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Biomedical subjects

B Meyrick

Publications and source records attributed to B Meyrick.

At least 73 records · Page 4Linked to original sources
PubMed1984

Chemotaxis of granulocytes across bovine pulmonary artery intimal explants without endothelial cell injury.

Emigration of granulocytes from vessel lumen to a site of injury is a hallmark of acute inflammation but whether this migration is necessarily associated with vascular damage is not clear. To follow the structural changes associated with granulocyte migration across an intact endothelial cell layer and to assess changes in vascular permeability, an in vitro technique was developed in which intimal explants were stripped from bovine pulmonary artery and mounted in chemotaxis chambers. All explants studied had granulocytes and trace amounts of 3H-water, 14C-sucrose and 125I-albumin in the upper well of the chambers. Experimental explants had zymosan-activated plasma in the lower well and control explants had either serum in the lower well or zymosan-activated plasma in the upper well. Explants were incubated at 37 degrees C for periods from 15 min to 3 hr. When the chemoattractant was added to the lower well, granulocytes migrated into the explants. Transmission and scanning electron microscopy showed an orderly sequence of granulocyte--endothelial interactions throughout which the two cell types maintained close opposition--granulocyte adherence to and exploration of the endothelial surface; penetration and migration through the interendothelial cell junction; reapposition and reformation of the luminal 'tight' junctions and finally passage of granulocytes through the endothelial basal lamina. After 60 min incubation, the majority of granulocytes seen in each section was through the endothelial cell layer and after 2 hr, they were through the basal lamina. Structural evidence of granulocyte or endothelial cell damage was not found at any of the times examined, neither was there any demonstrable increase in intimal permeability. In control explants, granulocyte migration was strikingly less frequent at 2 hr (approximately 10% of that seen towards the chemoattractant). Thus, granulocyte migration across an endothelial cell layer towards a chemoattractant is not necessarily associated with structural evidence of endothelial cell injury or increased vascular permeability.

Animals↗
PubMed1984

Trypsin-induced aggregation of bovine pulmonary artery endothelial cells cultured on microcarriers.

We studied adherence between 'luminal' surfaces of pulmonary artery endothelial cells by standard aggregometry techniques, widely used for measuring aggregation of platelets and granulocytes. Using suspensions of bovine pulmonary artery endothelial cells cultured on microcarrier beads, in an aggregometer, we found that trypsin caused endothelial aggregation. The aggregation response occurred at trypsin concentrations as low as 0.001%. The degree of trypsin-induced aggregation indicated by the magnitude of the change in light transmission through the endothelial suspensions was related to the trypsin concentration, reaching a maximum level at trypsin concentrations of 0.01%. We conclude that trypsin, even in very low concentrations, causes adherence between 'luminal' surfaces of pulmonary endothelial cells probably because the enzyme destroys cell surface proteins which are necessary to prevent intercellular adherence. The method we describe may be useful for studying cell-cell interactions of endothelium.

Animals↗
PubMed1984

Interactions of granulocytes with the lungs.

Under normal conditions, there is a sizeable pool of marginated granulocytes in the lung circulation which is in dynamic equilibrium with the circulating granulocyte pool. The number of granulocytes in the lungs' microcirculation may depend on pulmonary blood flow or biochemical interactions between granulocytes and pulmonary vascular endothelium, or both. There is some evidence that normal lung function may be affected by granulocytes. Several acute and chronic diseases may result, at least in part, from interactions of granulocytes with the lungs. Acute diffuse lung injury (adult respiratory distress syndrome) is characterized by diffuse pulmonary inflammation, and, in animal models, some of the lung dysfunction depends on the presence of granulocytes. Bronchoconstriction and airway hyperreactivity, characteristic of asthma, may be influenced by granulocyte-generated products of arachidonic acid. Granulocyte-derived proteases and oxidants may contribute to the pathogenesis of pulmonary emphysema and may affect connective tissue synthesis in interstitial pulmonary fibrosis. There is some evidence suggesting a connection between granulocytes and chronic pulmonary hypertension. The fact that some interventions which cause pulmonary leukostasis do not cause severe, persistent lung injury indicates that as yet unknown factors may determine whether interactions of granulocytes with the lungs are benign or pathological. Such factors could include the generation of humoral substances, and metabolites of arachidonic acid are particularly interesting in this regard. Research related to interactions of granulocytes with the lungs suggests strongly that such interactions are integral to the pathogenesis of several lung diseases. Understanding those diseases will require further basic studies of granulocyte behavior and the modes of communication between cells intrinsic to the lung and granulocytes.

