Capillary Filtration Coefficient Values Research Articles

Pathophysiological aspects of lower limb oedema in patients with proximal femoral fractures

Objectives: To examine the changes in Starling components, regulating the transcapillary fluid transport, in patients with proximal femoral fractures (PFF). Material and methods: Twenty-eight patients with proximal femoral fracture were classified into femoral column fracture (FCF) and pertrochanteric fracture (PTF) groups. The following measurements were made in both groups of patients on the 7th post-operative day: colloid osmotic pressure of plasma and subcutaneous interstitial fluid (COPpl and COPif), capillary filtration coefficient (CFC) and interstitial fluid pressure (Pif) in the anterior muscle compartment of the leg and calf muscle blood flow, in both lower extremities. Results: The transcapillary colloid osmotic gradient was significantly reduced (p<0.02) in patients with PTF, and they also showed a significant increase in CFC values (p=0.038). Moreover, Pif was elevated (1.9 mmHg, SD 2.1, p=0.01) and calf muscle blood flow was significantly higher (p=0.02), than in the contralateral limb in patients with PTF. Conclusion: The transcapillary colloid osmotic gradient is significantly reduced in patients with PTF. This may partly explain why patients with PTF develop more oedema in the lower limb than those with FCF. CFC and calf blood flow are also significantly increased in the fractured limb, which allows increased transcapillary filtration.

The capillary permeability reducing effect of prostacyclin compared with terbutaline and theophyllamine in cat skeletal mucle

An increase in capillary permeabilty is a common pathophysiological state in critical illness such as SIRS, capillary leak syndrome and after trauma. Terbutaline and theophyllamine have been used to reduce the capillary leakage without convincing effects. It has been shown in this laboratory and by others that the endothelial produced substance prostacyclin reduces capillary permeability. Prostacyclin is also an inhibitor of platelet aggregation, a vasodilator and has cytoprotective effects. The aim of this study was to compare the permeability reducing effect of prostacyclin with terbutaline and theophyllamine. The observations were made on an autoperfused, denervated cat gastrocnemius muscle enclosed in a plethysmograph with continuous recording of volume changes, arterial and venous blood pressures and flow. Twelve cats, anaesthetized with ketamine were used. The capillary filtration coefficient (CFC), reflecting the capillary surface area for fluid exchange, was determined by the rate of a steady-state increase in tissue volume per min after an increase in venous pressure of 5 mmHg. A change in CFC reflects a change in capillary permeability but the number of open capillaries is also of importance. CFC determinations were carried out using intravenous infusion of different doses of each drug alone. Further, the three drugs were given separately during simultaneous local intra-arterial infusion of TNFα (0.75 μg 100 g−1 muscle min−1) or histamine (50 μg 100 g−1 muscle min−1), respectively. Prostacyclin in doses of 2, 5, 10, 20, 40 and 60 ng kg−1 min−1 reduced CFC from a control value of 0.012±0.001 (SEM) ml (min mmHg 100 g−1) reaching maximum reduction of 28% at 20 ng kg−1 min−1 (P<0.001), 2 ng kg−1 reduced CFC by 16% and 5 ng kg−1 min−1 by 18% (P<0.01). TNFα and histamine significantly increased CFC by 57 and 72% respectively. Infusion of prostacyclin 2 ng kg−1 min−1 reduced the TNFα induced increase in CFC to 17% below the initial control value with maximal reduction of 23% obtained at 20 ng kg−1 min−1. During histamine infusion, the same reduction of 23% was obtained but at the dose of 10 ng kg−1 min−1 of prostacyclin. Terbutaline in doses of 3.5, 7 and 14 μg kg−1 bw h−1 and theophyllamine in doses of 12.5, 25 and 50 mg kg−1 h did not reduce CFC from the control value. Both terbutaline and theophyllamine had some, though non-significant, reducing effect on the increased CFC values during the TNFα and histamine infusions. However, terbutaline and theophyllamine caused vasodilation, which by increasing the number of open capillaries could mask some permeability reducing effects measured by this CFC method. Prostacyclin, at doses up to 20 ng kg−1 min−1, just slightly reduced vascular tone indicating that these doses are indeed low for the cat. This also indicates that the reduction in CFC must be as a result of decreased capillary permeability as the number of open capillaries must be roughly unchanged. Prostacyclin in this model is far superior to terbutaline and theophyllamine in reducing capillary permeability and especially when considering the differences in their vasodilator effects. All these drugs are known to act by increasing intracellular cAMP which relaxes endothelial cells, decreasing capillary permeability. Prostacyclin is also thought to reduce permeability through an influence on leukocytes and platelets which could explain its more powerful permeability effect. This study indicates that low dose prostacyclin may be useful in pathophysiological states with increased capillary permeability. The effects of prostacyclin are under further evaluation in this intensive care unit.

