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PubMed1977

Pulmonary capillary permeability to HRP in dogs: a physiological and morphological study.

Pulmonary capillary permeability was studied in 10 normal anesthetized dogs using horseradish peroxidase (HRP) as tracer. Physiological studies involved measurement of left ventricular, pulmonary arterial, and wedge pressures, and of right lymphatic duct (RLD) and thoracic duct lymph flows. Plasma and interstitial oncotic pressures were calculated from protein measurements. After 1 h of lymph collection, HRP was injected intravenously at three total dose levels, low (20-30 mg/kg), medium (55 mg/kg), and high (110-120 mg/kg) as a bolus followed by smaller doses over 1.5-3 h. HRP was measured colorimetrically in plasma and lymph and appeared in the first RLD lymph sample collected at all dose levels. Electron microscopic studies to examine the passage of HRP from plasma to RLD, while less sensitive in that HRP was seen only at the high dose, showed that it crossed pulmonary capillaries under normal physiological conditions. Freeze-cleaving studies suggest this may have occurred through pathways in the interendothelial space caused by discontinuities in the junctional strands of tight junctions.

Animals↗
PubMed1988

Neuropharmacologic control of cerebral capillary permeability: current implications for therapy of vasogenic brain edema.

Vasogenic brain edema occurs as a result of a diverse spectrum of central nervous system pathology. The fundamental physiologic abnormality of vasogenic brain edema is an increase in cerebral capillary permeability. It is hypothesized that the recent development of new, potent, synthetic vasopressin antagonists will make it possible to impede the formation of vasogenic brain edema by the intraventricular administration of such agents with the subsequent inhibition of the neural control of brain capillary permeability by the locus ceruleus. The action of the vasopressin antagonists should be synergistic with the anti-edema effects of central alpha-adrenergic blockade produced by phentolamine. The combination of these two modes of therapy is expected to produce an increase in intracranial pressure which will require additional forms of medical therapy to control, in spite of the overall decrease of brain parenchymal water content.

Blood-Brain Barrier↗
PubMed1990

Autoradiographic assessment of pineal gland glucose utilization and capillary permeability in the unanesthetized rat.

Pineal gland glucose utilization (GU) and capillary permeability (CP) were measured in unanesthetized rats, using complementary quantitative autoradiographic techniques. GU values within the pineal tissue were homogeneously distributed around 70 mumol of glucose/100 g each min, i.e., they were approximately 30% lower than in the cortical gray structures. The blood-to-brain transfer constant of [14C]-alpha-aminoisobutyric acid, as an index of CP, was up to ten orders of magnitude higher than that for the rest of the brain. These measurements were carried out at that point in the circadian rhythm that corresponds to the minimum level of neurosecretory activity of the pineal gland.

Aminoisobutyric Acids↗
PubMed1977

Increased capillary permeability in muscularis layer of rat intestine caused by kidney extract.

Kidney extract and synthetic angiotensin II were injected into bilaterally nephrectomized rats in dosages capable of raising the mean arterial pressure by about 20 mmHg. Changes in ultrastructure and permeability for ferritin molecules were then examined in capillaries located in muscularis layer of the intestinal walls. Kidney extract with a high renin content was obtained from the renal cortex of rats by means of stepwise centrifugation methods. Animals injected with saline served as controls. In rats receiving kidney extract tissue edema was observed in the spaces around the blood and lymphatic capillaries. In these spaces ferritin molecules accumulated in high concentration indicating plasma protein leakage. Ferritin molecules within the endothelium were restricted within plasmalemmal vesicles, but were not found within interendothelial junctions or within the cytoplasmic matrix. Morphometric analysis of vesicular transport in the endothelial cells revealed a significant increase in labeling rate for the vesicles with ferritin molecules. These results suggest that the kidney extract contains substance(s) which increase capillary permeability for plasma proteins at least via increased vesicular transport, resulting in tissue edema.

Angiotensin II↗
PubMed1997

Direct effects of platelet-activating factor on glomerular capillary permeability.

