Arteriolar Flow Research Articles

Arteriolar Blood Flow Pulsatility in a Patient Before and After Implantation of an Axial Flow Pump

In a patient with end stage ischemic heart failure scheduled for implantation of an axial flow pump small arteriolar flow pattern was recorded using a novel intravital microscope. Preoperative arteriolar blood flow velocity was highly pulsatile, ranging from about 7 to 16 mm per second in a 12.8 microm diameter arteriole. After implantation of the pump, this pulsatility was abrogated and arteriolar blood flow velocity changed instantaneously with changes in pump speed (eg, 2 mm/s at 5,000 rpm vs 3.5 mm/s at 8,000 rpm in an 8.9 microm diameter arteriole). This lack of flow velocity oscillations may have profound long-term effects on shear stress regulated arteriolar remodeling.

Polyethylene glycol and a novel developed polyethylene glycol-nitric oxide normalize arteriolar response and oxidative stress in ischemia-reperfusion

Polyethylene glycol (PEG) has been shown to repair cell membranes and, thus, inhibit free radical production in in vitro and in vivo models. We hypothesized that PEG and newly developed organic nitrate forms of PEG (PEG-NO) could repair endothelial dysfunction in ischemia-reperfusion (I/R) injury in the hamster cheek pouch visualized by intravital fluorescent microscopy. After treatments, we evaluated diameter and RBC velocity and flow in arterioles, as well as lipid peroxides in the systemic blood, perfused capillary length, vascular permeability, leukocyte adhesion, and amount of von Willebrand factor (vWF) in the blood after I/R injury. A control group was treated with 5,000- or 10,000-Da PEG, and three groups were treated with PG1 (1 NO molecule covalently bound to PEG, 5,170 Da), PG8 (8 NO molecules covalently bound to PEG, 11,860 Da), and PG16 (16 NO molecules covalently bound to PEG, 14,060 Da). All animals received 0.5 mg/0.5 ml. Lipid peroxides increased at 5 and 15 min of reperfusion, whereas diameter, RBC velocity, and blood flow decreased in arterioles after I/R injury. Vascular permeability, leukocyte adhesion, and vWF increased significantly. PEG and PG1 attenuated lipid peroxides and vasoconstriction during reperfusion and decreased leukocyte adhesion and vascular permeability. PG8 maintained lipid peroxides at normal levels, increased arteriolar diameter, flow, and perfused capillary length, and decreased vWF level and leukocyte adhesion (P < 0.05). PG16 was less effective than PG1 and PG8. In conclusion, PEG-NO shows promise as a compound that protects microvascular perfusion by normalizing the balance between NO level and excessive production of free radicals in endothelial cells during I/R injury.

Arteriolar vasoconstrictive response: comparing the effects of arginine vasopressin and norepinephrine

IntroductionThis study was designed to examine differences in the arteriolar vasoconstrictive response between arginine vasopressin (AVP) and norepinephrine (NE) on the microcirculatory level in the hamster window chamber model in unanesthetized, normotonic hamsters using intravital microscopy. It is known from patients with advanced vasodilatory shock that AVP exerts strong additional vasoconstriction when incremental dosage increases of NE have no further effect on mean arterial blood pressure (MAP).MethodsIn a prospective controlled experimental study, eleven awake, male golden Syrian hamsters were instrumented with a viewing window inserted into the dorsal skinfold. NE (2 μg/kg/minute) and AVP (0.0001 IU/kg/minute, equivalent to 4 IU/h in a 70 kg patient) were continuously infused to achieve a similar increase in MAP. According to their position within the arteriolar network, arterioles were grouped into five types: A0 (branch off small artery) to A4 (branch off A3 arteriole).ResultsReduction of arteriolar diameter (NE, -31 ± 12% versus AVP, -49 ± 7%; p = 0.002), cross sectional area (NE, -49 ± 17% versus AVP, -73 ± 7%; p = 0.002), and arteriolar blood flow (NE, -62 ± 13% versus AVP, -80 ± 6%; p = 0.004) in A0 arterioles was significantly more pronounced in AVP animals. There was no difference in red blood cell velocities in A0 arterioles between groups. The reduction of diameter, cross sectional area, red blood cell velocity, and arteriolar blood flow in A1 to A4 arterioles was comparable in AVP and NE animals.ConclusionWithin the microvascular network, AVP exerted significantly stronger vasoconstriction on large A0 arterioles than NE under physiological conditions. This observation may partly explain why AVP is such a potent vasopressor hormone and can increase systemic vascular resistance even in advanced vasodilatory shock unresponsive to increases in standard catecholamine therapy.

