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Biomedical subjects

D Bee

Publications and source records attributed to D Bee.

At least 37 records · Page 2Linked to original sources
PubMed1993

The carotid body: a review of its anatomy, physiology and clinical importance.

The carotid body is a peripheral chemoreceptor that monitors arterial blood gas tensions and pH. Its main function is to contribute to the regulation of breathing although there is evidence for a reflex influence on the pulmonary circulation and the kidney. The carotid body's acute response to hypoxia is a rapid increase in breathing. The chronic response to hypoxia such as would occur at high altitude or as a consequence of COPD, includes growth of the organ, both hyperplasia and hypertrophy, modification of amine content and an attenuation of its hypoxic sensitivity. It is the latter aspect that may cause severe problems of management of COPD for the clinician. It is postulated that the attenuated hypoxic sensitivity may play a role in the deterioration of the COPD patient.

Carotid Body↗
PubMed1992

An analysis of the action of an analogue of almitrine bismesylate in the rat model of hypoxic lung disease.

Chronically hypoxic (CH) and normoxic control rats were used to assess the action of S9581, a water-soluble analogue of almitrine bismesylate. S9581 increased ventilation (Ve) by 34% in control and 20% in CH rats. During acute hypoxia Ve was raised and S9581 caused a further increase of 20% in both groups. Low doses of S9581 and almitrine enhanced the hypoxic ventilatory response in CH rats while high doses depressed it in both groups. Effects of S9581 on the pulmonary circulation were assessed in the isolated perfused lung of rats. As with almitrine a complex relationship of dose-dependent vasoconstriction and dilatation was revealed. In low doses, S9581 enhanced the hypoxic pulmonary vasoconstrictor response to 2% O2 whilst this was attenuated by high doses in both control and CH rats. S9581 seemed to act like almitrine bismesylate on both the ventilation (peripheral chemoreceptor) and the pulmonary circulation. For studying almitrine-like activity the water solubility of S9581 provides considerable advantages for the researcher.

Almitrine↗
PubMed1991

Effects of ligustrazine on the pressure/flow relationship in isolated perfused rat lungs.

Ligustrazine, the synthesized principle of a Chinese herbal remedy shown previously to be a pulmonary vasodilator, was tested in chronically hypoxic and normal rats. Pressure/flow, (P/Q), relations were measured in isolated perfused lungs during normoxia, hypoxia and after reversal of hypoxic vasoconstriction by increasing doses of ligustrazine. P/Q lines were linear over a wide range and extrapolation to the pressure axis gave an intercept which was the effective downstream pressure for flow. In chronically hypoxic rats the slope of the line was steeper and the intercept greater than in control rats, which we attributed to newly muscularized arterioles with tone. Hypoxia caused an increase in slope and intercept in both groups but the intercept increase was greater in chronically hypoxic rats. In both groups of rats increasing doses of ligustrazine given during continued hypoxia caused a fan of lines which moved progressively towards the control normoxic line. In chronically hypoxic rats it required only 2 mg of ligustrazine to bring the line back to the normoxic position, whereas in controls it required 4 mg. In chronically hypoxic rats the change in intercept with every dose was greater than in control rats; this suggests that ligustrazine mainly relaxes the muscle of small collapsible vessels. The action of ligustrazine remained in both control and chronically hypoxic rats after administration of an arginine analogue which blocks synthesis of the endothelial relaxant factor nitric oxide. This and previous evidence suggest that ligustrazine is a non-endothelial-dependent pulmonary vasodilator.

Animals↗
PubMed1989

Structure and function of the carotid body in New Zealand genetically hypertensive rats.

Morphology of the carotid body and the ventilatory response to hypoxia were compared in New Zealand genetically hypertensive rats and 'normotensive' control rats from the same genetic stock. Hypertensive rats grew more slowly, had higher blood pressure from 6 weeks of age and developed left ventricular hypertrophy. Carotid bodies of both groups were similar in size but larger than those of a common Wistar strain. Intimal damage and proliferation were seen in 1st- and 2nd-order branches of the carotid body artery in hypertensive rats and point-counting showed that the volume proportion of Type 1 cell nuclei and vascular lumen was reduced and vascular wall increased. In age-matched anaesthetized rats, minute ventilation per 100 g was greater in hypertensives than 'normotensive' when inspiring O2 concentrations of 30, 21, 18, 15, 12, 10 and 8%. However, at each inspired O2 concentration, arterial Pa.O2 was higher and Pa.CO2 lower in hypertensive than in 'normotensive' rats. Hypertensive rats were hyperventilating. The shape of the ventilation/O2 tension curve was similar in hypertensive and 'normotensive' rats; thus carotid body sensitivity to hypoxia was probably unchanged. Possible causes of hyperventilation and the relation of carotid body morphology to hypertension are discussed.

