Biomedical subjects

J V Weil

Publications and source records attributed to J V Weil.

At least 55 records · Page 3Linked to original sources

PubMed1987

Propranolol blocks metabolic rate increase but not ventilatory acclimatization to 4300 m.

Previously, we found resting metabolic rate increased at high altitude but the mechanism and consequences of this increase were unclear. We sought to test the role of beta-sympathetic activation for increasing metabolic rate and the contribution of an increase in metabolic rate to raising total ventilation at altitude. Following baseline studies at sea level, two groups of six healthy male subjects received either placebo or propranolol (80 mg/8 h) for 3 days prior to ascent to Pikes Peak (4300 m) where treatment was continued for 15 days. O2 consumption increased in placebo-treated subjects with a rise of 20 +/- 5% (X +/- SEM) on day 1 and no change 0 +/- 7% in propranolol-treated subjects (difference between groups, P less than 0.05). The increase in total ventilation upon ascent was 28 +/- 2% in the placebo group vs 9 +/- 7% in the propranolol group (P less than 0.05) and was correlated with metabolic rate in individual subjects. Decreasing end-tidal PCO2, taken as an index of ventilatory acclimatization, was similar in both groups. Thus, beta-sympathetic activation appears to increase metabolic rate upon ascent to high altitude and lead to a proportionate elevation in total ventilation but does not alter ventilatory acclimatization.

Acclimatization↗

PubMed1987

Increased HVR in pregnancy: relationship to hormonal and metabolic changes.

In prior studies at high altitude, we have found that pregnancy increases maternal hypoxic ventilatory response (HVR) but the factors responsible are unknown. Changes in metabolic rate and hormones that occur during pregnancy have previously been shown to influence HVR. We therefore sought to determine the contribution of metabolic rate and hormonal changes to the pregnancy-associated rise in HVR. Pregnancy increased HVR in each of 20 normal, low-altitude (1,600 m) residents. As measured by the shape parameter A, HVR at week 36 was 237 +/- 26 (SE) or twofold higher than the 124 +/- 13 value measured 3 mo postpartum (P less than 0.01) despite the presence of the potentially depressant effects of hypocapnia [change in alveolar partial pressure of CO2 (delta PACO2) = -4 +/- 1 mmHg] and alkalosis [change in arterial pH (delta pHa) = 0.02 +/- 0.01 U] during pregnancy. Sixty percent of the increase in HVR values had occurred by week 20 of gestation at which time O2 consumption (VO2) and CO2 production (VCO2) were unchanged relative to values measured postpartum. The remaining 40% rise in HVR paralleled increases in VO2 and VCO2, and further elevation in VO2 and VCO2 with moderate exercise produced an additional increase in HVR. Serum estradiol and progesterone levels increased with pregnancy, but levels did not correlate with HVR. The women reporting the greatest symptoms of dyspnea had higher HVR A values at week 36 than the least dyspneic women (285 +/- 28 vs. 178 +/- 34, respectively, P less than 0.05). We concluded that factors intrinsic to pregnancy in combination with increased metabolic rate raised HVR twofold with pregnancy and may have contributed to the often-reported symptoms of dyspnea in pregnant women.

Adult↗

PubMed1987

Breathing pattern in hypoxic exposures of varying duration.

The relative contributions of breathing frequency and tidal volume to the increase in ventilation during acute or prolonged exposure to hypoxia is uncertain. We examined the changes in breathing pattern during hypoxic exposures lasting minutes, hours, and days using data from previous studies. Increased tidal volume accounted for the increased ventilation during 7-10 and 30 min of isocapnic and poikilocapnic (no CO2 added) hypoxic exposures as well as during 7 h of poikilocapnic hypobaric hypoxia (4,800 m). Tidal volume was also a greater overall contributor than frequency to increased ventilation in sea-level residents during 3 days of isocapnic hypobaric hypoxia (4,100-4,600 m) and in Denver (1,600 m) residents during 5 days on Pikes Peak (4,300 m). In sea-level residents during 3 days of poikilocapnic hypobaric hypoxia (3,600-4,300 m) and during 7-8 days on Pikes Peak, increased frequency accounted for the rise in ventilation. Tidal volume thus contributed more than frequency to increasing ventilation during brief hypoxia, whereas the contribution of frequency was increased in prolonged hypoxia involving a 4,300-m altitude ascent and hypocapnia.

