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B Rippe

Publications and source records attributed to B Rippe.

At least 73 records · Page 4Linked to original sources

Calcium dependence of histamine-induced increases in capillary permeability in isolated perfused rat hindquarters.

Experiments were performed on isolated maximally vasodilated perfused rat hindquarters to evaluate the role of calcium and magnesium for the capillary permeability increase(s) elicited by histamine. Changes in capillary permeability were quantified by determinations of capillary filtration coefficient (CFC) with gravimetric technique, and capillary diffusion capacity (PS) for vitamin B12 (MW = 1,355) with a single injection indicator dilution technique. During control, vascular resistance was 2.2 PRU100 at a flow of 9.4 ml min-1 per 100 g, and PS for B12 was 3.7 +/- 0.1 ml min-1 per 100 g, while CFC was 0.0377 +/- 0.0004 ml min-1 mmHg-1 per 100 g. Perfusion with 'Mg-free' solution for 1 h caused a 24% increase in CFC, while neither 'Ca-free' perfusion nor perfusion with verapamil (5 X 10(-5) M) nor felodipine (1 X 10(-6) M) induced any changes in CFC. Histamine (100-200 microM) caused in all preparations a 150-200% increase in CFC with only small changes in PS for B12. This histamine effect was absent after 1 h of 'Ca-free' perfusion and was partially blocked after 1 h of perfusion with 0.1 mM calcium, while the calcium antagonists verapamil and felodipine had no effects on the histamine-induced changes. The results imply that histamine exerts its action on the endothelial cells through a calcium-dependent process, probably involving low affinity calcium sites but this process could not be inhibited by the calcium antagonists used. Thus, endothelial cell contractility, which probably is responsible for the histamine-induced increase in capillary permeability, exhibits unique characteristics, differing from those of vascular smooth muscle.

Animals

Validation of double vascular occlusion method for Pc,i in lung and skeletal muscle.

Capillary pressures in isogravimetric lung and skeletal muscle measured with the double vascular occlusion technique (Pdo) were compared to those measured using the traditional gravimetric technique (Pc,i). Pressures were measured using both techniques in isolated blood-perfused canine lungs (n = 18), blood-perfused rat hindquarters before (n = 8) and after (n = 6) maximal dilatation with papaverine and in rat hindquarters perfused with an artificial plasma (n = 6). In both organs, regardless of vascular tone, the double vascular occlusion isogravimetric pressure was the same as the gravimetric Pc,i, and the two measurements were highly correlated. Lung: Pdo = -0.22 + 1.06 Pc,i (r = 0.85, P less than 0.01); hindquarter: Pdo = -1.03 + 0.99 Pc,i (r = 0.91, P less than 0.01). In addition, Pdo was the same at every combination of isogravimetric arterial and venous pressures tested. The results indicate that the more rapidly applied double vascular occlusion pressure yields an accurate measure of isogravimetric capillary pressure in isolated organs over a wide range of isogravimetric pressures.

Animals

Permselectivity of the peritoneal membrane.

To investigate the osmotic barrier characteristics of the peritoneal membrane during conditions similar to peritoneal dialysis in man, yet transperitoneal fluid movement was measured in 20 cats following intraabdominal placement of isotonic saline and hypertonic solutions of NaCl, glucose, raffinose, and inulin. Also, isooncotic solutions of hemoglobin and albumin and two sulfated high-molecular-weight dextrans were investigated. Transperitoneal fluid movement was measured by a volume recovery method. Oncotic pressures of test solutions and plasma were measured by osmometry. Peritoneal osmotic conductances were calculated from the rate of transperitoneal water movement and the difference in osmotic pressures between the test solution and isotonic saline. The average glucose osmotic conductance per unit body surface are was found to be 2.3 +/- 0.18 x 10(-3) ml . min-1 . mm Hg-1 . m-2, in good agreement with previous reports, and the glucose osmotic reflection coefficient (sigma) was estimated to be 0.02. All the osmotic conductances measured could be fitted to a peritoneal equivalent pore radius of approximately 6 nm according to current hydrodynamic theories. The peritoneal membrane filtration coefficient was estimated to be 0.12 ml . min-1 . mm Hg-1 . m-2, of which 0.5-1% was found to be due to transcellular water flow. In conclusion the results of this study indicate that the peritoneum is a highly selective membrane with restrictive properties comparable to those reported for continuous capillary beds.

