Biomedical subjects
R C Roach
Publications and source records attributed to R C Roach.
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.
Frontiers of hypoxia research: acute mountain sickness.
Traditionally, scientists and clinicians have explored peripheral physiological responses to acute hypoxia to explain the pathophysiological processes that lead to acute mountain sickness (AMS) and high-altitude cerebral edema (HACE). After more than 100 years of investigation, little is yet known about the fundamental causes of the headache and nausea that are the main symptoms of AMS. Thus, we review the evidence supporting a change in focus to the role of the central nervous system in AMS. Our justification is (i) that the symptoms of AMS and HACE are largely neurological, (ii) that HACE is considered to be the end-stage of severe AMS and was recently identified as a vasogenic edema, opening the door for a role for blood-brain barrier permeability in AMS, (iii) that new, non-invasive techniques make measurement of brain water levels and cerebral blood volume possible and (iv) that the available experimental evidence and theoretical arguments support a significant role for brain swelling in the pathophysiology of AMS. We believe that an examination of the responses of the central nervous system to acute hypoxia will reveal important new pathophysiological processes that may help explain AMS and HACE.
Oral contraceptives, exercise, and acute mountain sickness in women.
BACKGROUND: Previous research has found that exercise exacerbated acute mountain sickness (AMS) in men. PURPOSE: The current study tested this relationship in women taking oral contraceptives. METHODS: We studied seven women at 428 mmHg for 10 h; once while at rest (R) and once while performing intermittent exercise (EX). RESULTS: AMS scores had a slight increase at 9 vs. 0 h at altitude in both trials (p < 0.05). Resting measurements of ventilation (VE), arterial oxygen saturation (SPO2), end tidal O2 (PETO2), and end tidal CO2 (PETCO2) were not different over time or between trials (p > 0.05). While fluid intake did not change, urine output increased during the 0-3 h period, regardless of trial, and returned to baseline values by the 6-9 h period (218 +/- 37 vs. 121 +/- 22 ml x h(-1); p < 0.05). During exercise, SPO2 significantly dropped compared with similar time points in R (73.1 +/- 1.1 vs. 85.7 +/- 1.8%; p < 0.05). Despite exercise-induced desaturation, the AMS scores were not significantly different between R and EX. CONCLUSION: These results suggest that oral contraceptives may cause a compensation for the physiological responses to exercise critical for the development of AMS.
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.
Dynamic cerebral autoregulation at high altitude.
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Arterial O2 content and tension in regulation of cardiac output and leg blood flow during exercise in humans.
A universal O2 sensor presumes that compensation for impaired O2 delivery is triggered by low O2 tension, but in humans, comparisons of compensatory responses to altered arterial O2 content (CaO2) or tension (PaO2) have not been reported. To directly compare cardiac output (QTOT) and leg blood flow (LBF) responses to a range of CaO2 and PaO2, seven healthy young men were studied during two-legged knee extension exercise with control hemoglobin concentration ([Hb] = 144.4 +/- 4 g/l) and at least 1 wk later after isovolemic hemodilution ([Hb] = 115 +/- 2 g/l). On each study day, subjects exercised twice at 30 W and on to voluntary exhaustion with an FIO2 of 0.21 or 0.11. The interventions resulted in two conditions with matched CaO2 but markedly different PaO2 (hypoxia and anemia) and two conditions with matched PaO2 and different CaO2 (hypoxia and anemia + hypoxia). PaO2 varied from 46 +/- 3 Torr in hypoxia to 95 +/- 3 Torr (range 37 to >100) in anemia (P < 0.001), yet LBF at exercise was nearly identical. However, as CaO2 dropped from 190 +/- 5 ml/l in control to 132 +/- 2 ml/l in anemia + hypoxia (P < 0.001), QTOT and LBF at 30 W rose to 12.8 +/- 0.8 and 7.2 +/- 0.3 l/min, respectively, values 23 and 47% above control (P < 0.01). Thus regulation of QTOT, LBF, and arterial O2 delivery to contracting intact human skeletal muscle is dependent for signaling primarily on CaO2, not PaO2. This finding suggests that factors related to CaO2 or [Hb] may play an important role in the regulation of blood flow during exercise in humans.
The influence of PaO2, pH and SaO2 on maximal oxygen uptake.