Vascular flow capacity of hindlimb skeletal muscles in spontaneously hypertensive rats

Total and regional skeletal muscle flows (radiolabeled microspheres) were determined in isolated maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and age-matched (11-12 mo) normotensive Wistar-Kyoto rats (WKY) to assess the vascular flow capacity of the skeletal muscle vascular beds. Vascular flow capacity was estimated by measuring total hindquarters and regional muscle blood flows (under conditions of maximal vasodilation with papaverine or papaverine plus isoproterenol) over a wide range of perfusion pressures in WKY and SHR. Capillary exchange capacity was estimated by determining the capillary filtration coefficient. Isogravimetric capillary pressures and segmental vascular resistances were determined in each hindquarter. Isogravimetric flows and capillary pressures were not different between WKY and SHR. However, total and precapillary vascular resistances were significantly elevated in SHR, and postcapillary resistances were not different compared with WKY. Maximal capillary filtration coefficient values for the SHR group averaged 20% lower than WKY values, suggesting that hypertension was associated with a reduction in the microvascular surface area available for fluid exchange and, therefore, the capillary exchange capacity. Over the perfusion pressures studied, total hindquarters flows averaged 60% lower in SHR than in WKY. Flows to individual skeletal muscles averaged 76% lower in SHR than in WKY regardless of the muscle fiber type. Thus, modifications exist in the hindlimb skeletal muscle vasculature of SHR that reduces the capillary exchange capacity and limit the capacity of deliver flow at a given perfusion pressure gradient.

Much larger transcapillary hydrodynamic conductivity in skeletal muscle and skin of man than previously believed.

The capillary filtration coefficient (CFC) in the human forearm, determined with the 'venous occlusion' method, was found to be about 0.005 ml min-1 100 ml-1 soft tissue mmHg-1 when capillary pressure (Pc) was raised by about 30 mmHg, a finding in accordance with previous literature. With gradually smaller increments of Pc, however, the calculated CFC became gradually larger to reach maximal values of about 0.05 ml min-1 100 ml-1 mmHg-1 at increases in venous pressure that raised Pc by only 1.5-2 mmHg. It is suggested that these high CFC values, obtained at increases of intravascular pressure so low as to ensure minimal interference with the normal circulation, reflect the true prevailing transcapillary hydrodynamic conductivity in the tissue. The low CFC values during high increases in capillary (microvascular) pressure, on the other hand, seem to represent serious underestimations of the true CFC as a result of experimentally induced undesired active smooth muscle constrictor responses and/or passive deterioration of capillary exchange function. The conclusion is therefore reached that CFC in skeletal muscle and skin in man might be about 10 times higher than previously believed.

Filtration coefficient in cat hindlimb using protein concentration changes.

