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PubMed1997

Activation of thromboxane receptors and the induction of vasomotion in the hamster cheek pouch microcirculation.

1. The present study was designed to investigate a possible role of thromboxane A2 (TXA2) on arteriolar vasomotion (spontaneous rhythmic variations of the vessel diameter). Therefore the microcirculatory effects of the thromboxane-receptor (TP-receptor) agonist, U 46619, as well as the effects of the TP-receptor antagonists S 17733 and Bay U3405 were evaluated in the hamster cheek pouch microcirculation. For comparison some effects of angiotensin II were also investigated. 2. For microcirculatory measurements, the cheek pouch preparation was placed under an intravital microscope coupled to a closed circuit TV system. The TV monitor display was used to obtain arteriolar internal diameter measurements by means of an image shearing device. 3. Superfusion (0.1 nM to 1 microM) or bolus application (1 pmol to 10 nmol) of U 46619 concentration- or dose-dependently decreased the arteriolar diameter and induced vasomotion in arterioles with a mean initial diameter of 24+/-2 microm. Both the vasoconstriction and the vasomotion induced by U 46619 were inhibited by the TP-receptor antagonists S 17733 (100 mg kg(-1), i.v.) and Bay U3405 (10 mg kg(-1), i.v.). 4. Bolus applications of angiotensin II (0.1 pmol to 1 nmol) induced transient vasoconstriction followed by vasodilatation in the cheek pouch arterioles. The dilatation but not the constriction, was sensitive to treatment with the NO-synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG; 100 microM). Angiotensin II did not induce vasomotion in control conditions or in the presence of L-NOARG. 5. Bolus application of phenylephrine (10 pmol) induced vasoconstriction but no vasomotion in previously quiescent hamster cheek pouch arterioles. 6. These results indicate that activation of TP-receptors causes vasomotion in the hamster cheek pouch arterioles. These spontaneous rhythmic variations in arteriolar diameter are not observed with equipotent doses of angiotensin II and phenylephrine. Thus, the vasoconstriction by itself cannot explain the occurrence of vasomotion observed with the TP-receptor agonist.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

Histamine-induced biphasic macromolecular leakage in the microcirculation of the conscious hamster: evidence for a delayed nitric oxide-dependent leakage.

1. Late effects (up to 3 h) of intravenously-injected histamine on FITC-dextran extravasation were investigated in the conscious hamster, by use of computer-assisted image analysis of fluorescence distribution in a microscopic window of dorsal skin fold preparations. This analysis allowed measurement of local (skin) and general (all organs) extravasations caused by a bolus injection of histamine (1 mg kg(-1), i.v.) 2. Histamine doses higher than 0.01 mg kg(-1) caused biphasic local and general extravasations. Initial phases developed fully within 15 min (for local) and 60 min (for general) and were followed by late phases beginning 90 min after histamine injection. Although the initial and late phases of histamine-induced extravasations had differential apparent reactivities to the autacoid, all the effects of histamine on the microcirculation (1 mg kg[-1]) were inhibited by pyrilamine (1 mg kg(-1), i.v.) but not by cimetidine (1 mg kg(-1), i.v.). 3. Pretreatment with N(G)-monomethyl-L-arginine (L-NMMA, 30 mg kg(-1), i.v.) or N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg kg(-1), i.v.) did not affect the initial phases but did prevent the late phases of local and general extravasations triggered by 1 mg kg(-1) histamine. The inhibitory effects of L-NAME were reversed by L-arginine (30 mg kg[-1]) but not by D-arginine (30 mg kg[-1]) according to the enantioselectivity of nitric oxide synthase (NOS). A late NO-mediated venular dilatation occurred in response to plasma histamine. 4. A low dose of aminoguanidine (1 mg kg(-1), i.v.), a selective inhibitor of the inducible isoform of NOS (iNOS), mimicked the inhibitory effects of L-NAME on the late phases of histamine-induced macromolecular extravasations and venular dilatation. 5. Pretreatment with dexamethasone (1 mg kg(-1), i.v.) prevented both the initial and late phases of histamine-induced extravasations. Fucoidan (1 or 25 mg kg(-1), i.v.) prevented the late phases without affecting initial phases, consistent with a role for leukocytes adhesion in the development of the late NO-mediated effects of histamine. 6. We conclude that intravenous injection of histamine triggers a biphasic inflammatory cascade via initial activation of H1 receptors which induces a late NO-mediated PMN-dependent extravasation process.

Animals↗

PubMed2004

The fibrinolytic system attenuates vascular tone: effects of tissue plasminogen activator (tPA) and aminocaproic acid on renal microcirculation.

