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K L Brigham

Publications and source records attributed to K L Brigham.

At least 109 records · Page 6Linked to original sources
PubMed1985

Metabolites of arachidonic acid in experimental lung vascular injury.

Several metabolites of arachidonic acid have potent effects on lung vascular and airway function. Some of these substances are released from the lungs when the lungs are diffusely injured. For example, after infusion of Escherichia coli endotoxin into unanesthetized sheep, high concentrations of both cyclooxygenase and lipoxygenase products appear in lung lymph. These products appear in sequential waves: thromboxane B2 peaks early, coincident with peak pulmonary artery pressure and maximum changes in lung mechanics; a prostacyclin metabolite peaks slightly later as pulmonary artery pressure begins to fall; both 5- and 12-lipoxygenation products peak even later, as lung vascular permeability begins to increase. Cyclooxygenase inhibitors attenuate the early changes in lung mechanics and pulmonary artery pressure caused by endotoxemia in sheep but do not prevent the later increase in lung vascular permeability. High doses of corticosteroids attenuate both the late phase increase in lung lymph lipoxygenation products and the increase in vascular permeability. These unequivocal associations between lung injury and endogenous generation of biologically active arachidonate metabolites suggest but do not prove that these substances mediate the pathophysiology.

Animals↗
PubMed1985

Endothelial prostacyclin production is a late event in granulocyte migration into bovine pulmonary artery intimal explants.

Whether migration of granulocytes across pulmonary vascular endothelium in the absence of structural evidence of endothelial injury causes increased production of thromboxane or prostacyclin is not known. Using bovine pulmonary artery intimal explants mounted in Boyden chambers and homologous separated granulocytes, concentrations of thromboxane B2 and 6-keto-PGF1 alpha in the upper-well fluid were measured by radioimmunoassay over a three-hour period under the following conditions: (1) granulocyte chemotaxis (zymosan-activated plasma in the lower well, granulocytes in the upper well); (2) unstimulated granulocyte migration (serum or plasma in the lower well, granulocytes in the upper well); (3) granulocyte activation without migration (zymosan-activated plasma and granulocytes in the upper well); (4) granulocyte chemotaxis in the absence of endothelium (identical to condition 1 above except that endothelium was scraped from the explant surface); and (5) explants incubated in the absence of granulocytes. Minimal increases in thromboxane B2 concentrations in upper-well fluid occurred under all conditions. In contrast, granulocyte chemotaxis was accompanied by large increases in concentrations of 6-keto-PGF1 alpha evident by two hours of incubation and increasing markedly by three hours, to 524.3 +/- 69.0 ng/mL (m +/- SEM). Unstimulated migration of granulocytes toward serum or plasma and granulocyte activation without migration were accompanied, at three hours, by more modest increases in 6-keto-PGF1 alpha (296.5 +/- 46.4; 128.0 +/- 38.6, and 236.7 +/- 47.0 ng/mL, respectively) and, in the absence of granulocytes or in the absence of endothelium, only minimal increases in this prostacyclin metabolite occurred (137.2 +/- 16.9 and 53.9 +/- 12.6 ng/mL, respectively). The large rises in prostacyclin metabolite occurred at a time when the majority of granulocytes had migrated through the endothelial layer rather than during their adherence or transendothelial passage. We conclude that chemotaxis of granulocytes through pulmonary vascular endothelium causes endothelial production of large amounts of prostacyclin, but this occurs late in the chemotactic process, after granulocytes have transversed the endothelium.

Animals↗
PubMed1985

Pulmonary dysfunction caused by diffuse lung inflammation. Roles of metabolites of arachidonic acid.

Gram-negative endotoxemia in chronically instrumented sheep causes diffuse lung inflammation. Pathophysiologic responses of the lung include marked changes in lung mechanics, pulmonary vasoconstriction, increased lung vascular permeability, and capillary endothelial injury. Over the course of the response to endotoxemia, cyclooxygenase and lipoxygenase products of arachidonic acid are released into lung lymph and the time course of the two classes of compounds is different. Thromboxane concentrations in lung lymph increase early, coincident with the most marked changes in lung mechanics and the most severe pulmonary hypertension. Concentrations of a prostacyclin metabolite also increase during this early phase of the endotoxin response but peak levels in lung lymph appear slightly later than that for thromboxane. Concentrations of these cyclooxygenase products subside as the later phase of increased vascular permeability develops. Lung lymph concentrations of two lipoxygenase products, 5- and 12-HETE, increase late in the endotoxin reaction, approximately coincident with physiologic evidence of increased lung vascular permeability. Neutrophil chemotactic activity appears in lung lymph early after endotoxin infusion and persists for several hours. Drugs which inhibit cyclooxygenase attenuate the early changes in lung mechanics and the early pulmonary hypertension after endotoxemia, but do not prevent the late phase increase in vascular permeability, suggesting that the net effect of endogenous generation of cyclooxygenase products explains the early constrictor phase of the reaction, but not the later capillary injury. However, neutrophil depletion prevents the early changes in lung mechanics without preventing the coincident pulmonary hypertension or the increase in lung lymph thromboxane concentrations which may indicate that the cell source of constrictor cyclooxygenase products mediating changes in lung mechanics is different than that for products causing pulmonary vasoconstriction. The specific role of prostacyclin in the lungs' response to endotoxemia is not clear. The temporal course of prostacyclin release suggests that it may play a role in moderating the pulmonary hypertension and changes in lung mechanics. The fact that neutrophil depletion, corticosteroids, and the antioxidant n-acetylcysteine diminish both the endotoxin-induced increase in lung vascular permeability and lung prostacyclin release may indicate that the release of prostacyclin is a response to endothelial injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Permeability pulmonary edema. Diagnosis and management.