The maximum value of capillary filtration coefficient (CFC) in maximally vasodilated cat skeletal muscle is disputed. It was hypothesized that the wide range of reported values was caused by the inability of gravimetric and volumetric measurements of tissue volume to separate transcapillary filtration from vascular volume changes. Consequently, we developed a method of measuring filtration rates from changes in venous protein concentration using Evan's blue-labeled albumin in the isolated hindlimb (pentobarbital sodium anesthesia). The filtration coefficient (PFFC) calculated from these filtration rates after a step in venous pressure should not be influenced by vascular volume changes. When the perfusate flow rate through the hindlimb was greater than 15 ml.min-1.100 g muscle-1, PFFC was 0.0085 +/- 0.0015 (SD, n = 8) ml.min-1.mmHg-1.100 g muscle-1. PFFC was observed to be unvarying from 1 to 12 min after the venous pressure elevation, in contrast to CFC values, which fall during the same period. It is argued that the difference between CFC and PFFC values is caused by vascular volume changes.

Blood and isoproterenol reduce capillary permeability in cat hindlimb.

In an earlier study, plasma was observed to counteract the permeability-increasing effects of blood-free perfusion when papaverine was present in the perfusate. To determine if this plasma effect was still present in the absence of papaverine, cat hindlimbs were perfused with a blood-free albumin-electrolyte solution, and capillary filtration coefficient (CFC) was measured. These data were compared with CFC values obtained when blood, plasma, or isoproterenol were present in the albumin perfusate. In separate groups of animals, CFC was observed to be 0.017 +/- 0.006 (SD, n = 26) ml X min-1 X mmHg-1 X 100 g muscle-1 during blood-free albumin perfusion, 0.012 +/- 0.002 (n = 24) when blood was present, 0.014 +/- 0.003 when isoproterenol was present, and 0.010 +/- 0.002 (n = 33) when both blood and isoproterenol were present. In a separate study, it was observed that 1) isoproterenol could reduce CFC by 11% when added to blood-free perfusate, 2) plasma had a similar but smaller and more variable effect than isoproterenol, 3) plasma had no consistent effect on CFC when added to a blood-free albumin perfusate containing isoproterenol, and 4) blood could reduce CFC significantly (P less than 0.005), from 0.014 +/- 0.003 to 0.0094 +/- 0.002 (n = 7), when added to a blood-free albumin perfusate containing isoproterenol. It was concluded that, in the absence of papaverine, the principal CFC-reducing effect of blood lay in the cell fraction and that isoproterenol had a small CFC-reducing effect under blood-free conditions. This result contrasts with the plasma effect reported earlier.

Fibronectin decreases pulmonary vascular permeability under baseline conditions and after administration of arachidonic acid in rabbit lungs

In blood- and plasma-free perfused isolated rabbit lungs, the influence of albumin and soluble fibronectin on vascular permeability was investigated. The lungs were perfused with Krebs Henseleit buffer containing no protein (KHB), containing 1 g/100 ml bovine albumin (KHAB) or containing albumin together with 100 pg/ml soluble fibronectin. The absence or presence of albumin had no influence on the perfusion pressure, the vascular compliance and the capillary filtration coefficient (CFC), determined by zero time extrapolation of the slope of weight gain which was induced by a sudden venous pressure elevation. Fibronectin caused a slight increase in pulmonary artery pressure, a slight decrease in vascular compliance and an approximately 50 % reduction of CFC. In a second set of experiments, KHAB-perfused lungs were stimulated by the administration of 100 μM arachidonic acid (AA) during the second hydrostatic challenge within a sequence of three venous pressure elevations. In the presence of indomethacin, which blocks any significant increase in pulmonary vascular pressure after AA application, this procedure caused an immediate gain in lung weight due to increased pulmonary vascular permeability, with > 10-fold increased CFC values subsequent to the AA application. In the presence of 100 μg/ml fibronectin, this AA-induced increase in CFC was mitigated to less than 20 % of the controls without the glycoprotein, with correspondingly severalfold reduced lung weight gain. In conclusion, the present study provides evidence for a direct influence of circulating soluble fibronectin on lung microvascular integrity and fluid balance under baseline conditions and after stimulation of the pulmonary AA cascade.

Capillary filtration coefficient in the forearm of patients with essential hypertension.