1. The renal medulla is a major source of plasminogen activators (PA), recently shown to induce vasodilation in vitro. Treatment with PA inhibitors has been associated with renal dysfunction, suggesting compromised renal microvasculature. We investigated the impact of the PA inhibitor epsilon amino-caproic acid (EACA) upon vascular tone in vitro, and studied the effect of both tPA and EACA upon intrarenal hemodynamics in vivo. 2. In vitro experiments were carried out in isolated aortic rings and with cultured vascular smooth muscle cells. Studies of renal microcirculation and morphology were conducted in anesthetized Sprague-Dawley rats. 3. In isolated aortic rings, EACA (but not the other inhibitors of the fibrinolytic system PAI-1 or alpha-2 antiplasmin) reduced the half-maximal effective concentration of phenylephrine (PE) required to induce contraction (from 32 nm in control solution to 2 and 0.1 nm at EACA concentrations of 1 and 10 microm, respectively). Using reteplase (retavase) in the same model, we also provide evidence that the vasoactivity of tPA is in part kringle-dependent. In cultured vascular smooth muscle cells, Ca(2+) internalization following PE was enhanced by EACA, and retarded by tPA. 4. In anesthetized rats, EACA (150 mg x kg(-1)) did not affect systemic blood pressure, total renal or cortical blood flow. However, the outer medullary blood flow declined 12+/-2% below the baseline (P<0.03). By contrast, tPA (2 mg x kg(-1)), transiently increased outer medullary blood flow by 8+/-5% (P<0.02). Fibrin microthrombi were not found within the renal microvasculature in EACA-treated animals. 5. In conclusion, both fibrinolytic and antifibrinolytic agents modulate medullary renal blood flow with reciprocal effects of vasodilation (PA) and vasoconstriction (EACA). In vitro studies suggest that these hemodynamic responses are related to direct modulation of the vascular tone.

Aminocaproic Acid↗

PubMed2005

Vascular effects of anandamide and N-acylvanillylamines in the human forearm and skin microcirculation.

The endocannabinoid anandamide is an emerging potential signalling molecule in the cardiovascular system. Anandamide causes vasodilatation, bradycardia and hypotension in animals and has been implicated in the pathophysiology of endotoxic, haemorrhagic and cardiogenic shock, but its vascular effects have not been studied in man. Human forearm blood flow and skin microcirculatory flow were recorded using venous occlusion plethysmography and laser-Doppler perfusion imaging (LDPI), respectively. Each test drug was infused into the brachial artery or applied topically on the skin followed by a standardized pin-prick to disrupt the epidermal barrier. Anandamide failed to affect forearm blood flow when administered intra-arterially at infusion rates of 0.3-300 nmol min(-1). The highest infusion rate led to an anandamide concentration of approximately 1 microM in venous blood as measured by mass spectrometry. Dermal application of anandamide significantly increased skin microcirculatory flow and coapplication of the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine inhibited this effect. The TRPV1 agonists capsaicin, olvanil and arvanil all induced concentration-dependent increases in skin blood flow and burning pain when administered dermally. Coapplication of capsazepine inhibited blood flow and pain responses to all three TRPV1 agonists. This study shows that locally applied anandamide is a vasodilator in the human skin microcirculation. The results are consistent with this lipid being an activator of TRPV1 on primary sensory nerves, but do not support a role for anandamide as a circulating vasoactive hormone in the human forearm vascular bed.

Adult↗

PubMed2006

Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation.

The functional spatial resolution in most of hemodynamics-based functional neuroimaging techniques is limited by the fineness of hemodynamic control with the active vascular beds likely at submillimeter resolution. This study was designed to visualize changes of cerebral blood flow (CBF) at submillimeter spatial scale on the prolonged isoflurane-anesthetized rats model by using laser speckle contrast imaging (LSCI) technique. Recently, this old method has attracted an increasing interest in studies of brain activities under normal and pathophysiologic conditions. However, some paramount assumptions behind this imaging technique have been kept ignored in this field since 1981 firstly proposed by Fercher and Briers. Most recently, these assumptions are claimed as serious mistakes that made LSCI fail to reproducibly and correctly measure blood flow speed. In our study, these issues are also re-examined theoretically and re-evaluated experimentally based on the results from the classical carbon dioxide challenge model. The detailed distribution of CBF responses to the stimulation induced by different levels of carbon dioxide pressure was obtained with tens of micron spatial resolution. The relative CBF images over the exposed cortical area acquired by LSCI were also compared with laser-Doppler measurements. Our results show that these assumptions would not produce any significant errors on investigating changes of blood flow and also achieve high specificity to assess cerebral microcirculation, as would facilitate its broad application in functional imaging field.

