Breathing and brain blood flow during sleep in patients with chronic mountain sickness.

Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2) during sleep compared with healthy high-altitude residents, but whether nocturnal arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11 healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P < 0.05) because of more frequent apnea and hypoventilation episodes and longer duration of all types of episodes. SDB and unexplained arterial O2 desaturation caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the CMS patients spent 29%, whereas the other groups spent < 4%, of the night at values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity during wakefulness was similar in CMS patients and CMS controls despite higher end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB, internal carotid flow velocity increased in CMS controls but did not change in the CMS patients such that values were lower in the CMS patients than in CMS controls at the end and after SDB episodes. We concluded that SDB and episodes of unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a lack of compensatory increase in internal carotid artery flow velocity, likely decreased brain O2 delivery in CMS patients during a considerable portion of the night.

Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m).

Cerebral blood flow increases with acute exposure to high altitude, but the effect of hypoxia on the cerebral circulation at rest and during exercise appears influenced by the duration of high-altitude exposure. To determine whether internal carotid artery flow velocity increased with exercise in long-term residents of high altitude and whether resting values and the response to exercise differed in lifelong vs. acclimatized newcomer male residents of high altitude, we studied 15 native Tibetan and 11 Han ("Chinese") 6 +/- 2-yr residents of Lhasa (3,658 m), Tibet Autonomous Region, China. Noninvasive Doppler ultrasound was used to measure internal carotid artery diameter, mean flow velocity, and, in combination, hemoglobin and arterial O2 saturation to assess cerebral O2 delivery. Tibetan and Han groups were similar in body size and resting internal carotid artery diameter, blood pressure, hemoglobin concentration, internal carotid artery mean flow velocity, and calculated cerebral O2 delivery. Submaximal exercise increased internal carotid artery mean flow velocity and cerebral O2 delivery in the Tibetan and Han subjects. At peak exercise, the Tibetans sustained the increase in flow velocity and cerebral O2 delivery, whereas the Hans did not. Across all exercise levels up to and including peak effort, the Tibetans demonstrated a greater increase in internal carotid artery flow velocity and cerebral O2 delivery relative to resting values than did the Hans. The greater cerebral O2 delivery was accompanied by increased peak exercise capacity in the Tibetan compared with the Han group. Our findings suggest that the cerebral blood flow response to exercise is maintained in Tibetan lifelong residents of high altitude.

Rapid onset of hypoxic vasoconstriction in isolated lungs.

A fast-response O2 analyzer that samples air at low flow rates allows the quasi-instantaneous measurement of O2 concentration change in the airways of isolated blood-perfused rat lungs. This instrument and an oximeter were used to measure the stimulus-response delay time of hypoxic pulmonary vasoconstriction when the lungs were challenged with 10, 5, or 3% O2. The estimate for the shortest delay time between accomplished fall in airway O2 concentration and the onset of hypoxia-induced vasoconstriction was approximately 7 s. We found that the slope of pressure rise, but not the stimulus-response delay time, correlated with the magnitude of hypoxic vasoconstriction. Oscillations in pulmonary arterial pressure were observed when the lungs were challenged with 10% O2 but not when the challenge was 12, 5, or 3%, indicating perhaps that these oscillations were a threshold phenomenon. Established hypoxic vasoconstriction was sensitive to brief changes in airway O2 concentration. Vasodilation occurred when the gas mixture was switched from 3 to 21% O2 for two to five breaths, and vasoconstriction occurred when the gas was changed during a single breath from 5 to 3% O2.

Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m.