Adult↗

PubMed1987

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.

Adult↗

PubMed1987

Altitude acclimatization: influence on periodic breathing and chemoresponsiveness during sleep.

Although the influence of altitude acclimatization on respiration has been carefully studied, the associated changes in hypoxic and hypercapnic ventilatory responses are the subject of controversy with neither response being previously evaluated during sleep at altitude. Therefore, six healthy males were studied at sea level and on nights 1, 4, and 7 after arrival at altitude (14,110 ft). During wakefulness, ventilation and the ventilatory responses to hypoxia and hypercapnia were determined on each occasion. During both non-rapid-eye-movement and rapid-eye-movement sleep, ventilation, ventilatory pattern, and the hypercapnic ventilatory response (measured at ambient arterial O2 saturation) were determined. There were four primary observations from this study: 1) the hypoxic ventilatory response, although similar to sea level values on arrival at altitude, increased steadily with acclimatization up to 7 days; 2) the slope of the hypercapnic ventilatory response increased on initial exposure to a hypoxic environment (altitude) but did not increase further with acclimatization, although the position of this response shifted steadily to the left (lower PCO2 values); 3) the sleep-induced decrements in both ventilation and hypercapnic responsiveness at altitude were equivalent to those observed at sea level with similar acclimatization occurring during wakefulness and sleep; and 4) the quantity of periodic breathing during sleep at altitude was highly variable and tended to occur more frequently in individuals with higher ventilatory responses to both hypoxia and hypercapnia.

Acclimatization↗

PubMed1987

Biphasic ventilatory response of adult cats to sustained hypoxia has central origin.

Hypoxia stimulates ventilation, but when it is sustained, a decrease in the response is often seen. The mechanism of this depression or "roll off" is unclear. In this study we attempted to localize the responsible mechanism at one of three possible sites: the carotid bodies, the central nervous system (CNS), or the ventilatory apparatus. The ventilatory response to sustained hypoxia (PETO2, 40-50 Torr) was tested in 5 awake and 14 anesthetized adult cats. The roll off was found in both anesthetized and awake cats. Isocapnic hypoxia initially increased ventilation as well as phrenic and carotid sinus nerve activity in anesthetized cats (288 +/- 31, 269 +/- 31, 273 +/- 29% of control value, respectively). During the roll off, ventilation and phrenic nerve activity decreased similarly (to 230 +/- 26 and 222 +/- 28%, respectively after the roll off), but in contrast carotid sinus nerve activity remained unchanged (270 +/- 26%). Thus the ventilatory roll off was reflected in phrenic but not in carotid sinus nerve activity. We conclude that the cat represents a useful animal model of the roll off phenomenon and that the mechanism responsible for the secondary decrease in ventilation lays within the CNS.

Anesthesia↗

PubMed1987

Antiarrhythmic agents diminish thiourea-induced pulmonary vascular protein leak in rats.

Drugs possessing membrane stabilizing activity might act to diminish the augmented microvascular permeability resulting from acute lung injury. To test this rats were pretreated with quinidine, procainamide, or lidocaine and then given the lung injury-inducing agent thiourea. Vascular permeability, assessed as the extravascular accumulation of radiolabeled protein, was increased more than threefold by thiourea. This increase was diminished by 29, 34, and 43% after pretreatment with procainamide, quinidine, and lidocaine, respectively. Lidocaine also returned the thiourea-induced increase in lung wet weight-to-dry weight ratios to control levels. This protection was not likely due to hemodynamic effects of these agents, since no differences were noted in cardiac output between pretreated rats and those receiving thiourea alone and a small increase in mean pulmonary arterial pressure in the lidocaine-pretreatment group was the only difference noted. O2 metabolites have been implicated in the pathogenesis of thiourea-induced lung injury. None of these agents scavenged O2- or H2O2 directly, but quinidine and procainamide diminished in vitro neutrophil O2- and H2O2 production, and lidocaine inhibited neutrophil H2O2 production. However, neutropenia (PMN less than 100/ml) induced with either vinblastine or cyclophosphamide (Cytoxan) failed to prevent thiourea-induced increases in pulmonary vascular protein leak. In conclusion, procainamide, quinidine, and lidocaine diminished lung injury in rats after thiourea. Although these agents diminish PMN O2 metabolite production in vitro their salutary role in thiourea-induced lung injury appears to be through an unknown mechanism that is independent of their effects on neutrophil O2 metabolite-dependent toxicity.