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Serum factors other than albumin are needed for the maintenance of normal capillary permselectivity in rat hindlimb muscle.

To investigate the effects of different perfusates on capillary permeability, we determined the capillary filtration coefficient (CFC), the capillary diffusion capacity (PS) for Cr-EDTA and clearance of albumin during isogravimetric conditions and maximal vasodilatation in the isolated, perfused rat hindquarter preparation. Experiments were conducted in 30 rats with different perfusates. We were able to confirm the classical 'protein effect'. Absence of proteins, using pure dextran solution as perfusate, induced a 45% increase in CFC and a three-fold increase in albumin clearance. However, we also found evidence for a 'serum effect'. Hence, the clearance of albumin was normal when the serum content exceeded 5% (v/v) in perfusates otherwise composed of albumin in Tyrode, but increased three-fold from 0.0305 to 0.0912 ml (min X 100 g)-1 when the rats were perfused with albumin in Tyrode with no serum present, without any change in CFC, PS for Cr-EDTA or vascular resistance to flow. Thus, certain non-dialysable serum factors, other than albumin, seem to be needed for the maintenance of normal capillary permselectivity in rat hindquarters. These factors are probably needed for the capillary membrane to maintain its character of a negatively charged barrier.

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Evaluation of the 'stretched pore phenomenon' in isolated rat hindquarters.

In order to study the changes in capillary permeability occurring upon marked elevations in microvascular pressure, capillary filtration coefficient (CFC) and diffusion capacity (PS) for Cr-EDTA were repeatedly measured 'on-line' before and after brief periods (3 min) of large venous pressure (PV) elevations in maximally vasodilated perfused rat hindquarters. First at PV's greater than or equal to 55 mmHg, increases in CFC and Ps-Cr-EDTA were observed immediately after the pressure elevations. While the CFC increases were then always pronounced (up to 4-to 5-fold), the concomitant increases in Ps-Cr-EDTA were small (at most 30-40%). For PV greater than or equal to 55 mmHg there was a rough proportionality between PV and CFC. While PS for Cr-EDTA showed little reversibility with time upon PV normalization, CFC was usually almost completely reversed after 10-20 min. The mentioned CFC and PS increases at PV's greater than or equal to 55 mmHg were quantitatively similar to those induced by histamine-type mediators in the same preparation. It is concluded that capillary hydraulic conductivity can increase markedly but reversibly upon large PV elevations, and that this is mainly due to forceful opening of ordinarily closed 'large pores' in the microvascular membrane, rather than being caused by lesional rifts in the endothelium.

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Osmotic reflection coefficient for total plasma protein in lung microvessels.

The osmotic reflection coefficient (sigma) for total plasma proteins was estimated in 11 isolated blood-perfused canine lungs. Sigma's were determined by first measuring the capillary filtration coefficient (Kf,C in ml X min-1 X 100g-1 X cmH2O-1) using increased hydrostatic pressures and time 0 extrapolation of the slope of the weight gain curve. Kf,C averaged 0.19 +/- 0.05 (mean +/- SD) for 14 separate determinations in the 11 lungs. Following a Kf,C determination, the isogravimetric capillary pressure (Pc,i) was determined and averaged 9.9 +/- 0.5 cmH2O for all controls reported in this study. Then the blood colloids in the perfusate were either diluted or concentrated. The lung either gained or lost weight, respectively, and an initial slope of the weight gain curve (delta W/delta t)0 was estimated. The change in plasma protein colloid osmotic pressure (delta IIP) was measured using a membrane osmometer. The measured delta IIP was related to the effective colloid osmotic pressure (delta IIM) by delta IIM = (delta W/delta t)0/Kf,C = sigma delta IIP. Using this relationship, sigma averaged 0.65 +/- 0.06, and the least-squares linear regression equation relating Pc,i and the measured IIP was Pc,i = -3.1 + 0.67 IIP. The mean estimate of sigma (0.65) for total plasma proteins is similar to that reported for dog lung using lymphatic protein flux analyses, although lower than estimates made in skeletal muscle using the present methods (approximately 0.95).