Endothelin-1 in Human Intestine Resected for Necrotizing Enterocolitis

We asked if the tissue concentration of the potent vasoconstrictor endothelin-1 (ET-1) is greater in areas of human preterm intestine that demonstrate histologic evidence of necrotizing enterocolitis (NEC) when compared with relatively healthy areas within the same resection specimen. We then evaluated if ET-1 participates in hemodynamic regulation within intestinal subserosal arterioles harvested from portions of human preterm intestine that demonstrate NEC. Human preterm intestine resected for NEC was divided into three zones based on proximity to the perforation (zone 1 most proximal, zone 3 most distal). Histologic evidence of NEC was determined in each zone (normal = 0, advanced necrosis = 6). The tissue concentration of ET-1 was determined by enzyme-linked immunosorbent assay within intestinal homogenates prepared from each zone. Arteriolar hemodynamics were determined in vitro on subserosal arterioles harvested from different zones. Arteriolar flow rate, diameter, and resistance were determined at pressure gradients (DeltaP) of 20 and 40 mmHg under control conditions and again after blockade of endothelin ET A receptors with BQ610 (10 -9 mol/L). The tissue concentration of ET-1 (pg/mg protein) and histologic score in the three zones were: zone 1: 84 +/- 14, 5.5 +/- 0.3; zone 2: 99 +/- 12, 4.7 +/- 0.4, and zone 3: 33 +/- 9, 0.8 +/- 0.6, respectively (M +/- SD, n = 10 resection specimens, P < .05, zone 3 vs zones 1 and 2). Zone 2 arterioles demonstrated significantly lower flow rate and diameter and increased resistance under control conditions than zone 3 arterioles when DeltaP was either 20 or 40 mmHg (n = 7, P < .05). Treatment with BQ610 had no effect on zone 3 arterioles but significantly vasodilated zone 2 arterioles, increasing flow rate and vessel diameter, and decreasing vascular resistance (n = 7, P < .05). The tissue concentration of ET-1 is greater in human preterm intestine that demonstrates histologic evidence of NEC. Arterioles harvested from intestine exhibiting histologic evidence of NEC demonstrate vasoconstriction when compared with arterioles from relatively healthy intestine in the same resection specimen. This vasoconstriction was reversed by blockade of endothelin ET A receptors.

Velocity Profiles of Pulsatile Blood Flow in Arterioles with Bifurcation and Confluence in Rat Mesnetery Measured by Particle Image Velocimetry

Velocity Profiles of Pulsatile Blood Flow in Arterioles with Bifurcation and Confluence in Rat Mesnetery Measured by Particle Image Velocimetry

Increased tissue PO2 and decreased O2 delivery and consumption after 80% exchange transfusion with polymerized hemoglobin.

The O2-carrying blood substitute based on polymerized bovine hemoglobin (PBH) was used to determine efficacy in maintaining tissue Po2 after an 80% isovolemic blood exchange leading to a hematocrit of 19% [5.4 g Hb/dl from red blood cells (RBCs) and 6.3 g Hb/dl from PBH]. Effects were studied in terms of O2 delivery, O2 extraction, and tissue Po2 at the microcirculatory level at 1, 12, and 24 h after exchange transfusion in awake hamsters prepared with a window chamber model. At 1 h after exchange, arteriolar and venular diameters were decreased compared with baseline. Arteriolar diameter did not fully recover at 12 h after exchange, but venular diameter returned to normal. At 24 h after exchange, arteriolar and venular diameters were not different from baseline. Combining diameter and flow velocity data allowed us to calculate arteriolar and venular flows. At 1 h after exchange, arteriolar and venular flow was reduced compared with baseline. Arteriolar flow was lower at 12 h after exchange and recovered after 24 h. The number of capillaries with RBC passage [functional capillary density (FCD)] at 1 h after exchange with PBH was significantly lower than baseline. FCD remained decreased at 12 h; at 24 h after exchange transfusion, FCD was fully recovered. Tissue Po2 was maximal at 1 h after exchange and decreased progressively at 12 and 24 h after exchange. O2 release to the tissue was minimal at 1 h and increased at 12 and 24 h after exchange. These results suggest the impairment of tissue O2 metabolism after introduction of PBH into the circulation, which is mitigated as PBH concentration declines.

