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Biomedical subjects

R L Ge

Publications and source records attributed to R L Ge.

16 recordsLinked to original sources
PubMed2001

Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness.

BACKGROUND: Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood. METHODS: We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years. RESULTS: A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P < .01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects. CONCLUSIONS: These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

2,3-Diphosphoglycerate↗
PubMed2001

Current concept of chronic mountain sickness: pulmonary hypertension-related high-altitude heart disease.

High-altitude heart disease, a form of chronic mountain sickness, has been well established in both Tibet and Qinghai provinces of China, although little is known regarding this syndrome in other countries, particularly in the West. This review presents a general overview of high-altitude heart disease in China and briefly summarizes the existing data with regard to the prevalence, clinical features, and pathophysiology of the illness. The definition of high-altitude heart disease is right ventricular enlargement that develops primarily (by high-altitude exposure) to pulmonary hypertension without excessive polycythemia. The prevalence is higher in children than adults and in men than women, but is lower in both sexes of Tibetan high-altitude residents compared with acclimatized newcomers, such as Han Chinese. Clinical symptoms consist of headache, dyspnea, cough, irritability, and sleeplessness. Physical findings include a marked cyanosis, rapid heart and respiratory rates, edema of the face, liver enlargement, and rales. Most patients have complete recovery on descent to a lower altitude, but symptoms recur with a return to high altitude. Right ventricular enlargement, pulmonary hypertension, and remodeling of pulmonary arterioles are hallmarks of high-altitude heart disease. It is hoped that this information will assist in understanding this type of chronic mountain sickness, facilitate international exchange of data, and stimulate further research into this poorly understood condition.

Altitude Sickness↗
PubMed2000

Hypoxia-induced pulmonary blood redistribution in subjects with a history of high-altitude pulmonary edema.

BACKGROUND: Pulmonary hypertension has been suggested to play an important role in development of high-altitude pulmonary edema (HAPE), and individual susceptibility has been suggested to be associated with enhanced pulmonary vascular response to hypoxia. We hypothesized that much greater pulmonary vasoconstriction would be induced by acute alveolar hypoxia in HAPE-susceptible (HAPE-s) subjects and that changes in pulmonary blood flow distribution could be demonstrated by radionuclide study. METHODS AND RESULTS: We performed ventilation-perfusion scintigraphy in 8 HAPE-s subjects and 5 control subjects while each was in the supine position and acquired functional images of pulmonary blood flow and ventilation under separate normoxic and hypoxic (arterial oxygen saturation, 70%) conditions. We also measured acceleration time/right ventricular ejection time (AcT/RVET) with Doppler echocardiography under each condition in both groups. Moreover, we assayed human leukocyte antigen (HLA) alleles serologically in the HAPE-s group. Pulmonary blood flow was significantly shifted from the basal lung region to the apical lung region under hypoxia in HAPE-s subjects, although no significant change in regional ventilation was observed. With Doppler echocardiography, HAPE-s subjects showed increased pulmonary arterial pressure during hypoxia compared with control subjects. The magnitude of cephalad redistribution of lung blood flow was significantly higher in the HLA-DR6-positive than in HLA-DR6-negative HAPE-s subjects. CONCLUSIONS: These findings suggest that acute hypoxia induces much greater cephalad redistribution of pulmonary blood flow that results from exaggerated vasoconstriction in the basal lung in HAPE-s subjects. Furthermore, pulmonary vascular hyperreactivity to hypoxia may be associated with HLA-DR6.

Altitude Sickness↗
PubMed2000

Pulmonary artery remodeling modifies pulmonary hypertension during exercise in severe emphysema.