Cerebral blood flow and O2 delivery during exercise are important for well-being at altitude but have not been studied. We expected flow to increase on arrival at altitude and then to fall as O2 saturation and hemoglobin increased, thereby maintaining cerebral O2 delivery. We used Doppler ultrasound to measure internal carotid artery flow velocity at sea level and on Pikes Peak, CO (4,300 m). In an initial study (1987, n = 7 men) done to determine the effect of brief (5-min) exercises of increasing intensity, we found at sea level that velocity [24.8 +/- 1.4 (SE) cm/s rest] increased by 15 +/- 7, 30 +/- 6, and 22 +/- 8% for cycle exercises at 33, 71, and 96% of maximal O2 uptake, respectively. During acute hypobaric hypoxia in a decompression chamber (inspired PO2 = 83 Torr), velocity (23.2 +/- 1.4 cm/s rest) increased by 33 +/- 6, 20 +/- 5, and 17 +/- 9% for exercises at 45, 72, and 98% of maximal O2 uptake, respectively. After 18 days on Pikes Peak (inspired PO2 = 87 Torr), velocity (26.6 +/- 1.5 cm/s rest) did not increase with exercise. A subsequent study (1988, n = 7 men) of the effect of prolonged exercise (45 min at approximately 100 W) found at sea level that velocity (24.8 +/- 1.7 cm/s rest) increased by 22 +/- 6, 13 +/- 5, 17 +/- 4, and 12 +/- 3% at 5, 15, 30, and 45 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Venous occlusion plethysmography reduces arterial diameter and flow velocity.

The measurement of peripheral blood flow by plethysmography assumes that the cuff pressure required for venous occlusion does not decrease arterial inflow. However, studies in five normal subjects suggested that calf blood flow measured with a plethysmograph was less than arterial inflow calculated from Doppler velocity measurements. We hypothesized that the pressure required for venous occlusion may have decreased arterial velocity. Further studies revealed that systolic diameter of the superficial femoral artery under a thigh cuff decreased from 7.7 +/- 0.4 to 5.6 +/- 0.7 mm (P less than 0.05) when the inflation pressure was increased from 0 to 40 mmHg. Cuff inflation to 40 mmHg also reduced mean velocity 38% in the common femoral artery and 47% in the popliteal artery. Inflation of a cuff on the arm reduced mean velocity in the radial artery 22% at 20 mmHg, 26% at 40 mmHg, and 33% at 60 mmHg. We conclude that inflation of a cuff on an extremity to low pressures for venous occlusion also caused a reduction in arterial diameter and flow velocity.

Usual clinical dose of acetazolamide does not alter cerebral blood flow velocity.

Prior reports indicate that acetazolamide, an inhibitor of carbonic anhydrase, in moderate doses reduces symptoms of acute mountain sickness, and in large doses increases cerebral blood flow. The effect on flow is not known for a moderate dose, but were flow to increase, then increased cerebral oxygen delivery would be one mechanism of benefit from acetazolamide at high altitude. We utilized Doppler ultrasound in 8 volunteers to determine whether a usual acetazolamide dose (250 mg three times daily) would increase flow velocities in internal carotid and vertebral arteries. Acetazolamide during normoxia decreased pHa, PaCO2, and PETCO2, but baseline flow velocity remained unchanged. In 2 subjects without acetazolamide, voluntary hyperventilation decreased both PETCO2 and flow velocity. Both hypoxia and hypercapnia caused increases in arterial velocities. The increases were not altered by acetazolamide administration. In one subject, 1 g acetazolamide by acute i.v. injection induced an increase in flow velocity (40%) concomitant with a 5 mm Hg decrease in PETCO2, confirming prior reports using similar intravenous dose. In doses employed for prevention of acute mountain sickness, acetazolamide induced metabolic acidosis and may have prevented the fall in velocity usually associated with hypocapnia, but it neither increased baseline cerebral blood flow velocity nor velocity responses to hypoxia and hypercapnia. Benefit of acetazolamide at high altitude may relate to mechanisms other than increased cerebral blood flow.

Internal carotid and vertebral arterial flow velocity in men at high altitude.