Influence of wavelength on response to laser photothermolysis of blood vessels: implications for port wine stain laser therapy.

Treatment of port wine stains (PWS) by photothermolysis can be improved by optimizing laser parameters. We have studied the all-important role of wavelength (lambda) by performing pulsed laser photothermolysis in the vasculature of the chick chorioallantoic membrane (CAM) assay. The CAM contains an extensive microvascular network ranging from capillaries with diameter D < 20 microm to blood vessels of D approximately 120 microm. The CAM assay enables observation and real-time video documentation of blood flow in pre-capillary arterioles (A) and post-capillary venules (V). The ScleroPlus trade mark laser (Candela Corp., Wayland, MA) has a smooth output over its fixed 1.5 ms pulse duration and allows the operator to vary several treatment parameters such as wavelength, spot size, and energy. Blood vessels in the CAM were irradiated at two clinically relevant wavelengths, lambda = 587 or 597 nm, constant spot size (7 mm), and at different exposures (E = 5-12 J/cm(2)). Threshold exposure (E(th)) (at which non-reversible damage occurred) were 5 J/cm(2) at 587 nm and 8 J/cm(2) at 597 nm. Mathematical modeling was developed to interpret initial (within 30 seconds) injury of arterioles and venules at both wavelengths as a function of D when varying E. Vessel injury was graded off-line from videotapes. For all combinations of lambda and E, measurable injury was evident within 30 seconds of irradiation and maximal damage was reached in less than 10 minutes. Vessel damage was found to depend strongly on lambda. Damage decreased with increasing vessel size. For all D, damage of arterioles was greater than for corresponding venules. Selection of the correct wavelength is crucial for successful laser therapy of hypervascular lesions and, ideally, should be based on knowledge of vessel diameters for a specific PWS lesion and of optical penetration depths in blood. As a general statement, smaller blood vessels (D = 10-60 microm) should be treated using shorter wavelengths such as 585 nm. To ensure deposition of sufficient laser energy, irradiation at 585 nm, characterized by lower optical penetration depth in blood, may be preferable for PWS therapy.

EFFECTS OF AGING AND EXERCISE ON FUNCTION OF SKELETAL MUSCLE ARTERIOLES

Aging reduces in skeletal muscle blood flow capacity. This decrease in flow capacity may be due, in part, to decreased endothelium-dependent vasodilation of the skeletal muscle resistance vasculature. Experimental evidence indicates that age-related loss of endothelial function in the skeletal muscle resistance vasculature is attenuated by exercise training. We have used aged Fischer 344 rats to study endothelium-dependent function of skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles. Endothelium-mediated vasodilation to acetylcholine is reduced in arterioles from soleus but not gastrocnemius muscle of aged rats. Flow-induced vasodilation is reduced with age in arterioles from both soleus and gastrocnemius muscles. Blockade of endothelial nitric oxide synthase indicates that the age-related reduction of acetylcholine- and flow-induced vasodilation in soleus muscle results from a reduction in nitric oxide mediated dilation. The impairment of flow-induced vasodilation in gastrocnemius muscle arterioles does not occur because of a diminution in a nitroxidergic mechanism. In contrast, exercise training ameliorates endothelial responsiveness to flow and acetylcholine in arterioles from both soleus and gastrocnemius muscles. Training restores dilation to flow and acetylcholine through enhancement of a nitric oxide mechanism in both soleus and gastrocnemius muscle arterioles. Thus, our current data indicate that aging-induced impairment of endothelial function is muscle specific. In contrast, exercise training restores endothelial function through augmentation of nitric oxide function in arterioles from both soleus and gastrocnemius muscles.

Advective transport of nitric oxide in a mathematical model of the afferent arteriole.

