Increase In Capillary Filtration Research Articles

Capillary endothelial but not lymphatic function is restored under rosiglitazone in Zucker Diabetic Fatty rats

If thiazolidinediones have shown beneficial effects on macrovascular endothelial function, their effects on microcirculation and lymphatic function are not well documented. The aim of the study was to assess the effect of rosiglitazone on interstitial albumin retention and lymphatic function in Zucker Diabetic Fatty (ZDF) rats. Three series of 9–14 rats were studied: Lean ( fa/?) controls, ZDF (Gmi- fa/fa) rats and ZDF rats treated with rosiglitazone from 8 to 26 weeks of age (ZDF–ROSI). Albumin retention and lymphatic uptake of interstitial albumin (LF/HF ratio) were evaluated on hindquarters with a noninvasive isotopic test using technetium-labelled albumin. Vascular Endothelial Growth Factor (VEGF) was measured. At week 25, albumin retention was markedly higher in ZDF rats (9.9 ± 1.0%) than in control rats (1.0 ± 0.8%, p < 0.001), but did not differ significantly between the ZDF–ROSI group (2.5 ± 1.5%) and the control group. LF/HF ratio was similarly increased in the ZDF group (1.14 ± 0.07%) and the ZDF–ROSI group (1.07 ± 0.04%) as compared to control rats (0.65 ± 0.04%; p < 0.001 for both). We can deduce that the prevention of the increase of albumin retention under rosiglitazone results from a decrease in the capillary filtration of albumin. VEGF levels were 7.1 ± 1.5, 7.3 ± 1.9, 3.5 ± 1.6 pg/mL in the control, ZDF and ZDF–ROSI groups, respectively ( p = 0.23). In ZDF rats, rosiglitazone prevents interstitial albumin retention and the increase in capillary filtration of albumin. However lymphatic function is still impaired and might contribute to oedema.

Effect of rosuvastatin on capillary filtration of albumin and blood pressure in rats with streptozotocin-induced diabetes

An increase in capillary filtration of albumin (CFA) is well demonstrated in diabetes. Statins may exert a protective effect against endothelial dysfunction. The aim of this study was to test whether rosuvastatin may prevent the increase in peripheral CFA in diabetic rats and the role of blood pressure lowering. Rats with streptozotocin-induced diabetes were randomized to receive either rosuvastatin 20 mg/kg/d (group R) or both rosuvastatin 20 mg/kg/d and mevalonate 20 mg/kg/d (group RM) or no treatment (group U). CFA index was measured on a limb by a non-invasive isotopic test using technetium-labelled albumin, at three time points: at mean age of 3 months, before treatment; at 5 and 8 months, i.e. after 2 and 5 months of treatment. At 3 months, interstitial albumin retention (AR) was markedly increased in the 3 groups. From 3 to 5 months, AR increased significantly in group U, decreased in group R and in group RM. At 5 and 8 months, AR was significantly lower in groups R and RM than in group U. Systolic blood pressure (SBP) was measured at 8 months and was significantly lower in group R than in group U and RM. At 8 months, serum cholesterol levels were not different between the three groups whereas triglycerides were significantly lower in groups R and RM than in group U. In conclusion, in diabetic rats rosuvastatin prevents the increase in peripheral CFA and induces a decrease in blood pressure. The beneficial effect of rosuvastatin on endothelial function does not seem to result from blood pressure reduction nor lipid lowering effects.

Transdiaphragmatic transport of tracer albumin from peritoneal to pleural liquid measured in rats

In conscious Wistar-Kyoto rats, we studied the uptake of radioactive tracer (125)I-albumin into the pleural space and circulation after intraperitoneal (IP) injections with 1 or 5 ml of Ringer solution (3 g/dl albumin). Postmortem, we sampled pleural liquid, peritoneal liquid, and blood plasma 2-48 h after IP injection and measured their radioactivity and protein concentration. Tracer concentration was greater in pleural liquid than in plasma approximately 3 h after injection with both IP injection volumes. This behavior indicated transport of tracer through the diaphragm into the pleural space. A dynamic analysis of the tracer uptake with 5-ml IP injections showed that at least 50% of the total pleural flow was via the diaphragm. A similar estimate was derived from an analysis of total protein concentrations. Both estimates were based on restricted pleural capillary filtration and unrestricted transdiaphragmatic transport. The 5-ml IP injections did not change plasma protein concentration but increased pleural and peritoneal protein concentrations from control values by 22 and 30%, respectively. These changes were consistent with a small (approximately 8%) increase in capillary filtration and a small (approximately 20%) reduction in transdiaphragmatic flow from control values, consistent with the small (3%) decrease in hydration measured in diaphragm muscle. Thus the pleural uptake of tracer via the diaphragm with the IP injections occurred by the near-normal transport of liquid and protein.