To clarify the relation between the vessel remodeling and the physiology of pulmonary circulation in chronic obstructive pulmonary disease (COPD), we studied the pulmonary hemodynamics at rest and during exercise (25W) and the morphology of pulmonary arteries with external diameters of 100-200 microm in ten patients with severe emphysema. The wall thickness (WT) was defined as the intima plus media. The percent WT of the external diameter (% WT) in emphysema (36.0 +/- 4.3%) was significantly increased compared with that (22.6 +/- 3.3%) in five control lungs. The % WT was not related to pulmonary arterial pressure (Ppa) at rest, but was highly correlated with exercise Ppa (r = 0.721, P = 0.02) and with deltaPpa (Ppa during exercise-Ppa at rest) (r = 0.899, P = 0.0004). These findings suggest that pulmonary artery remodeling leads to reduced recruitability and distensibility of pulmonary vessels and is closely related to exercise pulmonary hypertension.

Aged↗
PubMed1999

Endothelin receptor blockade attenuates air embolization-induced pulmonary hypertension in sheep.

We investigated the effects of two types of endothelin receptor antagonists on pulmonary hypertension induced by pulmonary air embolization in awake sheep. We prepared awake sheep with indwelling catheters inserted in blood vessels for continuous monitoring of pulmonary artery pressure, left atrial pressure and systemic arterial pressure. Cardiac output was measured every 30 min. The study consisted of two experiments, one with FR139317 (100 microg/kg/min; (R)2-[(R)-2-[(S)-2-[1-(hexahydro-1H-azepinyl)]-carbonyl]amino-4-++ +methy l-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl)amino-3-(2-pyr idyl)propionic acid), a selective endothelin ET(A) receptor antagonist, and the other with TAK-044 (100 microg/kg/h; cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-yl)carbonyl]-L-alanyl -L- alpha- aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium salt), an endothelin ET(A) and ET(B) receptor antagonist. In the paired experiments, air was continuously (4.06 ml/min) infused into the main pulmonary artery for 3 h after the baseline pressures were stabilized. Sheep were treated or not treated with FR139317 or TAK-044. Pulmonary artery pressure was significantly higher than the baseline pressure after the start of air infusion. Both FR139317 and TAK-044 significantly attenuated the increase in pulmonary artery pressure during air embolization. Plasma endothelin -1 levels in both pulmonary and systemic arteries were equally and significantly increased after the start of air infusion. The results indicate that endothelin-1 release is attributable to the development of pulmonary hypertension during the course of air embolization in awake sheep.

Animals↗
PubMed1998

Blunted hypoxic pulmonary vasoconstrictive response in the rodent Ochotona curzoniae (pika) at high altitude.

To investigate the possible mechanisms of adaptation to chronic hypoxia in the pulmonary circulation, we made direct measurements of pulmonary arterial pressure (Ppa) in 10 awake pika rodents that were transported to Xining, People's Republic of China (altitude 2,260 m) after being captured at 4,300 m and in 10 Wistar rats in a decompression chamber (simulated altitudes of 4,300 and 5,000 m) in Xining. Ppa was obtained at 1 h of exposure to each simulated altitude. The histology and immunohistochemistry of the lung tissues were also studied. Ppa in the pikas after the 4,300- and 5,000-m altitude exposures did not significantly increase, whereas in the rats Ppa rose significantly. Mean changes in Ppa from 2,260 to 4,300 and 5,000 m were 1.48 +/- 0.49 and 4.80 +/- 0.67 mmHg in the pikas and 10.38 +/- 3.36 and 19.10 +/- 2.28 mmHg in the rats. The ratio of right ventricular to left ventricular plus septal weight in the pikas and rats was 0.22 and 0.45, respectively. The pikas maintained levels of Hb, hematocrit, and 2,3-diphosphoglycerate lower than those of the rats. The percent wall thickness of the small pulmonary arteries in the pikas and rats was 9.22 and 27.21%, respectively, and it was well correlated with the degree of Ppa in both groups. Mast cells were observed in the lungs of the rats (7.1 +/- 0.33 cells/mm2) but not in the pikas. There was highly positive staining for mast cell tryptase and transforming growth factor-beta around pulmonary vessels in the rats, whereas no demonstrable reaction was observed in the pikas. We conclude that the pika has adapted to high altitude by losing hypoxic pulmonary vasoconstriction and thin-walled pulmonary arterioles.