Endothelium-derived nitric oxide (NO) is thought to be short-lived in blood because of rapid removal from plasma, mainly by binding to Hb. The extent to which removal limits NO advection is unclear, especially for blood flow in the renal afferent arteriole (AA), which has a transit time of 3-30 ms. A mathematical model of AA fluid dynamics and myogenic response that includes NO diffusion, advection, degradation, and vasorelaxant action was used to estimate NO advective transport. Model simulations indicate that advective transport of locally produced NO is sufficient to yield physiologically significant NO concentrations along much of the AA. Advective transport is insensitive to NO scavenging by Hb because the NO-Hb binding rate is slow relative to AA transit time. Hence, plasma NO concentration near the vessel wall is influenced by both diffusion from endothelial cells and advection from upstream sites. Simulations also suggest that NO advection may constitute a mechanism to stabilize arteriolar flow in response to a localized vasoconstriction accompanied by enhanced NO release.

Lack of Nitric Oxide Mediation of Flow-Dependent Arteriolar Dilation in Type I Diabetes Is Restored by Sepiapterin

The mechanisms leading to microangiopathy in diabetes mellitus have still not been clearly elucidated. We hypothesized that type I diabetes mellitus affects the endothelium and alters flow-dependent dilation of arterioles, an important mechanism involved in local regulation of blood flow. Isolated, pressurized gracilis muscle arterioles (inside diameter approximately 150 µm at 80 mm Hg) from rats with streptozotocin (STZ)-induced diabetes mellitus exhibited reduced dilations induced by increases in perfusate flow compared to those of normal rats (plasma glucose: 25.7 ± 0.7 vs. 6.4 ± 0.5 mmol/l; maximum increase in diameter: 15 ± 4 vs. 31± 3 µm, p < 0.05). In control arterioles, both nitric oxide (NO) and prostaglandins mediated the flow-dependent dilation, whereas flow-induced dilations of diabetic arterioles were unaffected by N^ω-nitro-L-arginine methyl ester (L-NAME) and were abolished by indomethacin. Sepiapterin – precursor of the endothelial NO synthase (eNOS) cofactor tetrahydrobiopterin (BH₄) – restored the L-NAME-sensitive portion of flow-dependent dilations of diabetic arterioles. Furthermore, depletion of BH₄ by 2,4-diamino-6-hydroxypyrimidine (DAHP) in control arterioles also resulted in reduced flow-dependent dilations, which were restored by intraluminal sepiapterin [but not with superoxide dismutase (SOD) plus catalase (CAT) (SOD+CAT)] and then could be inhibited by L-NAME. Dilations induced by the NO donor sodium nitroprusside (SNP) were unaffected by L-NAME in diabetes mellitus arterioles or when eNOS was activated by intraluminal flow in DAHP-treated arterioles (with or without SOD+CAT). In contrast, pyrogallol (known to produce reactive oxygen species) substantially reduced acetylcholine- and SNP-induced dilation in a SOD+CAT-reversible manner. Collectively, these findings suggest that in diabetic arterioles, due to the reduced bioavailability of BH₄, the synthesis of NO by eNOS is limited, resulting in a reduced flow-induced dilation, a mechanism that may also be responsible for the development of diabetic microangiopathy and exacerbation of other vascular diseases.

Arteriolar Flow Recruitment with Vitronectin Receptor Stimulation Linked to Remote Wall Shear Stress

Our purpose was to investigate the hemodynamic mechanism of flow recruitment within arteriolar networks as stimulated by the vitronectin receptor. Since remote stimulation of the vitronectin receptor initiates a flow-mediated dilation, we tested whether the response could be mimicked by exogenous NO. Arteriolar diameter, red blood cell flux, and velocity were measured in terminal branch arterioles arising from a central feed (8–10 μm) arteriole (together previously defined as an arteriolar network) in the cheek pouch tissue of anesthetized hamsters ( n = 29, pentobarbital 70 mg/kg). Terminal branch arterioles were stimulated (micropipette, 10 s) with 10 μg/ml LM609 (agonist, vitronectin receptor), 10 −4 M nitroprusside (SNP), or control. The same amount of flow was recruited into the network by applying LM609 or SNP to only one branch of the network; however, flow distribution differed. With LM609, all recruited flow went directly to the branch that was stimulated. With SNP, recruited flow was distributed evenly throughout the network, no matter where the stimulus was applied. Thus, flow-mediated dilation induced by vitronectin receptor stimulation initiates a robust flow recruitment response, directing flow to the stimulus flow path. In contrast, NO alone initiates flow recruitment to the entire network, along multiple parallel flow paths.

