Milton V. Icenogle

Body Temperature, Autonomic Responses, and Acute Mountain Sickness

A few studies have reported increased body temperature (T(o)) associated with acute mountain sickness (AMS), but these usually include exercise, varying environmental conditions over days, and pulmonary edema. We wished to determine whether T(o) would increase with AMS during early exposure to simulated altitude at rest. Ninety-four exposures of 51 men and women to reduced P(B) (423 mmHg = 16,000 ft = 4850 m) were carried out for 8 to 12 h. AMS was evaluated by LL and AMS-C scores near end of exposure, and T(o) was measured by oral digital thermometer before altitude and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude. Other measurements included ventilation, O(2) consumption and autonomic indicators of plasma catecholamines, HR, and HR variability. Average T(o) increased by 0.5 degrees F from A1 to A12 in all subjects (p < 0.001). Comparison between 16 subjects with lowest AMS scores (mean LL = 1.0, range = 0 to 2.5) and 16 other subjects with highest AMS scores (mean LL = 7.4, range = 5 to 11) demonstrated a transient decline in T(o) from A1 to A6 in AMS, in contrast to a rise in non-AMS (p = 0.001). Catecholamines, HR, and HR variability (increased low F/high F ratio) indicated significant elevation of sympathetic activity in AMS, where T(o) fell, but no change in metabolic rate. The apparently greater heat loss during early AMS suggests increased hypoxic vasodilation in spite of enhanced sympathetic drive. Greater hypoxic vasodilation and elevated HR in AMS in the absence of other changes suggest that augmentation of beta-adrenergic tone may be involved in early AMS pathophysiology.

Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria

To investigate the possible effect of hypobaria on ventilation (VE) at high altitude, we exposed nine men to three conditions for 10 h in a chamber on separate occasions at least 1 week apart. These three conditions were: altitude (PB = 432, FIO2 = 0.207), normobaric hypoxia (PB = 614, FIO2 = 0.142) and normoxic hypobaria (PB = 434, FIO2 = 0.296). In addition, post-test measurements were made 2 h after returning to ambient conditions at normobaric normoxia (PB = 636, FIO2 = 0.204). In the first hour of exposure VE was increased similarly by altitude and normobaric hypoxia. The was 38% above post-test values and end-tidal CO2 (PET(CO2) was lower by 4 mmHg. After 3, 6 and 9 h, the average VE in normobaric hypoxia was 26% higher than at altitude (p < 0.01), resulting primarily from a decline in VE at altitude. The difference between altitude and normobaric hypoxia was greatest at 3 h (+ 39%). In spite of the higher VE during normobaric hypoxia, the PET(CO2) was higher than at altitude. Changes in VE and PET(CO2) in normoxic hypobaria were minimal relative to normobaric normoxia post-test measurements. One possible explanation for the lower VE at altitude is that CO2 elimination is relatively less at altitude because of a reduction in inspired gas density compared to normobaric hypoxia; this may reduce the work of breathing or alveolar deadspace. The greater VE during the first hour at altitude, relative to subsequent measurements, may be related to the appearance of microbubbles in the pulmonary circulation acting to transiently worsen matching. Results indicate that hypobaria per se effects ventilation under altitude conditions.

Ventilation is greater in women than men, but the increase during acute altitude hypoxia is the same

We wished to determine whether the previously reported lower arterial or alveolar P(CO2) in women than men, and in luteal (LUT) compared with follicular (FOL) menstrual cycle phase would persist during normal oral contraceptive use and during early altitude exposure. Ventilation and blood gases were measured at baseline (636 mmHg approximately 5400 ft, 1650 m) and during simulated altitude at 426 mmHg ( approximately 16000 ft, 4880 m), after 1 h (A1) and during the 12th h (A12), in 18 men (once) and in 19 women twice, during LUT and FOL and in 20 women twice while on placebo (PLA) or highest progestin dose (PIL) oral contraceptives. At baseline, Pa(CO2) was significantly higher in men than all women by 3.3 mmHg. When progesterone-progestin (PRO) was elevated in women, Pa(CO2) was significantly lower than in FOL and PLA, but the latter were still significantly lower than men. At altitude the P(CO2) differences between men and women and PRO levels persisted, with PA(CO2) falling by 3.6 and 7.3 mmHg at A1 and A12 in all, indicating an equivalent increase in alveolar ventilation. The mean arterial-end tidal P(CO2) difference was never >2 mmHg in the groups, indicating no VA/Q mismatch related to gender, PRO levels or altitude. All women had higher breathing frequency than men, resulting in greater deadspace ventilation. At altitude, the mean Pa(O2) was approximately 44 mmHg (Sa(O2) approximately 79%) for all, indicating equivalent oxygenation, but alveolar-arterial P(O2) differences were greater in women than men and higher when PRO was elevated. These results show that, relative to men, women have a compensated respiratory alkalosis, accentuated with elevated PRO. However, the ventilation response to acute altitude is the same in women and men.

