Change In Capillary Filtration Coefficient Research Articles

The permeability-reducing effects of prostacyclin and inhibition of Rho kinase do not counteract endotoxin-induced increase in permeability in cat skeletal muscle

cAMP stimulation and Rho kinase inhibition are shown to decrease microvascular permeability during noninflammatory conditions, most likely by decreasing contractility of actomyosin filaments in the endothelial cell, but their effects on permeability during inflammatory conditions are not clarified. The objective of this in vivo study, performed on the autoperfused and denervated calf muscle of the cat, was therefore to evaluate to what extent cAMP stimulation and inhibition of Rho kinase reduce permeability at endotoxemia. Change in osmotic reflection coefficient for albumin was used as a measure of altered protein permeability and change in capillary filtration coefficient (CFC) as a measure of altered fluid permeability. After inducing a significant increase in protein and fluid permeability by infusion of lipopolysaccharide (LPS), we determined to what extent the increased permeability was decreased by the cAMP stimulator prostacyclin [1.0 ng/kg/min intravenously (iv)] or the Rho kinase inhibitor Y-27632 [1.05 μg/ml plasma/h intraarterially (ia)]. These doses are known to decrease permeability under noninflammatory conditions. The reflection coefficient for albumin and CFC were determined before and during LPS, and during LPS plus prostacyclin ( n = 6) or LPS plus Y-27632 ( n = 6). The reflection coefficient was reduced by about 30% ( P < 0.05) and CFC was increased by about 25% ( P < 0.05) by LPS, and these permeability parameters were not affected by prostacyclin or Y-27632. We conclude that cAMP stimulation and Rho kinase inhibition reduce permeability by other pathways and mechanisms than those by which permeability is increased during endotoxemia.

Nitric oxide and prostacyclin play a role in the regulation of microvascular protein and hydraulic permeability in cat skeletal muscle.

To evaluate a possible role of nitric oxide (NO) and prostacyclin in the regulation of basal microvascular protein and hydraulic permeability. The study was performed on the autoperfused cat calf muscle. Changes in the osmotic reflection coefficient for albumin, calculated from the extended Starling equation, were used as a measure of altered protein permeability, whereas changes in capillary filtration coefficient (CFC) were used as a measure of altered hydraulic permeability. Inhibition of the endogenous NO production with L-nitro-arginine methyl ester given intra-arterially to the muscle decreased the reflection coefficient to 70% of the control (p < 0.05) and increased the CFC by 17% (p < 0.05). The addition of a simultaneous intra-arterial infusion of the NO precursor L-arginine restored both the reflection coefficient and the CFC back to control level. Blockade of the endogenous prostacyclin production with tranylcypromine given intra-arterially decreased the reflection coefficient to 72% of the control (p < 0.05) and increased the CFC by 24% (p < 0.05), and they were both restored to control levels by a simultaneous intravenous infusion of a nonvasodilating dose of prostacyclin (1.0 ng/kg per minute). The results support the view that endogenous NO and prostacyclin decrease both protein and hydraulic permeability. Assuming a dynamic endogenous release of these substances, they may act as bidirectional regulators of protein and hydraulic permeability.

Endotoxin increases both protein and fluid microvascular permeability in cat skeletal muscle.

