Biomedical subjects

L G Moore

Publications and source records attributed to L G Moore.

At least 127 records · Page 7Linked to original sources

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

Effect of systemic intravenous infusion of PGF-2 alpha and 13,14-dihydro-15-keto-PGF-2 alpha on the release of oxytocin-associated neurophysin from the ovary in the ewe.

Systemic intravenous infusion of physiological concentrations of PGF-2 alpha and its major metabolite, 13, 14-dihydro-15-keto-PGF-2 alpha (PGFM) into non-pregnant ewes possessing a corpus luteum induced the release of oxytocin-neurophysin. These results suggest that, during luteolysis, endogenous release of uterine PGF-2 alpha would be able to stimulate the release of ovarian oxytocin and oxytocin-neurophysin from the ovary.

Animals↗

PubMed1986

Meclofenamate potentiates vasoreactivity to alpha-adrenergic stimulation in chronically hypoxic guinea pigs.

The aim of this study was to examine the effect of chronic hypoxia on systemic vascular reactivity and the role of prostaglandins in modulating the vascular response to chronic hypoxia. Meclofenamate, a prostaglandin synthesis inhibitor, increased the systemic vascular resistance response to the alpha-adrenergic agonist, phenylephrine, in awake, unrestrained guinea pigs exposed for 6 wk to high altitude (3,900 m), but it did not alter the response in animals kept at low altitude (1,600 m). The systemic vascular resistance response to phenylephrine before treatment with meclofenamate was the same in high- and low-altitude animals. Meclofenamate also increased the contractile response to phenylephrine in aortic rings isolated from high- but not low-altitude animals. The systemic vascular resistance response to angiotensin II was the same in high- and low-altitude animals, and meclofenamate increased this response to the same extent in both groups. Thus chronic hypoxia appeared to enhance vascular production of dilator prostaglandins during beta-adrenergic stimulation.

Adrenergic alpha-Agonists↗

PubMed1986

Progesterone receptors and ventilatory stimulation by progestin.

Progestin is thought to be a ventilatory stimulant but its effectiveness in raising ventilation is variable in humans and other species. We hypothesized that the level of progesterone receptors was an important determinant of the ventilatory response to progestin. Since estradiol induces progesterone receptor formation, we compared the ventilatory effect of the synthetic progestin medroxyprogesterone acetate (MPA) given in combination with estradiol with the effects of estradiol alone, MPA alone, or vehicle (saline) in ovariectomized rats. Animals receiving MPA alone had low numbers of progesterone receptors (2.43 pmol/g uterine wt) and had no change in ventilation, arterial Pco2, or Po2. MPA administration raised ventilation 23 +/- 5%, lowered arterial Pco2 3.2 +/- 0.9 Torr (both P less than 0.01) and tended to raise arterial Po2 when given in combination with estradiol to animals with increased numbers of progesterone receptors (4.85 pmol/g uterine wt). Estradiol alone produced the highest number of progesterone receptors (12.3 pmol/g uterine wt) but had no effect on ventilation or arterial Pco2 and decreased arterial Po2. Combined estradiol plus MPA treatment produced a greater fall in arterial Pco2 than did treatment with MPA alone, estradiol, or saline (all P less than 0.05). These results suggest that both an elevation in progestin levels and progesterone receptor numbers are required to stimulate ventilation.

Animals↗

PubMed1986

Maternal hypoxic ventilatory response, ventilation, and infant birth weight at 4,300 m.

