Changes In Capillary Permeability Research Articles

Histopathological, hematological, condition-factor, and organ weight changes associated with selenium accumulation in fish from Belews Lake, North Carolina

Green sunfish (Lepomis cyanellus) were collected from two study sites in Belews Lake, North Carolina, for assessment of correlations between several biological parameters and bioaccumulation of selenium. The fish had elevated concentrations of selenium in the hepatopancreas (liver) and exhibited histopathological and other manifestations of selenium poisoning. Condition-factors of Belews Lake fish were significantly correlated with selenium concentrations in hepatopancreas and skeletal muscle, indicative of capillary permeability changes and resultant edema, supported by the occurrence of significantly increased hepatopancreas-weight-to-body weight ratios in the fish having the higher tissue selenium levels. Gill lamellae were noticeably swollen and vacuolated. Hematocrits of the selenium-contaminated fish were significantly lower than those of the reference fish. The hepatopancreas exhibited lymphocyte infiltration, vacuolation of parenchymal hepatocytes around the central veins, and increased numbers of Kupffer cells. The mesonephros exhibited focal intra-capillary proliferative glomerulonephritis. Hearts showed swollen, inflammatory cell-filled pericardial spaces, diagnosed as possible uremia-induced pericarditis. Ovaries in fish with the higher liver selenium levels exhibited numerous necrotic and ruptured egg follicles. These conditions were observed in the Belews Lake Site 2 fish, but did not occur in reference green sunfish, nor did they occur consistently in fish from the less-contaminated Belews Lake Site 1.

Capillary permeability in normal and hypertensive human pregnancy.

Capillary permeability (CP) is elevated in late normal pregnancy, when compared to postpartum values. In women with pregnancy associated hypertension (PAH), pregnancy CP levels are not different from postpartum and are less than in normal pregnancy. These changes in capillary permeability are not explained by alterations in serum albumin.

Ultrastructural aspects of capillary function in irradiated bowel. An experimental study in the cat.

Irradiated small intestine of the cat has decreased capillary function measured as capillary filtration. This decrease may be due to changes in capillary permeability or decreased capillary area. An electron microscopic study was carried out to examine whether there were any ultrastructural changes consistent with impaired permeability. Cat ileum was irradiated with doses from 10 to 25 Gy and examined 4 days, 1 month, and 4 months after irradiation. In the acute phase (4 days) degenerative endothelial changes were seen and increased with dose. Congestion and microthrombi were also observed. One month after irradiation endothelial changes were still seen after 20 and 25 Gy, and an aggregation of fibrous matter adjacent to the capillary wall was prominent. The endothelial changes were subtle after 4 months, but the pericapillary and stromal fibrosis increased, and an increasing number of collagen fibrils appeared. Micropores disappeared after 20 and 25 Gy but returned later. Pinocytic vesicles were observed after all doses and intervals. The initial decrease in capillary filtration coefficient after irradiation may partly be due to permeability changes caused by endothelial degeneration, whereas the late decrease parallels the increasing pericapillary fibrosis.

Fluorophotometric evaluation of capillary permeability in gram-negative shock.

We developed a new method by which capillary permeability changes secondary to gram-negative sepsis can be easily monitored. In a preliminary trial, ten dogs were injected intravenously with live Escherichia coli. Progressive extravasation of fluorescein from the retinal capillary bed was demonstrated by retinal angiography, thus indicating "capillary leak." In a subsequent trial, fluorophotometry facilitated direct quantitation of this leak. Three control and three septic dogs underwent continuous hemodynamic and physiologic monitoring. Hourly retinal fluorophotometric measurements were recorded. The control group demonstrated no capillary leak nor any change in hemodynamic and physiologic status. In the septic group, there was a dramatic increase in extravascular fluorescein concentration two to four hours after E coli infusion, correlating well with hemodynamic and physiologic parameters typical of gram-negative shock.

Pathogenesis of the postphlebitic syndrome.

