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Biomedical subjects

L C Ou

Publications and source records attributed to L C Ou.

At least 55 records · Page 3Linked to original sources
PubMed1984

Renal function in rats chronically exposed to high altitude.

Chronic exposure of rats to a simulated altitude of 18,000 ft (5,500 m) results in severe polycythemia and consequent reduction of the plasma fraction. However, glomerular filtration rate is usually well maintained. This study was conducted to determine whether an increase in effective renal blood flow (ERBF) plays a role in maintaining a normal glomerular filtration rate in the chronically hypoxic rats. Various measurements of renal function were made in conscious trained and chronically catheterized animals. After exposure to high altitude for 30 days, hematocrit ranged from 64 to 77%. Despite this severe reduction in the plasma fraction, however, renal plasma flow decreased by only 25%, primarily owing to an increase in ERBF. The glomerular filtration rate was within the normal range. Since blood pressure remained unchanged, the increase in ERBF must have resulted from renal vasodilation. Acute removal of the hypoxic stimulus did not reverse the increased ERBF, suggesting that the vasodilation may have been of structural origin.

Altitude↗
PubMed1984

Strain and sex differences in the cardiopulmonary adaptation of rats to high altitude.

On chronic exposure to hypoxia, the commercially available Hilltop (H) strain of male Sprague-Dawley rats develops severe pulmonary hypertension, right ventricular hypertrophy (RVH), and polycythemia. These signs of chronic mountain sickness are associated with a high mortality rate. In contrast, the Madison (M) strain of Sprague-Dawley rats remains healthy with significantly less severe cardiopulmonary and hematological responses. Breeding experiments under locally controlled conditions were undertaken to determine if the differences between the two strains were genetically determined and to look for possible sex differences. Following 30 to 50 days exposure to a simulated altitude of 18,000 ft, the first generation of male H rats exhibited a higher right ventricular peak systolic pressure (RVPP), a more pronounced RVH, and a greater degree of polycythemia than the male M rats. The H rats had a mortality rate of 40% in contrast to a rate of 0% in the male M rats. The first generation of female H rats also developed a higher RVPP, a greater RVH, and more severe polycythemia than that in the female M rats. There were no differences in RVPP or RVH between the males and females of either strain. Females of both strains tolerated the hypoxic exposure with a 0% mortality rate. The data suggest that the differences between the males of H and M strains in their cardiopulmonary and hematological responses and in their susceptibilities to chronic hypoxia are genetic in nature. They further suggest that the female resistance to hypoxia is not due to milder cardiopulmonary responses. Perhaps female rats tolerate RVH better than male rats, at least of the H strain.

Adaptation, Physiological↗
PubMed1983

The contribution of central mechanisms rostral to the pons in high altitude ventilatory acclimatization.

In order to explore the role of suprapontine mechanisms in the ventilatory features of acclimatization to high altitude (HAVA) a study was made of: (a) normal cats after 48 h of exposure to a simulated altitude of 5500 m; (b) those same acclimatized cats 6 h following mid-collicular decerebration; (c) decerebrate cats after 48 h of exposure to a simulated altitude of 5500 m; (d) decerebrate cats after 48 h of exposure to room air at sea level. In a pilot study in which high altitude exposure was maintained for 30 days it was determined that normal cats show all of the manifestations of HAVA after 48 h. These were: increase of VI over acute hypoxic value and a maintained hyperventilation with normoxic inhaled gas; increase of both VT and f, the latter predominantly due to shortened TE; increase of VT/TI. Following decerebration the ventilatory pattern of these cats reverted to the preoperative, acute hypoxic exposure characteristics. Decerebrate cats maintained under normoxic conditions for 48 h showed no changes that were statistically significant, but brief (20 min) hypoxic tests indicated an increase of ventilatory response at the end of the second day. Decerebrate cats maintained for 48 h in the hypoxic environment showed all of the main features of HAVA. We conclude that suprapontine mechanisms in the intact cat exert a facilitatory influence which supports the development of HAVA, but if the structures in which those mechanisms normally reside are chronically removed, a comparable mechanism in the ponto-medullary region is capable of assuming the same function.

Acclimatization↗
PubMed1983

Probable strain differences of rats in susceptibilities and cardiopulmonary responses to chronic hypoxia.

