摘要:

The purpose of our study was to see if selective denervation of sensory perivascular nerves leads to changes in release of vasoactive substances of endothelial origin from brain microvessels during increased flow. Male rats pups were treated with the neurotoxin, capsaicin, to destroy primary afferent sensory nerves. Three months later, brain microvessels were isolated, placed on a micro-pore filter and perfused with Krebs buffer. During the course of a 30-min experiment, the flow rate was increased from 0.5 to 3.0 ml/min for two 3-min periods. The levels of ATP, substance P, vasopressin and endothelin in the effluent were measured. Microvessels from 5 rats were pooled for each perfusion experiment. Data from 5 perfusion experiments showed that the release of substance P was significantly higher in the capsaicin-treated rats during the second period of increased flow (3.02 ± 1.04 pmol/min/mg protein) compared to the vehicle-treated controls (0.30 ± 0.21 pmol/min/mg protein; p < 0.02). In contrast, the release of ATP at low flow and during the second period of increased flow was significantly lower in the capsaicin-treated rats (0.21 ± 0.04 compared to 0.50 ± 0.03 pmol/min/mg protein for controls at low flow, p < 0.001; and 1.19 ± 0.15 compared to 2.11 ± 0.26 pmol/min/mg protein for controls during the second period of increased flow, p < 0.01). The release patterns of endothelin and vasopressin were similar in capsaicin-treated and vehicle-treated controls. In conclusion, chronic depletion of sensory innervation leads to altered release of two endothelium-dependent vasodilators, ATP and substance P from the brain microvasculature. These changes may be compensatory and suggest that there is an ongoing interaction between sensory perivascular nerves and the endothelium in brain microve

ISSN:0167-6865    

DOI:10.1159/000178942

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:0167-6865    

DOI:10.1159/000179086

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The haemodynamic hallmark of chronic venous disease in the legs is raised ambulatory venous pressure. This is probably the principal cause of both the symptoms of long-standing varicose veins and the trophic changes round the ankle characteristics of chronic venous insufficiency, presumably by an effect on the microcirculation. The microcirculatory consequences of raised venous pressure include morphological changes, as well as functional abnormalities ranging from haemorheological changes, increased capillary permeability and abnormalities of fibrinogen metabolism to trapping of white blood cells in the dependent legs. This last is now known to be accompanied by sequestration of platelets, which is irreversible. It is postulated that leucocyte activation releases cytokines, leucocyte-derived oxygen free radicals, proteolytic enzymes and platelet activating factor. It has been shown that external compression not only relieves stasis but also decreases white cell trapping. A strategy for management of the complications of venous disease should therefore be aimed at treatment of both the macrocirculatory haemodynamic defect and the microcirculatory abnormalities. The latter is an ideal target for systemic pharmacotherapy.

ISSN:0167-6865    

DOI:10.1159/000179087

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Intravital microscopy is used for analysis of the microcirculation in various organs, e.g. mesentery, intestine, heart, liver and lung, requiring either exteriorization or in situ visualization techniques in anaesthetized animals. In contrast, the implantation of transparent chambers has been employed to allow chronic observation of the microcirculation in intact, non-anaesthetized animals. This paper reports results with two transparent chamber models: the skin-fold chamber model in the hamster and the mouse. An overview is provided of the technical development of the chamber technique and of the various experimental studies that have been performed using these models in ischaemia-reperfusion of striated muscle. Particular emphasis is given to a description of the methods used to induce ischaemia and reperfusion, namely pressure-induced or tourniquet-induced ischaemia. While the former allows simulation of the pathophysiological situation in compartment syndromes, the latter provides an appropriate simulation of the clinical situation in vascular, transplantation and reconstructive surgery. Future possibilities for these microcirculation models in research into the pathophysiology of ischemia-reperfusion are outlined, and potential therapeutic measures to preserve postischaemic tissue are discussed.