The dependent edema, skin pigmentation, local inflammation associated with subcutaneous fibrosis, chronic ulceration, and current infection are the hallmarks of postphlebitic syndrome. In one fifth of the patients there is no evidence of antecedent deep venous occlusion. Current emphasis is therefore on improvement in investigation and the use of treatment programs designed to return venous patency and valve function to normal. Modern management must also take into account local changes in capillary permeability and fibrinolytic activity in the pathogenesis of the venous ulceration.

Simultaneous measurements of capillary filtration and diffusion capacities during graded infusions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) into the rat hindquarter vascular bed.

The relationships between capillary diffusion capacity (PS) for Cr-EDTA respective capillary filtration capacity (CFC) and vascular resistance during graded intraarterial infusions of NA and 5-HT into the artificially constant flow perfused rat hindquarter vascular bed were investigated. During maximal vasodilatation PS for Cr-EDTA was some 5.5--5.7 ml/min x 100 g, CFC some 0.04 ml/min x mmHg x 100 g, while vascular resistance was 2.8 mmHg x ml-1 x min x 100 g (PRU100) and isogravimetric capillary pressure 12.8 mmHg on an average. Setting out from maximal vasodilatation, increasing doses of NA and 5-HT produced graded reductions in capillary surface area as reflected by progressive decreases in both PS for Cr-EDTA and CFC. These changes occurred simultaneously with progressive increases in both pre- and postcapillary resistances, causing elevations in both arterial and capillary hydrostatic pressures and hance in capillary fluid filtration at constant flow. Capillary hydrostatic pressure increased maximally to 45 mmHg (calculated for NA) and vascular resistance to some 21 mmHg x ml-1 x min x 100 g on an average. PS for Cr-EDTA decreased maximally to some 0.7--1 ml/min x 100 g for both NA and 5-HT and furthermore, the relationships between PS for Cr-EDTA and PRU100 for NA respective 5-HT were almost identical. This was taken to indicate that capillary surface area for nutritional exchange is affected similarly by both drugs. However, the CFU-PRU100 relationship was shifted towards some 30--50% higher CFC values for 5-HT than for NA at almost every level of vasoconstriction. This might suggest that 5-HT besides reducing capillary surface area also induced moderate increases in capillary permeability though increases in number and/or radius of large pores (gaps) (cf. Rippe, Kamiya & Folkow 1978). Even during NA-induced vasoconstriction, when virtually no changes in capillary permeability occurred, PS for Cr-EDTA was reduced to a relatively greater extent than CFC, the discrepancy being most pronounced during marked vasoconstriction. The significance of this finding is discussed.

Changes in lung water and capillary permeability following sepsis and fluid overload

The presence or absence of permeability changes in the pulmonary parenchyma during sepsis is a controversial point in the literature. Clinical experience indicates an increase in pulmonary as well as systemic capillary permeability in septic patients. Eighteen dogs were studied. Ten received 4.8 × 10 9 organisms/kg of live Escherichia coli intravenously and were fluid overloaded in 5-cm H 2O increments during a 6-hr period to a left atrial pressure (LAP) of 35 cm H 2O; eight dogs were similarly volume overloaded without a septic insult. Cardiac output, extravascular lung water (EVLW), blood pressure, pulmonary artery pressure, LAP, and central venous pressure were measured in both groups at each LAP elevation. Results are: Group EVLW (ml/kg) Nonseptic + fluid ( N = 8) 6.3 6.8 8.6 11.7 - 11.2 Septic + fluid ( N = 10) 7.4 7.9 9.6 15.0 19.1 - LAP (cm H 2O) 2–4 15 20 25 30 35 As seen above the septic animals had a greater increase in EVLW than the volume-overloaded dogs, reaching statistical significance at a LAP of 35 cm H 2O ( P < 0.001). EVLW showed a strong positive correlation, as it has in the past, with increasing LAP. We conclude that there is a permeability change which occurs in the lung following sepsis but this does not occur immediately and requires increased pulmonary capillary pressure and/or time to become manifest; this finding implies that the permeability lesion is not a direct result of bacteremia or endotoxemia but results from an intermediary mechanism.