To evaluate effects of lipopolysaccharide (endotoxin) on protein and fluid permeability in a whole organ skeletal muscle preparation. Controlled, prospective laboratory study. University research laboratory. Eleven adult male cats. The study was performed on the autoperfused and denervated calf muscles of the cat hindlimb placed in a fluid-filled plethysmograph. The endotoxin-induced change in the osmotic reflection coefficient for albumin was used as a measure of alteration in protein permeability of the microvascular wall, and the simultaneous change in capillary filtration coefficient was used as a measure of alteration in fluid permeability. Endotoxin as a bolus infusion (1 mg/kg iv) was given to six cats, and another five cats given only the vehicle (NaCl) were used as control. Arterial blood flow, arterial and venous blood pressures, total vascular resistance, and tissue volume changes were measured continuously. The ratio between the osmotic reflection coefficients for albumin on two occasions (before and about 1.5 hr after endotoxin infusion) was calculated from the Starling fluid equilibrium equation. This was performed by measurement of the maximum absorption rate from an isovolumetric state by an intravenous bolus infusion of 20% human albumin (0.6 g/kg) and the capillary filtration coefficient. Albumin concentrations were measured before and after the albumin infusion to correct for effects of difference in plasma volume on the induced increase in colloid osmotic pressure. We found that the osmotic reflection coefficient for albumin was reduced by 30% (p <.05), and the capillary filtration coefficient was increased by 31% (p <.05) by endotoxin. No changes were seen in the vehicle experiments. Endotoxin causes a significant increase in both protein and fluid microvascular wall permeability. These effects may explain the marked leakage of plasma to the interstitium that is often seen in critically ill patients with sepsis and systemic inflammatory response syndrome.

Off-pump vs. on-pump coronary revascularization: changes in capillary filtration coefficient and isovolumetric venous pressure

Off-pump vs. on-pump coronary revascularization: changes in capillary filtration coefficient and isovolumetric venous pressure

Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle.

The capillary filtration coefficient (CFC) is assumed to reflect both microvascular hydraulic conductivity and the number of perfused capillaries at a given moment (precapillary sphincter activity). Estimation of hydraulic conductivity in vivo with the CFC method has therefore been performed under conditions of unchanged vascular tone and metabolic influence. There are studies, however, that did not show any change in CFC after changes in vascular tone and metabolic influence, and these studies indicate that CFC may not be influenced by alteration in the number of perfused capillaries. The present study reexamined to what extent CFC in a pressure-controlled preparation depends on the vascular tone and number of perfused capillaries by analyzing how CFC is influenced by 1) vasoconstriction, 2) increase in metabolic influence by decrease in arterial blood pressure, and 3) occlusion of precapillary microvessels by arterial infusion of microspheres. CFC was calculated from the filtration rate induced by a fixed decrease in tissue pressure. Vascular tone was increased in two steps by norepinephrine (n = 7) or angiotensin II (n = 6), causing a blood flow reduction from 7.2 +/- 0.8 to at most 2.7 +/- 0.2 ml x min(-1) x 100 g(-1) (P < 0.05). The decrease in arterial pressure reduced blood flow from 4.8 +/- 0.4 to 1.40 +/- 0.1 ml x min(-1) x 100 g(-1) (n = 6). Vascular resistance increased to 990 +/- 260% of control after the infusion of microspheres (n = 6). CFC was not significantly altered from control after any of the experimental interventions. We conclude that CFC under these conditions is independent of the vascular tone and number of perfused capillaries and that variation in CFC reflects variation in microvascular hydraulic conductivity.

Limb capillary filtration coefficient in human subjects: the importance of the site of measurement

Capillary filtration coefficient is a critical determinant of fluid flux across the microvascular wall. Changes in capillary filtration coefficient have been described in a number of disease processes. Measurement is typically made by venous occlusion plethysmography using either the upper or lower limb, but a variety of measurement protocols have been used and the importance of the site of measurement remains unclear. In this study, forearm and calf capillary filtration coefficient were measured in healthy volunteers, either simultaneously (group A; n = 11) or sequentially in random order (group B; n = 11) using venous occlusion plethysmography, with the subject supine and the limb at heart level. In both studies capillary filtration coefficient was significantly higher when measured at the forearm than at the calf (group A: versus , p < 0.01; group B: versus , p < 0.01). Isovolumetric venous pressure (the maximum pressure at which there is neither net filtration nor absorption at the microvascular wall) was similar in upper and lower limbs in both groups of subjects. We conclude that limb capillary filtration coefficient is dependent on the site of measurement. Caution is required when comparing data recorded at different sites even if corrected for the volume of soft tissue under study. Keywords: microcirculation, permeability, plethysmography

