International journal of microcirculation, clinical and experimental最新文献

The aim of our study was to investigate the vascular effects of recombinant human granulocyte colony-stimulating factor (rh G-CSF) in a rat model of irreversible vascular failure. Male anesthetized rats were subjected to the clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock) characterized by high mortality rate (0% survival, 120 min following the release of clamps), a profound hypotension and vascular dysfunction consisting of a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) of aortic rings. Administration of recombinant human granulocyte colony-stimulating factor (20 micrograms/kg i.v. 5 min after the release of occlusion) increased survival rate (90% 4 h after the release of occlusion), blunted the profound hypotension and reverted the marked vascular dysfunction. Finally, rh G-CSF inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. Our data suggest that rh G-CSF may influence vascular function when low-flow states occur.

The aim was to study the effect of oral administration of three different doses of S-5682 and alpha-tocopherol on an oxidant-induced injury by tert-butylhydroperoxide (TBOOH) resulting in increased plasma leakage from postcapillary venules in the hamster cheek pouch microcirculation. Hamsters were on a standard laboratory animal diet with normal vitamin E and C content. Five groups of hamsters (n = 6) were treated orally with placebo (10% lactose solution), S-5682 (5, 20 or 80 mg/kg/day) suspended in 10% lactose solution, or alpha-tocopherol (1 mg/kg/day) for 10 days prior to oxidant challenge with TBOOH. Topical application of 10(-4) M TBOOH for 5 min to hamsters given FITC-dextran 30 min prior to TBOOH resulted in reversible increases in the number (mean +/- SE) of leaks in postcapillary venules: placebo, 117+/-7 leaks/cm2; S-5682, 5 mg/kg/day, 68+/-3 leaks/cm2 (p < 0.01); S-5682, 20 mg/kg/day, 41+/-3 leaks/cm2 (p < 0.01); S-5682, 80 mg/kg/day, 25+/-2 leaks/cm2 (p < 0.001), and alpha-tocopherol, 1 mg/kg/day, 18+/-1 leaks/cm2 (p < 0.001). The efficacy of inhibition of oxidant-induced leakage by S-5682 was similar to that seen with the same dose (20 mg/kg/day) of histamine, bradykinin, leukotriene B4 or ischemia/reperfusion-induced leakage, suggesting a common pathway for the induction of plasma leakage by these mediators. The maximal dose of S-5682 (80 mg/kg/day) was as effective as alpha-tocopherol (1 mg/kg/day) in inhibiting plasma leakage.

The geometry of the coronary capillary bed in human hearts was studied using samples obtained during cardiac surgery of children operated for tetralogy of Fallot and samples from fresh normal hearts used for valve harvesting. The results revealed a similar coronary capillary density and heterogeneity of capillary spacing in samples from both groups. A double-staining method was used to distinguish between capillary segments close to the feeding arteriole (proximal capillaries) and segments distant from the arteriole (distal capillaries). In both groups of hearts, capillary segment length was consistently shorter on the venular than the arteriolar portion of the capillary. Similarly, capillary domain areas were also smaller and the resulting capillary supply unit was smaller along venular portions compared to arteriolar regions of the capillary bed. This distinctive geometry would provide advantageous geometric conditions for tissue oxygen supply.

Objective: To assess the efficacy of a micronized purified flavonoid fraction (Daflon 500 mg = Dios) in venous leg ulcer healing, in addition to compression therapy and standardized local care.

Design: Double-blind, multicentre, randomized, parallel groups, controlled versus placebo trial; stratification according to ulcer size.

Subjects: 107 patients, with venous ulcer of the leg for at least 3 months, and accepting bandaging therapy.

Results: 105 patients (Dios = 53, placebo = 52) were available for an intention to treat (ITT) analysis. Age (mean +/- SD, 71+/-11 years), gender (M = 33, F = 74) and ulcer size were evenly distributed among both groups. 99 patients completed the protocol (Dios = 51, placebo = 48). Among the 91 patients with ulcer size < or = 100 cm (Dios = 44, placebo = 47), a significantly higher number of patients had complete ulcer healing at 2 months in the Dios group (n = 14) in comparison to the placebo group (n = 6) after ITT analysis (32 vs. 13%, p = 0.028) and after per protocol analysis (32 vs. 14%, p = 0.048), and a shorter time duration of healing (p = 0.037). Among the 14 patients with ulcer size > 10 cm (Dios = 9, placebo = 5), no ulcer healed.

Conclusion: This study showed that a 2-month course of purified micronized flavonoid fraction (2 tablets/day), in addition to conventional treatment, is of benefit in patients by accelerating complete healing of venous leg ulcers which are < or = 10 cm in diameter.