Animals↗

PubMed1987

Interindividual variation in hypoxic ventilatory response: potential role of carotid body.

There is considerable interindividual variation in ventilatory response to hypoxia in humans but the mechanism remains unknown. To examine the potential contribution of variable peripheral chemorecptor function to variation in hypoxic ventilatory response (HVR), we compared the peripheral chemoreceptor and ventilatory response to hypoxia in 51 anesthetized cats. We found large interindividual differences in HVR spanning a sevenfold range. In 23 cats studied on two separate days, ventilatory measurements were correlated (r = 0.54, P less than 0.01), suggesting stable interindividual differences. Measurements during wakefulness and in anesthesia in nine cats showed that although anesthesia lowered the absolute HVR it had no influence on the range or the rank of the magnitude of the response of individuals in the group. We observed a positive correlation between ventilatory and carotid sinus nerve (CSN) responses to hypoxia measured during anesthesia in 51 cats (r = 0.63, P less than 0.001). To assess the translation of peripheral chemoreceptor activity into expiratory minute ventilation (VE) we used an index relating the increase of VE to the increase of CSN activity for a given hypoxic stimulus (delta VE/delta CSN). Comparison of this index for cats with lowest (n = 5, HVR A = 7.0 +/- 0.8) and cats with highest (n = 5, HVR A = 53.2 +/- 4.9) ventilatory responses showed similar efficiency of central translation (0.72 +/- 0.06 and 0.70 +/- 0.08, respectively). These results indicate that interindividual variation in HVR is associated with comparable variation in hypoxic sensitivity of carotid bodies. Thus differences in peripheral chemoreceptor sensitivity may contribute to interindividual variability of HVR.

Anesthesia↗

PubMed1987

Increased carotid body hypoxic sensitivity during acclimatization to hypobaric hypoxia.

Mechanisms of ventilatory acclimatization to chronic hypoxia remain unclear. To determine whether the sensitivity of peripheral chemoreceptors to hypoxia increases during acclimatization, we measured ventilatory and carotid sinus nerve responses to isocapnic hypoxia in seven cats exposed to simulated altitude of 15,000 ft (barometric pressure = 440 Torr) for 48 h. A control group (n = 7) was selected for hypoxic ventilatory responses matched to the preacclimatized measurements of the experimental group. Exposure to 48 h of hypobaric hypoxia produced acclimatization manifested as decrease in end-tidal PCO2 (PETCO2) in normoxia (34.5 +/- 0.9 Torr before, 28.9 +/- 1.2 after the exposure) as well as in hypoxia (28.1 +/- 1.9 Torr before, 21.8 +/- 1.9 after). Acclimatization produced an increase in hypoxic ventilatory response, measured as the shape parameter A (24.9 +/- 2.6 before, 35.2 +/- 5.6 after; P less than 0.05), whereas values in controls remained unchanged (25.7 +/- 3.2 and 23.1 +/- 2.7; NS). Hypoxic exposure was associated with an increase in the carotid body response to hypoxia, similarly measured as the shape parameter A (24.2 +/- 4.7 in control, 44.5 +/- 8.2 in acclimatized cats). We also found an increased dependency of ventilation on carotid body function (PETCO2 increased after unilateral section of carotid sinus nerve in acclimatized but not in control animals). These results suggest that acclimatization is associated with increased hypoxic ventilatory response accompanied by enhanced peripheral chemoreceptor responsiveness, which may contribute to the attendant rise in ventilation.

Acclimatization↗

PubMed1987

NHLBI workshop summary. Respiratory disorders of sleep. Pathophysiology, clinical implications, and therapeutic approaches.

