A comparison of umbilical cord blood gas values between newborns with and without true knots.

OBJECTIVE: To compare umbilical cord blood gas values in newborns with and without true knots, and to assess the potential impact of true knot formation on cord blood gases. METHODS: Twelve newborn infants with true umbilical cord knots were identified and compared with a random control population of 104 newborn infants without true knots. The two groups were analyzed for 11 maternal-fetal variables to determine if they were comparable. Subsequently, the principal outcome variable of the study was evaluated: a comparison between the umbilical arterial and venous blood gas results of the true knot and control populations. RESULTS: The true knot and control populations were comparable with respect to the maternal-fetal variables analyzed. The umbilical cord blood gas values did not differ between groups, except for a slightly lower umbilical artery bicarbonate value in the control group (22.0 mEq/L) versus the true knot group (24.5 mEq/L), P = .025. There was no significant difference in the incidence of acidemia (umbilical artery pH less than 7.20) between the two groups. CONCLUSION: The presence of true umbilical cord knots does not alter the incidence of umbilical artery acidemia or change umbilical cord blood gas values. Review of the pertinent obstetric literature supports the hypothesis that true umbilical cord knots lack clinical significance.

The effect of naproxen on acute mountain sickness and vascular responses to hypoxia.

The role of prostaglandins in the pathogenesis of acute mountain sickness and two hypoxia-induced vascular responses was evaluated using the cyclooxygenase inhibitor naproxen. Eleven men spent 24 hours at sea level, followed by 34 hours of decompression to 428 mm Hg while receiving naproxen (N), 250 mg twice daily or placebo (P) in a double-blind crossover trial. Serum naproxen levels measured by high pressure liquid chromatography were not changed by hypoxia. The severity of acute mountain sickness (AMS) by the Environmental Symptom Questionnaire scores and observer assessment were unaffected by drug treatment. Retinal artery diameter measured from projected fundus photographs was increased after 27 hours at altitude (11.4 +/- .5 mm) vs. sea level (9.4 +/- .5 mm, p less than 0.05) during both trials. Upright mean arterial pressure fell after 6 hours at altitude (79 +/- 3 mm Hg during N and P vs. 92 +/- 3 at sea level, p less than 0.01). Minute ventilation, end expiratory alveolar PO2 and PCO2 did not differ between drug trials. This study suggests vasodilating prostaglandins do not have a major role in the genesis of AMS, hypoxia-induced retinal vasodilatation, or postural blood pressure responses in man.

Anthropometric changes at high altitude.

Eight white males (18-25 yr) were evaluated before, during and after 18-d residence on the summit of Pikes Peak, CO (4300 m; high altitude, HA) to describe the anthropometric changes associated with weight loss and to test the accuracy of a number of previously published prediction equations in assessing any alteration of the relative fat-to-lean tissue ratio during exposure to HA. Body weight (BW), 10 circumference (C), and 7 skinfold (SF) measurements were obtained preprandial at sea level (SL) and on days 2,4,6,9,12,16, and 18 at HA. Body density was estimated by hydrostatic weighing (HW) pre- and post-HA. BW differed from SL (p less than 0.01) after day 9 at HA. HW indicated that the pre- to post-HA weight loss was partitioned into a 2.06 kg loss in fat-free body mass (p less than 0.001) and an insignificant increase in fat wt (0.58 kg). Percent body fat (BF) increased from 16.6 to 17.7 (p less than 0.02). After day 9 of HA, the sum of SF and C measurements increased (p less than 0.02) and decreased (p less than 0.05) from SL, respectively. The largest changes occurred in the chest and scapula SF and in the C of the hip, neck, calf, and two abdominal sites. The alterations in triceps, waist, and total SF were related to the increase in fat weight and BF (r greater than 0.71).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased metabolism contributes to increased resting ventilation at high altitude.