Algorithms↗

PubMed1998

Effects of losartan titrated to losartan/hydrochlorothiazide and amlodipine on blood pressure and peripheral capillary microcirculation in patients with mild-to-moderate hypertension.

OBJECTIVE: To measure the effects of losartan and amlodipine on peripheral capillary microcirculation in hypertension. SETTING: Medical out-patient clinic, Basel, in a university teaching hospital. METHODS: After a 4-week placebo run-in period 20 patients aged 50 +/- 8 (range 36-65) years with mild-to-moderate hypertension were randomly allocated to receive active treatment with losartan 50 mg titrated to losartan 50 mg/hydrochlorothiazide (HCT) 12.5 mg, or amlodipine 5 mg titrated to 10 mg for a 12 week period. Titration was performed if diastolic blood pressure (BP) was > or=90 mm Hg after 6 weeks of treatment. BP measurements as well as video capillary microscopy of the finger nailfold at the end of the placebo period and after 12 weeks of active treatment were compared. Capillary blood cell velocity was measured at rest and immediately, 1 min and 2 min after local finger cooling. RESULTS: After 3 months of treatment with amlodipine (n = 10) and losartan titrated to losartan-HCT (n = 10) sitting BP decreased significantly from 160 +/- 7/103 +/- 4 mm Hg and 147 +/- 7/98 +/- 6 mm Hg to 131 +/- 10/86 +/- 7 mm Hg and 134 +/- 17/89 +/- 9 mm Hg, respectively (P < 0.01). After local finger cooling the area under the curve (AUC) of capillary blood cell velocities was 1.13 +/- 0.58 mm (median +/- s.d.) at baseline and increased to 1.94 +/- 1.15 (P < 0.05) in losartan/losartan-HCT treated patients. In amlodipine treated patients the increase in AUC of capillary blood cell velocity did not reach the level of statistical significance (1.59 +/- 1.36 to 2.14 +/- 1.05 mm). CONCLUSION: This small trial shows that the area under the curve of capillary blood cell velocity increases in hypertensive patients treated with both losartan/losartan-HCT and amlodipine compared with baseline values.

Adult↗

PubMed2002

The inflammatory aspect of the microcirculation in hypertension: oxidative stress, leukocytes/endothelial interaction, apoptosis.

Evidence is increasing in hypertensive models for an inflammatory reaction in the microcirculation with abnormal leukocyte counts and adhesion to the endothelium, enhanced arteriolar tone, and microvascular and tissue apoptosis. The spontaneous form of hypertension (SHR) is accompanied by a glucocorticoid-dependent increase in circulating leukocyte count with elevated levels of activation and at the same time depressed leukocyte-endothelial interaction and endothelial P-selectin function. The SHR exhibits immune suppression with lymphocyte apoptosis in the thymus. Generation of reactive oxygen species (ROS) in and around microvascular endothelial cells may regulate signal transduction pathways responsible for controlling gene expression and protein modification and thereby cause an elevation of vascular tone and, in excess, may form an injury mechanism for cells and tissue. A series of enzyme systems such as xanthine oxidase, reduced nicotinamide adenine dinucleotide phosphate/reduced nicotinamide adenine dinucleotide oxidase, and cytochrome P450 monooxygenases in conjunction with suppression of ROS scavengers seem to be involved in the oxidative stress responses in hypertension. The increase in ROS generation contributes to vascular remodeling, apoptosis, and proliferation of vascular smooth muscle, whereas gaseous monoxides such as nitric oxide and carbon monoxide have the ability to modulate elevated vascular tone and proliferative cell responses. Such biological actions of gases not only regulate activation of soluble guanylate cyclase but could also be attributable to inhibition of cytochrome P450 monooxygenases. We examine here the molecular basis of signal transduction by ROS, NO, and CO and functional alterations in their sensor molecules. An inflammatory reaction may underlie the pathogenesis of hypertension and its associated lesion formation and organ dysfunction.

Apoptosis↗

PubMed2002

Adaptations of the renal microcirculation to hypertension.

