rest and oxygen without descent.

A15-YEAR-OLD BOY went with some friends on a trip to climb a 3700 m high mountain. The intention was to climb a nontechnical route to the summit and down over 2 days. The first day involves hiking from an elevation of 300 m to a campsite at 2600 m. The next day involves climbing to the summit and descending. On the first day, the boy started out hiking with the rest of his group, but lagged behind with one companion for most of the ascent. They all arrived at the 2600 m camp without any significant problems. However, within an hour or so the boy developed a severe headache, followed by progressive disorientation and marked shortness of breath. A helicopter rescue was organized and, several hours later, he was evacuated to the local base hospital. Throughout the evacuation, the boy was tachypneic, but remained conscious. Upon arrival at the hospital, he became unresponsive with a pulse of a 115/min, blood pressure of 60/40, and a respiratory rate of 28/min. A chest radiograph showed diffused fluffy opacities that were much more prominent in the right lung than in the left lung. Despite intubation and intensive attempts to reverse the process, the boy died within about 4 h of arriving at the hospital. The boy’s past medical history was significant. As an 8-year-old he experienced decreased exercise tolerance compared to his friends and was referred by his family physician to a pediatric pulmonologist and cardiologist. The subsequent work-up, including chest radiographic and echocardiographic studies, strongly suggested congenital absence of his left pulmonary artery. Ventilation–perfusion scans and right heart catheterization confirmed this suspicion. His pulmonary artery pressures were measured at 45 mmHg. The boy was advised to continue his activity level to within tolerance. He was an enthusiastic and positive participant in most school sports and group activities, but continued to have some limitation with shortness of breath and exercise intolerance compared to his colleagues. The postmortem examination revealed diffuse proteinaceous pulmonary edema in his right lung and confirmed the absence of his left pulmonary arterial trunk.

31P nuclear magnetic resonance spectroscopy (31P-NMRS) was performed on brain cross sections of four human subjects before and after 7 days in a hypobaric chamber at 447 Torr to test the hypothesis that brain intracellular acidosis develops during acclimatization to high altitude and accounts for the progressively increasing ventilation that develops (ventilatory acclimatization). Arterial blood gas measurements confirmed increased ventilation. At the end of 1 wk of hypobaria, brain intracellular pH was 7.023 +/- 0.046 (SD), unchanged from preexposure pH of 6.998 +/- 0.029. After return to sea level, however, it decreased to 6.918 +/- 0.032 at 15 min (P less than 0.01) and 6.920 +/- 0.046 at 12 h (P less than 0.01). The ventilatory response to hypoxia increased [from 0.35 +/- 0.11 (l/min)/(-%O2 saturation) before exposure to 0.69 +/- 0.19 after, P = 0.06]. Brain intracellular acidosis is probably not a supplemental stimulus to ventilatory acclimatization to high altitude. However, brain intracellular acidosis develops on return to normoxia from chronic hypoxia, suggesting that brain pH may follow changes in blood and cerebrospinal fluid pH as they are altered by changes in ventilation.

To assess the ventilatory adaptation during gradual ascent to extreme altitude, we studied seven healthy males as part of the 40 d simulated ascent of Mt. Everest in a hypobaric chamber. We measured resting ventilation (VE, l.min-1), arterial oxygen saturation (SaO2%), the ventilatory response to oxygen breathing, isocapnic hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) at sea level prior to the ascent (760 torr), 14,000 feet (428 torr), 24,000 feet (305 torr), and within 24 h of descent (765 torr). VE increased from 9.3 +/- 1.1 l.min-1 at 760 torr to 23.4 +/- 1.3 l.min-1 at 305 torr and remained elevated at 14.7 +/- 0.7 l.min-1 after descent. Oxygen breathing decreased VE by 9.6 +/- 1.3 l.min-1 at 305 torr. Isocapnic HVR (expressed as a positive slope of VE/SaO2, l.min-1.%SaO2(-1) increased from 0.18 +/- 0.07 at 760 torr to 0.34 +/- 0.11 and 0.38 +/- 0.5 at 428 torr and 305 torr (P less than 0.05) respectively. HVR was elevated further upon return to sea level (0.8 +/- 0.09, P less than 0.05). HCVR (S = VE/PETCO2, l.min-1.torr-1) increased from sea level (S = 4.4 +/- 0.09) to 305 torr (S = 18.7 +/- 3.5, P less than 0.01) and remained elevated upon return to sea level (S = 10.7 +/- 4.6, P less than 0.001). This study is the first to investigate the ventilatory response to such extreme altitude and so soon after descent and shows that hypoxic and hypercapnic responses increase during prolonged progressive hypoxic exposure and remain significantly elevated from pre-ascent levels immediately upon descent.