Animals↗
PubMed1989

Dopamine and ventilatory effects of hypoxia and almitrine in chronically hypoxic rats.

We hypothesized that the temporary blunted ventilatory response to hypoxia seen in chronically hypoxic rats could be related to the increased amount of dopamine found in their carotid bodies. Rats, kept 2-3 wk in 10% O2, showed reduced nonisocapnic ventilatory responses to 21-12% inspiratory O2 fraction compared with control rats. Stimulus-response curves to almitrine, which simulates the action of hypoxia on the carotid body, were also depressed in chronically hypoxic rats. Responses to hypoxia and almitrine were significantly correlated in the two groups of rats. Dopamine depressed ventilation during normoxia, hypoxia, and almitrine stimulation in both groups, an action abolished by the dopamine-2 antagonist domperidone. Domperidone slightly increased responses to hypoxia and almitrine in control rats but had a greater enhancing effect in chronically hypoxic rats, such that there was no longer a difference between the responses of the two groups.

Almitrine↗
PubMed1989

Pulmonary vasodilator action of ligustrazine, active principle of a traditional Chinese remedy, in rats and ferrets.

The action of ligustrazine on the pulmonary circulation was tested in isolated perfused rat lung in vitro and autoperfused ferret lower left lobe preparation in vivo. Ligustrazine reduced hypoxic pulmonary vasoconstriction in a dose-dependent manner. It had a lesser dilator effect on KCl-induced vasoconstriction than verapamil and a relatively small inhibitory effect on the pressor response to angiotensin II. Ligustrazine preferentially inhibited the vasoconstriction caused by hypoxia and almitrine. The increased slope and intercept of the pressure-flow line caused by hypoxic vasoconstriction was reduced to the normal range after administration of ligustrazine (4 mg). Thus ligustrazine proved to be a powerful pulmonary vasodilator; it had a relatively small depressor effect on systemic blood pressure.

Animals↗
PubMed1988

Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells of hypoxic rats.

The mammalian respiratory tract contains innervated groups of endocrine cells which are believed to respond to hypoxia. We have demonstrated the involvement of a specific regulatory peptide produced by the cells, calcitonin gene-related peptide (CGRP), in this response. Cells immunoreactive for CGRP or for protein gene product 9.5 (PGP 9.5), a general marker of nerves and endocrine cells, were quantified in sections of lungs from hypoxic (21 days, 10 per cent O2) and normoxic rats. An immunostaining method employing supra-optimal dilutions of primary antiserum was used. This detects variations in antigen concentration which may be masked if the routine, optimal dilution is used. The number of CGRP-immunoreactive endocrine cells was significantly (P less than 0.001) greater in the lungs of hypoxic rats (76.9 +/- 10.1 cells/cm2, mean +/- SEM) compared with controls (19.7 +/- 2.4). However, the numbers of PGP 9.5-immunoreactive cells were the same in both groups (81.3 +/- 12.2, hypoxic; 79.5 +/- 9.8 control), suggesting that the total number of endocrine cells did not change. It is concluded therefore that the apparent increase in CGRP-immunoreactive endocrine cells in hypoxic rat lungs is due to increased intracellular levels of the peptide. Since CGRP is a vasodilator, this could have important implications in the vasoconstrictor response to hypoxia.

APUD Cells↗
PubMed1988

Enzyme-linked immunosorbent assay for diagnosis of chronic Q fever.

From 1982 through 1987 we diagnosed 13 chronic Q fever cases. Clinically these patients presented a culture-negative endocarditis, and all but two had high complement-fixing antibody titers to Coxiella burnetii phase I (reciprocal titer above 200). With the enzyme-linked immunosorbent assay (ELISA), titers of immunoglobulin G (IgG) to phases I and II of C. burnetii averaged 158,000 and 69,900, respectively, whereas they reached 300 and 3,200 in acute Q fever cases. Similarly, IgA to both phases of C. burnetii and IgM to phase I were consistently higher during chronic than acute Q fever. The serological follow-up of one patient with chronic Q fever over a 4-year period showed a good correlation between the titers of IgG and IgM antibody titers detected by ELISA and indirect fluorescent-antibody test (IFA) to both phases of C. burnetii. Few discrepancies appeared with IgA. Shortly after initiation of antibiotic treatment, a slow and steady decrease of the antibody titers to C. burnetii phases I and II was observed. The complement fixation, IFA, and ELISA tests showed the same type of antibody response. The ELISA proved to be an excellent diagnostic test for chronic Q fever. It distinguished negative from positive reactions clearly, and results were highly reproducible. The reading is objective, and the test is simple to perform and more sensitive than the IFA and complement fixation tests. The ELISA is recommended for serologic evaluation of patients with chronic Q fever.

