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Biomedical subjects

B Rippe

Publications and source records attributed to B Rippe.

At least 109 records · Page 6Linked to original sources

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↗

Central blood volume in spontaneously hypertensive rats and Wistar-Kyoto normotensive rats.

Central blood volume and blood volume were determined in spontaneously hypertensive rats and Wistar Kyoto rats at two ages, 6 and 12 weeks, representing "borderline' hypertension and early "established' hypertension, respectively. A technique was used where plasma and erythrocyte indicators were injected into conscious rats. Blood volume in the cardiopulmonary compartment, present in the 'resting' awake steady-state, could then be estimated by sudden freezing of the entire rat. 12 week-old spontaneously hypertensive rats showed a decreased total blood volume, while the fraction of blood contained in the cardiopulmonary area was significantly increased compared with that of normotensive Wistar Kyoto rats. In 6-week-old spontaneously hypertensive rats, total blood volume was only marginally decreased but also here a tendency towards centralization of the blood was seen. Thus, alone with the development of hypertension in the spontaneously hypertensive rat their decreasing blood volume tends to become increasingly centralized to the cardiopulmonary area. Both neurohormonal influences and structural wall changes in the low-pressure capacitance side may contribute to this.

Animals↗

Central blood volume in spontaneously hypertensive rats and Wistar-Kyoto normotensive rats.

1. Central blood volume and total blood volume were determined in spontaneously hypertensive rats and Wistar-Kyoto rats at two ages (6 and 12 weeks), representing 'borderline' hypertension and early 'established' hypertension. 2. A technique was used where plasma and erythrocyte indicators were injected into conscious rats. Blood volume in the cardiopulmonary compartment, present in the 'resting' awake steady state, could then be estimated by sudden freezing of the entire rat. 3. Twelve week-old spontaneously hypertensive rats showed a decreased total blood volume, and the fraction of blood contained in the cardiopulmonary area was significantly increased compared with that of normotensive Wistar-Kyoto rats. 4. In 6 week-old spontaneously hypertensive rats, total blood volume was only marginally decreased but here also a tendency towards centralization of the blood was seen. 5. Thus, along with the development of spontaneously hypertensive rat hypertension, a decreasing blood volume tends to become increasingly centralized to the cardiopulmonary area. Both neuro-hormonal influences and structural wall changes in the low-pressure capacitance side may contribute to this.

Aging↗

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.

Animals↗

Transcapillary passage of albumin, effects of tissue cooling and of increases in filtration and plasma colloid osmotic pressure.

'Initial' clearance of radiolabelled serum albumin was measured in the perfused, maximally vasodilated muscle vascular bed of rat hindquarters during tissue cooling, during increases in filtration and during changes in serum colloid osmotic pressure. Albumin clearance during ordinary serum perfusion at isogravimetry amounted to 0.03 ml/min times 100 g, increasing linearly with filtration rate to some 0.07 ml/min times 100 g at 0.5 ml/min times 100 g of filtration. During cooling from 36 degrees C to 14 degrees C both CFC and initial albumin clearance at isogravimetry decreased some 40%, in due proportion to the increased viscosity of the fluid. Increases of the colloid osmotic pressure of the perfusate correspondingly increased both the isogravimetric capillary pressure and 'initial' albumin clearance during isogravimetry.--It is concluded that even during isogravimetry the transmicrovascular albumin passage is to about 70 per cent due to filtration, and only some 30 per cent of transport at ordinary serum colloid osmotic pressure takes place by diffusion, both events presumably via 'large pores'. There was no evidence that transendothelial vesicular transport should to any significant extent contribute to the passage of albumin from vessels to tissue.

Animals↗

An "on-line" colorimetric method for repeated, rapid determinations of capillary diffusion capacity.

The single injection indicator diffusion method for estimation of capillary diffusion capacity (Crone 1963) has been developed to provide directly visualized, continuous colorimetric recordings of the venous time-concentration curves by means of a two-colour densitometer system. Cardio-Green, bound to albumin, is used as the non-permeant ("reference") tracer and Cr-EDTA as the permeant one. The artificially perfused hindquarter muscle vascular bed of rats is used. Highly reproducible curve recordings can be obtained every fourth minute. Accidental disturbances of the recordings are readily detected. Thus, compared to the fractional venous sampling technique, the present technique has the great advantage of allowing immediately controlled and frequently repeated determinations of capillary diffusion capacity. It is therefore easily used together with measurements of filtration-absorption events, e.g. for frequent quantitative comparisons of capillary diffusion and filtration capacities over a wide range of induced changes in perfused capillary surface area and/or capillary permeability. The main limitation is that the employed permeant tracer necessitates the use of erythrocyte-free perfusates.

Animals↗

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.

Animals↗

Simultaneous measurements of capillary diffusion and filtration exchange during shifts in filtration-absorption and at graded alterations in the capillary permeability surface area products (PS).

The diffusion exchange of Cr-EDTA, using the single injection indicator diffusion method, was followed simultaneously with estimations of the capillary filtration capacity (CFC) in an "isogravimetric" rat hindquarter preparation during artificial perfusion and maximal dilatation. Measurements were performed at constant flow and during 1) shifts in filtration-absorbtion, 2) alterations of perfused capillary wall area (graded rarification of capillary network by microsphere injection) and 3) during alterations of permeability (i.a. infusion of histamine). At maximal vasodilatation CFC was 0.037 +/- 0.001 ml/min X mmHg X 100 g and PS for Cr-EDTA 5.67 +/- 0.13 ml/min X 100 g. During filtration or absorbtion, Cr-EDTA transfer from vessels to interstitium changed only slightly but the situation may well be different for solute transfer from interstitium to vessels. Alterations in capillary wall area resulted in proportional changes in PS for Cr-EDTA while the CFC changes were always relatively smaller. Histamine increased CFC some threefold with a marked increase in protein transfer, while PS for Cr-EDTA increased only marginally. This histamine effect could be ascribed mainly to an increase in the number of large pores which, because of their relative paucity, are of little importance for small molecular diffusion exchange but highly important for convective and macromolecular exchange.

Absorption↗

Plasma volume, blood volume and transcapillary escape rate (TER) of albumin in young spontaneously hypertensive rats (SHR) as compared with normotensive controls (NCR).

A detailed comparison of blood and plasma volumes and of the transcapillary escape rate (TER) of albumin was performed in SHR and matched NCR, particularly during the phase of rapid pressure rise in SHR. Throughout this early phase of life, the relative plasma and blood volumes tend to be lower, and TER higher in SHR, as would be expected when neurogenic mechanisms dominate the initiation of hypertension. Only in late established SHR hypertension, with increasing signs of cardiovascular complications, blood volume tends to be higher in SHR than in NCR. These results are in general agreement with most observations in early essential hypertension in man. They are of interest in contrast to recent findings in another variant of primary hypertension in rats, MHS. Also the apparently quite different initiating mechanisms in SHR and MHS primary hypertension are discussed.

Animals↗