The capillary filtration coefficient (CFC) in the forearm was followed in patients with essential hypertension and compared with controls, using the method of venous occlusion plethysmography and simultaneous recording of intravenous pressure in the measured segment of the extremity. Arterial blood-pressure was obtained in the contralateral arm by auscultation. The CFC averaged 0.0039 +/- 0.009 ml/100 ml/min/mmHg and 0.0095 +/- 0.0018 ml/100 ml/min/mmHg in hypertensives and controls respectively. The relation between CFC and arterial blood-pressure values was inversely non-linear. The results suggest reduction of the capillary area due to hypertension and possibly functional or structural changes in the microcirculatory bed accompanying systemic blood-pressure increase.

Frequency-Dependent Control of Nutritional and Nonnutritional Circuits in the Dog Paw

The neural control of blood flow and volume distribution between parallel nutritional and nonnutritional circuits has been investigated in 13 vascularly and neurally isolated dog hindpaws. The superficial and deep fibular nerves and the tibial nerve were cut and individually stimulated at frequencies of 0.1, 1, 5, 10 and 15 Hz. Increasing stimulation rates to each nerve progressively increased blood flow resistance. Vascular volume changes were determined by indicator dilution and tissue volume changes by plethysmography. The permeability surface area product of 86Rb (PS) and the capillary filtration coefficient (CFC) were determined. Superficial fibular nerve and deep fibular nerve stimulations caused progressively increased nonnutritional circuit constriction with increasing stimulation frequencies resulting in blood flow redistribution to the nutritional circuit as evidenced by increasing PS and CFC values. Tibial nerve stimulation at 0.1 Hz caused nonnutritional circuit constriction and blood flow redistribution to the nutritional circuit (PS and CFC increased). As the stimulation frequency was increased, there was progressive increase of the nutritional circuit constriction and altered blood flow distribution; i.e., CFC and PS decreased with increasing frequency of stimulation, presumably due to predominantly arterial segment resistance increase.

The quantitative morphology of skeletal muscle capillaries in relation to permeability

The numbers and dimensions of skeletal blood capillaries were observed in the gastrocnemii of eight dogs. The dimensions and proportions of the close and tight junctions were also recorded. (These were adjusted to take account of the random sectioning angles and the penetration of the section by the stain.) It was found that there were ∼260 km of capillaries, with a total area of ∼2 m 2 per 100 g of muscle. The close junctional length was ∼21 km; that of the tight junctions was ∼430 km. The ratio of close/(close + tight) junction was ∼4.8%. Using previously recorded, but newly adjusted figures for the vesicles, showed that there were ∼1.1 × 10 14 free vesicles and 2.5 × 10 14 attached ones per 100 g. It was considered best to calculate the resistances of the whole cross sections of each junction, obtain the flow through this, and then summate these for all the observed cross sections, corrected for the total close-junctional length per 100 g. The capillary filtration coefficient (CFC) so obtained was ∼0.023 ml/min/mm Hg/100 g, which is very similar to that obtained by experiment. (This is even closer when account is taken of the CFC values of vasodilated muscle.) Similar calculations were made for the capillary diffusion coefficients (CDC) for several molecules. Again it was found that the results were very similar to those obtained by experiment, especially those obtained during vasodilatation. (This is understandable since all junctions were measured, not just those in active capillaries.) The calculated resistance of the basement membrane was negligible for small molecules. Calculations using the vesicular parameters gave results for transit times, migration percentages, and the probabilities of fusion with a membrane. These accord well both with experiment and with a hypothetical model.

Dynamic analysis of gravimetric response of isolated dog hindlimb.

Previous gravimetric studies of transcapillary fluid movement have been based on capillary filtration coefficient (CFC) estimates. In these studies only a single CFC value is estimated for the entire isolated vascular bed. We have analyzed the dynamic gravimetric responses of isolated dog hindlimb to venous pressure steps and found it possible to estimate two different CFC values. Under control conditions, one CFC value averaged .0049 ml/mmHg min per 100g tissue wt, whichagrees with results of previous investigators. The other CFC value averaged 90304, which is very close to estimates we have previously made by an independent frequency-response methods. Changes in hindlimb properties to intra-arterial infusions of acetylcholine, papaverine, isoproterenol, and norepinephrine were also studied. Drug infusion results and the presence of similar dynamic components in experiments on gracilis muscle support the existence of inhomogeneous pathwaysin tissue, which lead to fluid-exchange nonuniformity.