Blood flow vs. venous pressure effects on filtration coefficient in oleic acid-injured lung

On the basis of changes in capillary filtration coefficient (Kfc) in 24 rabbit lungs, we determined whether elevations in pulmonary venous pressure (Ppv) or blood flow (BF) produced differences in filtration surface area in oleic acid-injured (OA) or control (Con) lungs. Lungs were cyclically ventilated and perfused under zone 3 conditions by using blood and 5% albumin with no pharmacological modulation of vascular tone. Pulmonary arterial, venous, and capillary pressures were measured by using arterial, venous, and double occlusion. Before and during each Kfc-measurement maneuver, microvascular/total vascular compliance was measured by using venous occlusion. Kfc was measured before and 30 min after injury, by using a Ppv elevation of 7 cmH2O or a BF elevation from 1 to 2 l . min-1 . 100 g-1 to obtain a similar double occlusion pressure. Pulmonary arterial pressure increased more with BF than with Ppv in both Con and OA lungs [29 +/- 2 vs. 19 +/- 0.7 (means +/- SE) cmH2O; P < 0. 001]. In OA lungs compared with Con lungs, values of Kfc (200 +/- 40 vs. 83 +/- 14%, respectively; P < 0.01) and microvascular/total vascular compliance ratio (86 +/- 4 vs. 68 +/- 5%, respectively; P < 0.01) increased more with BF than with Ppv. In conclusion, for a given OA-induced increase in hydraulic conductivity, BF elevation increased filtration surface area more than did Ppv elevation. The steep pulmonary pressure profile induced by increased BF could result in the recruitment of injured capillaries and could also shift downstream the compression point of blind (zone 1) and open injured vessels (zone 2).

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.

Microvascular hemodynamics in the sickle red blood cell perfused isolated rat lung.

In this study the effects of alveolar hypoxia on pulmonary microvascular hemodynamics in sickle red blood cell (HbSS-RBC) perfused rat lungs were studied under conditions of high and low oxygen tensions and compared with lung perfused with rat (HbRat) and normal human (HbAA) RBC controls. Independent of the RBC suspension (hematocrit 5%) used, ventilation with the room air gas mixture did not result in any significant differences in the pulmonary arterial pressure (Ppa), capillary pressure (Ppc), total pulmonary vascular resistance (RT), or angiotensin II pressor response. Ventilation of HbSS-RBC perfused lungs with a hypoxic gas mixture significantly increased the Ppa, Ppc, and RT above that which was seen in HbRat and HbAA controls. The increase in RT occurred mainly in the pulmonary artery independent of RBC suspension. In addition, no significant accumulation of lung water occurred in HbSS-RBC perfused lungs compared with HbRat and HbAA controls, as indicated by the change in capillary filtration coefficient and wet-to-dry lung weight ratio. In conclusion, deoxygenation of the HbSS-RBC and hypoxic pulmonary vasoconstriction is additive in altering pulmonary microvascular hemodynamics.

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.

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.

Transient effects of histamine on microvascular fluid movement

There have been many reports on the effect of local intraarterial (IA) histamine on the capillary filtration coefficient (CFC) and the isogravimetric capillary pressure (Pci). CFC has been reported to increase during infusion of this agent but the reported magnitude of increase is widely variable. Similarly, histamine has been reported to cause little change or a decrease in Pci. It was felt that histamine may have some time-dependent effect on CFC and Pci and that this might explain, at least in part, the variation. To test this hypothesis, CFC and Pci were measured in the isolated, denervated canine forelimb at timed intervals during infusion of local IA histamine (12 μg base/min). Also, lymph and plasma samples were collected and lymph flow and lymph and plasma protein concentration were determined. Permeability-surface area (PS) product ratios were estimated from steady-state lymph data. Propranolol (2–3 mg/kg iv priming dose and 123 μg/min locally) was administered throughout the experiment to inhibit possible catecholamine-mediated inhibition of histamine-induced increases in fluid and protein efflux. CFC averaged 0,013 ml/min/mm Hg/100 g at control and increased to 0.040 and 0.048 after 5 and 10 min of histamine, respectively. Subsequent CFC determinations were not different from control. Pci was not altered by histamine at this dose. The estimated PS ratio was 43. Control experiments were conducted in which propranolol and the saline vehicle were infused. No change in any variable in the control group occurred with time. These data indicate that the effect of histamine on the small-pore system, as reflected by changes in CFC, is highly transient.