Susceptibility to chronic hypoxia in the form of simulated high altitude (HA) have been compared in the adult male Hilltop (H) and Madison (M) Sprague-Dawley rats in terms of their metabolic, hematological and cardiopulmonary responses. Following exposure to either 18 000 or 20 000 ft for 30-40 days, 60-70% of the H rats died or became obviously morbid in contrast to a total absence of morbidity or mortality in the M rats. Autopsy of dead and morbid H rats revealed abdominal and pleural effusions. Oxygen consumption remained normal in both H and M rats. Hematocrits were slightly higher in the H rats than in the M rats. The lungs of both strains were hypertrophied but they showed no evidence of edema or gross lesions. The peak right ventricular pressures of the H and M strains were 73.6 +/- 7.4 and 49.5 +/- 6.5 mm Hg (mean +/- SD), respectively. The percent increase in total ventricular, right and left ventricular weights per 100 g body weights in the H rats were 80, 300 and 30, respectively, as compared to 20, 200 and 0 in the M rats. These changes suggest that the greater susceptibility to chronic HA exposure observed in the H rats is related to a more severe right ventricular overloading and perhaps failure, secondary to a more extreme pulmonary hypertension.

Altitude↗
PubMed1980

Splenic erythropoiesis in polycythemic response of the rat to high-altitude exposure.

Intact rats exposed for 30 days to various levels of simulated altitude from 12,000 (3,658 m) to 20,000 ft (6,096 m) showed a sharp increase in circulating red blood cells in reticulocytes, and in spleen-to-body weight ratios above 15,000 ft (4.572 m). Nucleated erythrocytes in splenic section increased significantly at 18,000 ft (5,486 m), but not at 12,000 ft. Acute splenectomy 1 day before killing sharply reduced the reticulocyte counts at 18,000 and 20,000 ft, but the red cell counts were not reduced at any altitude by the operation. Indeed, at 18,000 ft the splenectomy significantly increased the degree of polycythemia. With altitude exposure the spleen but not the liver or the bone marrow showed an increased 59Fe uptake that was related to the degree of hypoxia. These results suggest that the rat spleen of the present strain carries the full load of the erythropoietic effort in response to a hypoxic stimulus, and that it may exert an inhibitory influence on any extraerythropoietic effort by the bone marrow. In intact rats returned from 18,000 ft to sea level, the reticulocytosis is reversed much more slowly than it is in splenectomized rats, suggesting the presence of a persistent stimulus initiated by hypoxia or a committed pool of reticulocyte precursors.

Animals↗
PubMed1980

Hypoxia-induced hemoglobinemia: hypoxic threshold and pathogenic mechanism.

The effects of chronic exposure to graded hypoxia (inspired PO2 = 146, 90, 78, 73 and 60 torr) on the development of hypoxia-induced hemoglobinemia and the rate of hemoglobin degradation in intact and acutely splenectomized rats were studied. Hemoglobin mass increased with hypoxia over the whole range studied. Hemoglobinemia was not detectable until the inspired PO2 reached 78 torr, and became much more severe at inspired PO2 = 73 and 60 torr. The increased rate of hemoglobin degradation measured as bilirubin excretion, was largely accounted for by circulating red cell destruction at inspired PO2 = 146, 90 and 78 torr. However, the rate of hemoglobin degradation exceeded the estimated circulating red cell destruction by more than 100% at inspired PO2 = 73 and 60 torr. Acute splenectomy reduced both hemoglobinemia and the "extra" bilirubin production by 80%. The data suggest that 1) the hypoxic threshold for the occurrence of hypoxia-induced hemoglobinemia lies at inspired PO2 = 90 to 80 torr; 2) ineffective erythropoiesis is the most likely pathogenic mechanism of the hemoglobinemia and the "extra" bilirubin production and 3) the spleen plays a primary role in these phenomena.

Altitude↗
PubMed1979

Adrenocortical function in rats chronically exposed to high altitude.

In rats exposed to a simulated altitude of 5,486 m for 3 mo, pituitary and adrenal glands hypertrophied and plasma levels of corticosterone increased more than threefold over sea-level controls. The in vitro rates of corticosterone production by the quartered adrenal gland were significantly enhanced, but the responsiveness of the adrenal gland to ACTH remained normal.

Acclimatization↗
PubMed1978

Hemoglobinemia in rats exposed to high altitude.

A hemoglobinemia occurred in rats exposed to a simulated altitude of 18,000 ft. No biochemical deficits in the erythrocytes or plasma were apparent, and the erythrocytic survival time was normal. This hypoxia-induced hemoglobinemia was not due to intravascular hemolysis and it coexisted with polycythemia, representing a unique hematologic condition. As a result of the hemoglobinemia in altitude-exposed rats, plasma haptoglobin was depleted, a 5- and 10-fold increase in the activities of heme oxygenase were induced in the liver and kidney, respectively, and there was a hemoglobinuria. The possible mechanism for the genesis of this hypoxia-induced hemoglobinemia is discussed.

Altitude↗
PubMed1977

Hypoxic ventilatory response of cats at high altitude: an interpretation of 'blunting'.