The extensive investigation into complex interactions of breathing and sleep have produced answers to numerous important questions, but it is clear that many of the most important questions in this area remain unanswered. Our understanding of the mechanisms through which sleep alters breathing and how disordered breathing can, in turn, effect sleep is rudimentary. Although a large body of recent work has done much to elucidate the factors that act to maintain the patency of the upper airway during sleep, our understanding of such mechanisms and the relative importance of structure and function in this context remains primitive. A better understanding of these issues will be critical in elucidating the pathophysiology of respiratory disorders of sleep. Although some progress has been made in this area, new insights will be critically important to the design of novel, potentially more effective approaches to treatment. Therapeutic decisions are greatly hampered by major uncertainties regarding respiratory disorders of sleep and the clinical significance of symptoms, signs, and laboratory findings, and their relationship to morbidity and mortality. It seems clear that new information regarding the pathophysiology and natural history of these disorders will be important in the development of new, more effective strategies for therapeutic intervention, and this together with rigorous, systematic evaluation of new and future therapeutic approaches will be critical to clinical progress in this field.

Airway Resistance↗

PubMed1986

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.

Adult↗

PubMed1986

Influence of testosterone on breathing during sleep.

Apneas and hypopneas during sleep occur more frequently in men than women. Disordered breathing is also reported to increase in hypogonadal men following testosterone administration. This suggests a hormonal influence on sleeping respiratory pattern. We therefore studied respiratory rhythm during sleep in 11 hypogonadal males both on and off testosterone-replacement therapy. In four subjects the anatomy (computerized tomography) and airflow resistance of the upper airway were also determined on both occasions. Sleep stage distribution and duration were unchanged following androgen administration. However, both apneas and hypopneas increased significantly during testosterone replacement so that the total number of disordered breathing events (apneas + hypopneas) per hour of sleep rose from 6.4 +/- 2.1 to 15.4 +/- 7.0 (P less than 0.05). This was a highly variable event with some subjects demonstrating large increases in apneas and hypopneas when androgen was replaced, whereas others had little change in respiration during sleep. Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway.

Arousal↗

PubMed1986

Endotoxin increases pulmonary vascular protein permeability in the dog.

Endotoxin increases pulmonary vascular permeability consistently in some species but fails to reliably cause injury in the dog. We wondered whether this phenomenon depended on the method of injury assessment, as others have relied on edema measurement; we quantified injury by monitoring the rate of extravascular protein accumulation. 113mIn-labeled protein and 99mTc-labeled erythrocytes were injected into anesthetized dogs and monitored by an externally placed lung probe. A protein leak index, the rate of extravascular protein accumulation, was derived from the rate of increase in lung protein counts corrected for changes in intravascular protein activity. After administration of Salmonella enteriditis endotoxin (4 micrograms/kg), the protein leak index was elevated 2.5-fold (41.1 +/- 4.6 X 10(-4) min-1) compared with control (16.0 +/- 2.8 X 10(-4) min-1). In contrast, wet-to-dry weight ratios failed to increase after endotoxin (4.6 +/- 0.8 vs. control values of 4.2 +/- 0.5 g/g dry bloodless lung). However, we observed that endotoxin increased lung dry weight (per unit body weight), which may have attenuated the change in wet-to-dry weight ratios. To determine whether low microvascular pressures following endotoxin attenuated edema formation, we increased pulmonary arterial wedge pressures in five dogs by saline infusion, which caused an increase in wet-to-dry weight ratios following endotoxin but no change in the five controls. We conclude that low dose endotoxin causes pulmonary vascular protein leak in the dog while edema formation is minimal or absent.

Animals↗

PubMed1986

Propranolol does not impair exercise oxygen uptake in normal men at high altitude.

Decreased maximal O2 uptake (VO2max) and stimulation of the sympathetic nervous system have been previously shown to occur at high altitude. We hypothesized that tachycardia mediated by beta-adrenergic stimulation acted to defend VO2max at high altitude. Propranolol treatment beginning before high-altitude (4,300 m) ascent reduced heart rate during maximal and submaximal exercise in six healthy men treated with propranolol (80 mg three times daily) compared with five healthy subjects receiving placebo (lactose). Compared with sea-level values, the VO2max fell on day 2 at high altitude, but the magnitude of fall was similar in the placebo and propranolol treatment groups (26 +/- 6 vs. 32 +/- 5%, P = NS) and VO2max remained similar at high altitude in both groups once treatment was discontinued. During 30 min of submaximal (80% of VO2max) exercise, propranolol-treated subjects maintained O2 uptake levels that were as large as those in placebo subjects. The maintenance of maximal or submaximal levels of O2 uptake in propranolol-treated subjects at 4,300 m could not be attributed to increased minute ventilation, arterial O2 saturation, or hemoglobin concentration. Rather, it appeared that propranolol-treated subjects maintained O2 uptake by transporting a greater proportion of the O2 uptake with each heartbeat. Thus, contrary to our hypothesis, beta-adrenergic blockade did not impair maximal or submaximal O2 uptake at high altitude due perhaps to compensatory mechanisms acting to maintain stroke volume and cardiac output.