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Effects of plasma- and cell-free perfusates on filtration coefficient of perfused canine lungs.

The filtration coefficient (Kf,c) of the microvessels in isolated dog lungs were studied for whole and diluted blood, whole and diluted plasma, Tyrode's solution, and Tyrode's plus dextran (4%, 63,000 mol wt) perfusates. When whole blood and plasma were diluted, Kf,c increased abruptly at a plasma protein concentration between 4 and 5 g/l, an effect which was not dependent on the erythrocyte mass. Both Tyrode's and Tyrode's plus dextran produced increases in Kf,c (60 and 30%, respectively). The difference in Kf,c measured between these latter perfusates was completely abolished when Kf,c were corrected for viscosity differences. Thus the pulmonary microvasculature responds similarly to the systemic circulation in that complete removal of plasma proteins from the perfusate increases Kf,c by 50%. This effect is independent of erythrocyte mass or colloid osmotic pressure of the perfusate, since perfusion with dextran solutions alone also increased Kf,c.

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Transcapillary passage of albumin in mammary tumours and in normal lactating mammary glands of the rat.

A triple-isotope technique was used to obtain albumin clearances and blood flow in DMBA induced mammary tumours, normal lactating mammary glands and various other tissues of the rat. Albumin clearance was high both in tumours (0.0337 ml/min/100 g) and in lactating mammary glands (0.0414 ml/min/100 g). Albumin extraction (defined as the ratio of clearance over plasma flow) was exceptionally high in tumours (23 X 10(-4)) and lactating glands (18 X 10(-4)) as compared to all other tissues (1-7 X 10(-4)). This probably reflects an increased capillary permeability to macromolecules and/or a change in the relation between blood flow and available capillary surface area, both in the physiological, hormonally induced gland and in the abnormal neoplasia derived from the same tissue. Increased extravasation of albumin, together with other changes (e.g. impaired lymph formation) may be important factors behind the production of increased tumour interstitial pressure, which tend to reduce nutritional blood flow in tumours.

Albumins

Effects of histamine, serotonin, and norepinephrine on circulation of dog lungs.

The action of histamine (H), serotonin (5-HT), and norepinephrine (NE) on the lung vasculature was evaluated in isolated blood-perfused dog lung lobes using isogravimetric techniques. Pre- and postcapillary resistances, isogravimetric capillary pressure (Pc,i), capillary filtration pressure (Pc,f), capillary filtration coefficient (Kf,c), and vascular pressure-volume relationships were measured. For constant-flow conditions, all drugs induced marked increases in both pre- and postcapillary resistances and increased Pc,f. The rise in Pc,f was most pronounced for H and least marked for NE and 5-HT. For constant-pressure perfusion, Pc,f increased slightly for H but not for NE and 5-HT, while total vascular resistance increased 4-5 times for all drugs. Vascular distensibility and volumes decreased markedly for NE and 5-HT but only slightly for H. None of the drugs appeared to alter capillary permeability because Kf,c and Pc,i measured during the infusions were not different from control.

Animals

Effects of vascular pressure on the pulmonary microvasculature in isolated dog lungs.