The adult respiratory distress syndrome (ARDS) is a common syndrome of diffuse lung injury with high mortality. An underlying mechanism is pulmonary microvascular injury leading to increased permeability, pulmonary edema and impaired gas exchange. Currently ARDS can only be diagnosed as a constellation of symptoms and signs. The development of an accurate clinical marker of pulmonary microvascular injury or a technique to measure pulmonary microvascular permeability may allow earlier and more specific diagnosis. We review ARDS with emphasis on recent work concerning the mechanisms of lung injury, diagnosis, and therapy.

Adult↗
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

Effects of granulocyte depletion on pulmonary responsiveness to aerosol histamine.

The effects of granulocyte depletion with hydroxyurea on pulmonary responsiveness to aerosol histamine were studied in 10 chronically instrumented unanesthetized sheep. Sheep were studied when granulocyte counts were normal (B), after 3 days of hydroxyurea but before granulocyte counts had dropped below 700 cells/mm3 (H), and after granulocyte counts had fallen below 200 cells/mm3 (D). Hydroxyurea itself had no effect on aerosol histamine responsiveness and the results were unaffected by the order of experimentation. All 10 sheep were less responsive (P less than 0.05) to aerosol histamine when granulocyte depleted effective dose of histamine that caused a reduction to 65% of control dynamic compliance (ED65Cdyn = 23.98 +/- 4.70 mg/ml) compared with base line (ED65Cdyn = 7.06 +/- 1.86 mg/ml). Those sheep initially most responsive to aerosol histamine had the greatest attenuation in their airway responsiveness to aerosol histamine (P less than 0.05). There was a significant negative correlation between absolute granulocyte counts in peripheral blood and pulmonary responsiveness to aerosol histamine during base-line (B) condition (r = -0.74, P less than 0.05) and for the data as a whole [r = -0.69, P less than 0.05 (B + H + D)]. Circulating granulocytes and/or pulmonary inflammation may contribute to pulmonary responsiveness to bronchial challenge.

Aerosols↗
PubMed1984

Effects of left atrial pressure elevation and histamine infusion on lung lymph in awake sheep.

To study the mechanism by which infused histamine increases lung fluid and solute exchange, the effects of left atrial pressure elevation (using a Foley catheter positioned at the mitral valve orifice) on lung lymph flow and protein content were studied in the presence and absence of histamine infusion in nine chronically instrumented unanesthetized sheep. In six sheep, histamine infusion (1-3 micrograms X kg-1 X min-1) was begun 2 h before increasing left atrial pressure by 10 and 20 cmH2O for 3 h each. Control experiments were performed on the same sheep to study the effects of left atrial pressure elevation alone and histamine infusion alone. Left atrial pressure elevation in the presence of histamine infusion did not cause a disproportionate increase in lung lymph flow nor was the lymph-to-plasma protein concentration ratio (L/P) different from left atrial pressure elevation alone. This argues against the presence of increased microvascular permeability at the time of these elevations. In three sheep, left atrial pressure was elevated by 20 cmH2O, and then histamine was infused at 2 micrograms X kg-1 X min-1. Histamine infusion caused a transient increase in L/P and a large increase in lymph flow, findings like those we have previously taken to represent an increase in microvascular permeability. However, L/P decreased to values comparable to those seen with elevated left atrial pressure alone. These observations suggest that histamine infusion may have a biphasic effect on lung lymph. There is an early (1-3 h) transient increase in lymph protein clearance that could result from a transient increase in permeability followed by a sustained increase in microvascular surface area. The early response is difficult to interpret because the changes are transient and could be affected by alterations outside the lung.

Animals↗
PubMed1984

Effect of aerosol histamine on lung lymph in awake sheep.

