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Microvascular function in the peripheral vascular bed during ischaemia and oxygen-free perfusion.

OBJECTIVES: To determine the influence of acute ischaemia and absence of leukocytes on the microvascular function and capillary permeability in skeletal muscle. DESIGN: Prospective, open study. SETTING: University Department of Vascular Surgery and Institute of Medical Physiology. MATERIALS AND METHODS: Ten isolated cat gastrocnemius muscles were perfused with oxygen-free Ringer-albumin solution through the femoral artery. At 5 microliters bolus with 14.8 MBq 51Cr-EDTA was injected through a side branch into the femoral artery, and the response function was detected over the muscle by a scintillation detector connected to a spectrometer and a computer. The perfusion coefficient was measured directly at the venous outlet. The response function was analysed in accordance with non-compartmental black box kinetic principles to give perfusion rate, capillary extraction fraction and capillary diffusional permeability-surface area product (PdS). In separate experiments the molecular size and the free diffusion coefficient of 51Cr-EDTA in water at 37 degrees C were determined by a modified true transient diffusion method. MAIN RESULTS: During perfusion the PdS-product increased as a function of flow rate, f, in accordance with the linear regression line PdS = 1.78 + 0.15 f between 5 to 60 ml/100 g/min. This permeative conductance was identical to that found previously in a similar experimental set up with oxygenated whole blood perfusion. During oxygen free perfusion the perfusion rate was a linear function of arterial perfusion pressure, and autoregulation of blood flow did not occur in response to variations of arterial perfusion pressures. The free diffusion coefficient in water at 37 degrees C for 51Cr-EDTA was 7.4 x 10(-6) cm2/s (n = 36), which corresponds to a Stokes-Einstein molecular radius, rSE, of 0.439 nm. CONCLUSIONS: In spite of complete anoxia and absence of normal microcirculatory flow regulating mechanisms there is no sign of changes in capillary diffusional permeability for smaller hydrophilic molecules and functional membrane damage is not elicited in the absence of oxygen under these conditions.

Animals↗

Effects of noradrenaline on the transcapillary passage of albumin, fluid and CrEDTA in the perfused rat hindlimb.

Isolated rat hindlimbs were artificially perfused with serum solutions, either during maximal vasodilatation induced by papaverine or during infusions of noradrenaline (NA) at concentrations of 0.5-3.5 microM. Transcapillary exchange was followed with three independent techniques: clearance of albumin, measured after tissue accumulation of radiolabelled tracer, capillary filtration capacity (CFC), determined gravimetrically, and the capillary diffusion capacity (PS) for CrEDTA, calculated from venous indicator dilution curves after single bolus injection of dyes. During maximal vasodilation, when resistance to flow was 2.3 +/- 0.1 PRU100, albumin clearance was 0.0241 +/- 0.0012 ml min-1 100 g-1, CFC was 0.0367 +/- 0.0009 ml min-1 mmHg-1 100 g-1 and PS for CrEDTA was 8.2 +/- 0.4 ml min-1 100 g-1. Noradrenaline given before radiolabelled albumin increased vascular tone and reduced all three capillary exchange parameters in parallel. Albumin clearance was reduced also when NA was given after the introduction of radiolabelled albumin. When NA raised vascular tone to a level largely corresponding to that in resting skeletal muscle (PRU100 = 14) albumin clearance was 0.0067 ml min-1 100 g-1, CFC was 0.0141 ml min-1 mmHg-1 100 g-1 and PS for CrEDTA was 2.4 ml min-1 100 g-1. These findings suggest that albumin is transported by convective mechanisms and that the hydrostatic pressures fall in the exchange vessels as a consequence of functional precapillary 'sphincter' activity. Further, albumin clearance seems to be the same in the artificially perfused rat hindlimbs as in intact animals, at comparable vascular resistances, suggesting that capillary permeability is not influenced by the present surgical procedure.