To test the hypothesis that increased hypoxic ventilatory responsiveness (HVR) raised maternal ventilation and arterial oxygenation during high-altitude pregnancy and related to the birth weight of the offspring, we studied 21 residents of Cerro de Pasco, Peru (4,300 m), while eight of them were 36 +/- 0 wk pregnant and 15 of them 13 +/- 0 wk postpartum. HVR was low in the nonpregnant women (mean +/- SE shape parameter A = 23 +/- 8) but increased nearly fourfold with pregnancy (A = 87 +/- 17). The increase in HVR appeared to account for the 25% rise in resting ventilation with pregnancy (delta VE observed = 2.4 +/- 0.7 l/min BTPS vs. delta VE predicted from delta HVR = 2.6 +/- 1.7 l/min BTPS, P = NS). Hyperoxia decreased ventilation in the pregnant women (P less than 0.01) to levels similar to those measured when nonpregnant. The increased ventilation of pregnancy raised arterial O2 saturation (SaO2) from 83 +/- 1 to 87 +/- 0%, and SaO2 was correlated positively with HVR in the pregnant women. The rise in SaO2 compensated for a 0.9 g/100 ml decrease in hemoglobin concentration to preserve arterial O2 content at levels present when nonpregnant. Cardiac output in the 36th wk of pregnancy did not differ significantly from values measured postpartum. The increase in HVR correlated positively with infant birth weight. An increase in HVR may be an important contributor to increased maternal ventilation with pregnancy and infant birth weight at high altitude.

Adult↗

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

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

Evidence for the pulsatile release of PGF-2 alpha inducing the release of ovarian oxytocin during luteolysis in the ewe.

Frequent blood samples were removed from a utero-ovarian vein, a jugular vein and a femoral artery of 5 ewes during luteolysis. Analysis of these samples for oxytocin-associated neurophysin revealed a significant venous-arterial difference across the ovary and uterus but not across the head. This occurred during the pulsatile surges as well as when levels were basal and confirms the corpus luteum as a major source of the pulsatile surges of oxytocin-associated neurophysin and oxytocin that occur during CL regression and also of the elevated luteal phase concentrations of both hormones. The pulsatile surges of oxytocin-associated neurophysin measured in the utero-ovarian vein were accompanied by the release of an approximately equimolar amount of oxytocin. The concentration of PGF-2 alpha in the utero-ovarian vein samples began to increase before the levels of oxytocin and oxytocin-associated neurophysin started to increase. This suggests that uterine PGF-2 alpha initiates the release of ovarian oxytocin and oxytocin-associated neurophysin during luteolysis in the ewe.

Animals↗

PubMed1985

Migration of the elderly from high altitudes in Colorado.

The reason for the reported decline in the proportion of elderly (greater than 60 years) persons at high (greater than 2,456 m) compared with low altitude (less than 1,376 m) in Colorado was unknown. We hypothesized that adverse effects of high altitude on the elderly, particularly those with heart and lung diseases, prompted their migration to lower elevations. Colorado census data indicated that selective out-migration occurred from high to low altitude among the elderly. Interviews (n = 833) in high- and low-altitude Colorado towns revealed that the elderly were unique in that they moved down for reasons of poor health and that for the majority (81%) ill health meant heart and lung diseases. Elderly migrants from high altitude reported heart and lung diseases more frequently than those remaining and cited improvement in symptoms at low altitude. We suggest that symptoms of heart and lung disease are exacerbated with advancing age at high altitude and influence choice of residence.

Aged↗

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↗

PubMed1984

Increased incidence of neonatal hyperbilirubinemia at 3,100 m in Colorado.

The incidence of neonatal hyperbilirubinemia (defined as total serum bilirubin levels greater than 12 mg/dL) in all infants born in a 14-month period at 3,100 m of altitude (32.7%) was more than twice that in infants born at 1,600 m of altitude (13.0%) and four times the incidence reported in the literature for sea level. A systematic comparison of factors known to influence serum bilirubin levels between 150 infants at 3,100 m and 378 infants at 1,600 m failed to disclose any factor(s) other than altitude that could account for the increased incidence of hyperbilirubinemia at high altitude. The mechanism responsible for this phenomenon is unknown, but we speculate that it may involve an adverse influence of high altitude on bilirubin load, conjugation, and/or uptake in neonatal life.

Altitude↗

PubMed1984

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.

Acclimatization↗

PubMed1984

Effect of oxytocin on plasma concentrations of 13,14-dihydro-15-keto prostaglandin F and the oxytocin-associated neurophysin during the estrous cycle and early pregnancy in the ewe.