ISSN:0167-6865    

DOI:10.1159/000179088

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

When healthy volunteers were treated with human insulin-like growth factor-I (IGF-I), mild generalized edema often developed. In the present study, the effect of IGF-I on cutaneous capillary permeability and microvascular skin blood flow was investigated using fluorescence videomicroscopy and laser Doppler fluxmetry. Transcapillary diffusion of intravenously injected sodium fluorescein (NaF) was quantitated by videodensitometry in terms of fluorescent light intensities (FLIs) 5, 10, 20, 30, 60, 120, 180 and 300 s after the first appearance of the dye. Laser Doppler fluxmetry was performed at rest (LDFrest) and during postocclusive reactive hyperemia (LDFpeak)· Eight healthy subjects (3 women, 5 men; mean age 28 years, range 24-30 years) were investigated. The sensing site was the skin on the right dorsal wrist. Measurements were performed after 4 days of subcutaneous infusion of 0.9% saline (control) and of IGF-I. Mean values for the FLI were significantly higher after IGF-I than after saline infusion (p < 0.05), when the FLIs were expressed in arbitrary units. As percentages of their individual maxima, the differences were significant (p = 0.05) after 60s (23.6 ± 6.6% with NaCl and 31.9 ± 7.6% with IGF-I). LDFrest and LDFpeak tended to be higher after IGF-I treatment without achieving statistical significance (p = 0.176). The mean appearance time of the dye after injection was significantly shorter (p = 0.016) in the IGF-I group than in the control group (32.0 ± 8.4 s with IGF-I, 42.4 ± 8.3 s with NaCl). In conclusion, IGF-I does not increase skin blood flow, but significantly increases transcapillary diffusion of NaF. Both mechanisms may be responsible for the development of e

ISSN:0167-6865    

DOI:10.1159/000178943

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

During surgery of limbs tourniquet up to a maximum of 2 h is frequently applied which may cause ischemia/reperfusion injury (IRI). During this condition the presence of vasomotion may have consequences for the perfusion and nutritive state of the tissues. We used a noninvasive plethysmographic method to investigate periodic changes in limb circumference (volumotion) in healthy male patients (n = 24) undergoing surgery for knee injury. To facilitate surgery a tourniquet was applied to the thigh, which caused an IRI of the leg. Results are given as mean of all values ± SEM. Immediately after tourniquet release (duration 57.75 ± 5.19 min) blood lactate levels in the femoral vein increased significantly from 1.40 ± 0.08 to 2.59 ± 0.20 mmol/l (p < 0.001) and pH fell from 7.39 ± 0.01 to7.32 ± 0.01 (p < 0.01).Preoρeratively 10 out of 24 patients (42%) showed signs of volumotion on the injured leg with a periodicity ranging from 0.8 to 6.9 cycles/min, whereas none showed volumotion in the control leg (p < 0.001). In the second measurement, taken after surgery and reperfusion while peripheral sympathetic nerves were blocked, 7 out of 18 patients (39%) showed volumotion on the injured leg and 0 on the control leg (p < 0.004). 6 h after IRI, volumotion was observed in 11 out of 17 patients (65%) on the injured leg and in 1 patient (6%) on the control leg (p < 0.001). The mean volume change in the patients with volumotion on the injured leg was 0.057 ± 0.007 ml/100 ml tissues. Raising venous pressure to 55 mm Hg did neither significantly change the amplitude of volumotion (0.055 ± 0.008 ml/l00 ml tissue, p = 0.80), nor the incidence of volumotion. There was no significant difference in the incidence of volumotion in the injured leg during the three measurements. We observed periodic changes in limb circumference mainly in the injured leg; it therefore seems unlikely that these events are directly related to central hemodynamic changes. We suggest that volumotion reflects slow wave vasomotion possibly resulting from a change in sympathetic or parasympathetic activity in response to both the knee injury and the ischemia reperfusion injury. These events may originate either from arterioles or arteries in the leg or from cyclic coordinated vascular smooth muscle events, which may be either venous or arterial i

ISSN:0167-6865    

DOI:10.1159/000178944

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Inflammation activates leukocytes causing the release of agents that disrupt the endothelial barrier to such an extent that retention of plasma protein is impaired. This phenomenon can be observed using microvascular methods in which ischemia-reperfusion-induced inflammation-like condition are analyzed in terms of the increased adherence of leukocytes to the venular endothelium. Pretreatment with Daflon 500 mg, a purified, micronized, flavonoid fraction consisting of 90% diosmin and 10% hesperidin, prior to the induction of 4 h of tourniquet ischemia significantly lowers the number of adherent leukocytes. This observation is linked to the protective effect of flavonoids in the treatment of edema, as decreased activation is also associated with a decreased platelet and complement system activation, leading to a lowered release of histamine and decreased leukocyte-dependent endothelial damage. It is proposed that attenuation of leukocyte adherence during ischemia-reperfusion is evidence of the protective endothelial effect of Daflon 500 mg and its ability to control edema in clinical situation.