Animals↗
PubMed1984

Increased permeability associated with dilatation of endothelial cell junctions caused by histamine in intimal explants from bovine pulmonary artery.

Although histamine is known to cause increased vascular permeability in the systemic circulation, its effect on the pulmonary vessels is controversial. We have used a new technique to follow the effect of histamine on the pulmonary artery endothelial cell layer. Disks of intima were stripped from the wall of bovine pulmonary artery, floated endothelium uppermost onto nitrocellulose filters, and maintained in culture in chemotaxis chambers. The lower well of the chambers contained 0.2 ml of 10% bovine serum in medium 199, the upper well 0.5 ml of medium plus trace amounts of 3H-water (10 microCi/ml), 14C-sucrose (9 microCi/ml), and 125I-albumin (10 microCi/ml). Histamine diphosphate (10 microM) was added to the upper well of the experimental chambers. The chambers were incubated at 37 degrees C for 30, 60, 120, 180, or 240 min. At the end of each incubation period, 0.1-ml aliquots were removed from the upper and lower well of an experimental and a control chamber for radioactive counts and the intimal explant was fixed in glutaraldehyde for light and electron microscopy. From 60 min of incubation, histamine caused more rapid equilibration of 3H-water and 14C-sucrose across the intimal explant. Increased diffusion of 125I-albumin was not detected. After 30 and 60 min of incubation with histamine, microscopic examination of the endothelial layer of the explant revealed focal dilatations in the intercellular junctions. From 120 min, dilatations were no longer seen and at no time was there morphologic evidence of endothelial injury. Thus, histamine causes an increased permeability of the bovine pulmonary artery intimal layer that is associated with transient formation of dilatations in the interendothelial junctions.

Animals↗
PubMed1984

Facilitation of granulocyte migration into bovine pulmonary artery intimal explants by intact viable endothelium.

To characterize the role of normal endothelium in granulocyte chemotaxis, the authors measured granulocyte adherence to and migration into bovine pulmonary artery intimal explants. Explants were placed, endothelium uppermost, in chemotaxis chambers with zymosan-activated plasma in the lower well and 5 X 10(6)/ml 51Cr-labeled granulocytes in the upper well. After 15, 30, 60, 120, 180, or 240 minutes incubation at 37 C, granulocyte adherence was measured by removal of adherent granulocytes from the endothelial layer with a 0.1% trypsin wash and counting of radioactivity in the wash. Scanning electron microscopy confirmed that this technique removed the majority of adherent cells from the endothelial surface without disrupting its continuity. Migration was calculated by counting of the remaining radioactivity in the explant. Granulocyte migration with Medium 199 alone in the lower well (random migration) was 36 +/- 3% by 3 hours. Chemotaxis-induced migration at each time studied was 1.5-2 times random migration. Granulocyte adherence was between 4% and 9% in both groups at all times examined. In some experiments, either endothelium was removed from explants or explants were fixed with glutaraldehyde prior to experimentation. Removal of endothelium resulted in a two-fold increase in granulocyte adherence but no significant difference in migration, compared with intact intimal explants. Glutaraldehyde fixation of explants resulted in more tightly adherent granulocytes and significantly less migration. With lactate dehydrogenase as a marker of endothelial cell damage, granulocyte migration in response to zymosan-activated plasma did not injure endothelium. It is concluded that, in blood vessels, chemotaxis is an interactive process between granulocytes and endothelium and that intact, viable endothelium facilitates granulocyte migration.

Animals↗
PubMed1983

Polycythemia and the acute hypoxic response in awake rats following chronic hypoxia.