Temporal inhomogeneity in brachial artery blood flow during forearm exercise

The purpose of this study was to measure the influences of muscle contraction and exercise intensity on brachial artery blood flow during incremental forearm wrist flexion exercise to fatigue. Twelve subjects performed incremental forearm exercise (increments of 0.1 W every 5 min) with their nondominant arms. Doppler waveforms and two-dimensional images of the brachial artery were recorded during the last 2 min of each stage. Exercise intensities were expressed as a percent of the maximal workload achieved (%WLmax). Blood flow was calculated during each of the concentric (CP), eccentric (EP), and recovery phases (RP) of the contraction cycle. Blood flow during the CP of the contraction did not increase above resting values (25.0 +/- 10.5 mL.min-1) at any intensity (100%WLmax = 21.6 +/- 6.5 mL.min-1). Conversely, blood flow during the EP and RP increased from 25.6 +/- 3.0 to 169.1 +/- 12.8 (P < 0.05), and from 24.7 +/- 3.1 to 137.9 +/- 19.5 mL.min-1 (P < 0.05), respectively from rest to maximal exercise. Time averaged blood flow increased linearly from rest to maximal exercise (75.3 +/- 26.3 to 334.6 +/- 141.6 mL.min-1, P < 0.05). Thus, a significant impairment in blood flow occurs with concentric contractions during forearm dynamic exercise. The implications of a temporal disparity in blood flow to oxygen delivery and skeletal metabolism during exercise are discussed.

Hypoxemia and acute mountain sickness: which comes first?

Hypoxemia is usually associated with acute mountain sickness (AMS), but most studies have varied in time and magnitude of altitude exposure, exercise, diet, environmental conditions, and severity of pulmonary edema. We wished to determine whether hypoxemia occurred early in subjects who developed subsequent AMS while resting at a simulated altitude of 426 mmHg (approximately 16,000 ft or 4880 m). Exposures of 51 men and women were carried out for 8 to 12 h. AMS was determined by Lake Louise (LL) and AMS-C scores near the end of exposure, with spirometry and gas exchange measured the day before (C) and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude and arterial blood at C, A1, and A12. Responses of 16 subjects having the lowest AMS scores (nonAMS: mean LL=1.0, range=0-2.5) were compared with the 16 having the highest scores (+AMS: mean LL=7.4, range=5-11). Total and alveolar ventilation responses to altitude were not different between groups. +AMS had significantly lower PaO2 (4.6 mmHg) and SaO2 (4.8%) at A1 and 3.3 mmHg and 3.1% at A12. Spirometry changes were similar at A1, but at A6 and A12 reduced vital capacity (VC) and increased breathing frequency suggested interstitial pulmonary edema in +AMS. The early hypoxemia in +AMS appears to be the result of diffusion impairment or venous admixture, perhaps due to a unique autonomic response affecting pulmonary perfusion. Early hypoxemia may be useful to predict AMS susceptibility.

Validation of a two-compartment model of ventilation/perfusion distribution

Ventilation (V (A)) to perfusion (Q ) heterogeneity (V (A)/Q ) analyses by a two-compartment lung model (2C), utilizing routine gas exchange measurements and a computer solution to account for O(2) and CO(2) measurements, were compared with multiple inert gas elimination technique (MIGET) analyses and a multi-compartment (MC) model. The 2C and MC estimates of V (A)/Q mismatch were obtained in 10 healthy subjects, 43 patients having chronic obstructive pulmonary disease (COPD) and in 14 dog experiments where hemodynamics and acid-base status were manipulated with gas mixtures, fluid loading and tilt-table stressors. MIGET comparisons with 2C were made on 6 patients and 32 measurements in healthy subjects before and after exercise at normoxia and altitude hypoxia. Statistically significant correlations for logarithmic standard deviations of V (A)/Q distributions (SD(V (A)/Q )) were obtained for all 2C comparisons, with similar values between 2C and both other methods in the 1.1-1.5 range, compatible with mild to moderate COPD. 2C tended to overestimate MC and MIGET values at low and underestimate them at high SD(V (A)/Q ) values. SD(V (A)/Q ) weighted by Q agreed better with MC and MIGET estimates in the normal range, whereas SD(V (A)/Q ) weighted by V (A) was closer to MC at higher values because the V (A)-weighted SD(V (A)/Q ) is related to blood-to-gas PCO(2) differences that are elevated in disease, thereby allowing better discrimination. The 2C model accurately described functional V (A)/Q characteristics in 26 normal and bronchoconstricted dogs during non-steady state rebreathing and could be used to quantify the effect of reduced O(2) diffusing capacity in diseased lungs. These comparisons indicate that 2C adequately describes V (A)/Q mismatch and can be useful in clinical or experimental situations where other techniques are not feasible.

