Biomedical subjects

L G Moore

Publications and source records attributed to L G Moore.

At least 109 records · Page 6Linked to original sources

PubMed1990

Effects of estrogen and progesterone on carotid body neural output responsiveness to hypoxia.

Pregnancy increases ventilatory and carotid body neural output (CBNO) responsiveness to hypoxia in cats (J. Appl. Physiol. 67: 797-803, 1989). To determine whether progesterone and estrogen stimulated hypoxic ventilatory and CBNO responsiveness, we studied 24 castrated male cats before and after 1 wk of placebo, estrogen, progesterone, or estrogen plus progesterone treatment. Estrogen plus progesterone treatment decreased end-tidal PCO2 (-3.8 +/- 0.8 Torr) and increased hypoxic ventilatory responsiveness, whereas estrogen or progesterone alone had no effect. Animals receiving progesterone alone or in combination with estrogen had higher CBNO responsiveness than placebo or estrogen-treated animals (shape parameter A = 45 +/- 7 vs. 27 +/- 4, P less than 0.05). However, the group treated with estrogen plus progesterone did not have greater CBNO responsiveness to hypoxia than the group receiving progesterone alone. The cross plot of the simultaneously measured CBNO and ventilation during progressive hypoxia revealed a greater slope in the estrogen-treated than in the placebo animals, suggesting that estrogen treatment increased central nervous system transduction of CBNO into ventilation. Thus the data taken together suggested that progesterone and estrogen had a combination of peripheral (carotid body) and central sites of action such that the administration of both hormones together had a more consistent stimulatory effect on hypoxic ventilatory responsiveness than either hormone alone.

Animals↗

PubMed1990

Systemic vascular reactivity during high-altitude pregnancy.

There is an increased incidence of preeclampsia at high compared with low altitude. Increased vasoreactivity, possibly due to a deficiency of vasodilator prostaglandins, is thought to contribute to the etiology of preeclampsia. We sought to determine whether high-altitude exposure increased systemic vascular reactivity during pregnancy. We measured systemic vascular reactivity and contractile sensitivity of isolated aortic rings from pregnant and nonpregnant guinea pigs kept for 6 wk at either simulated high altitude (3,900 m) or low altitude (1,600 m). We found that pregnancy at high compared with low altitude increased baseline systemic vascular resistance (SVR) but not the SVR response to angiotensin II in awake unstressed guinea pigs. Contractile sensitivity to norepinephrine was also increased in aortic rings isolated from high-altitude compared with low-altitude pregnant animals. Meclofenamate, a prostaglandin synthesis inhibitor, did not equalize vasoreactivity in the high- and low-altitude pregnant guinea pigs or in their isolated aortic rings. We concluded that pregnancy at high compared with low altitude increased base-line SVR and aortic contractile sensitivity but that mechanisms other than decreased vasodilator prostaglandin production were responsible.

Altitude↗

PubMed1990

Decreased ventilation and hypoxic ventilatory responsiveness are not reversed by naloxone in Lhasa residents with chronic mountain sickness.

Persons with chronic mountain sickness (CMS) hypoventilate and are more hypoxemic than normal individuals, but the cause of the hypoventilation is unclear. Studies of 14 patients with CMS and 11 healthy age-matched control subjects residing in Lhasa, Tibet, China (3,658 m) were conducted to test the hypothesis that hypoventilation, blunted hypoxic ventilatory responsiveness (HVR), and hypoxic ventilatory depression of CMS were due to increased endogenous opioid production. Patients with CMS compared with control subjects exhibited hypoventilation (end-tidal carbon dioxide pressure [PETCO2] = 36.6 +/- 1.0 versus 31.5 +/- 0.5 mm Hg, p less than 0.05), lower tidal volume (VT = 0.54 +/- 0.02 versus 0.61 +/- 0.02 ml BTPS, p less than 0.05), blunted HVR (shape parameter A = 17 +/- 8 versus 114 +/- 22 mm Hg/L BTPS/min, p less than 0.05), and a depressant effect of ambient hypoxia on ventilation (delta PETCO2 with acute hyperoxia = -3.5 +/- 0.5 versus -1.0 +/- 0.6 mm Hg, p less than 0.05). Reduced forced expiratory volume in 1 s to vital capacity ratios (FEV1/VC) and a higher proportion of cigarette smokers in the group of patients with CMS compared with control subjects suggested that at least some patients with CMS had mild airway obstructive lung disease. Naloxone infusion (0.14 mg/kg) to six patients with CMS did not change resting VT, PETCO2, HVR, or SaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Altitude Sickness↗

PubMed1989

Neonatal hyperbilirubinemia at high altitude.

