Relationship of hypoxic ventilatory response to exercise performance ...

Relationship of hypoxic ventilatory response to exercise performance on Mount Everest R. B. SCHOENE, S. LAHIRI, P. H. HACKETT, R. M. PETERS, JR., J. S. MILLEDGE, C. J. PIZZO, F. H. SARNQUIST, S. J. BOYER, D. J. GRABER, K. H. MARET, AND J. B. WEST American Medical Research Expedition to Everest and Division of Respiratory Diseases, Department of Medicine, University of Washington, Seattle, Washington 98104

SCHOENE, R.B.,S. LAHIRI, P.H. HACKETT,R.M. PETERS, JR., J. S. MILLEDGE, C. J. PIZZO, F. H. SARNQUIST,S. J. BOYER,D. ~.GRABER, K. H. MARET, ANDJ.B. W~s~.Relationshipof hypoxic ventilatory responseto exerciseperformance on Mount Everest. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 56(6): 14’78-1483,1984.-At very high altitude, exerciseperformancein the human sojournermay dependon a sufficient hypoxic ventilatory response(HVR). To study the relationship of HVR to exerciseperformance at high altitude, we studied HVR at sealevel and 5,400 m and exerciseventilation at sealevel, 5,400m, and 6,300 m in nine membersof the American Medical ResearchExpedition to Everest. The relationship of HVR between individuals was maintained when HVR wasrepeatedafter acclimatization to 5,400m (P C 0.05). There wasa significant correlation in all subjectsbetweenHVR and ventilatory equivalent during exercise at sea level (r = 0.704,P < 0.05). Subjectswere then groupedinto high (H) and low (L) HVR responders(ventilation increaseto end-tidal Paz of 40 Torr = 21.2 k 5.4 and 5.6 t 0.9 1.min, respectively. At low and moderatelevelsof exercise,ventilation at sealevel and after acclimatization to 6,300 m was higher in the high HVR group. At 6,300 m blood O2saturation (Sh,%) decreasedfrom rest to maximum exercise: H = 8.3 t 1.8%, L = 20.0 t 2.5% (P < 0.01). HVR correlated inversely in all subjectswith the decreasein S&, from rest to maximum exercise (P < 0.05). Climbers with the highest HVR values reached and slept at higher altitudes. We concludethat 1) the relative value of HVR in our group of climbers was not significantly altered after acclimatization; 2) HVR predicts exercise ventilation at sea level and high altitude; 3) the drop in Sao,% that occurs with exerciseis inversely related to HVR; and 4) sojournerswith high HVR may perform better at extreme altitude. high altitude; chemosensitivity; ventilatory drives ACUTE EXPOSURE to the hypoxic

environment of high altitude results in an increase in ventilation (1,4, 11, 13, 21, 31), as a result of which alveolar, arterial, and subsequently tissue oxygenation is raised to a level higher than are otherwise would be without the increased ventilatory response. This hypoxic ventilatory response (HVR) is mediated by peripheral chemosensory input (25) and is dependent on the individual’s hypoxic chemosensitivity. In acute and prolonged hypoxia, this response increases over l-2 wk and continues despite a measurable arterial and cerebrospinal fluid alkalosis (8, 11, 12, 34). Brain intracellular fluid in dogs (29) and 1478

interstitial fluid in goats (lo), however, have been found to be acid during hypoxic exposure, probably secondary to increased lactate production. This increased hydrogen ion concentration in the brain may play an important role in the stimulation of ventilation during altitude acclimatization, but the mechanism is not fully understood. With increasing altitude and increasing hypoxic stimulus, ventilation increases (30). A brisk ventilatory response to high altitude hypoxia among sojourners from sea level may be advantageous for performance because it tends to minimize the drop in arterial oxygenation despite falling ambient partial pressure. The hypothesis is consistent with the theoretical considerations discussed by West and Wagner (42) and Schoene (32). The American Medical Research Expedition to Everest (AMREE) in 1981 afforded the opportunity to study the relationship between HVR and exercise performance among sojourning members of the expedition. The results support the contention that individuals with high HVR manifest high ventilation during hypoxic exercise and consequently may perform better than those individuals with lower hypoxic ventilatory drives. METHODS Subjects

Subjects were members of AMREE, all of whom were healthy nonsmokers who lived at an altitude of less than 1,900 m. Their anthropometric data have been given previously (39). All gave informed consent. Sea-Level Studies

These studies (performed at PB N 750 Torr) were carried out both at the University of Washington Pulmonary Function Laboratory in Seattle and the University of California, San Diego Respiratory Physiology Laboratories in La Jolla. In Seattle, HVR was measured in eight members by the method of progressive isocapnic hypoxia (38) as previously described (33). HVR was characterized by the increase in ventilation from normoxia to an end-tidal 02 partial pressure -40 Torr, referred to in the RESULTS as \jE*o. The higher value of vEdO indicated a greater vigor of HVR. Subjects were 0161-7567/84 $1.50 Copyright 0 1984 the AmericanPhysiological Society

HYPOXIC

DRIVES

AND

EXERCISE

AT

HIGH

tested in a resting fasting state in the supine position. End-tidal O2 and CO2 partial pressures were measured with a mass spectrometer, 02 saturation by an ear oximeter, and ventilation with a pneumotachograph. All variables were recorded on a multiple-channel recorder. Exercise tests were conducted in La Jolla in May 1981 prior to the expedition. The protocol was the same as that used subsequently on Mt. Everest at 6,300 m. A belted resistance bicycle ergometer, calibrated before each test, was used (30). After a warm-up period of 10 min at 300 kpm/min, measurements were made at that level and then 5 min at work load increments of 300 kpm/min until exhaustion. The collection system for the expired gas consisted of a low-resistance valve (Koegel, San Antonio, TX) and a circuit of large bore (3.8 cm) plastic tubing (39). Expired gas was collected in meteorological balloons during the last minute (last 2 min for 300-kpm/min load), and the volume was measured by a dry gas meter (Singer) and corrected to BTPS. O2 and COZ concentrations were analyzed, respectively, by polarographic 02 and infrared COn analyzers (Beckman) which were calibrated frequently with dry gases of known concentrations. An electrocardiogram was continuously recorded (Lumiscope), as was arterial O2 saturation (ear oximeter, Hewlett-Packard). These values were displayed on a strip-chart recorder (Gould model 222). High-Altitude