Effects of estrogen on the microcirculation and thrombus formation in pial vessels of the rat

Female Wistar/ST rats were ovariectomized at 14 weeks of age. Ethynylestradiol, 17β-estradiol (E 2β), medroxyprogesterone acetate (MPA) and 4-hydroxy-tamoxifen were administered subcutaneously every other day for 3 weeks from 1 week after ovariectomy. Closed cranial windows were created and the thrombotic potential was measured using the He–Ne laser-induced thrombosis method. The mean red cell velocity was measured with a fiber-optic laser-Doppler anemometer microscope. The plasma concentrations of nitrite/nitrate (nitric oxide (NO) metabolites) were determined using the Griess reagent. The diameters mean red cell velocity and blood flow in pial arterioles were reduced after ovariectomy, however, the thrombotic tendency was increased after ovariectomy. These parameters were reversed after E 2β treatment. In contrast, MPA had the opposite effects. The plasma concentrations of nitrite/nitrate were significantly decreased following ovariectomy and were increased after treatment with E 2β. MPA did not affect the concentration of NO metabolites. These results strongly indicated that estrogen in the female rat mediated beneficial effects on the cerebral microcirculation and moderated cerebral thrombotic mechanisms by enhancing the plasma levels of NO. The findings suggest that increased blood flow and inhibition of thrombosis might contribute to the prevention of cerebrovascular disease in a normal female.

Real-time microcirculatory changes due to spreading depression under focal ischemia

Laser-scanning confocal fluorescence microscopy was used to investigate microcirculatory influences of spreading depression (SD)-like depolarizations elicited by occlusion of the rat middle cerebral artery (MCA). Six rats underwent halothane anesthesia and mechanical ventilation. A closed cranial window was implanted over their frontoparietal cortex. They were placed under a Biorad Viewscan confocal microscope and intravenously given fluorescein isothiocyanate (FITC)-Dextran and FITC-labeled erythrocytes. The capillaries were visualized down to 200 μm below the brain surface and the images were video recorded (50/s). The MCA was occluded under the microscope using an intraluminal remotely controlled method and the reperfusion was induced 2 h later. Furthermore, the brains were histologically examined 24 h later. Under ischemia, the erythrocyte velocity through the capillaries was depressed by 35% and venous blood became highly sluggish. The arteriole diameter did not change significantly, however, the direction of arteriolar blood flow was episodically and transiently reversed. During spontaneous SD-like depolarization, the arteriole diameter significantly increased (+19% vs. MCAO) while capillary erythrocyte velocity was further depressed by 15%. This decrease in velocity was more pronounced (25%) when depolarization were associated with transient reversal of arteriolar flow. Following reperfusion, microcirculatory variables rapidly returned to the baseline. All rats exhibited infarcts 24 h after the occlusion. These results indicate that SD-like depolarizations have an adverse influence on penumbral microcirculation, i.e., a reduction in capillary perfusion by erythrocytes, despite arteriolar dilatation.

Hemodynamic effects of peritoneal dialysis solutions on the rat peritoneal membrane: role of acidity, buffer choice, glucose concentration, and glucose degradation products.

Conventional peritoneal dialysis fluids (PDF) are unphysiologic because of their hypertonicity, high glucose and lactate concentrations, acidic pH, and presence of glucose degradation products (GDP). Long-term exposure to conventional PDF may cause functional and structural alterations of the peritoneal membrane. New PDF have a neutral pH, a low GDP content, and contain bicarbonate or lactate as the buffer. Intravital microscopy was used to analyze the vasoactive effects of conventional and new PDF on the rat peritoneal membrane. A conventional, acidic pH, lactate-buffered 4.25% glucose PDF induced maximal vasodilation of mesenteric arteries, resulting in a doubling of the arteriolar flow and a 20% increase of the perfused capillary length per area. The hemodynamic effects of conventional PDF were similar after pH-adjustment with NaOH, indicating that acidity per se is not essential for the changes. Superfusion by a pH-neutral, lactate-buffered PDF with low GDP content caused only a transient arterial vasodilation despite continuous exposure, with a commensurate effect on arteriolar flow and capillary recruitment. Application of a pH-neutral, bicarbonate-buffered PDF with low GDP content did not affect the hemodynamic parameters. Resterilization of the bicarbonate solution increased GDP levels and completely restored the vasodilatory capacity. The corresponding 1.5% glucose PDF induced similar but less pronounced changes. Conventional PDF have important vasoactive effects on the peritoneal circulation, mainly because of the presence of GDP and transiently because of high lactate concentrations. Capillary recruitment may increase effective peritoneal vascular surface area. In addition, chronic vasodilation may induce structural adaptations in the blood vessel wall, contributing to vascular sclerosis. PDF with reduced GDP content induce no major hemodynamic effects and may thus have the potential to better preserve peritoneal vascular integrity.