Animals↗

Control of capillary hydraulic conductivity via membrane potential-dependent changes in Ca2+ influx.

Capillary permeability has been shown to be sensitive to the levels of intracellular calcium. We examined the role of membrane potential in the regulation of capillary water permeability by a Ca2+ leak mechanism. Repeated measures of Lp were taken in situ on individually perfused mesenteric capillaries of cerebrally pithed frogs (Rana pipiens). A rise in extracellular potassium ([K+]o) to 24 mM induced a 45% decrease in Lp (n = 20), whereas lowering [K+]o to 0.24 mM elevated Lp by twofold (n = 9). To investigate whether these changes in Lp were due specifically to changes in membrane potential and consequent changes in the driving force for Ca2+ influx, we performed the following experiments: 1) [K+]o was elevated while the product of [K+]o and extracellular chloride concentration [Cl-]o was kept constant, 2) [K+]o was elevated under nominally Ca(2+)-free conditions, 3) K+ leak was induced by addition of 10 microM valinomycin, and 4) Na(+)-K+ pump was blocked by 10 microM ouabain. A constant [K+]o [Cl-]o product did not prevent high K+ from lowering Lp. Nominally Ca(2+)-free conditions abolished the effect of high K+. Valinomycin mimicked the response to low K+, and ouabain failed to change Lp. The data from this study conform to the hypothesis that membrane potential is an important regulator of capillary barrier properties via changes in Ca2+ influx through leak channels.

Animals↗

Clinical efficacy of micronized purified flavonoid fraction (MPFF) in edema.

Swelling is one of the most frequent complaints of patients in daily clinical practice; leg edema is its objective confirmation. It can be associated with several diseases. Micronized purified flavonoid fraction (MPFF) is a phlebotropic drug commonly used to treat the signs and symptoms associated with chronic venous insufficiency (CVI). It has confirmed its clinical efficacy in different groups of patients suffering from edema: idiopathic cyclic edema, CVI-associated edema, postmastectomy lymphedema and might be beneficial in some of drug-induced edema. In a double-blind, placebo-controlled, randomized study including 30 outpatients suffering from idiopathic cyclic edema syndrome, MPFF 1000 mg/day for 6 weeks, normalized the capillary permeability, assessed by the Landis isotope test, in 3 out of 4 patients (p=0.01). The decrease in capillary hyperpermeability led to a clinically significant decrease in weight and edema. In 200 patients with functional or organic venous insufficiency of the lower limbs, a double-blind, placebo-controlled, randomized study with MPFF 1000 mg/day for 2 months provided strong evidence of a marked improvement in symptoms and signs. A significant reduction in supramalleolar edema (assessed by circumference measurement) was observed, whatever the origin of CVI: functional or organic. MPFF efficacy was also demonstrated in another randomized, multicenter controlled trial in 320 patients suffering from chronic venous insufficiency. In this study, a significant decrease in circumference of the most affected leg was observed after 2 months of treatment (p<0.001), whatever the schedule of administration of MPFF (1000 mg once daily or bid). The benefit of MPFF on edema has been further confirmed by the volometer technique (opto-electronic measuring system) which was performed in a population of 30 patients suffering from CVI and treated by MPFF 1000 mg/day over a 6-week period. The mean volume of the more affected lower leg decreased significantly after a 6-week period of treatment, correlating to a significant improvement in clinical symptoms. MPFF has been also tested on another type of edema, upper limb lymphedema secondary to mastectomy, during a double-blind, placebo-controlled, randomized study in 104 patients. MPFF 1000 mg/day improved all lymphoscintigraphic parameters such as half-life and clearance of the labelled colloid. With regard to evolution of lymphedema volume, a tendency in favor of MPFF was observed in the subgroup of patients with more severe lymphedema. Based on its action on capillary hyperpermeability, MPFF has been used with attractive results when combined with classic treatment for a pilot study carried out in patients with advanced breast cancer (n=21) or ovarian carcinoma (n=3), treated with docetaxel, which causes severe edema as a side effect, even when associated with corticoids. Further trials are under way to assess the possible benefit of MPFF in such patients. These results in different types of edema confirm that, by acting on all parameters involved in edema, veins, lymphatics, and microcirculation, MPFF represents a drug of choice for treating CVI-associated edema.