This study examined the effect of aerosol histamine on lung lymph in the awake sheep. Eleven sheep were chronically instrumented for measurement of lung lymph, lung mechanics, and vascular pressures. Aerosol histamine was given by use of a Collison nebulizer and delivered via a tracheostomy tube. Five breaths of a 30 mg/ml histamine solution caused lung lymph flow (QL) to increase from a base line of 5.5 +/- 0.5 (SE) ml/h to 14.3 +/- 1.5 (P less than 0.05) and the lymph-to-plasma protein concentration ratio (L/P) to increase from 0.63 +/- 0.02 to 0.72 +/- 0.02 (P less than 0.05). The concentration of aerosol histamine required to change QL by 30% (ED130QL) was determined by giving increasing concentrations of aerosol histamine every 15 min. The mean ED130QL was 22.2 mg/ml. The dose of histamine required to increase QL by 30% did not correlate (r = 0.04, n = 7) with the dose required to decrease dynamic compliance by 35%. The increase in QL lasted 100 +/- 19 min. Hourly exposure to five breaths of 30 mg/ml for 5 h caused a sustained increase in QL in two sheep and a waning effect in two sheep. The combination of aerosol histamine and elevated microvascular pressure (achieved by inflating a Foley catheter situated in the left atrium) caused changes in QL and L/P not totally consistent with the hypothesis that histamine increased pulmonary vascular permeability. Increased vascular permeability in the bronchial circulation was considered a likely explanation of the data.

Aerosols↗
PubMed1984

Cyclooxygenase inhibition during phorbol-induced granulocyte stimulation in awake sheep.

In vitro, phorbol myristate acetate (PMA) causes sheep granulocytes to release superoxide. Infused into sheep, PMA causes leukopenia, hypoxemia, pulmonary hypertension, and increased flow of protein-rich lung lymph. Lung lymph thromboxane B2 and 6-ketoprostaglandin F1 alpha levels rise markedly after PMA infusion. To see whether cyclooxygenase products of arachidonic acid mediate the lung vascular responses to PMA, we infused 5 micrograms/kg PMA twice in each of six sheep, once in the presence of sodium meclofenamate and once alone. We varied the order of paired experiments and allowed 4-7 days between experiments. Meclofenamate (5 mg/kg loading dose + 3 mg X kg-1 X h-1 infusion) given alone had no effect on base-line variables. Meclofenamate inhibited or delayed the initial pulmonary hypertension and hypoxemia after PMA but exaggerated the later increase in pulmonary arterial pressure; it prevented any increase in thromboxane B2 and 6-ketoprostaglandin F1 alpha after PMA. Meclofenamate did not affect the degree of leukopenia or the severity of the later hypoxemia nor did it prevent accumulation of granulocytes in the lung. Lung lymph flow was higher with meclofenamate + PMA than with PMA alone, but lymph-to-plasma protein concentration ratio was lower, suggesting that the main effect of meclofenamate on lymph production after PMA was related to the degree of pulmonary hypertension. We conclude that the early increase in pulmonary arterial pressure caused by PMA is mediated by a cyclooxygenase product of arachidonic acid, possibly thromboxane A2, but the later pulmonary hypertension and the increase in pulmonary vascular permeability are not the result of cyclooxygenase products.

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

Modification of pulmonary responses to endotoxemia in awake sheep by steroidal and nonsteroidal anti-inflammatory agents.

The effects of intravenous infusions of Escherichia coli endotoxin on white blood cell counts, hemodynamics, gas exchange, body temperature, and lung lymph flow were studied in chronically instrumented unanesthetized sheep. Six sheep received endotoxin (0.5 micrograms/kg) in the presence and absence of methylprednisolone treatment. Six sheep received the same dose of endotoxin with and without meclofenamate and methylprednisolone infusion. Endotoxemia caused an early increase in pulmonary artery pressure from 15.5 +/- 1.3 (mean +/- SEM) to 52.7 +/- 2.1 cmH2O (p less than 0.05), an initial phase of high flow of protein-poor lung lymph, an elevation in core body temperature, severe leukopenia, and an early increase in the alveolar to arterial oxygen difference (AaPO2) from 7.4 +/- 2.5 mmHg to 35.9 +/- 2.5 mmHg (p less than 0.05). From 2 to 5 h after endotoxin infusion, lung lymph flow averaged 4.8 times that of the baseline measurement, although lymph protein concentration relative to plasma was not different from the baseline measurement. Peripheral leukopenia and significantly increased AaPO2 (28.8 +/- 4.5 mmHg) persisted at 2 to 5 h. Methylprednisolone attenuated the early pulmonary artery hypertension (43.0 +/- 3.4 cmH2O), but did not inhibit the initial febrile response, severe leukopenia, or the early increase in AaPO2 (29.2 +/- 1.6 mmHg) in response to endotoxemia. Methylprednisolone did prevent the late phase increase in lung lymph flow, significantly attenuated the late phase leukopenia and hypoxemia (AaPO2, 13.3 +/- 5.9 mmHg), and attenuated accumulation of granulocytes in peripheral lung tissue throughout the endotoxin reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function.