Changes in gastric mucosal morphology, capillary permeability and blood flow during the first 3 days of acute gastritis in cats.

In the present investigation gastric morphology, blood flow, vascular permeability and water content were studied in cat stomachs with acetic acid-induced gastritis at different time intervals up to 3 days after induction of gastritis. The morphological changes including mucosal erosions, edema and hemorrhage showed normalization within 3 days. The mucosa and muscularis blood flow remained essentially unchanged compared with pre-gastritis values and with the control group. Gastritis was associated with leakage of circulating albumin into the stomach wall most pronounced 4 h after the induction of gastritis. The water content was high at 4 and 24 h after induction of gastritis with almost normalization at 3 days. The morphologaical characteristics of our model are very similar to those observed in man. Leakage of circulating albumin into the gastric wall seems to be the best parameter for quantifaication of the inflammatory changes found in acute gastritis, while blood flow seems to be a less important parameter.

Transcapillary exchange in the cat salivary gland during secretion, bradykinin infusion and after chronic duct ligation.

1. Capillary permeability-surface area products for 86Rb, [51Cr]EDTA (mol. wt. 357), [57Co]cyanocobalamin (mol. wt. 1353) and [125I]insulin (approximate mol. wt. 6000) have been measured using the single-circulation, multiple-tracer dilution technique in the in situ perfused submandibular salivary gland during parasympathetic nerve stimulation, close-arterial bradykinin infusion and following chronic duct ligation. 2. In glands with a natural blood supply, permeability-surface area for 86Rb and [51Cr]EDTA increased during parasympathetic stimulation, but this was shown to be related to the concomitant increase in blood flow rather than to a change in capillary permeability or in surface area. 3. In glands perfused at constant flow, parasympathetic stimulation led to a decrease in permeability-surface area for EDTA (-19.1 +/- 5.2%, mean +/- S.E., n = 5, P less than 0.05) cyanocobalamin (-12.3 +/- 6.0, n = 12, P less than 0.05), and insulin (-15.3 +/- 4.8, n = 11, P less than 0.02). It is suggested that this may be the result of a redistribution of flow from the acinar microcirculation to a less permeable ductal vasculature. 4. Bradykinin infusion had no significant effect on permeability-surface area for EDTA and cyanocobalamin in perfused glands. 5. In perfused glands, ligation of the submandibular duct for 3--12 days reduced permeability-surface area (ml.min-1.g-1) for [51Cr]EDTA from 5.26 +/- 0.60 (mean +/- S.E., n = 9) to 4.20 +/- 0.12 (n = 4, P less than 0.30), [57Co]cyanocobalamin from 3.22 +/- 0.12 (n = 48) to 2.02 +/- 0.08 (n = 15, P less than 0.001) and [125I]insulin from 1.52 +/- 0.07 (n = 39) to 0.72 +/- 0.23 (n = 11, P less than 0.001).

LEAKAGE OF FLUORESCEIN: FIRST SIGN OF JUVENILE DIABETIC RETINOPATHY: Role of Diabetic Control and of Duration of Diabetes

In order to ascertain the first vascular lesions responsible for juvenile diabetic retinopathy, 408 fluorescein angiographies were performed in 114 diabetic children and adolescents whose diabetes became clinically apparent before the age of 14 years. Compared with regular ophthalmoscopy, fluorescein angiography doubles the frequency of the diagnosis of incipient retinopathy. In addition to the classical diabetic lesions, fluorescein leakages are demonstrated in 50% of diabetic eyes with initial retinopathy. They probably reflect early changes in capillary permeability. They appear often before microaneurysms. Duration of diabetes as well as insufficient and poor metabolic control considerably increase the frequency of retinopathy.

Effects of isoprenaline and cooling on histamine induced changes of capillary permeability in the rat hindquarter vascular bed.