Anthropometry↗

Requirement of arteriovenular pairing for increased capillary filtration during acute inflammation.

OBJECTIVE: The purpose of this study was to determine whether the leukocyte chemoattractant N-formyl methionyl-leucyl-phenylalanine (FMLP) increases capillary fluid filtration rate (Jv/S), and if so, to determine whether the mechanism involves arteriovenular communication. METHODS: Intravital microscopy was used in the rat mesentery to measure capillary Jv/S by a micro-occlusion technique. FMLP was locally superfused through a micropipette near vessels in three different arrangements: 1) near a venule in close pairing with the arteriole feeding the monitored capillary, 2) near an unpaired arteriole feeding the capillary, or 3) near an unpaired venule draining the capillary. In separate experiments, arteriolar hydrostatic pressure (downstream of arteriovenular pairing sites exposed to FMLP) was measured with a micropressure system. RESULTS: FMLP increased capillary Jv/S when applied to arteriovenular pairing sites, but not when applied to unpaired arterioles or venules. Micropressure measurements in paired arterioles remained essentially constant during FMLP exposure, suggesting that the increase in Jv/S is primarily due to increased capillary permeability. CONCLUSIONS: With FMLP applied locally to stimulate leukocytes, arteriovenular pairing is required to observe an increase in capillary filtration rate.

Acute Disease↗

Histamine and protein transport in canine muscle.

The effect of intraarterial histamine infusion on transcapillary protein transport was determined in the constant flow pump-perfused isolated gracilis muscle of the dog. Muscle vascular resistance (MVR), the rate of net transcapillary protein transport (Js), net transcapillary fluid transport (Jv), changes in protein-free transcapillary fluid movement (delta Jo) and rubidium extraction (ERb) were calculated following four experimental manipulations. First, as a control, venous pressure was elevated by 20 mmHg; next, histamine was infused intraarterially; then venous pressure was elevated by 20 mmHg during histamine infusion; and finally, the recovery of the tissue from histamine infusion was determined. Although elevation of venous pressure produced no change in MVR, it significantly increased Js, Jv and delta Jo. Histamine infusion caused a significant decline in MVR, and increases in Js and in Jv. delta Jo did not change significantly. When venous pressure elevation was superimposed upon histamine infusion, MVR did not change; Js, Jv, and delta Jo increased but only by increments similar to venous pressure elevation alone. None of the manipulations altered Rb extraction. At the constant flow used in this study, histamine does not appear to increase either capillary hydrostatic pressure or capillary surface area, so that the small intestine in Js was probably due to a slight increase in capillary permeability.

Animals↗

Digital Starling forces and hemodynamics during early laminitis induced by an aqueous extract of black walnut (Juglans nigra) in horses.