This study explored the relationship between age-related elevations of plasma norepinephrine (NE) levels (thought to reflect heightened sympathetic nervous system activity) and sleep. Plasma NE levels were consistently and significantly greater in 8 aged than 10 young men across a 24-hr study period. For both groups, plasma catecholamine levels remained stable near bedtimes and rise times and during spontaneous and experimentally induced nighttime awakenings; reversal of the sleep/wake pattern (nighttime wakefulness, daytime sleep) had little effect on the 24-hr plasma NE or sleep patterns, indicating that elevated NE cannot be attributed to altered sleep/wakefulness per se. The aged group had significantly more wakefulness and significantly higher plasma NE levels while in bed in all study conditions. These two variables were significantly correlated, suggesting that heightened sympathetic activity may fragment sleep with wakefulness in the aged.

We studied 120 asbestos-exposed workers seeking compensation for asbestos-related ventilatory impairment who were referred to us for evaluation of their complaint of dyspnea. We reviewed history, chest radiographs, pulmonary function studies, and exercise tests. The workers were 59.9 ± 9.5 (mean ± SD) yr of age and their first asbestos exposure had been 34.4 ± 10 yr prior to the study; 63% were smokers, 19% were ex-smokers, and 18% were nonsmokers. Chest radiographs were normal in 4%, showed only pleural disease in 35%, only parenchymal diseases in 5%, and pleuroparenchymal disease in 56%. Restrictive pulmonary function abnormalities were present in 25% of the workers, and obstructive abnormalities were present in 27%. Because the impairment of one of several organ systems (i.e., ventilatory, cardiac, pulmonary vascular, or peripheral circulatory) may limit exercise performance, we designed an exercise test score in an attempt to identify the system causing the limitation. No abnormal limitation was detec...

Blunted chemosensitivity has been found in successful endurance athletes and some high-altitude natives. This characteristic, however, may not be beneficial to climbers at extreme altitude, where a vigorous ventilatory response to hypoxia may be of value in enhancing alveolar and arterial oxygenation. We studied 14 climbers who had climbed to 7,470 m or higher, 10 age-matched controls, and 10 outstanding middle- and long-distance runners. The ventilatory response to progressive hypoxia was determined at a constant, normal end-tidal Pco2 over 8–12 min and to CO2 by rebreathing a 7% CO2 hyperoxic mixture (Read technique). The hypoxic response parameter of Weil, A was used to determine the hypoxic responses and S (delta VE/ delta PACO2) the hypercapnic response. Climbers had A values significantly higher than the runners (means +/- SE: 158.9 +/- 29.9 vs. 49.3 +/- 7.1, P less than 0.001) but not significantly higher than the controls (109.9 +/- 21.0). delta VE/ delta PACO2 of climbers was higher (3.0 +/- 0.4) than both controls (2.2 +/- 0.2, P less than 0.025) and runners (1.4 +/- 0.2, P less than 0.0005). These data suggest that successful climbers to extreme altitude may be selected by virtue of their vigorous respiratory responses to hypoxia to maintain adequate oxygenation in the presence of extreme environmental hypoxia.

Lungs of mongrel dogs with permanent tracheostomies and implanted systemic pulmonary arterial catheters were injured by intravenous infusion of oleic acid (0.09 mg/kg). Injury resulted in extensive, multifocal, and nonrandomly distributed lung damage. Awake dogs were studied during a control period and 1, 4, and 7 days following injection of oleic acid. Standard gas exchange measurements, the inert gas elimination technique, and subsegmental bronchoalveolar lavage (BAL) were used. Five oleic acid dogs and two saline control dogs were killed after each study period for morphological evaluation. Control dogs did not develop significant gas exchange abnormalities but did have localized inflammatory reactions at the lavage site. The oleic acid dogs developed significant shunt at day 1 with resolution of shunt by day 7. The multifocal sites of oleic acid injury were virtually identical in appearance at a given time interval; they consisted of alveolar cell necrosis with varying amounts of hemorrhagic inflammatory exudation at day 1 followed by a proliferative reparative reaction resulting in substantial restoration of alveolar structure at day 7. BAL showed a suppurative inflammatory response with hemorrhage on day 1 and an increased number of macrophages by day 7. The oleic acid model of acute diffuse lung injury demonstrates several pathophysiological alterations that could be compared with pathomorphological changes during the acute injury phase and during the subsequent reparative phase.