Animals↗
PubMed1998

Pharmacokinetic characteristics of the novel anticancer agent CPT-11 and its active metabolite in plasma and lung lymph fluid following intravenous administration to sheep.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11, 100286-90-6) is one of the most promising novel anticancer agents, especially for lung cancer. 7-Ethyl-10-hydroxycamptothecin (SN-38), an active metabolic of CPT-11, has much stronger cytotoxicity than CPT-11. The present study was designed to evaluate the distribution and behavior of CPT-11 and SN-38 in lung lymph circulation following intravenous infusion. Awake sheep with chronically instrumented lung lymph fistulas were prepared. The concentrations of CPT-11 and SN-38 in plasma and lung lymph fluid were measured after intravenous infusion of 100 mg/body of CPT-11 for 90 min. SN-38 constantly showed higher lymph to plasma concentration ratios than those of CPT-11, and the % area under the curve (AUC) ratio of SN-38/CPT-11 in lymph fluid was significantly higher than that in plasma. These data indicated that SN-38 distributed in lung tissue moved more easily into lung lymph fluid than CPT-11, and might be more rapidly metabolized in lung tissue than plasma. CPT-11 may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis.

Animals↗
PubMed1997

Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300 m.

The difference was studied between O2 transport in lifelong Tibetan adolescents and in newcomer Han adolescents acclimatized to high altitude. We measured minute ventilation, maximal O2 uptake, maximal cardiac output, and arterial O2 saturation during maximal exercise, using the incremental exercise technique, at altitudes of 3,417 and 4,300 m. The groups were well matched for age, height, and nutritional status. The Tibetans had been living at the altitudes for a longer period than the Hans (14.5 +/- 0.2 vs. 7.8 +/- 0.8 yr at 3,417 m, P < 0.01; and 14.7 +/- 0.3 vs. 5.3 +/- 0.7 yr at 4,300 m, P < 0.01, respectively). At rest, Tibetans had significantly greater vital capacity and maximal voluntary ventilation than the Hans at both altitudes. At maximal exercise, Tibetans compared with Hans had higher maximal O2 uptake (42.2 +/- 1.7 vs. 36.7 +/- 1.2 ml . min-1 . kg-1 at 3,417 m, P < 0.01; and 36.8 +/- 1.9 vs. 30.0 +/- 1. 4 ml . min-1 . kg-1 at 4,300 m, P < 0.01, respectively) and greater maximal cardiac output (12.8 +/- 0.3 vs. 11.4 +/- 0.2 l/min at 3,417 m, P < 0.01; 11.5 +/- 0.5 vs. 10.0 +/- 0.5 l/min at 4,300 m, P < 0. 05, respectively). Although the differences in arterial O2 saturation between Tibetans and Hans were not significant at rest and during mild exercise, the differences became greater with increases in exercise workload at both altitudes. We concluded that exposure to high altitude from birth to adolescence resulted in an efficient O2 transport and a greater aerobic exercise performance that may reflect a successful adaptation to life at high altitude.

Acclimatization↗
PubMed1997

Low pulmonary diffusing capacity in subjects with acute mountain sickness.