Insulin resistance and impaired regulation of hemodynamic parameters

Insulin resistance (IR) is associated with poor cardiovascular prognosis. Various factors may be involved, including metabolic disorders, changes in cation contents of smooth muscle cells and changes in hemodynamic conditions. There is substantial evidence for cardiovascular autonomic disorders and endothelium dysfunction in the IR syndrome. In nondiabetic overweight subjects, heart rate variability (HRV) is decreased in more than 40% of the cases, and this disorder is associated with a higher IR index (HOMA). Sympathetic activity evaluated by the low-frequency peak of systolic blood pressure changes (spectral analysis) correlates with IR index. The HOORN study has shown that HRV is abnormal in the subjects with glucose intolerance. Insulin may be involved in the changes of vagosympathetic balance, and the role of free fatty acids has also been suggested. The Fredericia study has provided arguments for the role of genetic factors in autonomic dysfunction. Endothelium function also seems to be impaired in the IR syndrome. In overweight subjects, a decrease in coronary endothelium-dependent vasodilation has been reported, and we found that the cutaneous endothelium-dependent vasodilation is decreased and correlates negatively with HOMA index. Capillary filtration of albumin is increased in overweight women and improved by metformin. In Zucker fatty rats, we recently found a similar increase in capillary filtration of albumin. Some experimental data and therapeutic trials suggest that endothelium dysfunction may be improved by thiazolidinediones. Both autonomic and endothelium dysfunctions may have important cardiac consequences. Autonomic dysfunction is associated with a decrease in circadian blood pressure variations, and sympathetic activity correlates with arterial rigidity. Together with a depression of endothelium-dependent vasodilation, these disorders may contribute to left ventricle hypertrophy. Finally, several prospective studies have demonstrated the prognostic value of autonomic disorders and endothelium dysfunction of the coronary arteries. Thus, changes in hemodynamic conditions may account for the poor cardiovascular prognosis related to IR. Common genetic factors might be implicated in IR and such cardiovascular changes.

Extra cellular water and increase in capillary permeability to albumin in overweight women with swelling syndrome.

To evaluate extracellular water (ECW) in the recumbent and the upright position, in overweight and lean women with swelling syndrome, and to correlate the excess in ECW with an increase in capillary filtration of albumin (CFA). Fifty-one women with a swelling syndrome were investigated, 26 of whom were overweight. ECW was measured by the bioelectrical impedance method, in the recumbent position and again after a postural test which consisted of walking around for 30 min. CFA was studied by an isotopic test using 99m technetium-labelled albumin. ECW increased (>107% of the theoretical value) in 22 of the 26 overweight patients and 23 of the 25 lean patients. The CFA isotopic test was abnormal in half (11/22) of the overweight patients with increased ECW and in three of the four overweight patients with a normal ECW value. It was abnormal in 18 of the 23 lean patients with increased ECW and in the two lean patients with a normal ECW value. During the postural test, a significant (by> or =4%) increase in ECW occurred in a higher proportion of overweight patients tested (14/22) than among the lean women tested (0/5; P=0. 04). The swelling syndrome is indeed related to an increase in ECW in lean and overweight subjects and to a further increase in ECW after a postural test only in the overweight patients. It is also associated with microcirculatory disorders in most of the lean patients who complain of swelling and in only half of the overweight patients with the same complaints, which suggests that other factors (e.g. hormonal disorders) may be involved in the overweight patients. International Journal of Obesity (2000)24, 126-130

Increased capillary filtration of albumin in diabetic patients—relation with gender, hypertension, microangiopathy, and neuropathy

The aim of this study was to investigate the factors associated with an increase in capillary filtration of albumin (CFA) in a large series of diabetic patients and its relationship with gender, hypertension, microangiopathy, and neuropathy. One hundred sixty-three unselected diabetic patients, 74 type I and 89 type II, were included. An isotopic test of CFA was performed with 99m technetium—labeled albumin injected intravenously. Radioactivity was counted externally at the forearm with a gamma camera before, during, and after venous compression. After removal of venous compression, interstitial albumin retention (AR) was calculated and the radioactivity disappearance curve was analyzed by the Fast Fourier transform, which provides an index for lymphatic uptake of interstitial albumin (low-frequency to high-frequency amplitude peak ratio [ LF HF ]). An increase in AR and LF HF was found in 65 (39.9%) and 117 (71.7%) patients, respectively. Increased AR was significantly more frequent in women than in men ( P = .018) and in patients without microangiopathic complications than in those with them ( P = .028). In men, it was significantly more frequent in type I versus type II diabetic patients ( P = .004), and AR was significantly higher in patients with peripheral neuropathy than in those without ( P = .004). The LF HF was also significantly higher in men with peripheral neuropathy ( P = .045). In women, the AR level correlated negatively with postprandial glycemia ( P = .006) and was significantly higher in patients without microangiopathic complications ( P = .003). These data suggest the role of hormonal factors, both sex steroids and insulin, and the major role of peripheral neuropathy in the increase in CFA. The highly prevalent increase in CFA before the onset of microangiopathic complications is consistent with the presence of a functional microcirculatory disorder that might contribute to the occurrence of microangiopathic lesions.