The acute hypoxic pressor response was studied in 22 chronically catheterized awake rats, 13 in whom the pulmonary arterial circulation had been remodeled by 10 days of exposure to hypobaric hypoxia. Five of these had their hematocrit lowered to normocytic levels after the chronic hypoxic exposure. Nine were controls. After 24 h in room air the pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (Rp) of hypoxic-polycythemic rats was at least twice the control value; in the hypoxic-normocytic rats Ppa and Rp were less than that of hypoxic-polycythemic animals and greater than that of controls. Cardiac index, heart rate, and O2 saturation were similar in all groups. In 10% O2 a rise in Ppa and Rp occurred in all groups; in absolute terms the rise was greater in hypoxic rats than in controls and greater in polycythemic than in normocytic animals. In the intact animal the acute hypoxic pressor response can still be elicited in a pulmonary vascular bed structurally altered by chronic hypoxia. When calculated as a percent increase over base line, its intensity was greater than in room air controls and for Ppa was independent of hematocrit.

Acute Disease↗
PubMed1983

Septicemia and lung injury.

The results of investigations undertaken by the authors which deal with the functional and structural changes in the lungs resulting from gram-negative bacterial endotoxemia and the mechanisms of these changes are analyzed. The authors emphasize the major roles played by granulocytes and metabolites of arachidonic acid in mediating endotoxin-induced lung injury.

Adult↗
PubMed1983

Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep structure:function relationships.

Infusion of Escherichia coli endotoxin into sheep causes a syndrome analogous to the adult respiratory distress syndrome. Physiologic measurements show an initial phase of marked pulmonary hypertension followed by a phase characterized by the production of large quantities of protein-rich lung lymph. The present study relates the structural changes that occur during endotoxemia to concomitant functional changes. In five anesthetized open-chest sheep, we monitored pulmonary and systemic artery pressure for a 1 hour baseline period and for 4 hours after the start of E. coli endotoxin infusion (1.25 microgram/kg, intravenously). We also measured cardiac output, arterial blood gases and pH, and number of circulating leukocytes. In addition, we sequentially biopsied random lobes from the lungs of each sheep at baseline and at 15, 30, 60, 120, 180, and 240 minutes after the start of endotoxin. Five control sheep were treated identically except that they received saline instead of endotoxin. By 15 minutes after the start of endotoxin infusion, light microscopy revealed margination and accumulation of leukocytes in the lungs' microcirculation. Counts of the number of peripheral lung granulocytes in biopsy specimens showed a 3-fold increase above baseline by 15 minutes and a 6-fold increase by 4 hours. By electron microscopy, the leukocytes were identified as both granulocytes and lymphocytes, present in approximately equal numbers. Some granulocytes were fragmented, and specific granules were found free in the vessel lumen. By 30 minutes, some leukocytes were migrating into the interstitium. By 60 minutes, interstitial edema was seen, and there was focal endothelial cell damage. Correlation of the structural with the physiologic changes shows that the initial accumulation of leukocytes in the microcirculation occurs when pulmonary hypertension develops. The migration of leukocytes into the interstitium and endothelial cell damage precedes the physiologic changes that we interpret as increased pulmonary vascular permeability. Since gram negative septicemia is a frequent occurrence in the adult respiratory distress syndrome the changes described here may be similar to the alterations that occur early in the development of the syndrome in man.

Animals↗
PubMed1983

Pulmonary hypertension. Anatomic and physiologic correlates.

The types of pulmonary arterial hypertension described here all focus attention on the changes produced in the lung's microcirculation, particularly the precapillary unit. Although one senses intuitively that obliteration of resistance arteries is an effective cause of hypertension, we emphasize that cell metaplasia and adaptation by structural remodeling of the precapillary arterial wall is also effective in reducing the vascular bed. A question often asked is whether "pruning" is the cause of the hypertension . . . perhaps an inappropriate question. While the reduced cross-sectional area of the vascular bed is the basis for the rise in pulmonary vascular resistance and for its severity, the real question is what is the cause of the "pruning." Hypoxia, monocrotaline, and high flow each causes pulmonary artery hypertension--and pruning--but with differences in cell adaptation, timing, and severity that indicate different pathogenetic mechanisms and pathways. It is paradoxical that hypoxia, whose lesions are more reversible, produces a more severe hypertension and faster than the others. While the pathophysiologic aspects are important to clinical diagnosis and management, it is analysis of cause and pathways of pathogenesis that will give the keys to prevention and cure of the disease.

Animals↗
PubMed1982

Pulmonary arterial and alveolar development in normal postnatal rat lung.

