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.

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.

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.

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)

Changes in serum and sweat magnesium levels during work in the heat.

Serial changes in serum magnesium (Mg2+) were assessed in unacclimatized males during treadmill exercise in a hot (49 degrees/27 degrees C, dry/wet bulb) environment. Eight subjects walked at 5.6 km/h on a 0% grade, and at 90 min of exercise had a mean heart rate of increase of 70 plus or minus 5 (S.E.) beats/min, rise in rectal temperature of 2.1 degrees plus or minus 0.1 degrees C, and a weight loss of 2.07 plus or minus 0.10 kg. There was a significant (p less than 0.01) decrease in mean serum Mg2+ concentration (control: 1.87 plus or minus 0.06 mEq/I; 45 min: 1.81 plus or minus 0.07; 90 min: 1.72 plus or minus 0.08). The Mg2+ concentration in sweat samples collected over 90 min of work in the heat averaged 0.28 mEq/I (range 0.13 to 0.45). Thus, in normal man, exercise in an hot, dry environment resulted in a fall in serum magnesium which was not wholly explicable on the basis of sweat loss of this ion.

Acute mountain sickness: increased severity in eucapnic hypoxia.

This study examined the hypothesis that prevention of hypocapnia and alkalosis would ameliorate the symptoms of acute mountain sickness (AMS). Five subjects were exposed to simulated high altitude for 4 d with 3.8% CO2 added to the chamber to maintain normocapnia. Four other subjects were exposed for 4 d to hypobaric hypoxia without CO2 supplementation, and became hypocapnic. Barometric pressure was lower in the group with added CO2 so that alveolar oxygen tensions (55-60 mm Hg) would not be different. The severity of symptoms was clearly greater in normocapnic than in hypocapnic subjects. Thus, prevention of hypocapnia did not alleviate AMS symptoms. The efficacy of CO2 addition in reducing symptoms, as reported by earlier workers, was probably the result of induced hyperventilation and partial relief of hypoxia. Indeed, in the present study with two comparably hypoxic groups, CO2 addition augmented the sysptoms, possibly by causing increased cerebral vasodiladation and spinal fluid pressure.

Increased 2,3-diphosphoglycerate during normocapnic hypobaric hypoxia.

The effect of 96 h of exposure to hypobaric hypoxia with and without 3.8% CO2 supplementation was studied in two groups of subjects. Five subjects (CO2) were exposed to 440-465 mm Hg barometric pressure (4000-4400 m), and 4 subjects (no-CO2) were exposed to 455-492 mm Hg (3500-1400 m) in order to produce similar levels of resting end-tidal PO2. After 24 h, 2,3-DPG levels of both groups significantly increased and remained elevated. The CO2 group had higher levels than the non-CO2 group after 48 and 72 h. Concurrent measurements of P50 showed similar changes over the same time course. Mean corpuscular hemoglobin concentrations remained normal for 48 h and then decreased in both groups, the CO2 group showing the larger decrease. We conclude that altitude exposure may produce an increase in 2,3-DPG without the presence of respiratory alkalosis previously thought necessary.

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.

Human coagulation abnormalities during acute exposure to hypobaric hypoxia.

Multiple coagulation studies were carried out in eight healthy young men at sea level (SL) and after 1, 24, and 48 h at a simulated altitude of 4,400 m. Platelet aggregation, as induced by ADP, epinephrine, and collagen, was not significantly altered by high-altitude (HA) exposure. Mean 2,3-diphosphoglycerate, a physiological inhibitor of platelet aggregation, rose (P less than 0.001) after 24 h at HA and remained elevated while no changes in circulating catecholamines were observed. Platelet count, factor 3 availability, and membrane lipid peroxide formation were likewise unaltered at HA, as were prothrombin and thrombin times and protamine paracoagulation test. However, mean partial thromboplastin time was significantly shortened (P less than 0.01) after 1 and 24 h at HA, recovering to SL control by 48 h. Fibrinogen and factor VIII levels also fell (P less than 0.01 and P less than 0.02) after 1 h at HA but returned to the preexposure values by 24 h. Fibrin degradation products were transiently detectable in three subjects at HA. Thus, although normal platelet function did not appear to be modified by short-term exposure to simulated high altitude, evidence for a coagulopathy was obtained.

Cardiovascular responsiveness to beta-adrenergic stimulation and blockade in chronic hypoxia.

Previous studies have shown that exposure to high altitude results in an initial increase in heart rate, followed by a return to sea-level values within several days; circulating catecholamines rise progressively during this time. Nine conscious dogs were studied in normoxia (N) and after 10 days' exposure to 445 torr (CH). The mean (plus or minus SE) hematocrit was higher in CH (50 plus or minus 2 vs. 42 plus or minus 1%) while Pa-o2 (53 plus or minus 1 vs. 97 plus or minus 2 torr) and PaCO2 (27 plus or minus 1 vs. 35 plus or minus 1 torr) were lower than in N. A 3.5-fold increase in plasma norepinephrine above the N value was found in CH. Arterial pH, heart rate (HR), and mean femoral arterial pressure (MAP) did not differ significantly in N and CH. Isoproterenol (ISO), 0.5 mug/kg iv, produced an average increase in HR of 92 plus or minus 9 beats/min in N, but only 66 plus or minus 8 beats/min in CH (P smaller than .02). Reduction in MAP after ISO were similar. Pretreatment with propranolol, 0.15 mg/kg iv, reduced HR equally in N and CH without affecting MAP, but diminished the HR response to ISO significantly more in CH than in N. The attenuated chronotropic response to beta-adrenoceptor stimulation following chronic hypobaric hypoxia suggests a relative cardiac refractoriness secondary to an increased level of sympathetic activity.

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.

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.

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.

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.

Measurement of cardiac output by electrical impedance at rest and during exercise.

A comparison was made between cardiac output values determined by the dye dilution and electrical impedance methods in ten subjects at rest and during graded exercise on a bicycle ergometer. The cardiac output values determined by the two methods were linearly related and significantly (P less than 0.001) correlated (r = 0.90). Movement artifact associated with exercise at maximum or near-maximum work loads caused severe distortion of the dZ/dt wave form and prevented calculation of impedance cardiac output at these levels of work. Use of the lowest value of L (distance between mean value of L in the impedance stroke volume equation (SV = p(L2/ZO2) (dZ/dt)mt), resulted in nearly identical values for the least-squares line and equalvalue line of impedance and dye cardiac outputs. Although absolute values of cardiac output determined by the two methods were not identical in all subjects the changes in cardiac output were nearly identical during the different levels of exercise. The data support the validity of the impedance method as a noninvasive, atraumatic measure of cardiac output at rest and during graded exercise.