Cats acclimatized to a simulated altitude of 5500 m developed attenuated ventilatory response in the hypoxic test range of PAO2 = 60-45 torr, but their CO2 response remained normal, although the curve was shifted to a lower PACO2 range. The acclimatized cats a high respiratory frequency and maintained hyperventilation under normoxia. Cats from 3100 m altitude had hypoxic reponses which were, on the average, slightly below sea level standards, but the difference was not statistically significant. Two cats raised at 4640 m had a normal hypoxic ventilatory response even though the frequency response was 'blunted'. These data suggest the possibility of hypoxic 'threshold' near 5500 m to produce an attenuation effect. Another series of cats acclimatized to 5500 m were tested with more severe hypoxia, and they exhibited brisk ventilatory response in range PAO2, 40-25 torr, although they showed typical 'blunting' in the range PAO2, 60-45 torr. These results suggested that the phenomenon of attenuated hypoxic response at high altitude was a reflection of shift of hypoxic set point to a lower PAO2. Finally, it was shown that the hypoxic responses of 'blunted' animals were restored to normal after mid-collicular decerebration; and that decortication resulted in a typical hyperexcitability of the hypoxic response. These results are discussed in terms of hypothesized suprapontine modulating influences on the control of breathing, and possiblities for a contribution of these mechanisms in pathogenesis of hypoxic 'blunting' are raised.

Acclimatization↗
PubMed1977

Ventilatory response of decorticate and decerebrate cats to hypoxia and CO2.

The steady state ventilatory response of normal, fully awake cats was studied under graded hypoxia (at PAO2 = 110, 55, 45 torr) with PACO2 controlled throughout at the resting, normoxic level and at +5 torr. Subsequently, either a mid-collicular decerebration or a decortication was performed, and the ventilatory studies were repeated. Respiratory frequency, tidal volume, and ventilation in the decerebrate state responded to hypoxia and hypercapnia in a manner indistinguishable from the control. The decorticate cats, however, exhibited an exaggerated response to hypoxia, principally the result of increased frequency. The negative hypoxic, hypercapnic interaction, characteristic of awake cats, was demonstrable in both the decerebrate and decorticate animals. The findings are interpreted as revealing coupled descending influences on the medullary respiratory centers in hypoxia--one that is facilitatory and originates in the diencephalon, and the other, inhibitory, from the cerebrum. The significance of this suprapontine system in normal hypoxic ventilatory control is discussed.

Animals↗
PubMed1976

The role of brief hypocapnia in the ventilatory response to CO2 with hypoxia.

In conscious cats the ventilatory response curve to physiological range of CO2 is displaced upward by hypoxia (about 45 torr), but it rises, either parallel with, or convergent on, the normoxic curve. Thus, a positive interaction of hypoxia and hypercapnic stimuli is not observed under these circumstances. However, if during the hypoxic exposure, hypocapnia is allowed to develop, the subsequently determined CO2 ventilatory response curve will shift to the left, rise steeply, particularly in the early phase, and demonstrate a positive hypoxic hypercapnic interaction. A demonstrable interactive effect was dependent on a conditioning period of hypocapnia, and this was shown to be associated with an elevated level of lactic acid to a greater degree in cerebral venous blood than in CSF or arterial blood. The interpretation is discussed without reaching a firm conclusion of mechanism, but the results emphasize how a minor change of experimental protocol affects a basic phenomenon in the chemical control of breathing.

Animals↗
PubMed1976

Hypoxia and carbon dioxide as separate and interactive depressants of ventilation.

The respiratory frequency, tidal volume and ventilization responses of 20 conscious cats to hypoxia, at controlled levels of alveolar CO2, revealed a characteristic steady state response in the majority of animals which indicated a negative interaction of stimuli on tidal volume and minute volume of ventilation, but a positive interaction on frequency. Another series of studies, conducted on seven conscious cats, sought to identify hypoxic response thresholds and depression thresholds, by determining responses over a wide range of hypoxic stimulus intensities, and at different controlled alveolar PCO2. Response threshold was at about 65 torr PAO2. Under eucapnic conditions, ventilation began to fail at PAO2 about 30 torr due to failure of tidal volume. The frequency continued to increase even in the lowest range of PAO2. With hypocapnia no failure of ventilation, frequency, or tidal volume was seen even at the lowest PAO2, but with hypercapnia, the tidal volume began to fail at PAO2 about 50 torr. The minute volume however, continued to increase into the lowest range of PAO2, because the frequency continued to respond at a rate greater than the tidal volume was failing. The results are discussed in terms of interactive depression manifest through the coupled responses of peripheral and central mechanisms.

Animals↗