Histamine infused intra-arterially into artificially perfused, maximally dilated rat hindquarters markedly increased fluid filtration and CFC but had essentially no effect on the diffusion capacity to small molecules. Isoprenaline largely prevented the increase in fluid filtration and CFC if infused prior to the start of the histamine infusion and, if infused after the start of the histamine infusion, promptly reduced fluid filtration and CFC to near control levels. Additionally, it was noted that severe cooling of the perfusate also largely prevented the marked increase in fluid filtration and CFC by histamine. This antagonism of histamine induced increases in macromolecular permeability represents a direct action of isoprenaline on the microvascular membrane which effectively counteracts that of histamine. The data also suggest that the large pores created by histamine are different from the large pore through which macromolecules normally transverse the microvascular membrane, and that catecholamines may exert a regulatory function in the control of microvascular permeability to macromolecules in pathophysiological states associated with massive histamine release.

Angiotensin II induced reduction of peritubular capillary diameter in the rat kidney.

Large peritubular capillaries were infused consecutively (20 nl-min-1) in random sequence with isotonic saline and angiotensin II (20-80 ng-ml-1). The diameters of the infused capillaries were measured, without knowledge of the infusate used, from colour photographs of the infused area. Angiotensin II induced a significant (p less than 0.001) decrease in capillary diameter (delta = 1.2 +/- 0.2 (SE) micron and delta = 2.1 +/- 0.2 (SE) micron with 20 ng-ml-1 and 80 ng-ml-1 angiotensin II infusates, respectively). This decrease was shown to be independent of external tubular compression: separate experiments in which the surrounding tubules were collapsed by injection of oil blocks yielded similar results. The possibility that the observed reduction in diameter was caused by an angiotensin II induced change in capillary permeability to the staining solution was excluded, since the angiotensin II effect was unchanged when fluorescent dextran (mol. wt. 150 000) was substituted for lissamin green. These experiments indicate that peritubular capillaries contract actively when infused with angiotensin II.

EFFECTS OF ALBUMIN AND/OR FUROSEMIDE THERAPY ON PULMONARY EDEMA INDUCED BY HYDROCHLORIC ACID ASPIRATION IN RABBITS

Aspiration of hydrochloric acid in rabbits resulted in an increased P(A-a)O2 together with increases in both lung water volume and lung extravascular albumin. This finding suggests lung damage following acid aspiration is related to changes in capillary permeability, with pulmonary edema resulting from the movement of albumin and water into the interstitial space. Therapy with albumin and furosemide together reduced the lung water and albumin accumulation and decreased P(A-a)O2. Treatment with albumin or furosemide alone was ineffective. Caution should be exercised in administering albumin alone for therapy of pulmonary edema when plasma protein is not clearly decreased, or when increased pulmonary capillary permeability is suspected.

Starling's Law and Albumin Therapy-Reply

The ongoing controversy over the relative merits of albumin vs large volumes of crystalloid solution as replacement for effective plasma volume has raged for many decades. Evidence can be cited by proponents of each type of solution. Indeed, the symposium which served as the basis for my communication, carefully presented both sides of this controversy. Although Starling's law of fluid movement across a semipermeable membrane does not fit all experimental conditions, it still remains the keystone for the consideration of movement in and out of the vascular space in isolated organs or extremities. In addition to these interrelating hydrostatic and colloid osmotic pressures on the two sides of a membrane, it is necessary to invoke multiple additional forces. As clearly outlined in the review, these include tissue compliance, rates of lymph flow, changes in capillary permeability, and an intrinsic elastic recoil mechanism of connectivetissue mucopolysaccharides that exhibit inhibition

DIGITAL VASCULAR PHYSIOLOGY IN EQUINE LAMINITIS OF ALIMENTARY ORIGIN

SummaryWe measured digital blood flow, vascular pressures, vascular resistance, lymph flow rates, and lymph protein concentration in eight anesthesized equidaewith acute alimentary laminitis and eleven control animals. Digital blood flow was increased in laminitis as a result of decreased vascular resistance, primarily prevenous resistance. Ponies with laminitis were hypertensive and had elevated digital venous pressures. Lymph flow and lymph protein concentration were not different in the two groups of animals, indicating there is no change in capillary permeability in laminitis.