Platelet-activating factor (PAF) is an important mediator of injury in acute renal failure and glomerulonephritis. Intrarenal infusion of PAF reduces glomerular filtration rate and renal plasma flow and increases glomerular permselectivity via its renal hemodynamic and/or immunologic effects. Direct effects of PAF on glomerular capillary permeability are not known. We studied the direct effects of PAF on mesangial contraction (a measure of filtration area), glomerular capillary hydraulic conductivity (L[p]) and capillary albumin permeability (P[albumin]). Glomeruli were isolated from Sprague-Dawley rats and incubated with or without various concentrations of PAF (10[-9], 10[-7] and 10[-5] M) for up to 5 h at 37 degrees C. Mesangial contraction (percent change in glomerular volume) was assessed from the gradual decrease in volume of glomeruli during 20 min of incubation with PAF. L(p) was calculated from the rate of change in glomerular volume during the 0.1 s of capillary expansion in response to a transcapillary oncotic gradient. P(albumin) was calculated from a change in relative volume of glomeruli in response to an oncotic gradient. Mesangial contraction was maximal after 20 min of incubation and was concentration dependent (5.2+/-0.9, 7.9+/-1.0 and 10.0+/-1.0%, respectively, with PAF 10(-9), 10(-7) and 10(-5) M). Incubation of glomeruli with PAF 10(-7) M for 60 min at 37 degrees C caused a significant decrease in L(p) (2.25+/-0.30 vs. control 3.12+/-0.28 microl x min(-1) x mm Hg(-1) x cm(-1), n = 5). P(albumin) of glomeruli incubated with PAF was unchanged up to 2 h but increased significantly with the highest concentration of PAF (10(-5) M) after 3 h of incubation (0.60+/-0.18, n=15, vs. control 0.00+/-0.08, n = 20), whereas lower concentrations of PAF (10[-7] or 10[-9] M) required at least 5 h of incubation with glomeruli to cause a significant increase in P(albumin) (0.45+/-0.09 and 0.48+/-0.07, respectively, n=15, vs. control 0.00+/-0.08, n=15). We conclude that PAF has multiple direct effects on glomerular functions, which are time dependent and may contribute to the altered capillary permeability in vivo.

Albumins↗
PubMed1994

Myocardial blood flow rate and capillary permeability for 99mTc-DTPA in patients with angiographically normal coronary arteries. Evaluation of the single-injection, residue detection method with intracoronary indicator bolus injection and the use of a mobile gamma camera.

The aims of the present study were to quantitate myocardial perfusion and capillary permeability in the human heart by means of the single-injection, residue detection method using a mobile gamma camera. With this method, the intravascular mean transit time and the capillary extraction fraction (E) can be determined in one experiment and in the same myocardial region. Eighteen patients with a history of chest pain episodes and angiographically normal coronary arteries were studied after intracoronary bolus injections of 99mTc-DTPA during elective coronary angiography. Two measurements were performed at a 15-min interval during resting conditions, and a third measurement was made during atrial pacing. Regions of interest were drawn in the left anterior descending (LAD) and the circumflex (CX) coronary artery perfusion beds. Sources of variation in plasma flow rate (fpl), E, and the calculated capillary permeability area product (PS) were determined. Spontaneous 15 min variations (mean of two values) for the LAD and the CX territory, respectively, gave a mean fpl(LAD) of 74.2 (measurement 1) and 77.8 ml.(100 g.min)-1 (measurement 2) (SD of the difference 7.5 ml.(100 g.min)-1) and fpl(CX) of 82.7 and 92.1 ml. (100 g.min)-1, respectively (SD of the difference 16.1 ml.(100 g.min)-1), and E(LAD) was 51.0 and 55.7%, respectively (SD of the difference 8.4%), and E(CX) was 52.9 and 50.4%, respectively (SD of the difference 5.9%). During atrial pacing, the rate-pressure product increased by 97%, and in the LAD area fpl increased by 46% (p < 0.05), E decreased by 6% (NS), and PS increased by 39% (NS), whereas in the CX region flow increased by only 9% (p < 0.01), E decreased by 15% (p < 0.05), and PS decreased by 15% (NS) compared with baseline values. Both the spontaneous variation and the observer variation are low. The reduced vasodilator response in the CX region in combination with the decrease in E, which reduce the supply of nutrients, may play a role in the symptoms of these patients.