Volumetric assessment of the capillary filtration coefficient in the cat small intestine.

The capillary filtration coefficient of the cat small intestine was measured in four ways; the conventional measurement was compared with the "zero time extrapolation" technique, and with two methods designed to assess the end of the blood volume shift due to venous pressure elevation. If the capillary filtration coefficient (CFC) was determined using small elevations of venous pressure (10 mm Hg or less), there was good agreement between the techniques. Larger elevations of venous pressure resulted in apparent over-estimates of CFC measured by the conventional technique, probably because of increased "smearing" of the blood volume shift into the component of the response measured as the CFC. In general, larger elevations of venous pressure gave smaller CFC's, and using venous pressure elevations of 10 mm Hg or less, the CFC was greater if the final elevated venous pressure was 10 mm Hg than if it was 20 or 30 mm Hg. Changes in CFC due to noradrenaline and isoprenaline (about 15 ng/ml arterial blood concentration) were in agreement when small venous pressure elevations were used and CFC measured in three different ways.

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.

Effects of norepinephrine infusions on mesenteric arterial blood flow and its tissue distribution.

Infusions of norepinephrine into the superior mesenteric artery or stimulation of the mesenteric periarterial nerves of cats or dogs produces a transient reduction in mesenteric blood flow but, as stimulation or infusion continues, flow returns to near control values (1-3). Studies based on India ink injections, changes in capillary filtration coefficient and isotope clearances suggested that a redistribution of intestinal blood flow occurred during the “escape” from the vasoconstrictor influence (4, 5). Vasoconstriction in the mucosa appeared to be well maintained throughout whereas blood flow in the submucosa increased. However, other observations (6, 7) have indicated that escape may be due to relaxation of the same vascular elements which were initially constricted.The purpose of the present investigation was to determine whether norepinephrine escape occurred in animals other than the dog and cat and to reexamine the possibility that escape is associated with a redistribution of blood flow among the ...

Capillary filtration coefficient in the extremities of man in high environmental temperatures.

The capillary filtration coefficient was measured in human extremities by a simplified technique using the capacitance plethysmograph. The method was validated in terms of consistency of values obtained on the same individual at various times, the correspondence between values obtained on a group of normal persons, and the agreement between values reported here and those of earlier workers made under corresponding environmental conditions and duration of measurement after venous occlusion. The technique was used to evaluate the change in capillary filtration coefficient in the calves of subjects when ambient temperature was increased from 20° to 35°C. Corresponding measurements of total blood flow in this segment and determinations of the clearance of iodide ion from pretibial intradermal depots were made in both environments. Cutaneous blood flow increased by almost 170% and the capillary filtration coefficient by about 40%, whereas the clearance did not change. It is concluded that neither the capillary filtration coefficient nor the clearance of isotopes from tissue depots has been established as a valid measure of capillary surface area. The possibility that during venous occlusion, fluid accumulated primarily in the subcutaneous tissues of the extremity is suggested and discussed.

Changes in capillary filtration coefficient in the forearm during emotional and postexercise hyperemia and after intra-arterial adrenaline, acetylcholine, and isopropylnoradrenaline

1. 1. Capillary filtration coefficient (CFC) in the forearm increases after exercise of the forearm muscle. 2. 2. An increase in blood flow during stressful mental arithmetic, comparable in degree to the increase in blood flow after exercise, either is not accompanied by any change in CFC or even leads to a drop in the CFC. 3. 3. Adrenaline, acetylcholine, and isopropylnoradrenaline, which produce an increase in forearm blood flow, do not effect any change in the CFC.