Antibodies, Bacterial↗
PubMed1987

Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats.

The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection point below which the line was nearly horizontal in control but negative in chronically hypoxic rats. During hypoxia the inflection point increased in control but not in chronically hypoxic rats, whereas the preinflection slope became negative. Apart from a rise in pulmonary artery pressure at all values of alveolar pressure, which occurred in both groups of rats, there was no change in the form of the curve in chronically hypoxic rats during hypoxia. These results also suggest constriction of extra-alveolar vessels in control rats and alveolar vessels in chronically hypoxic rats during hypoxia.

Animals↗
PubMed1987

Size of the carotid body and ventilatory responses to hypoxia in genetically hypertensive rats.

Structural and functional abnormalities of peripheral chemoreceptors have been found in association with hypertension in both man and rat. In New Zealand (NZ), Kyoto and Milan hypertensive (HT) rats carotid body volume was similar in HT and normotensive (NT) individuals of the same original genetic stock. Arteries within the carotid body showed changes typical of hypertension. Under anaesthesia, NZ HT rats had higher PaO2, lower PaCO2 tensions than NT rats; ventilation/100 g body weight was higher in the HT than NT rats over a wide range of inspired O2 tensions. Thus in HT rats we found evidence of hyperventilation without carotid body enlargement.

Animals↗
PubMed1986

Action of almitrine bismesylate on ventilation-perfusion matching in cats and dogs with part of the lung hypoventilated.

Ventilation to one lobe of lung was reduced in anaesthetized open-chest cats and dogs to simulate the ventilation/perfusion (V/Q) mismatching of chronic lung disease. Blood flow to this lobe fell less than ventilation; thus lobar V/Q diminished. In seven cats almitrine (0.5 mg/kg + 10 micrograms/kg per min, i.v.) caused a rise in pulmonary artery pressure (PPA), increased flow through the hypoventilated lobe in six out of seven cats and both increased or decreased lobar vascular resistance (PVR); the lobar V/Q ratio therefore fell. Arterial and lobar venous oxygen tension (PO2) fell. In five dogs almitrine caused a rise in PPA and PVR but lobar flow changes were variable. Arterial and lobar venous PO2 fell. With fixed ventilation, almitrine failed to improve V/Q matching; there was no improvement in gas exchange in the hypoventilated lobe. In eight dogs the hypoventilated lobe was perfused at constant flow with right atrial blood (i.e. while V/Q was held constant). Almitrine caused a rise in perfusion pressure, vasoconstriction, followed, in five out of eight dogs, by vasodilatation. In six similar cat preparations, vasoconstriction but not vasodilatation was clearly shown. In two cats dilatation after almitrine was demonstrated during ventilation with Nitrogen. In all experiments there was no significant effect of the solvent. Thus the dual action of almitrine seen in other species was seen in a proportion of cats and dogs. Results do not support the view that improved arterial gas tensions in patients after almitrine are attributable to diversion of blood flow away from hypoxic lung. Alternative mechanisms are discussed.

Almitrine↗
PubMed1986

Division of type I and endothelial cells in the hypoxic rat carotid body.

The mammalian carotid body is enlarged under conditions of chronic hypoxaemia. There has been some discussion as to whether this is due to hypertrophy or to hyperplasia. We have subjected rats to 1, 2 or 7 days of 10% oxygen and, 4 h before removing the carotid bodies, injected each animal with vincristine sulphate, an inhibitor of mitosis. The results of this study indicate that numerous mitoses can be found in the carotid bodies of rats exposed to 10% oxygen, but not in control animals maintained in air. These experiments thus provide direct evidence that at least a proportion of the increase in size of the carotid body induced by chronic hypoxaemia is due to a cellular hyperplasia.

Animals↗
PubMed1986

Pediatric resident performance. The reliability and validity of rating forms.

A large pediatric residency program conducted an extensive analysis of the reliability and validity of the rating forms used to evaluate the pediatric residents enrolled in the program. Analyses were conducted on groups of residents who took the Pediatric In-Training Program (PITE) from 1977 through 1981. An average of 7.1 faculty members rated each resident on a standard form. The data indicate that although the reliability of individual ratings is very low, several factors achieved acceptable levels of reliability when aggregated. The first-year rating of history-taking ability correlated significantly with the PITE but ratings for more advanced residents did not correlate with PITE scores, mostly because of ceiling effects.

