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Biomedical subjects

B Rippe

Publications and source records attributed to B Rippe.

At least 91 records · Page 5Linked to original sources

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

Capillary permeability to albumin in normotensive and spontaneously hypertensive rats.

Transcapillary passage of plasma proteins is enhanced in man's primary hypertension and it is debated whether this reflects increased permeability or merely a raised capillary pressure. To elucidate this problem, maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and normotensive controls (NCR) were perfused in parallel at constant flow with dextran, horse serum or mixtures of the two, using labelled albumin as indicator of capillary permeability to macromolecules. By equal increases of venous pressure modest filtration was maintained during one hour, after which the edema and its albumin content were determined.--There was less edema in SHR, reflectin a slightly lower postcapillary resistance and a much higher precapillary resistance compared with NCR, which here resulted in a lower capillary pressure in SHR. In both SHR and NCR the presence of dextran slightly enhanced the capillary filtration coefficient but increased albumin permeability up to tenfold, also after antihistamine drugs. However, for each perfusate the SHR capillaries were, if anything, slightly less permeable to albumin than the NCR ones.--The results suggest that the enhanced transcapillary passage of plasma proteins in primary hypertension reflects an increased capillary pressure in some circuit(s), probably mainly skeletal muscle, resulting from the functional balance in vivo between the pre- and postcapillary resistances.

Animals

The influence of rheological and collapse factors on pre- and post-capillary flow resistances in the skeletal muscle vascular bed of the cat.

The importance of passive-elastic changes of vascular dimensions and shifts in regional effective viscosity for the pre-/postcapillary resistance ratio (RA/RV), and hence mean capillary pressure (PC), was analyzed in cat calf muscles. Reductions of mean venous distending pressure below 6-8 mm Hg induced marked RV increases due to escalating venous collapse. This mechanism tends to delimit the PC reductions and rate of transcapillary fluid absorption during intense precapillary vasoconstriction. Comparisons of RA/RV for erythrocyte suspensions (Hct 40-50) and cellfree perfusates at identical vascular dimensions showed that RA/RV was considerably higher, and PC correspondingly lower, for the erythrocyte suspension except at very low flows. This RA/RV difference increased with increasing flow and at very high flows PC was about 10 mm Hg lower during perfusion with the erythrocyte suspension. These findings apparently diverge from the known influence of the tube radius and linear flow velocity on effective in vitro viscosity of blood. Since distal precapillary and proximal capillary sections, both having smaller diameters than the erythrocytes, are located upstream to the point of filtration-absorption equilibrium, they contribute in this respect to RA. It is therefore suggested that the increasing RA/RV with erythrocyte perfusion, particularly at higher flows, is not due to genuine viscosity factors but to friction losses when cells in "bolus flow" are squeezed through the narrowest precapillary sections.

Animals