The effects of short periods of high pulmonary vascular pressures on the filtration characteristics of the lung's microcirculation have been studied in isolated dog lungs. When left atrial pressures (Pla) were less than 30 cmH2O, the capillary filtration coefficient (Kf,c) was not different from that of controls (0.192 +/- 0.009 ml X min-1 X cmH2O-1 X 100 g-1). In 17 of 23 observations, where Pla exceeded 55 cmH2O, Kf,c was at least 1.5 times control. In 10 of 13 lungs, Kf,c returned to control values within 2 h after the Pla increase. However, in the other three experiments, Kf,c did not return to control values. These findings indicate that the filtration coefficient of pulmonary microvessels increases at high left atrial pressures (greater than 55 cmH2O) and may represent either a "stretching" of existing pores or opening of a few large pores.

Animals

Increased microvascular permeability in dog lungs due to high peak airway pressures.

The effect of peak airway pressure (Paw) on vascular permeability and the "safety factor" against edema formation was determined in isolated blood-perfused lower lobes of dog lungs. Microvascular permeability was evaluated using the measured filtration coefficient (Kf,C), isogravimetric capillary pressure (Pc,i), and critical capillary pressure (Pcrit) for exhaustion of tissue safety factors. Airway pressure was maintained constant at -3 cmH2O except for the test period of 20 min when the lungs were ventilated at 6/min with sufficient volume to generate a peak inflation pressure ranging from 5 to 60 cmH2O. Mean Kf,C (in ml X min-1 X cmH2O X 100 g-1) were measured before and immediately after the period of peak airway pressures. Kf,C was significantly increased in all lungs where Paw exceeded 42 cmH2O, but in only two experiments at a lower Paw. Mean Pc,i was significantly reduced from control in the 45-55 and 55-65 cmH2O Paw groups, and both Pc,i and Pcrit were found to be inversely related to Kf,C measured after Paw ventilation. These data indicate that ventilation with Paw above 42 cmH2O (30.9 Torr) and in some cases lower pressures for 20 min significantly increased capillary hydraulic conductivity, reduced the effective osmotic effect of plasma proteins at the capillary wall, and reduced the total tissue safety factor against edema formation.

Animals

Estimation of isogravimetric capillary pressure by a filtration method in skeletal muscle and lung.

Pre- to postcapillary resistance ratios (Ra/Rv) and isogravimetric capillary pressures (Pc,i) were estimated using a modified filtration method and compared with estimates obtained by application of traditional isogravimetric techniques in isolated rat hindquarters and canine lungs. Pc,i's and Ra/Rv's were estimated using both methods in rat hindquarters perfused with whole blood or an artificial plasma and in blood-perfused canine lung. In each of the three experimental conditions studied, the modified filtration method yielded the same Pc,i and Ra/Rv as the isogravimetric technique. Maximal vasodilation of the rat hindquarter with papaverine reduced Ra/Rv approximately fourfold to a level which was not different from that obtained in hindquarters perfused with artificial plasma, although Pc,i was unchanged. These results indicate that the more easily applied modified filtration method provides an excellent measurement of Ra/Rv and Pc,i in whole organ studies.

Animals

Importance of molecular charge for the passage of endogenous macromolecules across continuous capillary walls, studied by serum clearance of lactate dehydrogenase (LDH) isoenzymes.

Electrostatic capillary barrier characteristics was studied in the isolated maximally vasodilated rat hindquarter by use of a modified "tissue uptake" technique (Rippe et al. 1979). The hindquarters were artificially perfused with oxygenated horse serum at isogravimetry. As tracers two isoenzymes of lactate dehydrogenase (LDH) were used, having identical size (41 A, Mw approximately 140 000) but with differing molecular charge and labelled with two separable isotopes. LDH-H4 (125I) is negatively charged and LDH-M4 (131I) slightly positive, at physiological pH. The negatively charged protein LDH-H4 was more retarded in its transcapillary passage than LDH-M4. Net clearance of H4 was 0.0242 +/- 0.0045 ml/min X 100 g and that of M4 was 0.0748 +/- 0.0092 ml/min X 100 g (n = 11, p less than 0.001). This difference is suggested to be due to an interaction of the polyanionic tracer with a barrier of negative molecular charge, most effective at the small pore equivalent. Clearance data for H4 and for albumin (Rippe et al. 1979) are compatible with an equivalent large pore radius of 520 A. Neither vesicular transport (Palade 1953) nor the impact of fibre pore matrix (Michel 1980) is considered to be involved in the transcapillary passage of proteins. Negatively charged proteins probably pass through the large pore equivalent exclusively, while neutral macromolecules also utilize part of the small pore equivalent, for their transcapillary passage.