Clinical Competence↗
PubMed1984

Hypoxic pulmonary vasoconstriction in chronically hypoxic rats.

Reactivity of lung vessels to acute hypoxia was found increased or decreased in chronically hypoxic (CH) rats by different authors. We examined severity and duration of hypoxia and age as possible explanations. Isolated blood-perfused lungs of CH rats ventilated with low-O2 mixtures were compared with control (C) rats. Juvenile CH rats (10 or 12% O2, 3 weeks) showed increased reactivity; reactivity of mature CH rats (10% O2, 3 weeks) was not significantly different from controls. Reactivity declined with age in CH but not C rats. Juvenile and mature rats exposed to 10% O2 for 48 h showed reduced reactivity; after 3 weeks but not 48 h hypoxia, pulmonary arterioles are narrowed by new muscle. The pressure/flow relationship differed in CH from C rats in that resistance and critical closing pressure (CCP) were greater during normoxia. Hypoxia caused increased resistance and CCP in C rats but mainly an increase in CCP in CH rats. The difference may be attributable to muscularisation of collapsible alveolar vessels in chronic hypoxia.

Acute Disease↗
PubMed1983

Contribution of polycythaemia to pulmonary hypertension in simulated high altitude in rats.

A rat model was used to assess the viscosity factor in pulmonary hypertension of high altitude. Rats exposed to 10% O2 for three weeks developed increased pulmonary vascular resistance (p.v.r.) and polycythaemia; the haematocrit (Hct) was 50-60%, values similar to those in normal men at high altitudes. The contribution of high Hct to the increased p.v.r. was assessed in isolated perfused lungs of chronically hypoxic rats perfused with their own high Hct blood, or normal Hct blood from control rats. Pressure/flow relationships were measured over a wide range and the slope (P/Q) of this relationship and its extrapolated intercept on the pressure axis were increased by high Hct blood. A return to low Hct blood did not restore initial conditions although a second perfusion with high Hct blood again increased p.v.r. and intercept. Lack of reversibility was attributed to changes with time in blood or lung. In a second experiment designed to eliminate time changes, chronically hypoxic or litter-mate control rats were each perfused with only one blood, their own or each other's and P/Q relations were rapidly measured. The P/Q slope and pressure intercept increased progressively in the following groups: control rats perfused with their own blood (Hct 34%), control rats perfused with chronically hypoxic blood (Hct 56%), chronically hypoxic rats perfused with control blood (Hct 35%) and chronically hypoxic rats perfused with chronically hypoxic blood (Hct 53%). To exclude factors in chronically hypoxic blood other than high Hct which might increase p.v.r., control rats were perfused with blood of different Hct obtained by centrifugation. High Hct again increased p.v.r. There was a significant relationship in all rats between pulmonary artery pressure (Ppa), which takes into account both P/Q slope, intercept and Hct. There was substantial batch variation which may reflect sensitivity to hypoxia. In chronically hypoxic rats with high Hct blood, Ppa varied from 29-47 mmHg; with low Hct blood the range was 26-38 mmHg. Comparable values for control rats were 21-29 and 17-20 mmHg. We conclude that the polycythaemic blood of chronic hypoxia contributes substantially to pulmonary hypertension. Where it is excessive, it may prejudice tissue blood flow.

Altitude↗
PubMed1983

Does almitrine bismesylate improve V/Q matching? An animal study.

Pulmonary vascular actions of almitrine bismesylate were studied in ferrets, rats, cats and dogs in conditions which simulated those of patients with hypoxic lung disease. All or part of a lung was made hypoxic or hypoventilated so that affected vessels were constricted. Rats were made chronically hypoxic (10%, O2, normobaric chamber). In vivo and isolated preparations were used. In all preparations and species almitrine bismesylate caused vasoconstriction in normoxia, constriction followed by dilation in hypoxia or hypoventilation. In hypoventilated lung there is ventilation/perfusion mismatching which was not improved by almitrine bismesylate . Ventilatory measurements in chronically hypoxic/hypercapnic rats showed that almitrine bismesylate increased tidal volume but not frequency. It is uncertain whether vascular (Q) or small ventilatory (V) changes are the cause of the improved gas tensions and V/Q matching in patients with chronic obstructive lung disease receiving almitrine bismesylate .

Almitrine↗