This study was undertaken to determine the effect of exogenous oxytocin on plasma concentrations of the prostaglandin (PG) F metabolite 13,14-dihydro-15-keto-PGF (PGFM) and the oxytocin-associated neurophysin (OT-N) during the estrous cycle and early pregnancy in the ewe. Ewes were given oxytocin (250 mU, i.v.) on Days 3 (n = 4), 8 (n = 5), 13 (n = 4) or 14 (n = 5) of the estrous cycle, and a further 6 ewes were injected on Days 13 (n = 2) and 14 (n = 4) of pregnancy. No significant rises in plasma concentrations of PGFM were observed on Days 3 and 8 of the estrous cycle and on Days 13 and 14 of pregnancy. A marked increase in plasma PGFM concentrations occurred on Day 14 of the estrous cycle with the PGFM levels rising from a mean basal value of 120 pg/ml to a mean maximum value of 415 pg/ml within 2-10 min of administering oxytocin (P less than 0.001). No increases in plasma OT-N concentrations were found in early pregnancy and only 1 of 4 ewes at Day 14 of the cycle showed any significant increase in OT-N concentrations. It is concluded that there is an increase in the responsiveness of the uterine-PGF secretory system to oxytocin during the latter stages of the estrous cycle. During early pregnancy this response was blocked by the presence of the embryo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

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.

Adult↗

PubMed1984

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.

Adult↗

PubMed1984

Respiratory function in normal Chinese: comparison with Caucasians.

We found that respiratory measurements in Chinese visitors to Colorado differed from those in height- and weight-matched Western residents of Denver, Colo., in the following ways (p less than 0.05): The Chinese had higher respiratory frequencies (15.5 +/- 0.93 vs. 11.4 +/- 0.85 breaths/min), lower tidal volumes (530 +/- 35.9 vs. 693 +/- 477.7 ml), lower alveolar ventilation (4.0 +/- 0.15 vs. 4.7 +/- 0.21 liters), lower forced vital capacities (4.53 +/- 0.16 vs. 5.43 +/- 0.12 liters), lower total lung capacities (6.25 +/- 0.26 vs. 7.16 +/- 0.17 liters), higher resting PaCO2 (36.3 +/- 0.94 vs. 33.6 +/- 0.74 Torr) and lower pHa (7.406 +/- 0.004 vs. 7.419 +/- 0.004). The Chinese also had lower ventilatory responses to CO2 (1.40 +/- 0.10 vs. 2.00 +/- 0.201/min/mm Hg) than did the Caucasians. The measurements made in the Chinese in Denver were similar to those reported for Chinese in China. Thus there may be differences in respiratory function between normal Chinese and normal Western subjects.

Adult↗

PubMed1984

Bilirubin metabolism in the rat at high altitude.

Bilirubin metabolism was studied in rats injected with unconjugated bilirubin (0, 0.5, 1.5, 3.0, or 4.5 mg X 100 g-1) after 2 and 6 weeks continuous exposure to 4,600 m (15,000 ft) simulated altitude. Exogenous loads of bilirubin were used to exceed any effect of polycythemia, thereby allowing assessment of defects in conjugation and excretion due to the exposure to high altitude. Rats given no exogenous bilirubin showed polycythemia when exposed to high altitude which may have contributed to the small but significant elevations in their serum bilirubin levels. Compared to sea-level controls, mean serum concentrations of total and unconjugated bilirubin were significantly elevated in altitude-exposed rats given exogenous bilirubin. Mean serum conjugated bilirubin levels did not rise at any dose. Thus, bilirubin uptake and/or conjugation rather than excretion are impaired in rats at high altitude. We conclude that while polycythemia may contribute to high altitude-induced bilirubinemia, an impairment in uptake and/or conjugation also exists.

Animals↗

PubMed1983

Colocalization of oxytocin and neurophysin-I/II and of vasopressin and neurophysin-III in neurons of the sheep hypothalamus. An immunohistochemical study.

Antisera raised against, oxytocin, vasopressin and ovine neurophysins-I, -II and -III (oN-I, oN-II and oN-III respectively) were used in association with the immunohistochemical procedure to stain neurons of the formalin-fixed sheep hypothalamus. Cells that stain for oxytocin also contain oN-I and oN-II and differ from those that stain for vasopressin and oN-III. The observations support our earlier findings in the sheep that oxytocin- and vasopressin-related events are accompanied by the release of oN-I/II and oN-III respectively.

Animals↗