Ventilatory acclimation to high altitude results in an increase in total or minute ventilation, and is associated with a fall in alveolar PCO2, i.e. alveolar hyperventilation. However, the extent to which the increase in total ventilation is matched by a greater metabolic rate (VO2, VCO2) vs alveolar hyperventilation is unclear. We sought to determine the contribution of changes in metabolic rate to the increase in minute ventilation observed during exposure to high altitude. In 12 healthy male subjects taken from Denver, Colorado (1600 m) to Pikes Peak, Colorado (4300 m) for 5 days, resting minute ventilation increased from low to high altitude (+ 26% for the 5 days) and arterialized PCO2 fell. Resting metabolic rate increased 16% for the 5 days and could account for more than half of the increase in minute ventilation. Among subjects the increases in ventilation on days 1, 2 and 4 were positively correlated with increased CO2 production; they were not correlated with arterial oxygen saturation on any day. During exercise at high altitude, PCO2 values were not different from those at rest and minute ventilation rose above low altitude values (+ 58% by day 5), but the increase could not be accounted for by an increased CO2 production. Thus at rest but not during exercise a substantial portion of the rise in minute ventilation could be attributed to increased metabolic rate.

Hypocapnia and sustained hypoxia blunt ventilation on arrival at high altitude.

Hypoxia at high altitude stimulates ventilation, but inhibitory influences in the first days after arrival limit the ventilatory response. Possible inhibitory influences include hypocapnia and depression of ventilation during sustained hypoxia. Our approach was to compare hypoxic ventilatory responses at low altitude with ventilation at high altitude. In 12 subjects we compared responses both to isocapnic hypoxia and poikilocapnic (no CO2 added) hypoxia during acute (less than 10 min) and sustained (30 min) hypoxia in Denver (1,600 m) with ventilations measured on each of 5 days on Pikes Peak (4,300 m). On Pikes Peak, day 1 ventilation [minute ventilation = 10.0 1/min, BTPS; arterial O2 saturation (Sao2) = 82%] was less than predicted by either acute isocapnic or poikilocapnic tests. However, sustained poikilocapnic hypoxia (Sao2 approximately = 82%) in Denver yielded ventilation similar to that on Pikes Peak on day 1. By Pikes Peak days 4 and 5, endtidal PCO2, pHa, and Sao2 approached plateaus, and ventilation (12.4 1/min, BTPS) on these days was as predicted by the acute isocapnic test. Thus the combination of hypocapnia and sustained hypoxia may have blunted the ventilatory increase on Pikes Peak day 1 but apparently not after 4 or 5 days of acclimatization.

Prevention of acute mountain sickness by dexamethasone.

Acute mountain sickness is a syndrome that occurs when unacclimatized persons ascend rapidly to high altitudes. It is postulated that cerebral edema causes its symptoms. Since dexamethasone is useful in treating some forms of cerebral edema, we investigated its role in the prevention of acute mountain sickness. Using a double-blind crossover design, we exposed eight young men to a simulated altitude of 4570 m (15,000 ft) on two occasions. By random assignment, each subject received dexamethasone (4 mg every 6 hours) or placebo for 48 hours before and throughout the 42-hour exposure. The presence of symptoms of acute mountain sickness was established by two methods: a questionnaire and an interview by a physician. Dexamethasone significantly reduced the symptoms of acute mountain sickness. During dexamethasone treatment, the cerebral-symptom score (mean +/- S.E.) decreased from 1.09 +/- 0.18 to 0.26 +/- 0.08, and the respiratory-symptom score decreased from 0.64 +/- 0.09 to 0.31 +/- 0.06 (both, P less than 0.05). As judged by the interviewing physician, the symptom score decreased from 1.10 +/- 0.11 to 0.28 +/- 0.07 (P = 0.01). We conclude that dexamethasone may be effective in preventing the symptoms of acute mountain sickness.

Skeletal muscle metabolism of sea-level natives following short-term high-altitude residence.

The influence of short-term high-altitude (HA) residence on intramuscular pH and skeletal muscle enzyme activity of sea-level (SL) residents was investigated. Vastus lateralis muscle samples were obtained by biopsy from rested subjects (n = 5) at SL (50 m) and on the 18th day of HA residence (4,300 m) for determination of glycogen phosphorylase, hexokinase, malate dehydrogenase, and total lactate dehydrogenase activities. A second group of subjects (n = 6) performed cycle exercise of the same absolute intensity (mean +/- SE = 195 +/- 5 W) at SL and on the 15th day of residence at HA. Before and immediately after exercise, vastus lateralis muscle samples were obtained for the determination of intramuscular pH, and venous blood was obtained for determination of lactate concentration. The first group of subjects showed no significant changes in skeletal muscle enzyme activity after 18 days at HA. The second group of subjects were instructed to exercise for exactly 30 min, and all but one could complete the entire bout at SL. However, at HA, none could continue 30 min, and time to exhaustion (mean +/- SE) was 11.9 +/- 1.6 min. Resting intramuscular pH was not significantly different after HA residence as compared to SL. The fall in intramuscular pH was less with exercise on day 15 at HA than during SL exercise. Likewise, the increase in blood lactate concentration with exercise at HA was less than at SL. These data indicate that, after 15-18 days of HA residence, limitations in exercise performance are not due to inordinate intramuscular acidosis or to changes in the activity of glycolytic and oxidative enzymes.