Vascular response to laser photothermolysis as a function of pulse duration, vessel type, and diameter: Implications for port wine stain laser therapy

Background and Objective Treatment of port wine stains (PWS) by photothermolysis can be improved by optimizing laser parameters on an individual patient basis. We have studied the critical role of pulse duration (tp) on the treatment efficacy. Study Design/Materials and Methods The V-beam laser (Candela) allowed changing tp over user-specified discrete values between 1.5 and 40 milliseconds by delivering a series of 100 microsecond spikes. For the 1.5 and 3 millisecond pulses, three spikes were observed at intervals tp/2 and for tp ≥ 6 milliseconds, four spikes separated by tp/3. The ScleroPlus laser (Candela) has a smooth output over its fixed 1.5 milliseconds duration. Blood vessels in the chick chorioallantoic membrane (CAM) were irradiated at fixed wavelength (595 nm), spot size (7 mm), radiant exposure (15 Jcm−2), and at variable tp. The CAM contains an extensive microvascular network ranging from capillaries with diameter D < 30 μm to blood vessels of D ≈ 120 μm. The CAM assay allows real-time video documentation, and observation of blood flow in pre-capillary arterioles (A) and post-capillary venules (V). Vessel injury was graded from recorded videotapes. Mathematical modeling was developed to interpret results of vessel injury when varying tp and D. A modified thermal relaxation time was introduced to calculate vessel wall temperature following laser exposure. Results Arterioles. For increasing tp, overall damage was found to decrease. For fixed tp, damage decreased with vessel size. Venules. For all D, damage was smaller than for corresponding arterioles. There was no dependence of damage on tp. For given tp, no variation of damage with D was observed. Photothermolysis due to spiked (V-beam) vs. smooth (Scleroplus) delivery of laser energy at fixed tp (1.5 milliseconds), showed similar vessel injuries for al values of D (P>0.05). Conclusions The difference between initial arteriole and venule damage could be explained by the threefold higher absorption coefficient at 595 nm in (oxygen-poor!) arterioles. In human patients, PWS consist of ectatic venules (characterized by higher absorption), so that these considerations favor the use of 595-nm irradiation for laser photothermolysis. For optimal treatment of PWS it is proposed that tp be between 0.1 and 1.5 milliseconds. This is based on a modified relaxation time τd′, defined as the time required for heat conduction into the full thickness of the vessel wall, which is assumed to have a thickness ΔD ≈ 0.1D. The corresponding τd′ will be a factor of about six smaller than given in the literature. For vessels with D between 30 and 300 μm, τd′ ranges from 0.1 to 1.5 milliseconds. Lasers Surg. Med. 30:160–169, 2002. © 2002 Wiley-Liss, Inc.

Cerebral Thrombosis And Microcirculation Of The Rat During The Oestrous Cycle And After Ovariectomy

1. The effects of oestrogen on thrombogenesis and the cerebral microcirculation of the female rat were studied during the oestrous cycle and after ovariectomy. 2. Serum levels of oestradiol (E2) and plasma concentrations of nitric oxide (NO) metabolites were significantly greater at pro-oestrus than at dioestrus. Blood vessel diameter, mean red cell velocity, wall shear rate and blood flow at pro-oestrus were significantly higher than at dioestrus. Thrombotic tendency, assessed using a He-Ne laser-induced thrombosis model, was significantly decreased at pro-oestrus compared with dioestrus. 3. The long-term deprivation of oestrogen by ovariectomy significantly depressed serum levels of E2 and plasma concentrations of NO metabolites. Thrombotic tendency was significantly increased 4 weeks after ovariectomy. Vessel diameter, mean red cell velocity, wall shear rate and blood flow in pial arterioles were significantly reduced after ovariectomy. 4. Exogenous administration of oestrogen (17 beta-oestradiol) after surgery reversed the increased thrombotic tendency mediated by ovariectomy. 5. These results strongly indicate that oestrogen mediates beneficial effects on the cerebral microcirculation and moderates cerebral thrombotic mechanisms in the female rat.