Oxygen free radicals released during endotoxemia may contribute to the lung injury of the adult respiratory distress syndrome (ARDS). As this syndrome occurs frequently after gram-negative sepsis in humans, we studied the effect of intravenous N-acetylcysteine (NAC), a free radical scavenger, upon the endotoxin (E)-induced model of ARDS in awake sheep. In vivo studies demonstrated that NAC attenuates the endotoxin-induced rise in pulmonary artery pressure (62 +/- 3 torr with E control vs. 43 +/- 3 torr for E + NAC), and markedly diminishes the rise in lymph flow at 1 h (8.5 +/- 1.2 vs 4.5 +/- 0.6 ml/15 min) and 4 h (5.0 +/- 0.6 vs. 3.3 +/- 0.4 ml/15 min), respectively, for E control vs. E + NAC. NAC also markedly attenuated the alterations in lung mechanics after endotoxemia. Dynamic compliance at 2 h after endotoxemia was 44 +/- 6% of base line for E vs. 76 +/- 10% of base line for E + NAC. Resistance to airflow across the lung at 1 h postendotoxin was 811 +/- 280% of base line for E vs. 391 +/- 233% of base line for E + NAC. NAC substantially reduced the 1 h postendotoxin rise in lymph concentrations of thromboxane B2 (8.29 +/- 3.28 vs. 2.75 +/- 1.93 ng/ml for E vs. E + NAC) and 6-keto-prostaglandin-F1 alpha (0.91 +/- 0.27 vs. 0.23 +/- 0.12 ng/ml for E vs. E + NAC). In addition, in vitro studies were performed which revealed NAC to be a potent free radical scavenger in both biologic and nonbiologic free radical generating systems. NAC decreased phorbol-stimulated granulocyte aggregation in a concentration-dependent manner in vitro. Minimal effects were observed, however, upon leukocyte degranulation at the concentrations of NAC achieved during the in vivo tests. Thus, NAC significantly attenuated all monitored pathophysiologic changes in the endotoxin model of ARDS in sheep, possibly by its ability to scavenge toxic oxygen free radicals. A direct impairment of the ability of inflammatory cells to generate oxygen radicals cannot be ruled out.

Acetylcysteine↗
PubMed1984

Effects of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia.

The effect of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia was studied in eight unanesthetized sheep. Platelets were depleted with rabbit anti-sheep platelet antibodies (APA). Bolus injections of APA alone caused marked pulmonary hypertension (PPA increased from 21 +/- 2 to 62 +/- 5 cm H2O +/- SE) and alterations in lung mechanics (dynamic compliance of the lung [Cdyn] decreased to 38.5 +/- 4.6% and resistance to air flow across the lung [RL] increased to 705 +/- 162% +/- SE of control), which were attenuated by pretreatment with meclofenamate. It was possible to deplete platelets before endotoxemia through a slow continuous infusion of APA without altering base-line values of the measured variables. Platelet depletion did not significantly attenuate the alterations in pulmonary hemodynamics, lung mechanics, lung fluid and solute exchange, or the normal increase in lung lymph concentrations of thromboxane B2 or 6-keto-PGF1 alpha observed following endotoxemia in the sheep. We conclude that normal circulating platelet counts are not required for the full expression of the sheep's response to endotoxemia.

Animals↗
PubMed1984

Effects of methylprednisolone on the response to group B streptococcal toxin in sheep.

The effects of pretreatment with methylprednisolone on the reaction to a toxin isolated from group B beta-hemolytic streptococci, type III, were studied in seven sheep instrumented for chronic measurements of pulmonary lymph flow and pulmonary artery and left atrial pressure. Each sheep was infused with toxin alone on one day and with methylprednisolone plus toxin on a different day in random order. The toxin alone caused a two-phase reaction. After the infusion of toxin, alone, in the initial phase, pulmonary artery pressure increased from 16 +/- 1 to 45 +/- 5 mm Hg and the rectal temperature rose from 39.5 +/- 0.14 to 40.8 +/- 0.18 degree C. During the second phase, the peripheral blood granulocyte count decreased to 10% of baseline values and the lung lymph protein clearance increased from 5.1 +/- 1.1 to 11.2 +/- 1.8 ml/h, suggesting increased pulmonary vascular permeability. Methylprednisolone pretreatment did not alter the initial phase of pulmonary hypertension or the febrile response but completely abolished the granulocytopenia and the increased pulmonary vascular permeability. These effects are unlikely to be related to inhibition of prostaglandin synthesis. Prevention of the lung vascular injury by methylprednisolone may be related to inhibition of granulocyte accumulation in the lung.

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↗