Influence of arterial oxygen pressure (PaO2) and pH on haemoglobin saturation (SaO2) and in turn on O2 uptake (VO2) was evaluated during ergometer rowing (156, 276 and 376 W; VO2max, 5.0 L min-1; n = 11). During low intensity exercise, neither pH nor SaO2 were affected significantly. In response to the higher work intensities, ventilations (VE) of 129 +/- 10 and 155 +/- 8 L min-1 enhanced the end tidal PO2 (PETO2) to the same extent (117 +/- 2 mmHg), but PaO2 became reduced (from 102 +/- 2 to 78 +/- 2 and 81 +/- 3 mmHg, respectively). As pH decreased during maximal exercise (7.14 +/- 0.02 vs. 7.30 +/- 0.02), SaO2 also became lower (92.9 +/- 0.7 vs. 95.1 +/- 0.1%) and arterial O2 content (CaO2) was 202 +/- 3 mL L-1. An inspired O2 fraction (F1O2) of 0.30 (n = 8) did not affect VE, but increased PETO2 and PaO2 to 175 +/- 4 and 164 +/- 5 mmHg and the PETO2-PaO2 difference was reduced (21 +/- 4 vs. 36 +/- 4 mmHg). pH did not change when compared with normoxia and SaO2 remained within 1% of the level at rest in hyperoxia (99 +/- 0.1%). Thus, CaO2 and VO2max increased to 212 +/- 3 mL L-1 and 5.7 +/- 0.2 L min-1, respectively. The reduced PaO2 became of importance for SaO2 when a low pH inhibited the affinity of O2 to haemoglobin. An increased F1O2 reduced the gradient over the alveolar-arterial membrane, maintained haemoglobin saturation despite the reduction in pH and resulted in increases of the arterial oxygen content and uptake.
Skeletal muscle blood flow in humans and its regulation during exercise.
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 approximately 0.3 L min(-1) at rest and increases linearly with dynamical knee-extensor exercise as a function of the power output to 6-10 L min[-1] (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(-1) min(-1), i.e. approximately 100-fold elevation from rest. The onset of hyperaemia is very fast at the start of exercise with T 1/2 of 2-10 s related to the power output with the muscle pump bringing about the very first increase in blood flow. A steady level is reached within approximately 10-150 s of exercise. At all exercise intensities the blood flow fluctuates primarily due to the variation in intramuscular pressure, resulting in a phase shift with the pulse pressure as a superimposed minor influence. Among the many vasoactive compounds likely to contribute to the vasodilation after the first contraction adenosine is a primary candidate as it can be demonstrated to (1) cause a change in limb blood flow 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 flow 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 IIl-IV sensory nerves (the muscle reflex) 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 flow also to exercising muscles.
Arterial oxygen saturation for prediction of acute mountain sickness.
BACKGROUND: Acute mountain sickness (AMS) is a usually self-limiting syndrome encompassing headache, nausea and dizziness. AMS is seen in those that go from low to high altitudes too quickly, without allowing sufficient time to acclimatize. At present, susceptibility to AMS cannot be predicted. One feature of AMS noted in some studies is impaired gas exchange. If impaired gas exchange presages AMS then those individuals with exaggerated hypoxemia at high altitude may be more likely to develop AMS. If true, then monitoring of arterial oxygen saturation (SaO2%) may differentiate AMS-resistant individuals from those with impending AMS. METHODS: To test this hypothesis, we measured SaO2% and AMS symptom scores in 102 healthy asymptomatic climbers at 4200 m on Denali (Mt. McKinley) prior to their further ascent toward the summit at 6194 m, and on their return from higher altitudes to 4200 m. RESULTS: The results show that exaggerated hypoxemia in asymptomatic climbers prior to further ascent correlates with subsequent AMS (r = -0.48, p < 0.001). Criteria are presented for identification of 80-100% of those climbers who later become ill with AMS. CONCLUSION: We conclude that resting arterial hypoxemia is related to later development of clinical AMS, and can exclude the occurrence and caution those at risk for development of subsequent AMS. Likely mechanisms are hypoventilation relative to normally acclimatizing individuals and/or abnormalities of gas exchange. Thus, non-invasive oximetry provides a simple, specific indicator of inadequate acclimatization to high altitudes and impending AMS.
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.
Hypoxia and the cardiovascular response to dynamic knee-extensor exercise.