The postnatal development of rat lung was studied by quantitative light microscopic techniques at 12 hours and at 3, 8, 11, 15, 22, and 36 days of age. Particular emphasis was placed on the pulmonary arterial circulation. At birth the lung is not the adult lung in miniature; adaptation occurs through a series of relatively fast steps. A spurt of alveolar multiplication occurs between 3 and 8 days of age, followed, between 8 and 11 days, by one of arterial multiplication. Muscular, partially muscular, and nonmuscular arteries are present within the acinus from birth and their proportion, in each intra-acinar region, is similar at all ages examined except in the alveolar wall where muscular arteries are not found before 11 days of age. Between 12 hours and 8 days, medial thickness of the intra-acinar arteries decreases. At about 15 days of age this decrease is followed, in both pre-acinar and intra-acinar regions, by an increase in medial thickness. Between 12 hours and 3 days, absolute weight of the right ventricle decreases. This pattern of growth indicates that, at certain times, lung development is especially susceptible to injury and, also, that the nature of the disturbance is determined by its timing.

Angiography↗
PubMed1982

Normal postnatal development of the media of the rat hilar pulmonary artery and its remodeling by chronic hypoxia.

The present morphometric and electron microscopic study follows the development of the hilar intrapulmonary artery of rat form 12 hours to 36 days of age and its structural adaptation to hypobaric hypoxia (380 torr) when exposed for periods of 3, 7, 14, and 28 days starting at 8 days of age. In control animals a striking increase in medial thickness is seen at 11 and 15 days of age and is accompanied, at 11 days, by an increase in the organelles of smooth muscle contraction-the myofilaments-and at 15 days, by an increase in rough sarcoplasmic reticulum. From 15 days, a gradual increase in collagen fibrils and elastin occurs in the extracellular ground substance. With exposure to hypoxia, from day 14 medial thickness increases more than the age-matched controls due to an increase in extracellular ground substance and to thickening of the elastic laminae. At all times studied, smooth muscle diameter is similar to the age-matched controls, but the normal fluctuations in volume density of the contractile elements and the rough sarcoplasmic reticulum are blunted. In the extracellular ground substance, the matrix is increased and collagen fibrils reduced, both in concentration and diameter. Thus, in young hypoxic rats, the narrowed lumen and external diameter of the large muscular arteries is associated with abnormal collagen formation. The hypoxia-induced changes in the young rat are different from those reported in the adult in which medial thickening is the result of increased extracellular ground substance with a normal concentration of collagen fibrils and hypertrophy of the smooth muscle cells. In the young lung, the structural changes have more far-reaching effects than the adult since they also interfere with lung growth.

Aging↗
PubMed1981

The effect of chronic hypoxia on pulmonary arteries in young rats.

The effect of hypoxia on the postnatal development of rat lung from 8 days of life and continuing for 3, 7, 14, 21 and 28 days is described, with particular emphasis on the pulmonary arterial circulation. In hypoxic rats, absolute lung volume and body weight increases more slowly than in age-matched controls but lung volume relative to body weight is greater. After three days hypoxia intra-acinar arterial concentration is reduced and medial thickness of small arteries increased but by Day 7, both features return to "normal" values. By Day 14, right ventricular hypertrophy is apparent as is reduction in lumen diameter of preacinar arteries. From Day 21, muscle is seen in smaller and more peripheral arteries than normal: By Day 28 arteries of all sizes show increased medial thickness, and arterial and alveolar concentration is reduced. Compared with adult rats the growing lung seems to be somewhat "protected" in that the hypoxia-induced changes occur slowly although ultimately their severity is similar. At the end of the exposure period, however, the young lung is small for age suggesting that the changes are more severe than in the adult.

Animals↗
PubMed1981

Smooth muscle myosin in precursor and mature smooth muscle cells in normal pulmonary arteries and the effect of hypoxia.

Exposure to hypoxia increases pulmonary arterial muscularity-in the intra-acinar arteries "new" muscle appears in the normally nonmuscular regions and in the preacinar arteries, medial thickness increases. In the present study by immunofluorescence techniques, the myosin content of the pulmonary arterial walls at two levels of the circulation (intra-acinar and preacinar) were studied in control rats and those exposed to hypobaric hypoxia of 380 torr for 3,7, 10, or 14 days. In control animals, we show that the precursor smooth muscle cells, pericytes and intermediate cells normally present in the nonmuscular regions of the intra-acinar arteries, contain smooth muscle myosin. With exposure to hypoxia, smooth muscle myosin in the intra-acinar arteries increases to Day 10, both in area of staining and fluorescent intensity. This is in contrast to the preacinar arteries were only the area of myosin increases. Antihuman platelet (non-muscle) myosin shows a little faint staining in both control and hypoxic animals. Adaptations to hypoxia by the intra-acinar precursor and preacinar mature smooth muscle cells is different, and suggests that the functions subserved by the myosin filaments at each of the two levels differs.