Possibility of linear dependence between vascular wall tension and blood flow in precortical arterioles.

Intravital microscopy was used to determine the diameter and length of pial cortical arterioles in rat brain. Mathematical model yielded a formula showing that regulation of arteriolar wall tension results in autoregulation of the blood flow.

The pathogenesis of clostridial myonecrosis

These pieces of evidence can be assimilated into a molecular and cellular model of pathogenesis which is initiated by direct toxin effects upon venous capillary endothelial cell function, leading to expression of pro-inflammatory mediators and adhesion molecules, and initiation of platelet aggregation. Toxin-induced hyperadhesion of leukocytes (see above section) with enhanced respiratory burst activity (due to toxins directly or to toxin-induced IL-8 or PAF synthesis by host cells) and toxin-induced chemotaxis deficits could result in neutrophil-mediated vascular injury. Direct toxin-induced cytopathic effects on EC may also contribute to vascular abnormalities associated with gas gangrene. Over prolonged incubation periods, PLC at sublytic concentrations causes EC to undergo profound shape changes similar to those described following prolonged TNF or interferon gamma exposure. In vivo, conversion of EC to this fibroblastoid morphology could contribute to the localized vascular leakage and massive swelling observed clinically with this infection. Similarly, the direct cytotoxicity of PFO could disrupt endothelial integrity and contribute to progressive edema both locally and systemically. Thus, via the mechanisms outlined above, both PLC and PFO may cause local, regional and systemic vascular dysfunction. For instance, local absorption of exotoxins within the capillary beds could affect the physiological function of the endothelium lining the postcapillary venules, resulting in impairment of phagocyte delivery at the site of infection. Toxin-induced endothelial dysfunction and microvascular injury could also cause loss of albumin, electrolytes, and water into the interstitial space resulting in marked localized edema. These events, combined with intravascular platelet aggregation and leukostasis, would increase venous pressures and favor further loss of fluid and protein in the distal capillary bed. Ultimately, a reduced arteriolar flow would impair oxygen delivery thereby attenuating phagocyte oxidative killing and facilitating anaerobic glycolysis of muscle tissue. The resultant drop in tissue pH, together with reduced oxygen tension, might further decrease the redox potential of viable tissues to a point suitable for growth of this anaerobic bacillus. As infection progresses and additional toxin is absorbed, larger venous channels would become affected, causing regional vascular compromise, increased compartment pressures and rapid anoxic necrosis of large muscle groups. When toxins reach arterial circulation, systemic shock and multiorgan failure rapidly ensue, and death is common.

Abstracts of literature

Abstracts of literature

Leukocyte-endothelium-interaction in pial vessels following global, cerebral ischaemia.

Investigations have shown an increase of leukocyte-endothelium-interaction in a variety of organs following an ischaemic insult. To elucidate the role of leukocyte-endothelium-interaction following global, cerebral ischaemia the present study was performed. Global, cerebral ischaemia was induced for twenty minutes by four-vessel-occlusion (PULSINELLI). Leukocyte-endothelium-interaction was studied in the cerebral microcirculation using a rat closed cranial window and intravital microscopy. Leukocytes were stained intravenously using rhodamine 6G. Diameters of pial vessels, leukocyte centreline velocity and number of rolling or adhering leukocytes were determined off-line up to 2 h following global cerebral ischaemia. To confirm these results immunohistochemistry of the brain was performed. Four-vessel-occlusion induced an iso-electric EEG, venular stasis and minimal rest flow in arterioles. Reperfusion yielded a significant increase of the arteriolar (p < 0.001) and a smaller increase of the venular diameters (p < 0.01). Up to 2 h after ischaemia no significant increase of the number of rolling or adhering leukocytes was measured which was confirmed by immunohistochemistry. In contrast to other studies, in particular regarding focal cerebral ischaemia, an increase of leukocyte-endothelium-interaction in rat brain following 20 min of global cerebral ischaemia was not observed despite histological evidence of ischaemic damage. Thus in our model leukocytes seem not to contribute to the brain damage following global ischaemia.