Adult↗

PubMed1986

Cardiovascular adaptation to exercise at high altitude.

To exercise at high altitude means working in an environment with reduced atmospheric pressure. The oxygen tension of the inspired air is therefore decreased, that is, there is atmospheric hypoxia. Exercise increases oxygen requirements which must now be met in the face of this decreased oxygen driving pressure. The initial handicap is less complete oxygenation of blood within the lung. In an effort to preserve oxygen delivery, a greater volume of blood is circulated, that is, cardiac output is increased. However, this pattern of compensation is only temporary. Within days, hemoconcentration increases the oxygen-carrying capacity of the blood, and as a consequence, less cardiac output is required to maintain oxygen delivery. In fact, cardiac output decreases to levels lower than existed prior to ascent. This reduction in cardiac output results primarily from a decrease in stroke volume due to less venous return secondary to the smaller blood volume produced by hemoconcentration. The hypoxia of high altitude produces sustained stimulation of the sympathetic nervous system. Initially, this increases heart rate, but, with time, the responsiveness of the heart decreases, so the initial tachycardia may not be sustained. Other consequences of sympathetic stimulation include an increase in resting metabolic rate, a shift away from glycogen toward free fatty acids as primary energy sources, and bone marrow stimulation to increase red cell production. The parasympathetic nervous system may also be stimulated at high altitude, which may explain the reduction in maximum heart rate. Upon arrival at high altitude, aerobic working capacity is reduced. Although this may or may not be attenuated following adaptation, endurance capacity does seem to improve. Several parallels therefore emerge between adaptation to the hypoxia of high altitude and adaptation to the struggle for oxygen created by exercise training at low altitude. Sympathetic stimulation is common to both forms of hypoxic stress, and similar responses, particularly metabolic, result. Not surprisingly, then, exercise training provides an advantage to adaptation to high altitude.

Acclimatization↗

PubMed1985

Metabolic rate and breathing during sleep.

Recent investigation suggests that both ventilation (VE) and the chemical sensitivity of the respiratory control system correlate closely with measures of metabolic rate [O2 consumption (VO2) and CO2 production (VCO2)]. However, these associations have not been carefully investigated during sleep, and what little information is available suggests a deterioration of the relationships. As a result we measured VE, ventilatory pattern, VO2, and VCO2 during sleep in 21 normal subjects (11 males and 10 females) between the ages of 21 and 77 yr. When compared with values for awake subjects, expired ventilation decreased 8.2 +/- 2.3% (SE) during sleep and was associated with a 8.5 +/- 1.6% decrement in VO2 and a 12.3 +/- 1.7% reduction in VCO2, all P less than 0.01. The decrease in ventilation was a product primarily of a significant decrease in tidal volume with little change in frequency. None of these findings were dependent on sleep stage with results in rapid-eye-movement (REM) and non-rapid-eye-movement sleep being similar. Through all sleep stages ventilation remained tightly correlated with VO2 and VCO2 both within a given individual and between subjects. Although respiratory rhythmicity was somewhat variable during REM sleep, minute ventilation continued to correlate with VO2 and VCO2. None of the parameters described above were influenced by age or gender, with male and female subjects demonstrating similar findings. Ten of the subjects demonstrated at least occasional apneas. These individuals, however, were not found to differ from those without apnea in any other measure of ventilation or metabolic rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak.

Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. We tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. We calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability we normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. We measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity we compared hydrostatic and high-dose thiourea edema. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 X 10-4 vs. 7.6 +/- 0.9 X 10-4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 X 10-4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity we compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. We conclude that a noninvasive double radioisotope measurement of pulmonary vascular protein leak, employing external counting techniques and a simplified method of calculation, is specific for lung injury and is also sensitive enough to detect lung injury insufficient to produce detectable pulmonary edema.

Animals↗

PubMed1985

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.

Adult↗