Effects of ischemic training on leg exercise endurance

This study tested whether ischemic exercise training (Tr(IS+EX)) would increase endurance of ischemic (Ex(IS)) and ramp exercise (Ex(RA)) knee-extension tests more than exercise training (Tr(EX)) alone. Ten healthy subjects performed pre- and posttraining tests with each leg. For Ex(RA), after subjects warmed up, a weight was added each minute until they were exhausted. Ex(IS) was similar, but after warm-up, we inflated a thigh cuff to 150 mmHg instead of adding weights. One leg was chosen for Tr(IS+EX) (cuff inflated to 150 mmHg during exercise) and the other for Tr(EX), both with a small weight on each leg, four to six times per daily session for 3 to 5 min each, 5 days per week for 6 weeks. Ex(IS) duration increased 120% more (p = 0.002) in the Tr(IS+EX) leg than in the contralateral Tr(EX) leg, whereas Ex(RA) duration increased only 16% (nonsignificant). Tr(IS+EX )and Tr(EX) significantly attenuated the ventilation increase (ergoreflex) during Ex(IS). TheO(2) debt for Ex(IS )was significantly lower and systolic blood pressure recovery was faster after Tr(IS+EX) than after Tr(EX). Heart rate recovery after Ex(RA )andEx(IS )was faster after Tr(IS+EX). Apparently, Tr(IS+EX) with low-intensity resistance increases exercise endurance and attenuates the ergoreflex and therefore may be a useful tool to increase regional muscle endurance to improve systemic exercise capacity in patients.

Effects of acute leg ischemia during cycling on oxygen and carbon dioxide stores

This study estimated changes in whole body oxygen stores (O(2)s) and carbon dioxide stores (CO(2)s) during steady state exercise with leg ischemia induced by leg cuff inflation. Six physically fit subjects performed 75 W steady state exercise for 15 min on a cycle ergometer. After 5 min of exercise, cuffs on the upper and lower legs were inflated to 140 mmHg. Cuffs were deflated after 5 min and exercise continued for another 5 min. O(2 )uptake (VO(2)) and CO(2) output (VCO(2)) significantly increased during the first 30 s after inflation, significantly decreased between 60 and 90 s, and then rose linearly until deflation. VO(2) and VCO(2) significantly increased further after cuff deflation, peaking between 30 and 60 s and then returned to near baseline exercise levels. Model-estimated changes in total O(2)s and CO(2)s were compared with time-integrated store changes from VO(2) and VCO(2). During 5 min after cuff deflation, VO(2) and VCO(2) exceeded the model-estimated change in stores by 273 and 697 mL, respectively. These results reflect the O(2) cost repayment of the anaerobic component and lactate buffering to neutralize circulating metabolites caused by the preceding ischemia.

Resolution of exercise intolerance secondary to ischemic sinus node dysfunction following percutaneous transluminal angioplasty

We report on a case of significant exertional symptoms secondary to occlusion of a nondominant right coronary artery proximal to the sino-atrial branch, with associated exercise-induced sinus node dysfunction. Successful angioplasty of the occluded right coronary artery restored a normal functional capacity and sinus tachycardia response to exercise.

EXERCISE EXACERBATES ACUTE MOUNTAIN SICKNESS AT SIMULATED HIGH ALTITUDE.

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 = 429 Torr, approximately 4,800 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 (VE), 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 +/- 1.0 and 1.3 +/- 0.4 in Ex and Sed, respectively (P < 0.01); but resting VE and Sa(O(2)) were not different between trials. However, Sa(O(2)) during the exercise bouts in Ex was at 76.3 +/- 1.7%, lower than during either Sed or at rest in Ex (81.4 +/- 1.8 and 82.2 +/- 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 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.