EFFECTS OF ALBUMIN AND/OR FUROSEMIDE THERAPY ON PULMONARY EDEMA INDUCED BY HYDROCHLORIC ACID ASPIRATION IN RABBITS

Aspiration of hydrochloric acid in rabbits resulted in an increased P(A-a)O2 together with increases in both lung water volume and lung extravascular albumin. This finding suggests lung damage following acid aspiration is related to changes in capillary permeability, with pulmonary edema resulting from the movement of albumin and water into the interstitial space. Therapy with albumin and furosemide together reduced the lung water and albumin accumulation and decreased P(A-a)O2. Treatment with albumin or furosemide alone was ineffective. Caution should be exercised in administering albumin alone for therapy of pulmonary edema when plasma protein is not clearly decreased, or when increased pulmonary capillary permeability is suspected.

Acetic acid-induced gastritis in cats changes in blood flow and capillary permeability

Acetic acid-induced gastritis in cats changes in blood flow and capillary permeability

Tannic acid as an electron-dense probe in the testis.

The use of tannic acid to preserve and promote the staining of protein constituents of the extracellular fluid is described. Its usefulness for delineating the extracellular compartment and detecting changes in capillary permeability is illustrated in experiments on the testis.

Aspiration pneumonia: experimental evaluation of albumin and steroid therapy.

An experimental model using an ex vivo perfused ventilated canine pulmonary lobe was used to study aspiration pneumonia. After intrabronchial acid instillation, the lobe weight tripled, air way pressure and pulmonary artery pressure doubled, and intrapulmonary shunting increased from 5.5% to 53.4%. If large quantities of albumin were added to the lobe perfusate 5 minutes after intrabronchial acid instillation, weight gain, air way and pulmonary artery pressure, and intrapulmonary shunting were unchanged from control levels. If large quantities of steroid were added to the lobe perfusate 5 minutes after intrabronchial acid instillation, the lobe weight doubled but air way pressure and pulmonary artery pressure, and intrapulmonary shunting were not significantly different from control values. It is surmised that intrapulmonary acid aspiration causes an immediate and marked changed in pulmonary capillary permeability. Albumin administration by counteracting this permeability change, and steroid administration by modifying the permeability change, are both beneficial following acid aspiration.

Renal cortical blood flow in glycerol-induced acute renal failure in the rat.

Renal hemodynamics and renal function were evaluated in rats at 3, 24, and 48 hours and at 7 days after the induction of acute renal failure (ARF) by glycerol injection. Three hours after induction of ARF, creatinine clearance was 0.04 ml/min/100 g; renal blood flow (RBF), 1.99 ml/min/100 g; and filtration fraction, 3.7%. All were abnormally low. Although the administration of isotonic saline (total dose, 3% of body weight) to rats 3 hours after glycerol injection significantly improved creatinine clearance (0.17 ml/min/100 g), RBF (2.54 ml/min/100 g), and filtration fraction (12.9%), these values still were significantly lower than those of controls (creatinine clearance = 0.50 ml. ml/min/100 g, RBF = 4.92 ml/min/100 g, filtration fraction = 20.0%, all P values less than 0.001). Serum creatinine concentrations were significantly elevated at 24 hours (3.72% gm/100 ml), 48 hours (4.69 mg/100 ml), and 7 days (0.66 mg/100 ml) after glycerol injection compared to control (0.46 mg/100 ml, all P less than 0.01). RBF during these phases was not different from normal (4.41 ml/min/100 g). RBF 3 hours after bilateral ureteral obstruction was measured to determine the effects of tubular obstruction on renal hemodynamics. The RBF of rats with ureteral obstruction (4.12 ml/min/100 g) was not significantly different from controls (4.41 ml/min/100 g), suggesting that tubular obstruction in this model of ARF is probably not the cause of decreased RBF. The depressed glomerular filtration, as reflected by the decreased creatinine clearance that occurs during glycerol-induced ARF, is probably related to altered intrarenal vascular resistance or to changes in glomerular capillary permeability, or both.