Variable inhibition by falling CO2 of hypoxic ventilatory response in humans.

Acute hypoxia stimulates an increase in ventilation but the resulting hypocapnia limits the magnitude of the increase. Thus the hypoxic ventilatory response is usually measured during isocapnia, but this may not reflect events at high altitude. We hypothesized that the degree of inhibition by hypocapnia might depend on individual ventilatory response to CO2 and thus vary between persons. To test this hypothesis we compared the isocapnic hypoxic ventilatory response (end-tidal PCO2 maintained by CO2 addition) with the response in which CO2 was not added and the end-tidal PCO2 fell to a variable extent (poikilocapnic hypoxia). In 14 healthy persons we found that the poikilocapnic hypoxic ventilatory response was determined by two factors: sensitivity to isocapnic hypoxia acting to increase ventilation and sensitivity to CO2 acting to decrease the hypoxic ventilatory response. The ventilatory response to poikilocapnic hypoxia correlated with but was generally less than the isocapnic hypoxic response. The magnitude of the difference between them related to the hypercapnic response. Further, the results suggested that the CO2 response in the high CO2 range related to ventilatory events in the low CO2 range. Thus the magnitude of ventilatory inhibition by hypocapnia may depend on individual ventilatory responsiveness to CO2.

Procedures for the measurement of acute mountain sickness.

Although acute mountain sickness (AMS) has been studied for well over a century, a standard measure or index of the degree of illness for use in experimental research does not exist. This paper outlines a definition and procedures for an operational measurement of AMS using the Environmental Symptoms Questionnaire (ESQ). After 58 men completed over 650 ESQs during a stay of 1-3 weeks atop Pike's Peak (4300 m), factor analysis produced nine distinct symptom groups, with two factors representing AMS. The first factor contains symptoms indicative of cerebral hypoxia and is labeled AMS-C. The second reflects respiratory distress and is called AMS-R. Signal detection theory was used to establish a criterion score value for each factor. Standard deviation values were used to derive indices of sickness severity. Discussion is given to the possible relationships between the two types of AMS and the more serious conditions of cerebral and pulmonary edema.

Operation Everest II.

OEII is an ambitious and complex project which is only possible through the full and enthusiastic support of the U.S. Army Institute of Environmental Medicine. The support staff at the hypobaric chamber will man the chamber controls 24 hours a day throughout the study, and full use of laboratories and equipment has been assured. We will maximize the opportunities for research by involving many other scientists active in altitude research, and with widely differing areas of expertise. Many measurements will be made at extreme altitudes which--at least today--are not possible in the mountain environment. Though some may be possible in a hospital setting, using hypoxic patients, OEII is the only method by which the adjustments to graded induced hypoxia can be studied from their beginning. Thus we will not only shed light on the ability of healthy persons to work on the highest point on earth, but also on the mechanisms which permit survival of many seriously ill patients.

Antidiuretic hormone responses to eucapnic and hypocapnic hypoxia in humans.

Urinary excretion rate of antidiuretic hormone (UADHV) was studied in male volunteers in response to hypobaric hypoxia. The first series consisted of three groups. The chamber was decompressed to 465, 495, and 438 Torr during high-altitude (HA) exposure for groups I (n = 5), II (n = 5), and III (n = 4), respectively. In group I, the chamber air contained 3.77% CO2 to prevent alkalosis. The level of hypoxemia was similar in groups I and II. Mean 24-h UADHV was unchanged in group I, but increased 96% (P less than 0.05) and 180% (P less than 0.05) in groups II and III, respectively, on day 1 at HA and was normal during subsequent days at HA regardless of symptoms of acute mountain sickness. Shorter sampling intervals employed in a second series of experiments conducted at 495 Torr revealed a twofold increase in UADHV (P less than 0.05) 8-12 h after ascent in eight asymptomatic subjects; UADHV returned to base line within 9 h and remained low. The symptomatic subjects both had increased UADHV (3- and 8-fold from base line) between 2 and 4 h after ascent. Increased UADHV in asymptomatic subjects may be a result of the concomitant decrease in plasma volume, both of which appeared to be eliminated by CO2 supplementation.

