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The Hypoxia Hilton: recollections of a visit, with a postscript by J W Severinghaus on mechanisms of acute mountain sickness

J G Jones MD FRCP  

Woodlands, Rufforth, York YO2 3QF, UK

Correspondence to: Professor J G Jones E-mail: gareth{at}garjons.demon.co.uk

	INTRODUCTION

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
During a training fellowship thirty years ago at the Cardiovascular Research Institute (CVRI) in San Francisco, I joined an expedition led by Professor John Severinghaus. Its purpose was to study pulmonary complications of acute hypoxia after a one-day ascent, by helicopter and hike, from sea level to the summit of White Mountain, 14 246 feet (4342 m) above sea level¹, on the California—Nevada border.

Originally a physicist at the Massachusetts Institute of Technology, Severinghaus became a physician then chief of anaesthesia research in the University of California at CVRI. He invented the first reliable PO₂ and PCO₂ blood gas analysis systems, which are now used routinely in hospitals throughout the world. His research into the control of breathing, altitude physiology and oximetry continue to the present day. Before I joined the expedition he tested my ventilatory drive with a vital capacity breath of 15% CO₂ in nitrogen² (i.e. no oxygen). For what seemed like ages nothing happened. I gazed at the posters on the walls of his laboratory and continued to breathe normally into the spirometer. Then, suddenly, it was like the first huge breath that I experienced in an iron lung, but at 40 breaths per minute. The spirometer bell leapt out of the water. Severinghaus was expressionless. Then I lost consciousness.

	Acute exposure to altitude

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
The symptoms of hypoxia depend on its rate of onset, the partial pressure of oxygen, individual differences in susceptibility and adaptation. You can experience them for yourself by rebreathing through an anaesthetist's CO₂ absorber (but do not try this on your own). A mountaineering expedition is a more socially acceptable alternative although not entirely safe. If things go wrong you may experience acute mountain sickness, high altitude cerebral oedema, or high altitude pulmonary oedema³. Note that exercise, cold and particularly rapid ascent to altitude can precipitate these complications.

	To the High Sierras

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
At dawn on the first morning of the study we headed east out of San Francisco with a carload of volunteers, including two hitchhikers Severinghaus had picked up the week before and who had accepted free bed and breakfast for four days. We sped through Yosemite, high into the Sierra Nevada and down to the remote one-street ‘town’ of Lee Vining. This lay in the dazzling, volcanic, Pumice Valley, described by Mark Twain as ‘a lifeless, treeless, hideous desert’. A store in Lee Vining sold ‘Not tonite deer, deer repellent’. Few overseas tourists went there. This was a remote and ghostly country with the smell of gunfire and Clint Eastwood hiding behind every corner. We pressed on south to the University of California support base at Bishop, 4000 feet above sea level. Leaning against a tired looking hangar was a tandem welded together out of three old bicycles. Nearby were ex-army jeeps, tracked snow vehicles and one of the university's Hiller UH 12 helicopters. This machine, a type used in French Indo-China, was our transport to White Mountain. Its upward pointing exhausts meant that there were no worries about burning yourself to a crisp by landing in long grass. My nervous colleagues preferred the tandem. As the helicopter flew over serried rows of canyon ridges our oculovestibular systems were severely tested. The ground below seemed to fall away suddenly, giving the unhappy illusion that we were rocketing vertically upwards. Gusts sweeping up the canyons added to the effect. Shortly afterwards such gusts wrecked this machine as well as a subsequent helicopter and today these are long gone from Bishop.

	Barcroft laboratory to White Mountain summit

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
The summit of White Mountain was higher than our helicopter could fly. So after hovering over the 4500-year-old trees of the Bristlecone Pine Forest we were decanted at the desolate moonscape surrounding the Barcroft laboratory at 12 470 feet. Immediately we felt cold, dizzy and breathless on the slightest effort. We climbed the remaining 5 miles (8 km) with haversacks filled with rocks to increase the workload. Hours later and the last to arrive in darkness, I was at a nadir of physical fitness, coughing and gasping for breath, cold, nauseated and with head pounding. Death seemed close and, with the jeers from my companions ringing in my ears, I was carried the last few hundred yards to the vomit-spattered rocks of the summit. Severinghaus, chairman of the reception committee, stepped forward with an impedance device which he had developed for measuring pulmonary oedema⁴. This saucer-sized transducer was attached through electrolyte to the naked chest wall as soon as we arrived and gave each of us a short cracking electric shock as it was switched on.