Starling forces and hemodynamics in the digits of 5 horses were studied during early laminitis induced by oral administration of an aqueous extract of black walnut (Juglans nigra). The black walnut extract was prepared from heartwood shavings and was administered by nasogastric tube. Heart and respiratory rates, rectal temperature, central venous and arterial pressures, digital pulses, and signs of lameness were monitored. Blood samples were collected for determination of WBC count, hemoglobin concentration, and PCV and for endotoxin and tumor necrosis factor assays. Total WBC count and central venous pressure were monitored until they decreased by 30 or 20%, respectively. These decreases in WBC count and central venous pressure were observed 2 to 3 hours after dosing with black walnut extract. Respiratory and heart rates, body temperature, systolic and diastolic blood pressures, PCV, and hemoglobin concentration did not change significantly. Anesthesia was induced, heparin (500 IU/kg of body weight) was administered IV, and a pump-perfused extracorporeal digital preparation was established. Digital arterial and venous pressures were maintained at 100 and 30 mm of Hg, respectively. Blood flow, capillary pressure, lymph and plasma protein concentrations, and weight of the isolated digit during rapid increase in venous pressure were measured. Isogravimetric capillary filtration coefficient, vascular compliance, vascular and tissue oncotic pressures, tissue pressure, osmotic reflection coefficient, and precapillary and postcapillary resistances were calculated. Mean digital blood flow was 14 ml/min/100 capillary pressure was 52 mm of Hg, and vascular compliance was 0.06 ml/mm of Hg. The vascular and tissue oncotic pressures were 21.49 and 4.93 mm of Hg, respectively. The osmotic reflection coefficient was 0.71, and tissue pressure was 41 mm of Hg. The precapillary and postcapillary resistances were 7 and 2 mm of Hg/ml, respectively. Capillary permeability to proteins was not significantly different from that previously measured in healthy horses, suggesting that the increased capillary filtration coefficient reflected increased capillary hydrostatic pressure and perfusion of previously nonperfused capillaries. Neither endotoxin nor serum tumor necrosis factor activity was detected in any samples. The hemodynamic and Starling forces observed in this study were similar to those observed after laminitis was induced by administration of a carbohydrate gruel. Significant differences between the 2 models were detected for total vascular resistance, postcapillary resistance, and capillary filtration coefficient. It is likely that these differences were identified because the horses administered the black walnut extract were at an earlier stage in the disease process. The findings of this study suggest that the increase in capillary pressure causes transvascular fluid movement, resulting in increased tissue pressure and edema. We hypothesize that further increases in tissue pressure may collapse capillary beds and lead to tissue ischemia.

Animals↗

A fibre matrix model for the restricting junction of the blood-brain barrier in a cephalopod mollusc: implications for capillary and epithelial permeability.

A model is proposed for the novel restricting junction forming the blood-brain barrier in a cephalopod mollusc, the cuttlefish Sepia officinalis. The model is based on electron-microscopic findings, from both thin-section and freeze-fracture material, the distribution of electron-dense tracers, and radioisotopic measurements of permeability using small non-electrolytes. Biochemical properties of Sepia plasma proteins are also considered. It is proposed that an effective blood-brain barrier is achieved by a combination of mechanisms. As much as 90% of the Sepia brain microvessel wall is covered by a 'seamless' glial sheath, without intercellular clefts, limiting the number of potential leakage sites. The remaining clefts follow a tortuous course increasing the diffusion path to the neuropile. Entry into the clefts is reduced by a restricting junctional region at the luminal end, characterized by delicate striations spanning the cleft, and forming an effective barrier to both horseradish peroxidase and ionic lanthanum. This is a novel junctional type, different from previously-described vertebrate and invertebrate occluding junctions. It is proposed that the junction acts as a fine-mesh molecular filter, with condensed extracellular material in the cleft, cross-linked and consolidated by bound plasma protein. Cephalopod haemocyanin or its subcomponents are considered likely candidates for the bound protein. The model predicts that blood-brain barrier permeability should be sensitive to the charge structure of the extracellular matrix and the presence of protein, and is analogous to the 'fibre matrix' model of vertebrate capillary permeability. The Sepia blood-brain barrier also highlights the different strategies available for constructing a restricting cell layer, and suggests a possible evolutionary pattern underlying the present range of junctional mechanisms in vertebrate and invertebrate epithelia.

Animals↗

Hemoglobin as a tracer in hemodynamic pulmonary edema.

Stroma-free hemoglobin is an electron-opaque molecule useful as a tracer for the ultrastructural stuty of pulmonary capillary permeability. After this tracer was infused into the isolated pulmonary lobe of the dog, the endothelial junctions of the capillaries, as revealed by electron microscopy, act like distensible pores, thus allowing the tracer to escape when the pulmonary artery pressure was raised above 50 millimeters of mercury.