The use of Daflon 500 mg has been shown to improve venous tone, microvascular permeability, lymphatic activity, and microcirculatory nutritive flow. This study aimed to assess the effects of Daflon 500 mg at a daily dose of 2 tab/day on microcirculatory, haemorheologic parameters, white blood cell counts and neutrophil activation in patients suffering from chronic venous insufficiency (CVI). This was a single-centre double-blind placebo-controlled study comparing two parallel groups of CVI patients who were treated for 2 months with Daflon 500 mg (n = 39) or placebo (n = 38). Evaluations were performed before treatment (D0) and at the end of treatment (D60). Blood samples were drawn from a foot vein before and at the end of a 15-min period of venous hypertension provoked by a cuff inflated to 100 mm Hg. Red blood cell (RBC) deformability was determined by the initial flow rate filtration technique using a Hanss haemorheometer. RBC aggregation was evaluated by a Myrenne aggregometer based on analysis of transmitted light through a blood sample during flow. RBC disaggregation was evaluated by Sefam erythro-aggregometer based on analysis of the backscattered light through a blood sample in a Couette flow. Microcirculatory parameters were assessed by means of laser Doppler fluxmetry and transcutaneous oxymetry measurements and consisted of continuous records of blood flux (BF) and TcPO2 before and during 15 min of venous hypertension. Results are expressed as absolute values at baseline (before stasis) and at the end of stasis, before and after 2 months of treatment. Univariate analysis showed a significant reduction of the stasis-induced RBC aggregation index (Daflon 500 mg: -0.07+/-0.20; placebo: 0.04+/-0.18; mean +/- SD; p = 0.03). Multivariate analysis identified a subset of 5 variables (RBC aggregation, RBC count, microcirculatory BF, amplitude and frequency of vasomotion) that produced a good discrimination model between the two treatments. Linear combination of these 5 variables in 48 patients with complete data showed a significant difference (p < 0.001) between the groups. These changes suggest a protective effect of Daflon 500 mg on the deleterious influence of stasis on microcirculatory (BF) and hemorheologic (RBC aggregation) parameters in CVI patients in comparison to patients receiving placebo.

The aim of this study was to investigate the relationships between laser Doppler perfusion monitoring (LDPM) measurements and different systemic hematocrits in microcirculation in terms of changes in oscillatory flow patterns. The hamster cheek pouch microvasculature was visualized by a fluorescent microscopy technique, and LDPM signals were derived from arterioles and venules under control conditions and after isovolemic hemodilution with saline and 6% dextran, MW 70,000 to 26.1 +/- 2.1%. Vasomotion, oscillations of microvascular blood flow (flow motion) and red blood cell (RBC) velocity were analyzed with Fourier transform and autoregressive modeling. LDPM recordings presented a significant increase in perfusion units (PU) during hemodilution-184 +/- 15 versus baseline 137 +/- 11 PU in arterioles and 40.2 +/- 3.5 versus 28.6 +/- 4.3 PU in venules-that was correlated with a significant increment in arteriolar and venular RBC velocity. There was a rise in the frequency [2.9 +/- 0.5 cycles per min (cpm) vs. 1.8 +/- 0.5 cpm] and spectral power of flow motion in arterioles whereas the increase in spectral power was related to a decrease in frequency (12.6 +/- 2.1 vs. 3.6 +/- 0.7 cpm) in venules. Oscillations in arteriolar and venular RBC velocity revealed coincident frequency components with flow motion patterns. The present data suggest that the LDPM measurements are more sensitive to velocity than hematocrit. Furthermore, hemodilution appears to affect differently arteriolar and venular flow motion patterns.

Basic fibroblast growth factor (bFGF), a constituent of bone and cartilage matrix, has been shown to be a potent mitogen for osteoblasts and chondrocytes and yet an inhibitor of chondrocyte terminal differentiation in cell culture. To characterize the effect of bFGF on bone formation, whole neonatal murine femora were cultured in the presence or absence of bFGF and a neutralizing antibody against bFGF. In vitro, femoral elongation was provided by cartilage growth only; the calcified diaphyseal zone stained by oxytetracycline did not increase. When bFGF was added to the culture medium, longitudinal growth of the proximal and distal cartilage was inhibited in a dose-dependent manner (p < 0.05), and the number of hypertrophic chondrocytes in the growth plate was reduced. This phenomenon was absent in the presence of a neutralizing antibody, which when given alone significantly promoted femoral elongation. In contrast, in vivo after transplantation into adult mice bearing dorsal skin fold chambers, femora rapidly calcified after revascularization. This observation supports the notion that bone formation largely depends on angiogenesis-mediated events. To verify this hypothesis, angiogenesis and bone formation were quantified using bFGF known to be a stimulator of angiogenesis. Calcification of grafted femora was accelerated by bFGF given intraperitoneally. The neutralizing antibody slightly suppressed angiogenesis and femoral elongation (not statistically significant), whereas intravenous injections of both substances did not reveal a significant modulatory effect. In vivo the effect of systemically administered bFGF was inhomogeneous, but there was a strong correlation between angiogenesis and endochondral calcification (p < 0.001). These results suggest that exogenous bFGF modulates bone formation in vitro by inhibition of terminal differentiation of chondrocytes in the growth plate, and angiogenesis and concomitant in vivo events are pivotal in the promotion of rapid bone formation.

The aim of this study was to investigate the effect of a moderate degree of hypoxia on coronary vascular permeability to various lipophobic solutes. Using the multiple indicator dilution method the permeability-surface area (PS) products were determined for 125I-albumin, 125I-insulin and 57Co-cyanocobalamin in perfused rat hearts (flow approximately 10 ml.min-1.g-1) either with well-oxygenated (pO2 approximately 96 kPa) or hypoxic (pO2 approximately 45 kPa) solutions. The PS products for albumin, insulin and cyanocobalamin during the well-oxygenated equilibration period were 0.20 +/- 0.03, 0.29 +/- 0.06 and 2.0 +/- 0.3 ml.min-1.g-1 (mean +/- SE), respectively, relative to 131I-gamma-globulin. The PS products for these solutes 15 min after the induction of hypoxia were 1.3 +/- 0.3, 0.8 +/- 0.1 (p < 0.05) and 2.1 +/- 0.2 (p < 0.05), respectively. In hearts perfused with well-oxygenated solution for 75 min, the PS products for these solutes remained stable throughout the period of the study. Electron-microscopic examination of hypoxic tissues showed the presence of endothelial gaps of approximately 1 micron which were underlined by an intact basal lamina. We conclude that a moderate degree of hypoxia produces a large increase in permeability of albumin and insulin but has no effect on the PS products for cyanocobalamin and that the endothelial gaps are the likely mechanism of the observed increase in permeability.