A previous retrospective study showed an increased frequency of neonatal hyperbilirubinemia at high altitude in Colorado. In a prospective study we found that 39% of newborns at 3100 m altitude vs 16% at 1600 m exhibited hyperbilirubinemia, defined as a day 3 serum bilirubin level of 205 mumol/L or higher. Increased bilirubin production at 3100 m vs 1600 m was shown by increased levels of corrected carboxyhemoglobin. This finding was supported by increased erythropoietin and bilirubin values in cord blood and increased hematocrit values at day 3 among infants at 3100 m vs 1600 m. The sustained elevation in bilirubin for breast-fed vs formula-fed infants at 1600 m was observed for both feeding types at 3100 m. The findings suggested that there is a hematologic response to decreased oxygen availability at high altitude, resulting in increased bilirubin production accompanied by delayed bilirubin clearance.

Adult↗

PubMed1989

Blunted vasoreactivity in pregnant guinea pigs is not restored by meclofenamate.

Pregnant women show a reduced pressor responsiveness to angiotensin II, but the mechanism responsible in unclear. We sought to determine whether reduced pressor responsiveness was due to decreased vasoreactivity and the involvement of increased vasodilator prostaglandin production in decreases observed. We found that pregnancy decreased systemic vascular resistance and the systemic vascular resistance response to angiotensin II infusion but not to phenylephrine hydrochloride infusion in awake, unstressed guinea pigs. The decreased systemic vascular resistance response to angiotensin II in the pregnant animals was accompanied by a reduced pressor response. Contractility to phenylephrine hydrochloride and norepinephrine was reduced in aortic rings isolated from pregnant, compared with nonpregnant, guinea pigs. Treatment with meclofenamate, a prostaglandin synthesis inhibitor, did not restore vasoreactivity in either the pregnant animal or the isolated vessel to levels observed in the nonpregnant state. We concluded that pregnancy reduced systemic vascular resistance and vasoreactivity but that mechanisms other than increased vasodilator prostaglandin production were likely responsible.

Angiotensin II↗

PubMed1989

Combined effects of female hormones and metabolic rate on ventilatory drives in women.

Increased resting ventilation (VE) and hypoxic and hypercapnic ventilatory responses occur during pregnancy in association with elevations in female hormones and metabolic rate. To determine whether increases in progestin, estrogen, and metabolic rate produced a rise in VE and hypoxic ventilatory response (HVR) similar in magnitude to that observed at full-term pregnancy, we studied 12 postmenopausal women after 1 wk of treatment with placebo, progestin (20 mg tid medroxyprogesterone acetate), estrogen (1.25 mg bid conjugated equine estrogens), and combined progestin and estrogen. Progestin alone or with estrogen raised VE at rest and decreased end-tidal PCO2 (PETCO2) by 3.9 +/- 0.8 and 3.3 +/- 0.6 Torr, respectively (both P less than 0.05), accounting for approximately one-fourth of the rise in VE and three-fourths of the PETCO2 reduction seen at full-term pregnancy. The addition of mild exercise sufficient to raise metabolic rate by 33-36% produced the remaining three-fourths of the rise in VE but no further decline in PETCO2. Combined progestin and estrogen raised HVR and hypercapnic ventilatory response more consistently than progestin alone and could account for one-half of the increase in HVR seen at full-term pregnancy. Mild exercise alone did not raise HVR, but when exercise was combined with progestin and estrogen administration, HVR rose by amounts equal to that seen at full-term pregnancy. We concluded that female hormones together with mild elevation in metabolic rate were likely responsible for the pregnancy-associated increases in VE and HVR.

Adult↗

PubMed1989

Progestin and estrogen reduce sleep-disordered breathing in postmenopausal women.

Women exhibit sleep-disordered breathing syndromes less commonly than men before but not after the age of menopause, suggesting that female hormones may exert a protective effect. We sought to determine whether combined progestin and estrogen treatment decreased sleep-disordered breathing in healthy postmenopausal women. Nine ovarihysterectomized women [50 +/- 2 (SE) yr of age] were studied after 1 wk of treatment with placebo (lactose) or combined progestin and estrogen (medroxyprogesterone acetate, 20 mg tid, and Premarin, 1.25 mg bid). Subjects showed few respiratory disturbances during placebo treatment. Despite this, combined progestin and estrogen administration reduced the number of sleep-disordered breathing episodes in every subject, decreasing the average number of episodes per subject from 15 +/- 4 to 3 +/- 1. The duration of hypopneas also decreased with hormone treatment. Thus the presence of progestin and estrogen may be involved in protecting premenopausal women against sleep-disordered breathing.

Drug Combinations↗

PubMed1989

Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats.