Animals↗

Histochemical and biochemical modifications induced by experimental irradiation of human skin maintained in survival conditions and modulation by application of an emulsion containing trolamine.

Radiotherapy continues to cause skin disorders. In this article, with the aid of our human skin model maintained in ex vivo survival conditions for 15 days, we describe the modifications caused by irradiation and their modulation by a trolamine-containing emulsion (Biafine). Normal human skin fragments were maintained in organ culture. One ionizing radiation session with 5 Gy was applied. Skin parameters were evaluated 24 h after the radiation session and were compared with a nonirradiated skin fragment: vascular modifications (histology), edema, epithelial proliferation, interleukin (IL)-1alpha and IL-6. Another series of skin fragments was maintained in survival conditions for 15 days after the radiation session to evaluate collagen neosynthesis by fibroblasts and any vascular changes (CD34). After irradiation the basal cell proliferation was reduced by approximately 50%. Extensive vasodilation occurred with altered capillary permeability accompanied by decreased CD34 transmembrane protein expression. Collagen synthesis and IL-1 secretion were increased. Biafine significantly reduced capillary alterations, restored CD34 expression as well as epithelial cell proliferation and significantly decreased collagen synthesis and IL-1 expression. With this ex vivo human skin model we confirmed the main modifications induced by radiotherapy as previously described in animal models: decreased basal cell proliferation and endothelial cell alterations and increased collagen synthesis by fibroblasts, probably under the influence of IL-1. The effect of Biafine emulsion on these histological and biochemical parameters may support its clinical efficacy.

Adult↗

Albumin decreases myocardial permeability of unbound quinidine in perfused rat heart.

With the single-pass, isolated, perfused rat heart preparation, we examined the effect of different perfusate albumin concentrations on the capillary permeability and pharmacodynamic effects of quinidine. Nine hearts were perfused for five consecutive 35-min phases with buffer containing quinidine and albumin concentrations of 0%, 0.1%, 1%, 6% and 0%, in that order, with a 55-min washout between each phase. Compared with 0% albumin perfusate, the equilibrium rate of quinidine perfusate output concentration (Cout) was slower with 0.1% albumin but faster with 1% and 6% albumin. Quinidine Cout, unbound fraction (fu) and perfusion flow rate (Q) for each phase of each experiment were fitted by a modified Kety-Renkin-Crone equation. Estimates of the capillary permeability-surface product (PS) for the two 0% albumin phases (14.4 +/- 5.6 and 12.3 +/- 4.4 ml/min) were significantly higher than those for the three albumin phases (5.3 +/- 1.0, 6.7 +/- 1.2 and 7.4 +/- 2.2 ml/min, respectively; P < .05). There was a direct, linear relationship between lengthening of the QT interval of the ECG and total and unbound quinidine concentrations, but the relationship for unbound concentration was independent of fu, showing that the pharmacodynamic effect was mediated by unbound concentration. In four additional experiments with antipyrine instead of quinidine, PS for the two 0% albumin phases (24.7 +/- 6.5 and 23.2 +/- 2.4 ml/min) was not significantly different than that for the three albumin phases (25.5 +/- 6.1, 22.5 +/- 2.9 and 22.9 +/- 3.6 ml/min, respectively). Albumin had no effect on the volume of distribution referenced to unbound drug for either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transcytosis of alpha1-acidic glycoprotein in the continuous microvascular endothelium.

By using perfusions and bolus administration, coupled with postembedding immunocytochemical procedures, we have identified the structures involved in the transport of derivatized orosomucoid (alpha1-acidic glycoprotein) across the continuous microvascular endothelium of the murine myocardium. Our findings indicate that: (i) monomeric orosomucoid binds to the luminal surface of the endothelium; (ii) it is restricted to caveolae during its transport across the endothelium; (iii) it is detected in the perivascular spaces at early time points (by 1 min) and in larger quantities at later time points (>5 min) from the beginning of its perfusion or its intravascular administration; (iv) no orosomucoid molecules are found in the intercellular junctions or at the abluminal exits of interendothelial spaces; and (v) the vesicular transport of orosomucoid is strongly inhibited by N-ethylmaleimide (>80%). Because, by size and shape, the orosomucoid qualifies as a preferential probe for the postulated small pore system, our results are discussed in relation to the pore theory of capillary permeability.