Adult↗
PubMed1976

Lung water and capillary permeability in pulmonary sarcoid-like granulomatosis.

The subject of our research was the use of multiple indicators to study the lungs of rats during a pathological process induced by complete Freund's adjuvant (CFA). The parameters studied were extravascular water (idQwl), the capillary permeability of [14C]sucrose, and the unrecovered fraction of [3H5glucose. We ascertained that idQwl gives a valuable estimate of total pulmonary water (r=0.91, n=30) and allows a satisfactory quantification of granulomatosis, as is shown by the comparison between the values of idQwl measured at different stages of the lesional process with average number of nodules per slice of right middle pulmonary lobe. The capillary permeability of sucrose is normal both at early and late stages of the CFA granulomatosis process. The fraction of [3H]glucose not recovered increases significantly (p less than 0.001) during the initial stage of the CFA process. This apparent loss of indicator can be explained by the existence of a slow cellular compartment.

Animals↗
PubMed1981

Alveolo-capillary permeability in human septic ARDS. Effect of high-dose corticosteroid therapy.

High-dose corticosteroid therapy has been advocated as adjunctive therapy in the adult respiratory distress syndrome (ARDS). We evaluated the effect of pharmacologic doses of corticosteroid (methylprednisolone and dexamethasone) on alveolo-capillary permeability in human septic ARDS by examining the change in appearance of intravenously administered iodine 131 (131I) human serum albumin (I-HSA) into broncho-alveolar secretions, before and after corticosteroid administration. Of 19 patients examined, in 14 (group 1) the clearance of I-HSA was reduced by corticosteroid (pre, .204 +/- .08 ml;/hr; post, .096 +/- .01 ml/hr; P less than .001), while in five (group 2) it was unaffected (pre, .23 +/- .02 ml/hr; post, .215 +/- .01 ml/hr; P=NS). Group 2 patients were more severely ill than group 1 patients in that their mean intrapulmonary shunt fractions and mean pulmonary artery pressures were higher. We conclude that high-dose corticosteroid therapy may reduce alveolo-capillary permeability in human septic ARDS if used early in the course of the illness.

Bronchi↗
PubMed1979

The effect of hyperglycemia on brain capillary permeability in the lizard, Anolis carolinensis. A freeze-fracture analysis of blood-brain barrier pathology.

The anatomical basis of the blood-brain barrier in the American chameleon, Anolis carolinensis, is the system of tight intercellular junctions that occurs between apposed endothelial cells of brain capillaries. Under normal physiological conditions, capillaries in the brain cortex of these animals remain sealed by interendothelial zonulae occludentes and, consequently, escape of exogenous tracer proteins such as horseradish peroxidase (HRP) into the extracellular compartment of the central nervous system is prevented. Systemic injection of 2.7 mg of D-glucose into chameleons results in increased brain capillary permeability, as evidenced by escape of HRP or Trypan blue into the intercellular spaces of central neuropil. Freeze-fracture analysis of brain capillary endothelia of glucose-hyperglycemic lizards revealed no alteration of the ridge and groove construction of endothelial tight junctions, indicating that although the blood-brain interface becomes leaky during severe hyperglycemia, the capillary zonulae occludentes are not affected. Evidence obtained in this study strongly supports the notion that the increased capillary permeability is the result of amplified transendothelial transport. The effect is manifest as and facilitated by the formation of chains of pinocytotic vesicles derived from the luminal surface of the endothelial cells, which fuse to create open trans-endothelial conduits. It is likely that formation of open channels that traverse brain capillary endothelial cells, as a response to hyperglycemia, could allow temporarily unrestricted passage of a wide range of molecules, some potentially toxic, into the CNS extracellular milieu. This is the first report to unequivocally document with freeze-cleave techniques, that abnormally elevated levels of blood sugar can affect blood-brain interface permeability. This finding suggests that similar consequences may be expected to result from diabetic hyperglycemia in humans.

Animals↗