Sparing effect of chronic high-altitude exposure on muscle glycogen utilization.

Substrate utilization during heavy [approximately 85% maximum O2 consumption (VO2max)] bicycle exercise was examined in eight low-altitude residents at sea level (SL) and after acute (2 h) and chronic (18 days) high-altitude (HA) exposure at 4,300 m. Mean VO2max was approximately 27% lower at acute HA than at SL and did not change significantly with continued HA exposure. Biopsies from the vastus lateralis muscle and venous blood samples were obtained before and after 30 min of exercise, whereas determinations of the respiratory exchange ratio (R) were made at 10-min intervals during each of the submaximal bouts. Resting levels of serum-free fatty acids at acute and chronic HA were, respectively, two and three times higher than SL but were unchanged with exercise. Exercise did not alter resting serum glycerol levels at SL or during acute HA, but during chronic HA resting glycerol levels were increased 11-fold. Although mean blood lactate concentrations following exercise at SL and acute HA were not significantly different, postexercise lactate concentrations were 87% lower after chronic HA. During exercise at SL and acute HA, muscle glycogen utilization and R were not different. At chronic HA, muscle glycogen utilization and R were 41 and 15% lower, respectively. These data suggest that after chronic HA exposure, increased mobilization and use of free fatty acids during exercise resulted in sparing of muscle glycogen.

Phenytoin: ineffective against acute mountain sickness.

Phenytoin sodium was evaluated for its effect on the development and intensity of acute mountain sickness (AMS) because of its ability to reduce intracellular Na+ concentrations in brain and thereby minimize any tendency to increase cellular volume, a hypothetical cause of AMS. Six men aged 19-35 were exposed to approximately 4600 m altitude in a hypobaric chamber for 52 h on two occasions separated by 10 d at sea level. Subjects received wither phenytoin or placebo for 18 h before (700 mg, divided dose) and throughout (100 mg t.i.d.) each altitude exposure in a double-blind, repeated-measures (crossover) design. Phenytoin serum concentrations ranged from 4.4-13.9 micrograms/ml during altitude exposure. Twice daily questionnaires and clinical evaluations showed no marked benefit from phenytoin on the occurrence, severity, or duration of AMS symptoms: headache, nausea, insomnia, and general malaise. Overall, 1 subject felt better, 2 felt worse, 1 felt the same; 2 were not suitably comparable. There was no observed relationship between serum levels and symptoms of AMS. Moderate degrees of weakness and dizziness were each reported by 3 subjects with phenytoin but not with placebo, however. Resting pulmonary ventilation, end-tidal PO2 and PCO2, map reading abilities and respiratory mask donning times were not affected by phenytoin. Under the conditions of this trial, phenytoin did not appear to be useful in managing AMS.

Energy expenditure during load carriage at high altitude.

To determine the applicability of a prediction equation for energy expenditure during load carriage at high altitude that was previously validated at sea level, oxygen uptake (Vo2) was determined in five young men at 4,300 m while they walked with backpack loads of 0, 15, and 30 kg at treadmill grades of 0,8, and 16% at 1.12 m.s-1 for 10 min. Mean +/- SE maximal Vo2, determined on the cycle ergometer, was 42.2 +/- 2.3 at sea level and 35.6 +/- 1.7 ml.kg-1 .min-1 at altitude. There were no significant differences in daily Vo2 at any specific exercise intensity on days 1, 5, and 9 of exposure, nor were there any differences in endurance times at the two most difficult exercise intensities. Endurance times for 15- and 30-kg loads at 16% grade were 7.3 and 4.2 min, respectively. Measured energy expenditure was compared with that predicted by the formula of Pandolf et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 43: 577-581, 1977) and found to be significantly different. The differences could be attributed to measurements at metabolic rates exceeding 730 W or 2.1 1.min-1 Vo2. These data indicate that the prediction equation can be used at altitude for exercise intensities not exceeding this upper limit. The observed deviations from predicted values at the high exercise intensities could possibly be attributed to the occurrence of appreciable oxygen deficits and the inability to achieve steady-state conditions.