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.

Animals↗

PubMed1989

Metabolic clearance of insulin-like growth factor-II in sheep.

The metabolic clearance of ovine insulin-like growth factor-II (IGF-II) was examined in sheep using 131I-labelled IGF-II. Following i.v. administration the tracer was distributed in a volume similar to that of the vascular space (58.5 +/- 3.3 ml/kg; mean +/- S.E.M., n = 5) and demonstrated a triphasic pattern of clearance. Size-exclusion chromatography of a plasma sample collected 1 min after injection revealed peaks of radioactivity corresponding to hormone complexed to binding proteins of 150 and 40-50 kDa (relative abundance 21 and 65% respectively), a high molecular weight binding protein (greater than 200 kDa; 5%) and 'free' tracer (9%). Chromatography of sequential plasma samples revealed different patterns of clearance for these constituents. Half-lives of 131I-labelled IGF-II complexed to the 150 and 40-50 kDa binding proteins, as calculated from rate constants for their decay, were 351 +/- 30 and 9.6 +/- 1.8 min respectively (n = 5). These differ markedly from estimates for the clearance of IGF-I (545 +/- 25 min, n = 8, and 34 +/- 2.3 min, n = 6) associated with carrier proteins of the same apparent molecular weights. This was reflected in calculated metabolic clearance rates for IGF-I (3.9 +/- 0.5 ml/min) and IGF-II (7.8 +/- 1.0 ml/min). Chromatography also revealed that free IGF-II was reduced to negligible levels by 12 min. In contrast, radioactivity eluting in the position expected for the greater than 200 kDa binding protein was cleared from the circulation very slowly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Improved estimates of clearance of 131I-labelled insulin-like growth factor-I carrier protein complexes from blood plasma of sheep.

Clearance of protein-bound forms of insulin-like growth factor-I (IGF-I) from the circulation of sheep was determined using single injections of 131I-labelled ovine or [Thr59]-human IGF-I, in the 'free' form or prebound to 50 or 150 kDa plasma binding protein fractions. The half-life of circulating protein-bound forms of IGF-I was determined by size-exclusion chromatography of plasma samples taken over a 24- to 26-h experimental period. IGF-I bound to lower molecular weight binding protein(s) (approximately 50 kDa) showed a half-life of 26-40 min (mean 34 min; n = 6), while the half-life of a high molecular weight fraction (150 kDa) was considerably longer (range 398-603 min; mean 545 min; n = 8). Metabolic clearance of IGF-I following administration of free tracer ranged from 3.0 to 5.3 ml/min in sheep (n = 4) weighing 26.0-28.5 kg. Tracer distribution volume was 59 ml/kg liveweight (n = 4). Tracer degradation products were first detected in plasma 8 h after i.v. administration. No differences in stability of the purified ovine and recombinant human IGF-I tracer preparations were observed. However, a fraction of the [Thr59]-IGF-I tracer did not possess binding activity and this was associated with excretion of a greater proportion of administered radioactivity (over 22 h) in urine in animals receiving [Thr59]-IGF-I tracer (18.4-19.3%) compared with ovine IGF-I (7.1-11.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Altitude, low birth weight, and infant mortality in Colorado.

A decrease in birth weight occurs at high altitude, but its relationship to infant mortality is unclear. We examined Colorado vital statistics recorded from 1979 through 1982 to determine whether high altitude increased infant mortality and whether decreased birth weight contributed to the mortality observed. Retardation of intrauterine growth reduced birth weight and doubled the frequency of low-birth-weight infants from the lowest (915 to 1523 m [3000 to 4999 ft]) to the highest (greater than or equal to 2744 m [greater than or equal to 9000 ft]) altitude in the state. Low birth weight increased mortality risk, but the mortality risk of low birth weight was decreased at high compared with low altitudes, resulting in similar infant mortality rates throughout the state. This finding differed from that of 1969 through 1973 when infant mortality doubled at high altitude. A 46% infant mortality reduction had occurred statewide over the ten years due chiefly to decreased mortality risk for preterm low-birth-weight infants. This reduction, particularly pronounced at high altitude, might have been due to better identification and transport of high-risk pregnancies to hospitals with tertiary neonatal treatment centers.

Altitude↗

PubMed1988

Characterization of neurophysin in the anterior pituitary gland of sheep.

Portions of sheep anterior pituitary lobe tissue were extracted under acid conditions and assayed for the two neurophysins (oN-III and oN-I/II) by radioimmunoassay. In all tissues examined, oN-III and oN-I/II immunoreactivities were detected. Using a combination of isoelectric focusing and polyacrylamide gel electrophoresis, the neurophysins of the anterior pituitary gland behaved like oN-III and oN-I/II. oN-III of the anterior pituitary was purified by affinity chromatography and high-performance liquid chromatography. This corticotroph oN possessed an amino acid analysis similar to that of oN-III and an N-terminal amino acid sequence, including residues 1-24, identical to that of authentic oN-III. These findings support the work of others who have identified neurohypophysial hormones in the anterior pituitary gland.