Animals↗
PubMed1980

Hypoxia and pulmonary vascular endothelium.

The steady development of pulmonary hypertension in the rat between Days 1 and 14 of exposure to hypoxia is based largely on structural remodelling of the pulmonary arterial circulation. The changes induced by hypobaric hypoxia (380 Torr; PaO2 of 40 mmHg) are different in the pre-acinar muscular arteries from the intra-acinar (alveolar wall) arteries, including the effect on the endothelial cell. Quantitative analysis of normal lungs has revealed structural features peculiar to the pulmonary microcirculation. The precapillary arterial unit that lies within the alveolar region includes (i) a non-muscular region and (ii) a partially muscular region as well as (iii) a muscular region. The endothelial cells in these segments or 'compartments' appear different from each other in the normal animal and behave differently in disease. In the various segments the endothelial cell has different neighbours and there are differences in its boundary markers (the basement membrane and elastic lamina). In the normal precapillary arterial unit the neighbour may be a pericyte, intermediate cell or smooth muscle cell. The pericyte and intermediate cell are precursor smooth muscle cells that under the influence of hypoxia develop into mature muscle.

Animals↗
PubMed1980

Development of Crotalaria pulmonary hypertension: hemodynamic and structural study.

In awake rats with indwelling catheters, the development of pulmonary hypertension after feeding Crotalaria spectabilis seeds is followed. Hypoxemia is excluded as a factor. Other hemodynamic changes are found before hypertension. After 7 days, pulmonary artery pressure (Ppa) is normal, 17.17 +/- 0.30 (SE) mmHg and from 14 days significantly increased (P < 0.01). Oxygen consumption (Vo2) is significantly increased by day 7 (control 22.72 +/- 2.13 ml . min-1 . kg-1; Crotalaria 42.47 +/- 2.95; P < 0.001). and cardiac index (CI) is significantly above normal after 7, 14, and 21 days (control 350 +/- 31 ml . min-1 . kg-1; 7 days Crotalaria 476 +/- 28; P < 0.02); pulmonary vascular resistance (PVR) increases to six times normal at day 33 (control 0.033 +/- 0.003 U/kg; 33 days Crotalaria 0.194 +/- 0.020; P < 0.001). The pulmonary arteries of these same rats were studied by quantitative morphometric techniques. The first change, muscle in smaller and more peripheral arteries than normal, is detected when Vo2 and CI are increased. Increased medial thickness of arteries < 200 micrometer diameter follows with Ppa rises. Even later, the larger arteries increase their media as the number of peripheral arteries falls and right ventricular hypertrophy becomes apparent, and hypertension and increased PVR are well established.

Animals↗
PubMed1980

Morphologic disturbance of lung maturation in fetuses of alloxan diabetic rabbits.

Maturation of lungs was studied morphologically in fetuses of does made diabetic with alloxan. The lungs of fetuses of does treated with alloxan 24 h after mating appeared to be less mature than control lungs, as shown by significant decrease in areal density of air space (p < 0.01) and by increases in areal density of alveolar epithelium and capillaries (p < 0.02). In alloxan fetuses, ultrastructural techniques revealed that type II cells had 10 times the control value for areal density of glycogen (p < 0.01) and 2.5 times that of rough endoplasmic reticulum (p < 0.05), but the proportion of type II cells and the number of lamellar bodies per type II cell profile were similar in both groups. Ultrastructural examination of capillaries demonstrated that their migration and the fusion of their basement membrane with that of alveolar epithelium did not occur as frequently in alloxan fetuses as in control fetuses. Biochemically, the lungs of alloxan fetuses contained significantly more glycogen and protein (p < 0.01) than control lungs, but the deoxyribonucleic acid was similar. The alloxan fetuses had a disturbance of lung structural maturation that was consistent with our previous findings of delayed functional maturation without accompanying change in disaturated phosphatidylcholine levels and ratio of lecithin to sphingomyelin.

Animals↗