Skin flow the venoarteriolar response and capillary filtration in diabetics. A 3-year follow-up.

Resting skin blood flow (RF) and the venoarteriolar response (VAR = the vasoconstrictor response on standing) have been studied in 100 patients with diabetic neuropathy, in 100 diabetics without neuropathy, and in 100 normal subjects by laser Doppler flowmetry. Capillary filtration was also studied with strain gauge plethysmography. The authors followed up these patients by evaluating their microcirculation again after three years. At the beginning of the study in patients with neuropathy, RF and capillary filtration were increased. The VAR and the microangiopathy index (MI = VAR/RF) were reduced in all diabetics, to a greater extent to those with neuropathy. After three years the authors observed an increase in capillary filtration associated with a further impairment in VAR and MI, suggesting progression of microangiopathy in both groups of diabetics. These results suggest that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in neuropathics. Increased skin blood flow and capillary filtration and the impaired venoarteriolar response cause edema and may contribute to the thickening of capillary basement membranes and the progressive evolution of diabetic microangiopathy.

Analysis of pulmonary microvascular permeability after smoke inhalation

We estimated the reflection (sigma) and filtration coefficients (Kf) in a chronic sheep lung lymphatic preparation after smoke inhalation. Group I (n = 7) sheep were insufflated with cotton smoke and group II animals (n = 5) with room air. After inhalation injury, the lung lymph flow increased nearly four times the baseline value by 24 h after injury. There was a concomitant reduction of sigma (0.81 +/- 0.02 to 0.64 +/- 0.02) and elevation of Kf (0.020 +/- 0.002 to 0.042 +/- 0.009 ml.min-1.mmHg-1); pulmonary capillary pressure was also elevated (13 +/- 1 to 17 +/- 1 mmHg). By 48 h postinjury, sigma and Kf returned toward baseline but pulmonary capillary pressure was still elevated. We determined that 34% of the increase in capillary filtration was attributable to increased capillary pressure and 66% to increased permeability 24 h after inhalation, but 48 h after injury, 75% of the increase in capillary filtration was attributable to increased capillary pressure and 25% to increased permeability. We conclude that the lung edema formation following smoke inhalation is the result of marked increases in both capillary pressure and permeability.

Analysis of altered capillary pressure and permeability after thermal injury

In order to investigate the effects of thermal injury on microvascular hemodynamics and permeability, hindpaw arterial ( P A), venous ( P V), and capillary ( P C) pressures, blood ( Q B) and lymph ( Q L) flows, and lymph ( C L) and plasma ( C P) total protein concentrations were measured before and for 3 hr after a 10-sec 100°C scald burn in 11 dogs. Prior to injury in eight experiments (Group I—permeability analysis) venous pressure was elevated by outflow restriction until the minimal C L C P was obtained. In three experiments (Group II—hemodynamic analysis) outflow was not restricted. Lymph and plasma protein fractions ranging in size from 37 to 120 Å were measured using gradient gel electrophoresis and capillary equivalent pore sizes were calculated. In the early postburn period, P C increased from 24 ± 2 (mean ± SE)to 47 ± 5 mm Hg ( P < 0.05) and precapillary resistance ( R A) decreased from 6.6 ± 0.2 to 2.5 ± 0.2 mm Hg/ml/min/100 g ( P < 0.05) while postcapillary resistance ( R V) remained unchanged. Pre- to postcapillary resistance ( R A R V ) fell by 74%. The reflection coefficient for total proteins (calculated as σ = 1 − C L C P ) decreased from 0.87 ± 0.01 to 0.45 ± 0.02 ( P < 0.01). Permeability of the postburn capillary endothelium was described by using two populations of equivalent pores. Preburn pore radii were 50 and 300 Å with 13% of the capillary filtrate passing through the large pores. Pore radii increased after injury to 70 and 400 Å with 49% of the filtrate passing through the large pores. The postburn total tissue filtration coefficient ( K f) increased to 2.4 times the control. Over the first 3 hr postburn, 53% of the increase in capillary filtration was attributable to increased capillary pressure and 47% to increased permeability. We conclude that the early rapid edema formation following thermal injury is the result of marked increases in both capillary filtration pressure and filtration through large nonsieving pores.

The edema of arterial reconstruction.

Edema of the foot and leg incident to successful arterial surgery was evaluated in 137 arterial reconstructions on the lower extremity. Both the postoperative hyperemia and the edema appeared to be directly related to the degree of pre-existent ischemia. When employed, heparin or dextran or both were effective in preventing postoperative phlebitis but did not alter the postoperative hyperemia and edema. Furthermore, phlebograms and pressure studies obtained in edematous extremities disclosed normal venous morphology and hemodynamics. The underlying mechanism for this edema is believed to be the sudden re-establishment of high pressure in an atrophic arterial tree previously exposed to a reduced intravascular pressure of long duration. This effects overstretching of the arterial bed and a remarkable increase in capillary filtration. A significant secondary factor is the compromised venous return incident to muscular atrophy and limited joint movements that are prevalent in ischemic limbs.