	Summit hotel

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
At the summit was a rough stone hut, The Hypoxia Hilton, which provided laboratory and living quarters (Figure 1). Its slab roof and red shutters combined the architectural styles of a Riviera villa and a Maginot Line pillbox⁵. We were beginning our first night at altitude, shivering in our Colditz-style bunk beds; our arterial oxygen saturation (SaO₂) was 75%. That morning in San Francisco our SaO₂ had been > 95%. Outside it was freezing and there was a continuous roar from a petrol-engined generator needed to maintain the blood gas electrodes in the hut at 37°C. Almost everyone had Cheyne—Stokes breathing. Those lucky enough to sleep were awakened periodically by the snorting crescendos of hyperventilation; once you were awake, nausea and a pounding headache took over. During an apnoeic phase I thought that I had developed Ondine's curse⁶. In pitch darkness someone was climbing down the bunk beds and groping around on the lower levels. Then there was a soft hiss of gas. Propane? Lethal asphyxia? A match? A violent explosion? No, someone was giving him/herself a therapeutic fix from the emergency oxygen cylinder. Soon afterwards the generator stopped and there was a welcome silence. Immediately John Severinghaus, torch in hand, was off into the icy night to fix the engine. I thought of Captain Oates. No one else moved. Who knows how long he had been gone before the engine roared back into life. Recently I asked John why the engine had stopped. He could not remember the details but recalled ‘having to sit up for an hour and do Valsalvas to quell incipient pulmonary oedema’. Possibly while he changed the cylinder head gasket.

View larger version (130K): [in this window] [in a new window]   Figure 1. The Hypoxia Hilton on the summit of White Mountain, photographed from a glider

 

	Room with a view

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
Next morning, with profound anorexia, we staggered out of the hut. The slightest exertion left us gasping. Whichever way you looked the view was prefaced by dazzling rock and distant snow. Eastward, the glowing desert disappeared into a haze. Westward the panorama was pink, blue and white, the horizon being dominated by the snow capped façade of the Sierra Nevada⁵. Inside and outside the hut was a jumble of cables, oil drums, bunk beds, a centrifuge, kitchen utensils, blood gas electrodes, oil lanterns, an oscilloscope, gas cylinders, bag-in-box spirometers, syringes, a reflectance oximeter, data books and a barometer. There were no radios, telephones, TVs, computers, hard drugs or guitars. The bathroom, sans bath or shower, was a medieval garderobe.

The three days at the summit saw Severinghaus dashing about extracting our daily arterial blood samples (via a butterfly stab into the brachial artery without local anaesthetic), taking end-tidal gas samples and measuring our carbon monoxide diffusing capacity (Figure 2). In contrast, the experimental subjects, still with headache and nausea, and with added lethargy, exertional dyspnoea, tachycardia, dizziness and oliguria, slumped in the sun on mattresses scattered over the rocks on the 100 foot wide mountaintop. All we could do was look down into the parched Owens valley 10 000 feet below. We experimented to see if hyperventilation would reduce headache. It seemed to work. The headache and nausea were immediately relieved by the oxygen given as part of the diffusing capacity test. As far as the eye could see there was no sign of life. On the second day, to try to exacerbate symptoms, we scrambled 1 300 feet down from the summit and then staggered back to the hut. That certainly made things a lot worse. Afterwards most of us could only lie down as if stoned and enjoy the psychic bonding.