Amino Acid Sequence↗

PubMed1988

Possible gender differences in the effect of exercise on hypoxic ventilatory response.

Gender differences in resting ventilation and hypoxic ventilatory response (HVR) have been reported. Ventilation and HVR are closely related to changes in metabolic rate in men. However, it is unclear whether there is a comparable relationship between metabolic rate and ventilation or HVR in women. We studied 13 men and 12 women to determine whether exercise-induced increases in metabolic rate influenced ventilation, HVR, and hypercapnic ventilatory response (HCVR) differently in men and women. Minute ventilation per unit metabolic rate was higher (lower end-tidal PCO2) in women than men during rest and mild exercise. Resting HVR values were similar in men and women. With mild, exercise-induced increases in O2 consumption (24 +/- 4% in men and 27 +/- 2% in women, p = NS), HVR increased in men (p less than 0.05) but not in women. Moderate exercise-induced increases in O2 consumption (313 +/- 13% in men and 330 +/- 13% in women, p = NS), raised hypoxic responses in both sexes. HCVR values were similar in men and women at rest and during mild exercise. Moderate exercise increased HCVR equally in the sexes. Thus the higher resting ventilation and lesser change in HVR during mild exercise suggested that women were less sensitive to mild metabolic rate stimulation than men.

Adult↗

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

Altitude-aggravated illness: examples from pregnancy and prenatal life.

Nearly 40 million persons worldwide live permanently at elevation above 8,000 ft (2,439 m) and perhaps as great a number visit high-altitude regions annually. Health effects include the well-recognized altitude-specific syndromes of acute mountain sickness and high-altitude pulmonary edema. Emphasis is placed in this article on altitude-aggravated illness or those preexisting conditions that may be adversely affected by reduced O2 availability at high altitude. Examples from studies of pregnant women and their infants at high altitude are reviewed to demonstrate the effect of high altitude on maternal and fetal well-being. Increased maternal ventilation and ventilatory response to hypoxia during pregnancy at 10,200 ft (3,110 m) and 14,200 ft (4,329 m) raised arterial O2 saturation, helped to preserve arterial O2 content at levels present when nonpregnant, and correlated positively with the offspring's birth weight. Fetal growth retardation and an increased incidence of the complications of pre-eclampsia and neonatal hyperbilirubinemia at high altitude suggested that altitude may aggravate complications of pregnancy and prenatal life. Other conditions that may be aggravated at high altitude are reviewed. Virtually all studies on altitude-aggravated illness have been conducted on permanent residents. Future studies should seek to determine whether high altitude aggravates pre-existing conditions among the large and growing number of high-altitude visitors.

Adaptation, Physiological↗

PubMed1987

Effect of systemic or intrauterine injections of indomethacin on plasma oxytocin-neurophysin concentrations in ewes over the time of normal corpus luteum regression.

This study was undertaken to investigate the effect of systemic or intrauterine injections of indomethacin, a known prostaglandin (PG) synthetase inhibitor, on peripheral plasma oxytocin-associated neurophysin (OT-N) concentrations in ewes over the time of expected luteolysis. In the first experiment, 9 ewes were given i.m. injections of indomethacin (4 mg/kg live weight, n = 4) or vehicle (n = 5) 3 times/day over Days 13-15 of the estrous cycle. Blood samples were collected at hourly intervals from 0700 h on Day 13 to 1800 h on Day 15 post-estrus. In the second experiment, indomethacin (20 mg, n = 5) or the injection vehicle (n = 4) was given twice daily into the uterine horn over Days 12-14 post-estrus. Blood samples were collected at hourly intervals from Day 12 to 14. In the third experiment, 4 additional ewes were bled at 5-min intervals from 1200 to 1600 h on Day 13 of the estrous cycle. Plasma samples were analyzed for OT-N and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) to provide an indirect index for ovarian oxytocin and uterine prostaglandin F2 alpha release, respectively. Results from the first experiment indicated that surges in plasma OT-N concentrations occurred in the vehicle-treated ewes but were suppressed in ewes given systemic injections of indomethacin. Intrauterine indomethacin injections did not cause a significant reduction in the maximum peak height or number of peaks when compared with the control ewes. In the third experiment, there was a marked increase in plasma OT-N concentrations, but no significant rise in plasma PGFM concentrations in one ewe.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