Cerebral blood flow increases at high altitude, but the mechanism of the increase and its role in adaptation to high altitude are unclear. We hypothesized that the hypoxemia at high altitude would increase cerebral blood flow, which would in turn defend O2 delivery to the brain. Noninvasive Doppler ultrasound was used to measure the flow velocities in the internal carotid and the vertebral arteries in six healthy male subjects. Within 2-4 h of arrival on Pikes Peak (4,300 m), velocities in both arteries were slightly and not significantly increased above sea-level values. By 18-44 h a peak increase of 20% was observed (combined P less than 0.025). Subsequently (days 4-12) velocities declined to values similar to those at sea level. At altitude the lowest arterial O2 saturation (SaO2) and the highest end-tidal PCO2 was observed on arrival. By day 4 and thereafter, when the flow velocities had returned toward sea-level values, hemoglobin concentration and SaO2 were increased over initial high-altitude values such that calculated O2 transport values were even higher than those at sea level. Although the cause of the failure for cerebral flow velocity to increase on arrival is not understood, the subsequent increase may act to defend brain O2 transport. With further increase in hemoglobin and SaO2 over time at high altitude, flow velocity returned to sea-level values.

Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness.

Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2's than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude.

Headache at high altitude is not related to internal carotid arterial blood velocity.

The cause of headache in persons going to high altitude is unknown. Relatively severe hypoxemia in susceptible subjects could induce large increases in cerebral blood flow that then could initiate the headache. Thus we measured noninvasively, by Doppler ultrasound, changes in internal carotid arterial blood velocity (velocity) in 12 subjects in Denver (1,600 m) and repeatedly up to 7 h at a simulated altitude of 4,800 m (barometric pressure = 430 Torr). Six subjects, selected because of prior history of high-altitude headache, developed comparatively severe headache at 4,800 m, and four subjects, without such history, remained well. Two subjects developed moderate headache. Velocity at 4,800 m did not correlate with symptom development, arterial O2 saturation, or end-tidal PCO2. Also, neither velocity nor blood pressure was consistently elevated above the Denver base-line values. During measurements of hypercapnic ventilatory response in Denver, velocity increased linearly with end-tidal PCO2, confirming that our Doppler method could demonstrate an increase. Also, 30 min of isocapnic or poikilocapnic hypoxia caused small increases in velocity (+8 and +6%) during the base-line measurement at low altitude. Although even a small increase in cerebral perfusion could contribute to headache symptoms at high altitude, cerebral blood flow does not appear to play a primary role.

A computerized mass spectrometer and flowmeter system for respiratory gas measurements.

Instrumentation systems for breath-to-breath analysis of respiratory gas exchange have been faulted by phase lags between various flow and composition signals and by difficulties in gathering and processing large amounts of data. The system described here represents an attempt to overcome these problems. Phase delays have been minimized by using a direct, piezoelectrically operated mass spectrometer inlet rather than an inlet capillary, by locating the mass spectrometer inlet and flow sensors in the same plane, and by incorporating design features which enhance the mass spectrometer response. Convenience in system operation and data analysis has been enhanced by integrating a computer into the system design so that the computer performs on-line data analysis and control functions and provides the primary interface between the experimenter and the instruments. Miniaturization of the instruments permits close coupling to an exercising subject.

A fast gas-mixing system for breath-to-breath respiratory control studies.

A computer-controlled gas-mixing system that manipulates inspired CO2 and O2 on a breath-to-breath basis has been developed. The system uses pairs of solenoid valves, one pair for each gas. These valves can either be fully shut when a low voltage is applied, or fully open when a high voltage is applied. The valves cycle open and shut every 1/12 s. A circuit converts signals from the computer, which dictates the flows of the gases, into a special form for driving the valve pairs. These signals determine the percentage of time within the 1/12-s cycle each valve spends in a open state and the percentage of time it spends shut, which, in effect, set the average flows of the various gases to the mixing chamber. The delay for response of the system to commanded CO2 or O2 changes is less than 200 ms. The system has application for the manipulation of inspired gas fractions so as to achieve desired end-tidal forcing functions.