Hypoxia affects O2 transport and aerobic exercise capacity. In two previous studies, conflicting results have been reported regarding whether O2 delivery to the muscle is increased with hypoxia or whether there is a more efficient O2 extraction to allow for compensation of the decreased O2 availability at submaximal and maximal exercise. To reconcile this discrepancy, we measured limb blood flow (LBF), cardiac output, and O2 uptake during two-legged knee-extensor exercise in eight healthy young men. They completed studies at rest, at two submaximal workloads, and at peak effort under normoxia (inspired O2 fraction 0.21) and two levels of hypoxia (inspired O2 fractions 0.16 and 0.11). During submaximal exercise, LBF increased in hypoxia and compensated for the decrement in arterial O2 content. At peak effort, however, our subjects did not achieve a higher cardiac output or LBF. Thus O2 delivery was not maintained and peak power output and leg O2 uptake were reduced proportionately. These data are consistent then with the findings of an increased LBF to compensate for hypoxemia at submaximal exercise, but no such increase occurs at peak effort despite substantial cardiac capacity for an elevation in LBF.
Cardiovascular responses to dynamic exercise with acute anemia in humans.
We hypothesized that reducing arterial O2 content (CaO2) by lowering the hemoglobin concentration ([Hb]) would result in a higher blood flow, as observed with a low PO2, and maintenance of O2 delivery. Seven young healthy men were studied twice, at rest and during two-legged submaximal and peak dynamic knee extensor exercise in a control condition (mean control [Hb] 144 g/l) and after 1-1.5 liters of whole blood had been withdrawn and replaced with albumin [mean drop in [Hb] 29 g/l (range 19-38 g/l); low [Hb]]. Limb blood flow (LBF) was higher (P < 0.01) with low [Hb] during submaximal exercise (i.e., at 30 W, LBF was 2.5 +/- 0.1 and 3.0 +/- 0.1 l/min for control [Hb] and low [Hb], respectively; P < 0.01), resulting in a maintained O2 delivery and O2 uptake for a given workload. However, at peak exercise, LBF was unaltered (6.5 +/- 0.4 and 6.6 +/- 0.6 l/min for control [Hb] and low [Hb], respectively), which resulted in an 18% reduction in O2 delivery (P < 0.01). This occurred despite peak cardiac output in neither condition reaching >75% of maximal cardiac output (approximately 26 l/min). It is concluded that a low CaO2 induces an elevation in submaximal muscle blood flow and that O2 delivery to contracting muscles is tightly regulated.
Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia.
Acute mountain sickness (AMS) strikes those in the mountains who go too high too fast. Although AMS has been long assumed to be due solely to the hypoxia of high altitude, recent evidence suggests that hypobaria may also make a significant contribution to the pathophysiology of AMS. We studied nine healthy men exposed to simulated altitude, normobaric hypoxia, and normoxic hypobaria in an environmental chamber for 9 h on separate occasions. To simulate altitude, the barometric pressure was lowered to 432 +/- 2 (SE) mmHg (simulated terrestrial altitude 4,564 m). Normobaric hypoxia resulted from adding nitrogen to the chamber (maintained near normobaric conditions) to match the inspired PO2 of the altitude exposure. By lowering the barometric pressure and adding oxygen, we achieved normoxic hypobaria with the same inspired PO2 as in our laboratory at normal pressure. AMS symptom scores (average scores from 6 and 9 h of exposure) were higher during simulated altitude (3.7 +/- 0.8) compared with either normobaric hypoxia (2.0 +/- 0.8; P < 0.01) or normoxic hypobaria (0.4 +/- 0.2; P < 0.01). In conclusion, simulated altitude induces AMS to a greater extent than does either normobaric hypoxia or normoxic hypobaria, although normobaric hypoxia induced some AMS.
Acute ventilatory response to simulated altitude, normobaric hypoxia, and hypobaria.
BACKGROUND: Some reports claim that ventilation (VE) is greater in human subjects in normobaric hypoxia than at altitude following an equivalent drop in inspired PO2 (PIO2). It has been suggested that reduced barometric pressure (PB) may decrease chemoreceptor sensitivity and account for these results. In this pilot study we tested the hypothesis that VE and hypoxic chemoresponsiveness would not be different after 30 min of normobaric hypoxia and altitude. METHODS: We exposed three male and three female subjects to four conditions in an environmental chamber, varying the order. The four conditions were: air (PB = 640, FIO2 = 0.204), hypobaria (434, 0.298), hypoxia (640, 0.141) and altitude (434, 0.203). We measured VE, end-tidal O2 and CO2 and arterial O2 saturation (SpO2) after 30 min in each environment, and while breathing 100% O2 for 1 min immediately thereafter. RESULTS: The mean increase in VE relative to air was 14%, 20% and 26% for hypobaria, hypoxia and altitude, respectively, with corresponding reductions in PETCO2 in the three conditions. The reduction in VE with 100% O2 was inversely proportional to the rise in SpO2 in all cases, indicating that chemoresponsiveness was unchanged by PB. When hypobaria preceded altitude, the VE at altitude increased less, relative to air, than when altitude was given first (not significant). CONCLUSIONS: The VE and chemosensitivity are about the same after 30 min of altitude and equivalent hypoxia. However, when the drop in PIO2 is not synchronous with the drop in PB, like at altitude, the VE values may be altered. Air density, hypoxic pulmonary vasoconstriction and circulating microbubbles may interact to account for the observed findings.