Ventilatory acclimatization to high altitude is prevented by CO2 breathing.

The hypoxia of high altitude stimulates ventilation. If the resultant respiratory alkalosis inhibits the initial increase in ventilation, then with prevention of alkalosis, ventilation should rise immediately to a stable plateau. 4 subjects inspired CO2 (3.77%) from ambient air in a hypobaric chamber (PB = 440-455 Torr) during 100 h at high altitude. Ventilation (for given oxygen uptakes at rest and during exercise) increased promptly and remained stable. 4 control subjects exposed to high altitude without CO2 supplementation showed the expected progressive increases in ventilation with time. The hyperoxic CO2 ventilatory response curve shifted progressively to the left with time in the control subjects, but not in those given supplemental CO2. The latter group also failed to increase the ventilatory response to isocapnic hypoxia. Thus, CO2 supplementation at high altitude prevented the so-called "ventilatory acclimatization' from occurring. Prevention of respiratory alkalosis at high altitude probably permitted maintenance of [H+] at some central nervous system locus, thus allowing an uninhibited hypoxic stimulation of ventilation.

Evidence for increased intrathoracic fluid volume in man at high altitude.

To determine if subclinical pulmonary edema occurs commonly at high altitude, 25 soldiers participated in two consecutive 72-h field exercises, the first at low altitude (200-875 m) and the second at high altitude (3,000-4,300 m). Various aspects of ventilatory function and pulmonary mechanics were measured at 0, 36, and 72 h of each exercise. Based on physical examination and chest radiographs there was no evidence of pulmonary edema at high altitude. There was, however, an immediate and sustained decrease in vital capacity and transthoracic electrical impedance as well as a clockwise rotation of the transpulmonary pressure-volume curve. In contrast, closing capacity and residual volume did not change immediately upon arrival at high altitude but did increase later during the exposure. These observations are consistent with an abrupt increase in thoracic intravascular fluid volume upon arrival at high altitude followed by a more gradual increase in extravascular fluid volume in the peribronchial spaces of dependent lung regions.

Mechanism of the attenuated cardiac response to beta-adrenergic stimulation in chronic hypoxia.

A blunting of the chronotropic and inotropic responses of the heart to beta-adrenergic stimulation occurs following chronic exposure to hypobaric hypoxia. To pursue the mechanism(s) involved, observations were made in six intact, conscious goats at sea level and in another six goats maintained in a decompression chamber at 445 Torr (approximately 4,300m) for 10 days (Pao2 = 43 Torr). No significant group differences in cardiac frequency and various indices of myocardial performance (peak dP/dt, time-to-peak dP/dt, Vmax) were demonstrable either before or after cholinergic blockade with intravenous atropine methyl bromide, 1 mg/kg. Following hemodynamic studies, thoracotomies were performed and full-thickness biopsies were obtained from the free wall of each of the cardiac chambers. Neither monoamine oxidase activity nor norepinephrine level of any region of the heart was altered by chronic hypoxia. However, a twofold increase (P less than 0.001) in catechol O-methyltransferase activity above sea-level values was found in both the atria and ventricles of the hypoxic animals. Thus, the attenuation in cardiac responsiveness to beta-adrenoceptor stimulation in chronic hypoxia appears unrelated to the level of vagal activity, but may be attributable to enhanced enzymatic inactivation of catecholamines.

Recurrent heat exposure: enzymatic responses in resting and exercising men.

Heat acclimatization was induced in a group of healthy male test subjects by repetitive treadmill walking (5.6 km-h-1, 49 degrees/27 degrees C dry/wet bulb, 90 min-day-1, 7 days). A second group of men, paired for maximal O2 consumption and body weight, remained sedentary under identical environmental conditions. Total plasma protein increased significantly after 45 (P less than 0.05) and 90 (P less than 0.025) min of exercise on the first day of heat exposure, yet after 7 days no increments occurred. Even after heat acclimatization was achieved (day 7), plasma levels of creatine phosphokinase increased during the 90-min walk in the heat (time O vs. 90, P less than 0.025), as was also the case on day 1 (P less than 0.05). Levels of lactate dehydrogenase, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were not significantly affected by exercise in the heat either before or after heat acclimatization. No correlations could be drawn between base-line enzyme levels and state of physical conditioning.