View larger version (112K): [in this window] [in a new window]   Figure 2. John Severinghaus, standing with alveolar gas sampling system

 

	Adaptation

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
We all had a fall in our lung diffusing capacity and pulmonary capillary blood volume, which explained the increase in the alveolar to arterial oxygen difference and confirmed Severinghaus' hypothesis. Suddenly, on the third day, adaptation was as abrupt as it was miraculous. All felt vastly better, symptoms disappeared and lung function began to return to normal. We were euphoric. The experiment was over, we seemed to be unscathed and it was time to leave our summit hotel (Figure 3).

View larger version (169K): [in this window] [in a new window]   Figure 3. The research group outside the Hypoxia Hilton. JWS back left, JGJ front right

 

	An update from Severinghaus

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 
Thirty years later the consequences of acute exposure to high altitude are extensively reviewed but still not fully explained³. I wrote to John Severinghaus to ask his opinion about mechanisms. He had celebrated his 80th birthday this year (2002) by completing another research project on the summit of White Mountain (see [www.wmrs.edu]), and offered the following postscript:

‘My bias is that headache is due to stretch of cerebral vasculature. It may come on in less than an hour of hypoxia and is probably due to water movement into brain cells. This is because they become hyperosmotic due to increased glycolysis without increased CO₂ production. All intermediates pile up due to the redox change with limited O₂ while O₂ consumption is forced to stay constant by the internal demands of the cells. Later high altitude cerebral edema gives more serious headache. I think angiogenesis, step 1, is to blame, that being the effect of vascular endothelial growth factor (VEGF) dissolving brain capillary basement membranes causing leak of plasma and red cells^7,8. Nausea is certainly ischemia and or hypoxia of the vomiting centers. This is probably in the area of the 4th ventricle and happens in seconds with the combination of sudden exertion and hypoxia which causes extreme vascular dilatation in muscles, reduced systemic blood pressure and, combined with hyperventilation, cuts cerebral blood flow.

As for high altitude pulmonary edema [HAPE], it is caused by pulmonary arterial hypertension without capillary hypertension⁹. I still believe, as I did 30+ years ago, that the elastic larger vessels overdistend, separating endothelial cell junctions and leaking water into perivascular spaces. Very hard to prove and almost no one believes it. John West believes HAPE is due to capillary stress failure, but there are no good data on getting capillary pressures high enough in man or in animals with HAPE.’

	REFERENCES

TOP INTRODUCTION Acute exposure to altitude To the High Sierras Barcroft laboratory to White... Summit hotel Room with a view Adaptation An update from Severinghaus REFERENCES

 

1. Weiskopf RB, Severinghaus JW. Diffusing capacity of the lung for CO in man during acute acclimation to 14 246 ft. J Appl Physiol 1972;32:285 -9[Free Full Text]

2. Gabel RA, Kronenberg RS, Severinghaus JW. Vital capacity breaths of 5% or 15% CO₂ in N₂ or O₂ to test carotid chemosensitivity. Resp Physiol1973; 17:195 -208[CrossRef][Medline]

3. Hornbein TF, Schoene RB. High altitude: an exploration of human adaptation. In: Lenfant C, ed. Lung Biology in Health and Disease. Vol. 161. New York: Marcel Dekker, 2001

4. Severinghaus JW. Electrical measurement of pulmonary edema with a focusing conductivity bridge. J Physiol1971; 215:53 -5

5. Fletcher C. The Thousand Mile Summer in Desert and High Sierra. Berkeley: Howell-North Books, 1964:141 -4

6. Severinghaus JW, Mitchell RA. Ondine's curse: failure of respiratory center automaticity while awake. Clin Res1962; 10:122

7. Severinghaus JW. Hypothetical roles of angiogenesis, osmotic swelling and ischemia in high altitude cerebral edema. J Appl Physiol 1995;79:375 -9[Abstract/Free Full Text]

8. Xu FP, Severinghaus JW. Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude cerebral edema. J Appl Physiol 1998;85:53 -7[Abstract/Free Full Text]

9. Jerome EH, Severinghaus JW. High altitude pulmonary edema [Editorial]. New Engl. J Med1996; 334:662 -3[Free Full Text]

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