Animals↗

Effects of low-dose hydrogen peroxide in the isolated perfused rat lung.

Isolated perfused rat lungs (IPRL) were used to determine if treatment with hydrogen peroxide would result in measurable changes in exhaled ethane during the early stages of capillary leak. Pulmonary capillary filtration coefficient, pulmonary vascular resistance, and dynamic pulmonary compliance were measured at two time points in an IPRL. Additionally, exhaled ethane was determined before and after the addition of 0.25 mM H2O2 to the perfusate in a second group of lungs. Lung wet/dry weight ratios were measured at the termination of the experiments. The ethane in the exhaled alveolar gas from IPRLs ventilated with 5%CO2/20%O2/balance N2 was quantitated using gas chromatography before and after the addition of 0.25 mM H2O2 to Krebs Ringer's 5% albumin perfusate. H2O2 (0.25 mM) caused a small but significant increase in capillary filtration coefficient from 0.0122 (+/- 0.0008) to 0.0173 (+/- 0.0013) mL/min/cm H2O/g dry lung weight (p < .05). Wet/dry lung weight ratios were increased in the H2O2-treated lungs (6.0654 +/- 0.1024 versus 5.4149 +/- 0.1143; p < .05). Exhaled ethane did not increase over the period of time hydrogen peroxide was present in the perfusate. In other experiments in closed-chested rats, 0.25 mM peroxide did not cause increased exhaled ethane, whereas 1 mM H2O2 did. This latter increase in ethane was not noted in similarly perfused open-chested rats. These data indicate that small amounts of H2O2 may increase pulmonary capillary permeability without affecting exhaled ethane measurements.

Animals↗

Slightly altered permeability-surface area products imply some cerebral capillary recruitment during hypercapnia.

To test the capillary recruitment hypothesis in brain, cerebral blood flow was raised markedly in rats by exposure to 8% CO2 (hypercapnia), and capillary permeability-surface area (PS) products were measured. Local cerebral blood flow (LCBF), volume of radiolabeled blood in parenchymal microvessels (also referred to as the blood space or Vb), plus the local capillary influx rate constants (K1) and PS products of [14C]antipyrine and 3-O-[14C]methyl-D-glucose (3OMG) were estimated in 44 brain areas. Hypercapnia raised PaO2 to 140 mm Hg, elevated LCBF by two- to threefold through out the brain, and increased Vb from 5 to 33% (mean = 22%) in 42 of 44 brain areas; hypercapnia did not, however, alter microvessel hematocrit. With hypercapnia, the influx of antipyrine was increased by 40-65% in all brain areas, and the PS products of antipyrine were elevated from 0-35% (mean = 17%). The PS products of antipyrine plus the parenchymal blood spaces suggest modest (< 30%) capillary recruitment in most brain areas as well as some microvessel dilation, mainly in forebrain gray matter and white matter areas. In contrast, hypercapnia did not appreciably alter K1 nor PS of 3OMG; it slightly but not significantly raised the blood levels of glucose. In view of the blood space and antipyrine evidence for modest capillary recruitment and vasodilation, the lack of change in PS of 3OMG implies that glucose transporter activity was lowered by hypercapnia, an effect similar to that reported for high-dose pentobarbital. Finally, the microvessel hematocrit and 3OMG data suggest that cerebral capillary permeability (P) was not increased by hypercapnia. Overall, hypercapnia seems to increase LCBF mainly by raising the velocity of blood flow; capillary recruitment and dilation appear to play relatively minor roles in this flow increase.