Animals

Permeability of fenestrated capillaries in the isolated pig pancreas, with effects of bradykinin and histamine, as studied by simultaneous registration of filtration and diffusion capacities.

Combining an isogravimetric technique and a colorimetric 'on-line' method (Rippe & Stage 1978), filtration capacity (CFC) and diffusion capacity (PS) were simultaneously measured in the maximally vasodilated 'fenestrated' capillary bed of isolated, artificially perfused pancreatic glands in 12 juvenile pigs. Both CFC and PS for Cr-EDTA were about 20 times greater than in the 'continuous' capillary bed of skeletal muscle. With perfusate flow rates of 250 ml/min x 100 g during isogravimetry, PS-Cr-EDTA averaged 110 +/- 10.0 (S.E.) ml/min X 100 g, and diffusion limitation occurred first at flow rates above 300 ml/min X 100 g. CFC was independent of flow rate and averaged 0.641 +/- 0.027 ml/min X 100 g X mmHg. The parallel augmentation of PS-Cr-EDTA and CFC in the fenestrated capillary bed compared with continuous ones seems to reflect both a higher number of capillaries per unit tissue and an increased number of 'small pores' per unit capillary surface, whilst the 'large pore system' appears to be similar. Following bradykinin or histamine infusion, results were similar to those for continuous capillaries (e.g. Rippe, Kamiya & Folkow 1978). Thus, without further vasodilatation CFC increased 3-fold While PS-Cr-EDTA increased only some 25%, and subsequent isoprenaline infusion reversed these effects. Previous studies on continuous capillaries indicate that histamine-type agents act by opening additional 'large pores' in the venular exchange sections (cf. Rippe & Grega (1978, Svensjö 1978), while beta-adrenergic agonists block this effect. The results further suggest that the fenestrae are not involved in these bradykinin-histamine effects, but rather function as a high-density, small pore population.

Animals

Capillary permeability of sulphate-substituted and neutral dextran fractions in the rat hindquarter vascular bed.

In order to investigate the impact of molecular charge on capillary permeability to macromolecules, capillary reflection coefficients (sigma) for various concentrations of two neutral dextran fractions (Mw 70 000 and 139 000) and one negatively charged, sulphate-substituted dextran fraction (Mw 109 000) were determined in the isolated perfused rat hindquarter preparation, during stable haemodynamic conditions. The capillary reflection coefficient was calculated as the ratio between the estimated colloid osmotic pressure in vivo, determined by an osmotic transient technique, and that in vitro, measured with an osmometer. Despite its intermediate size the sulphated dextran (D 109-S) showed a markedly higher sigma than the two neutral ones (D 70 and D 139) and, further, whereas sigma for D 70 and D 139 decreased with increasing dextran concentration, sigma for D 109-S remained constant over the whole range of concentrations investigated. At dextran concentrations equivalent to an in vivo colloid osmotic pressure of 23.5 mmHg, sigma averaged 0.901 for D 109-S, compared with 0.547 and 0.693 for D 70 and D 139, respectively, and with 0.87 for albumin in normal plasma. It is suggested that capillary macromolecular permeability is due to both structural and electrophysical properties of the microvascular barrier, where negative charges of the endothelial glycocalyx and of wall-adsorbed plasma proteins cause repulsion of circulating large polyanions.

Animals