This study was conducted to investigate whether the changes in the pulmonary diffusing capacity found in individuals with acute mountain sickness (AMS) reflect the early stage of high-altitude pulmonary edema (HAPE). We measured the pulmonary diffusion capacity for carbon monoxide (DCO) by the single-breath method, arterialized capillary blood gas, and spirometry in a group of 32 healthy subjects (24 men, eight women) at an altitude of 2,260 m and after ascent to 4,700 m. Twelve subjects (10 men, two women) had symptoms of AMS (AMS group) by the second day after arrival at 4,700 m, but none had clinical signs of pulmonary or cerebral edema. In the non-AMS group, almost all subjects exhibited an increase in DCO at 2,260 to 4,700 m (delta DCO, 10.7 +/- 1.25 mL/min/mm Hg), while the degree of increase in DCO in the AMS group (n = 12) was significantly lower (delta DCO, 1.26 +/- 1.74 mL/min/mm Hg) than that of the non-AMS group (p < 0.01). In four of the 12 subjects with AMS who had a high AMS score, DCO decreased from 38.4 +/- 4.5 to 33.2 +/- 5.3 mL/min/mm Hg (delta DCO, -5.84 +/- 1.1 mL/min/mm Hg). The AMS group showed significantly lower vital capacity, forced expiratory flow during the middle half of FVC, PaO2, and a greater alveolar-arterial oxygen pressure difference at 4,700 m compared with the non-AMS group. DCO showed a significant negative correlation with AMS score (r = -0.885) and a positive correlation with PaO2 (r = 0.757) at 4,700 m. These results suggest that the decreased pulmonary diffusing capacity in subjects with AMS reflects the presence of pulmonary gas exchange abnormality, which is probably due to subclinical interstitial edema of the lung.

Acute Disease↗
PubMed1997

Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.

We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.

Animals↗
PubMed1996

Influence of hypoxia and pulmonary air embolism on lung injury in perfused rat lungs.

We investigated the influence of low oxygen ventilation, air-bubble infusion into the pulmonary artery and their synergistic effect on pulmonary hemodynamics and microvascular permeability in isolated perfused rat lungs. Pulmonary arterial pressure was significantly increased by 70 min of ventilation with 3% O2 (hypoxia, group H); by 0.2-ml air-bubble infusion (pulmonary air embolism, group AE), and by 0.2-ml air-bubble infusion and 70 min of 3% O2 ventilation (hypoxia and pulmonary air embolism, group H & AE) compared with that of a control group (0.2 ml saline infusion, group C). Neither total (TPR) nor arterial (Ra) pulmonary vascular resistance in group H showed any difference compared to control values. TPR and Ra in groups AE and H & AE were significantly higher than those in group C. However, there was no significant difference in TPR or Ra between groups AE and H & AE. The pulmonary capillary fluid filtration coefficient, dry lung to wet lung weight ratio and white blood cell count in the perfusate of group H were not changed, while those of the groups AE and H & AE were significantly increased compared to those of controls. However, there was no significant difference in these values between groups AE and H & AE. Since hypoxia did not damage isolated perfused rat lungs, as determined by hemodynamics and permeability, nor enhance lung injury caused by air embolism, it was suggested that air embolism contributed more to high-altitude lung injury than low oxygen.

Analysis of Variance↗
PubMed1996

Sound stimulation-induced vasomotor reflex in the central artery of the rabbit ear.

Effects of sound stimulation on the central artery of the rabbit ear were studied as a somato-autonomic reflex. Vasoconstriction and dilatation, caused by metronome sound stimulation, were estimated from the temperature fluctuations in the central artery of the ear, measured by a thermistor. To enhance the detection of temperature rises, moderately high background levels of arterial tone were established by exposing the tips of the ears to water at a temperature of 10 degrees C or 5 degrees C, prior to sound stimulation. A fall in arterial temperature due to vasoconstriction was observed immediately after the start of the 1-min sound stimulation, with a subsequent temperature rise which overshot the original basal level due to vasodilatation. A positive correlation between the ear temperature before sound stimulation and the temperature fall (p < 0.01), and a negative correlation between the ear temperature and the temperature rise (p < 0.05) were obtained. The temperature fall was blocked by phenoxybenzamine (9 mg/kg, i.p., p < 0.01). The subsequent rise was not influenced by atropine (3 mg/kg, i.p.) or phenoxybenzamine, however, it was attenuated by hexamethonium (6 mg/kg, i.p., p < 0.05). The temperature fall at the beginning of sound stimulation was related to alpha-adrenergic mechanism. The subsequent temperature rise was thought to be related to parasympathetic mechanism, excluding cholinergic mechanism.