1479

ALTITUDE

Studies

Base camp (5,400 m). After a 3.5wk trek to Base Camp [PB = 400 Torr, from West et al. (39)] and a further 5to lo-day stay at that altitude, HVR was measured with a modified Dejour’s transient Nz and 02 test. Subjects were seated in a chair in the Base Camp laboratory and breathed through a two- -way valve with noseclips in place. A cardboard shield was placed in front of the subjects to make them unaware of changes in the inspired gases. O2 saturation was monitored by an ear oximeter, ventilation by a pneumotachograph calibrated with l-liter syringe, and end-tidal O2 and CO2 by analyzers (Beckman). All variables were recorded on strip-chart recorders. In steady state, one to four breaths of N2 or 02 we re given surreptitiously. Tests were repeated 6 to 12 times on each subject. In a given series of trials, maximal ventilation wa plotted against each minimal O2 saturation after the N 2 tests, and each minimal ventilation against each maximal saturation was plotted after 02 administration. Slope [change in inspired minute ventilation/blood 02 saturation (AVr/Saoz%)] of the response was used as HVR. This technique has been previously described (9). 6,300 m. Exercise studies were performed in the laboratory (temp = 8-20°C) at 6,300 m [PB N 350 Torr, from West et al. (39)] after 4-7 wk of further altitude exposure above 5,400 m. Subjects spent most of that time at 6,300 m. A similar exercise protocol described in the previous section was utilized. In addition, the oximeter was calibrated against six arterial blood samples from three subjects. Three of these samples were taken in steady state while subjects inhaled a gas of low O2 concentration. These results have been previously reported (39) and indicate that there was an accurate correlation between

the measured arterial blood and the oximeter reading down to 35-40%. Below that range the reading was lower than the actual Sao,%. The lowest Sao,% found during the exercise tests breathing ambient air was above 35% and hence adequate for the present study. Statistical

Analysis

The Kendall rank correlation test (17) was used to compare HVR values within individuals at sea level and Base Camp. The unpaired Student’s t test was used to compare O2 desaturation with exercise and climbing performance of the groups of high (H) and low (L) responders. To test the hypothesis that HVR is related to exercise ventilation and 02 desaturation, correlation coefficients were calculated between HVR and ventilatory equivalents [expired minute ventilation (VE) and O2 uptake (VOW), (vE/v02)] as well as Sao,%. When significant correlations were found, the relationship was further characterized by dividing the subjects into two groups of H and L HVR responders based on an observed difference of sea level HVR values between subjects (CK, CP, PH, DJ vs. St, FS, JE, RS, JL) (Table I). O2 saturation and vE/v02 in the groups of H and L responders were plotted against work loads, and a two-way analysis of variance with multiple factors and repeated measures with a Tukey’s post hoc test was used to examine the differences in the responses of the two groups. P c 0.05 was considered significant. RESULTS Resting Hypoxic Drives

Values of HVR for sea level and 5,400 m are given in Table 1 as ACERBand AVI/ASao,%, respectively. The TABLE 1. Summary of hypoxic ventilatory response and climbing

Subj

Sea Level HVR %,,,, 1. min-’

5,400 m HVR* irE, 1. min-’ S&%-’

CK CP PH DJ

33.9 26.6 12.7 11.7

0.8 0.75 0.7 0.6

Highest Sleeping Altitude on AMREE, m

Highest Climbing Altitude on AMREE, m

8,050 8,050

8,848

High

.s

Mean

k SE

SB FS JE RS JL Mean

t SE

21.2k5.4 7.1 7.0 4.9 3.2 5.6k0.93

0.7t0.04 1.0

0.55 0.15 0.22 0.17 0.5Iko.17

8,050 8,050 8,050+200 7,500 7,250 7,250 6,300 7,500 7,160*222’f

8,848 8,848 8,050 8,649+200 8,050 8,050 7,250 7,250 7,700 7,660*179t

1480

SCHOENE

ET

AL.

Altitude - 6300 meters

A Altitude - sea level Workload - 600 KPM* min-l

Barometric pressure-350 Workload-600 KPM=min”

mmHg

FIG. 1. Correlation of hypoxic ventilatory response (.HVR) with ventilatory equivalent [VE(~ . min-‘)/ Voz(l. min-‘)I at moderate work load (600 kpm . min-‘) is demonstrated at sea level. (A) and 6,300 m (B). Correlation at sea level is statistically significant (P < 0.05) while at 6,300 m relationship reached only borderline significance (P c 0.1).

r=0.46

p40.1 25 1

00 0

0 10

20

30

HVR A$40(&min-‘)

1

0

1

I

10

20

I

30

HVR

A \;rE40 (.& min-‘1

Kendall rank correlation test was used and found a significant correlation between HVR at sea level and 5,400 m (P < 0.05), indicating that after altitude exposure and acclimatization, individuals maintain their same relative values for HVR. All but one subject (JL) was included in the comparison of sea level and 5,400 m HVR, because he was not tested before the high-altitude trip.

Sea level Barometric

pressure

-755

mm Hg

FI02 -0.209

p