3-O-Methylglucose↗

The pathogenetic and prognostic significance of blood-brain barrier damage at the acute stage of aneurysmal subarachnoid haemorrhage. Clinical and experimental studies.

In a retrospective study, pathological tissue enhancement was found in nearly two fifths of patients with acute SAH on contrast-enhanced cranial computed tomography. By means of absorption measurements with the region of interest technique over the basal ganglia, it was proved indirectly that pathological tissue enhancement should be brought about not only by hyperaemia, i.e., a blood volume increase, but also by extravasation of the contrast material, i.e., blood-brain barrier (BBB) disruption. A similar conclusion was drawn from the retrospective isotope brain scintigraphy study. It was further established that, although the pathological contrast enhancement was most obvious in the cortex, and particularly in the neighbourhood of the subarachnoid spaces, the phenomenon is probably widespread throughout the brain. Patients with abnormal enhancement are likely to be in less favourable clinical grades, have a high incidence of marked or diffuse spasm, have a poorer outcome independent of surgical or conservative treatment, and develop cerebral infarction more frequently. Systemic arterial hypertension was associated with an increased incidence of abnormal enhancement. Pathological tissue contrast enhancement or isotope accumulation in the first few days of SAH may serve as prognostic signs indicative of the late development of vasospasm and ischaemia. As ischaemic disruption of the capillary system is not prominent in the initial days following any stroke, vasoactive substances arising from the breakdown of the blood clot should play important part in the BBB damage in the acute stage of SAH. The "cortical SAH" model developed in the animal experiments ensured a constant subarachnoid blood volume with minimal local brain damage. The intracranial pressure and mean arterial blood pressure did not change significantly, and perfusion defects did not arise. Thus, this model proved suitable for studying the influence on the BBB of vasoactive blood breakdown products (responsible for arterial spasm) without the accompanying effects of pathological conditions such as raised intracranial pressure, systemic hypertension, non-reflow phenomena, which also disrupt the BBB. Measurements on the water, electrolyte, albumin contents of brain tissue, as well as the immunohistochemical localization of albumin, clearly indicated that the brain oedema developing at the acute stage of experimental SAH could be classified as having a primary vasogenic component in addition to the cytotoxic component. This increased capillary permeability was found to be brought about by opening of tight junctions and pinocytosis in the endothelial cells. The pathological capillary permeabilit

Adolescent↗

Retinal phlebitis in the Irvine-Gass syndrome.

We reviewed the pathology records from January 1965 through July 1975 for aphakic eyes. After exclusion of unsuitable cases, ten eyes (nine patients) with cystoid macular edema and 142 eyes without cystoid macular edema were studied. Clinical ophthalmic records were available for five of the ten eyes with the Irvine-Gass syndrome. Histologic sections were examined, revealing a significant correlation between the Irvine-Gass syndrome and retinal phlebitis, which has not been reported previously, as well as cyclitis and vitritis. Anterior segment operative complications tended to be more prevalent in eyes with the Irvine-Gass syndrome than in those without the Irvine-Gass syndrome, although the assocation was not statistically significant (P less than .1). Retinal trypsin digestion showed the phlebitis to be distributed posteriorly within primary and secondary retinal veins, frequently occurring near points of bifurcation. The changes in permeability seen in the Irvine-Gass syndrome may be due to this retinal phlebitis and to a generalized inflammation-induced increase in capillary permeability. The case of the phlebitis is not known.

Adult↗

Vascular permeability increasing action of the saline extract of Dictyocaulus filaria--a preliminary report.

The cutaneous hypersensitivity reaction in sheep infected with Dictyocaulus filaria was investigated. The saline extract of the worms increased the cutaneous capillary permeability in both the infected and uninfected control animals. Similar increase in the permeability was also observed in uninfected healthy rabbits. The results suggest that the vascular permeability increasing action of the worm extract is, partly, due to histamine release.

Animals↗