Acoustic Stimulation↗
PubMed1996

Acute hypoxic pulmonary vascular response does not accompany plasma endothelin-1 elevation in subjects susceptible to high altitude pulmonary edema.

We have previously shown that high altitude pulmonary edema-susceptible subjects (HAPE-S) have an accentuated pulmonary vascular response to hypoxia. In this study, we investigated the relationship between plasma endothelin-1 (ET-1) levels and the acute hypoxic pulmonary vascular response in HAPE-S and control subjects. In six HAPE-S and seven healthy subjects, we evaluated acceleration time/right ventricular ejection time (AcT/RVET) using Doppler echocardiography, and measured plasma ET-1 levels by radioimmunoassay (RIA) before and after 5 minutes of breathing 10% oxygen. The HAPE-S showed a significantly increased pulmonary vascular response to hypoxia compared with healthy subjects. However, no statistically significant changes of plasma ET-1 levels were observed before and after hypoxia in both groups. We conclude that the increased pulmonary vascular response to acute hypoxia in HAPE-S may not be related to ET-1 release.

Acute Disease↗
PubMed1994

Higher exercise performance and lower VO2max in Tibetan than Han residents at 4,700 m altitude.

To examine the hypothesis that the pathway of adaptation to high altitude in natives differs considerably from that in newcomers, we measured maximal O2 uptake (VO2max), minute ventilation, anaerobic threshold (AT), blood lactate, and blood gases during maximal exercise in 17 lifelong Tibetan residents and 14 acclimatized Han Chinese newcomers living at the altitude of 4,700 m. The two groups were similar in age, height, and weight, and the subjects were nonathletes. Although VO2max was significantly lower in the Tibetans than in the Hans (30.4 +/- 1.5 vs. 36.0 +/- 1.9 ml.min-1.kg-1 STPD; P < 0.05), at maximal exercise effort the exercise workload was greater (167.7 +/- 4.2 vs. 150.0 +/- 5.9 W; P < 0.05). The mean AT values (in % VO2max) in the Tibetan and Han subjects were 84.1 and 61.6%, respectively (P < 0.01). Minute ventilation at maximal exercise was significantly lower in the Tibetans than in the Hans (68.4 +/- 3.4 vs. 79.7 +/- 4.1 l/min BTPS; P < 0.05), whereas heart rate at maximal effort was equivalent in the two groups. The Tibetans showed lower blood lactate value than did the Hans both before and at the end of exercise. We conclude that the Tibetan natives have higher exercise performance and AT but lower VO2max and blood lactate concentration than do acclimatized Han newcomers. These results may reflect the effects of genetic or peripheral adaptation factors in the Tibetan natives.

Acclimatization↗
PubMed1994

[Characteristics of hypoxic ventilatory response in Tibetan living at moderate and high altitudes].

Hypoxic and exercises ventilatory responses measured in Tibetan who lived at moderate (2000-3000m, M-Tibetan) and high (4000-4700m, H-Tibetan) altitude areas. The result showed that the slope of hypoxic ventilatory response (HVR; VE/SaO2) in M- and H-Tibetan was 0.81 +/- 0.07 and 0.46 +/- 0.04 L/min/%SaO2 (P < 0.01) and the maximal exercise ventilation (VEmax) was 78.3 +/- 3.5 and 68.2 +/- 2.1 L/min (P < 0.05), respectively. There were positive correlation between delta VE/delta SaO2 and VEmax, which gamma = 47.0 +/- 37.3x, r = 0.70 in M-Tibetan, and gamma = 53.8 +/- 31.4x, r = 0.67 in H-Tibetan. Maximal heart rate of the H-Tibetan was significantly lower than that in the M-Tibetan (P < 0.01). It is suggested that the attenuation of HVR depends on the magnitude of the hypoxic stimulus. Therefore, there are differences even among the high-altitude natives in ventilatory response to hypoxia, e.g. normal respiratory sensitivity to hypoxia in moderate-altitude natives, and blunted in high-altitude natives.

Adaptation, Physiological↗