Sea-level physical activity and acute mountain sickness at moderate altitude.
The effect of previous physical conditioning on young well-conditioned mountaineers in relationship to acquiring acute mountain sickness is controversial. Data show both increased and decreased effects on the incidence of altitude illness. How general tourists at moderate altitudes are affected is unknown. To determine the influence of sea-level habitual physical activity on the incidence of mountain sickness, we surveyed 205 participants in a scientific conference at 3,000 m (9,840 ft). A 36-item questionnaire was distributed to the subjects 48 hours after arrival at altitude. Their sea-level physical activity (SLPA) was measured by a published and validated instrument that included questions about patterns of work, sporting, and leisure-time activities. Acute mountain sickness was defined as the presence of 3 or more of the following symptoms: headache, dyspnea, anorexia, fatigue, insomnia, dizziness, or vomiting. Most of the respondents were male (62%) from sea level (89%) with a mean age of 36 +/- 8.7 (standard deviation) years (range, 22 to 65). Nearly all (94%) were nonsmokers, and 28% had acute mountain sickness. The mean SLPA score was 8.0 +/- 1.3 (range, 5.1 to 12.0). No statistically significant difference in mean SLPA scores was found between those with and without acute mountain sickness (8.1 versus 7.8), nor in the individual indices (work, 2.5 versus 2.4; sport, 2.9 versus 2.7; leisure, 2.8 versus 2.7). We conclude that habitual physical activity performed at sea level does not play a role in the development of altitude illness at moderate altitude in a general tourist group.
How well do older persons tolerate moderate altitude?
We studied the physiologic and clinical responses to moderate altitude in 97 older men and women (aged 59 to 83 years) over 5 days in Vail, Colorado, at an elevation of 2,500 m (8,200 ft). The incidence of acute mountain sickness was 16%, which is slightly lower than that reported for younger persons. The occurrence of symptoms of acute mountain sickness did not parallel arterial oxygen saturation or spirometric or blood pressure measurements. Chronic diseases were present in percentages typical for ambulatory elderly persons: 19 (20%) had coronary artery disease, 33 (34%) had hypertension, and 9 (9%) had lung disease. Despite this, no adverse signs or symptoms occurred in our subjects during their stay at this altitude. Our findings suggest that persons with preexisting, generally asymptomatic, cardiovascular or pulmonary disease can safely visit moderate altitudes.
Relationship between whole blood base excess and CO2 content in vivo.
Empirical relationships are demonstrated for whole blood base excess (BE) and CO2 content (CCO2), both calculated from in vivo measurements of PCO2, pH, hemoglobin concentration and O2 saturation. Comparisons are provided by measurements from three separate studies: (1) supine exercise (arterial and mixed venous samples); (2) chronic obstructive disease patients (arterial samples) breathing air and 100% O2; and (3) maximal seated exercise on a bicycle ergometer with and without added inspired CO2 (arterial samples before, during and after). Two standardized values of CCO2 (vol.%) are derived which closely relate to BE (mmol/l). The CCO2 at a PCO2 of 40 mmHG [CCO2(40)] for all samples (n = 220) demonstrated a curvilinear relationship: CCO2 (40) = 45.37 + 1.48(BE) + 0.0156(BE)2, r = + 0.996, SEE = 0.88 vol.%. The CCO2 at a pH of 7.4 [CCO2(7.4)] gave a linear relationship: CCO2(7.4) = 45.09 + 2.58(BE), r = + 0.998, SEE = 1.19 vol.%. Empirical computations for the Haldane factor from studies 1 and 2 gave values of 0.285 in terms of CCO2 (vol.%/vol.%) and 0.266 for BE (mmol/l/mmol reduced Hb). The BE values can serve as useful estimates of lactate concentrations during exercise and the excellent relationships between standardized CCO2 and BE demonstrate their equivalency and either can be utilized, depending on whether quantification of the CO2 dissociation curve or acid-base status is desired.