ISSN:0167-6865    

DOI:10.1159/000179090

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Blackfoot disease (BFD) is an endemic peripheral arterial disease confined to the southwestern coast of Taiwan. The cause of the disease has been ascribed to the high-arsenic artesian well water. The purpose of this study was to examine the possible association between the long-term exposure to artesian well water and the change in microvascular circulation in the absence of peripheral arterial insufficiency. A total of 45 men living in the BFD-hyperendemic villages and another 51 age- sex- body-mass index-matched men who lived in nonendemic villages nearby were recruited into this study. All subjects were free from peripheral vascular disease (resting ankle-brachial index > 1.00), clinical claudication, cigarette smoking, diabetes mellitus, hypertension, ischemic heart disease, cerebral infarction and obesity. Laser Doppler flowmetry was used to measure the peripheral microcirculation on the big toes both at 36 °C (basal perfusion, Pb) and after a hyperthermic test at 42 °C (Ph). The time required to reach Ph (T), and the average rate (R) of increase from Pb to Ph measured by (Ph -Pb)/T were also calculated. Results showed that those living in the BFD-hyperendemic area had a lower Pb [32.8 ± 6.0 perfusion units (PU) vs. 67.0 ± 4.3 PU, p < 0.001], a lower Ph (193.2 ± 13.6 vs. 231.1 ± 6.3 PU, p < 0.005), a longer T (3.04 ± 0.19 vs. 1.31 ± 0.08 min, p < 0.001) and a slower rate of increase from Pb to Ph (48.0 ± 4.8 vs. 76.2 ± 5.4 PU/min, p < 0.001). The results remained similar after excluding 13 subjects with minor arterial insufficiency defined as a postexercise ankle-brachial index < 0.90. We conclude that deficits in cutaneous microcirculation of the toes were demonstrated among seemingly normal subjects living in the BFD end

ISSN:0167-6865    

DOI:10.1159/000178945

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Daflon 500 mg1 (S 5682) is a purified, micronized, flavonoid fraction containing 90% diosmin and 10% hesperidin, which is currently used to treat chronic venous insufficiency and haemorrhoidal disease. In the present study, the effects of Daflon 500 mg on increased microvascular permeability induced by histamine, bradykinin and leukotriene B4 (LTB4) were investigated by intravital microscopy in the hamster cheek pouch preparation. Daflon 500 mg, suspended in 10% lactose solution, or vehicle (10% lactose) was administered orally to male hamsters for 10 days at a dose of 20 mg/kg/day (10 mg/kg twice daily). Fluorescein iso-thiocyanate-labeled dextran 150 was given intravenously, 30 min after completion of the cheek pouch preparation. Histamine, 2 µmol/l, bradykinin, 0.1 µmol/l, and LTB4, 0.01 µmol/l, applied topically for 5 min increased the number of fluorescent vascular leakage sites in postcapillary venules. The maximum number of leaky sites per cm2 in the prepared area that occurred 5 min after the beginning of each topical application was quantified by UV light microscopy. In comparison with vehicle, Daflon 500 mg significantly inhibited the macromolecular permeability-increasing effect of histamine (343.5 ± 22.3 vs. 207.5 ± 32.0; p < 0.01), bradykinin (345.2 ± 19.0 vs. 206.2 ± 21.6; p < 0.01) and LTB4 (353.3 ± 27.5 vs. 242.7 ± 33.6; p < 0.05). These results demonstrate that oral administration of Daflon 500 mg for 10 days at 20 mg/kg body weight/day has a protective effect against leakage of macromolecules after application of permeability-increasing substances in the cheek pouch microvasculature. These data, which illustrate the inhibitory effect of a clinically relevant dose of Daflon 500 mg on the inflammatory processes induced in this in vivo model of microcirculation, may serve as a rational basis to explain the clinical efficacy of Daflo

ISSN:0167-6865    

DOI:10.1159/000179091

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effect of Daflon 500 mg1, purified, micronized flavonoid fraction (90% diosmin, 10% hesperidin) was studied on stroke index, levels of free radicals and electroretinography in the gerbil after ischemia-reperfusion injury. The drug was administered orally at doses of 200, 100 and 50 mg/kg, for 6 days before left carotid occlusion. Daflon 500 mg significantly reversed the increase of stroke index only at the dose of 100 mg/kg and significantly decreased levels of hydroxyl free radicals at all 3 doses with a maximum effectiveness for the dose of 100 mg/kg. Amplitude and latency of the b wave were disturbed after ischemia-reperfusion insult. Daflon 500 mg, 100 mg/kg for 6 days, significantly reversed these modifications. In conclusion, Daflon 500 mg could interact with hydroxyl free radicals, which have a deleterious effect in ischemic tissues, particularly in the retina.

ISSN:0167-6865    

DOI:10.1159/000179092

出版商:S. Karger AG    

年代:1995

数据来源: Karger