Low molecular weight dextran therapy for scleroderma. Effects of dextran 40 on blood flow and capillary filtration coefficient in scleroderma.

Seven patients with scleroderma were each treated with an infusion of one liter of a 10% solution of dextran 40 in physiological saline during an 18-hour period. Measurements of total blood flow and capillary filtration coefficient (CFC) by electro-capacitance plethysmography as well as by sodium iodide I 131 clearance were recorded before and after treatment with low molecular weight dextran. All posttreatment blood flow and CFC values for these patients were significantly increased, and all of the patients experienced subjective improvement of their lesions.

Changes in the capillary filtration coefficient of cutaneous vessels in women with premenstrual tension

In an attempt to explain excessive fluid retention, the most common feature in the syndrome of subjective and objective changes called premenstrual tension, we investigated changes in the peripheral circulations of women with this complaint. To obtain evidence on the vascular system's ability to maintain a constant circulating fluid volume, we measured capillary filtration coefficient in the forearm. Women who complained of premenstrual distress showed a significant change in capillary filtration coefficient (CFC) during the month; the lowest CFC values were found immediately after the onset of the menses; the highest values occurred just before the beginning of menstruation. In a group of women who claim to be completely free of the complaint, the CFC was uniform throughout the cycle.

Sympathetic control of consecutive vascular sections in canine subcutaneous adipose tissue.

AbstractThe effects of electrical stimulation of sympathetic nerves to subcutaneous adipose tissue in the dog on the flow resistance, regional blood volume and the capillary filtration coefficient (CFC) were studied. The resting blood flow varied between 3.2–12 ml/min × 100 g and resting CFC between 0.02–0.035 ml/min × 100 g × mm Hg (mean=0.027). The regional blood content was approximately 5 ml/100 g. Stimulation of the regional sympathetic nerves induced a pronounced decrease in blood flow, a two to threefold increase in CFC, a net transcapillary fluid absorption and a decreased regional blood volume. Stimulation following administration of an α‐blocking agent produced a blood flow increase up to 25–30 ml/min × 100 g, a small CFC increase and a small venous dilation. These vascular respones were blocked by a β‐blocking agent (propranolol). In comparison with skeletal muscle the vascular bed of subcutaneous adipose tissue was found to be well dimensioned for transcapillary exchange at comparable total blood flows. This was shown by the relatively high CFC values, which indicated a large capillary surface area and/or a high capillary permeability.

THE EFFECT OF SOME PHYSIOLOGICAL VASODILATORS ON THE VASCULAR BED OF SKELETAL MUSCLE.

AbstractThe effects of i. a. infused ACh, ATP, histamine and bradykinin (and kallidin) were studied on the isolated calf muscle preparation of cats and compared with the vascular response to graded exercise elicited by stimulating the sciatic nerve. With a plethysmographic technique the effects on the resistance vessels, the capillary filtration coefficient (CFC) and the capacitance vessels were assessed and through a more indirect approach the occurrence of an increased capillary permeability was estimated. All procedures decreased flow resistance. ACh and ATP increased CFC approximately as much as exercise and, like exercise, without any signs of increased capillary permeability. As a contrast bradykinin and particularly histamine produced higher CFC values at every degree of diminished flow resistance, together with other signs of increased capillary permeability. The increased permeability vanished as rapidly as the vasodilator response after infusion. ACh and ATP dilated the capacitance vessels but bradykinin, histamine and exercise did not. It is concluded: 1) that all procedures studied increase nutritional blood flow, 2) that bradykinin and histamine produce a promptly reversible increase of capillary permeability in the same doses that are needed for dilatation and 3) that none of the substances when infused i. a. could exactly reproduce the vascular response of exercise.