Control of glomerular filtration involves sensitive regulation of glomerular filtration pressure over a widely varying range of systemic arterial pressures. This control is exerted through precise adjustments in preglomerular resistance involving numerous activation and feedback mechanisms. Under physiological conditions, these mechanisms succeed in maintaining renal blood flow and glomerular filtration rate in normal ranges and they provide protection of the glomerulus from elevated arterial pressure. However, under pathophysiological conditions, the accuracy of that regulation can be compromised. In hypertension, the efficiency with which preglomerular resistance is controlled is impaired. This can result in greater transmission of arterial pressure to glomerular capillaries, leading to inappropriately high glomerular filtration pressures and glomerular damage. Chronic exposure to hypertensive conditions can also lead to modification of the structure and/or function of the renal microvasculature as an adaptive response to the hypertension. Distinguishing adaptive, and thus protective, alterations in renal microvascular function from those that reflect deterioration of microvascular function is an important challenge. Inappropriate modifications in renal microvascular performance can lead to deterioration of glomerular function and can ultimately result in end-stage renal disease. This review will take a detailed look at the alterations in autoregulatory, vasoconstrictor, and vasodilatory responsiveness of the renal microcirculation during hypertension. It is anticipated that a more thorough understanding of the renal microcirculatory adaptations to hypertension will lead to better therapeutic approaches to managing hypertension while at the same time providing better protection to long term kidney function.

Adaptation, Physiological↗

PubMed1999

Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibitor SU5416 as assessed by intravital multi-fluorescence videomicroscopy.

Vascular endothelial growth factor (VEGF) plays a fundamental role in mediating tumor angiogenesis and tumor growth. Here we investigate the direct effect of a novel small molecule inhibitor of the Flk-1-mediated signal transduction pathway of VEGF, SU5416, on tumor angiogenesis and microhemodynamics of an experimental glioblastoma by using intravital multifluorescence videomicroscopy. SU5416 treatment significantly suppressed tumor growth. In parallel, SU5416 demonstrated a potent antiangiogenic activity, resulting in a significant reduction of both the total and functional vascular density of the tumor microvasculature, which indicates an impaired vascularization as well as significant perfusion failure in treated tumors. This malperfusion was not compensated for by changes in vessel diameter or recruitment of nonperfused vessels. Analyses of the tumor microcirculation revealed significant microhemodynamic changes after angiogenesis blockage such as a higher red blood cell velocity and blood flow in remnant tumor vessels when compared with controls. Our results demonstrate that the novel antiangiogenic concept of targeting the tyrosine kinase of Flk-1/KDR by means of a small molecule inhibitor represents an efficient strategy to control growth and progression of angiogenesis-dependent tumors. This study provides insight into microvascular consequences of Flk-1/KDR targeting in vivo and may have important implications for the future treatment of angiogenesis-dependent neoplasms.

Animals↗

PubMed2001

Distribution of angiotensin II receptor expression in the microcirculation of striated muscle.

OBJECTIVE: The current study was undertaken to localize and identify angiotensin II (Ang II) receptor subtypes in the microcirculation of striated muscle. METHODS: Cremaster muscles from 7- to 8-week-old Sprague-Dawley rats were excised, placed in a dissection solution maintained at 4 degrees C, and 3 branch orders of arterioles and venules, as well as capillaries and a muscle specimen, were microdissected under a stereomicroscope. Reverse transcription polymerase chain reaction (RT-PCR) methods were developed for purification and amplification of extremely small amounts of RNA (<5 ng/microL) from whole tissue samples. RNA was isolated from each sample, reverse transcribed, and the cDNA products were amplified by polymerase chain reactions (PCR) specifically primed with either AT(1a), AT(1b), or AT(2) receptor primers. The products were electrophoretically size-fractionated on an agarose gel, stained with ethidium bromide to visualize DNA bands, and analyzed to determine the presence or absence of AT receptor subtypes. Protein expression was confirmed by Western blotting pooled samples with specific antiserum. RESULTS: AT(1a) and AT(2) receptors were found in nearly all orders of both arterioles and venules, as well as the skeletal muscle biopsies. AT(1b) receptors, if present, were only observed on a few instances in the arterioles. Furthermore, PCR reactions specifically primed for skeletal muscle cell (MHC(2B)) and endothelial cell (eNOS) specific proteins demonstrated that there was no cross-contamination between the vessels and the skeletal muscle biopsies. CONCLUSIONS: This study describes a unique method for the isolation and preparation of microvessels and provides the first data directly demonstrating the presence of AT(1) and AT(2) receptors in microvessels as well as in skeletal muscle fibers.

Animals↗

PubMed2001

The peritoneal microcirculation in peritoneal dialysis.

This paper deals with the peritoneal microcirculation and with peritoneal exchange occurring in peritoneal dialysis (PD). The capillary wall is a major barrier to solute and water exchange across the peritoneal membrane. There is a bimodal size-selectivity of solute transport between blood and the peritoneal cavity, through pores of radius approximately 40-50 A as well as through a very low number of large pores of radius approximately 250 A. Furthermore, during glucose-induced osmosis during PD, nearly 40% of the total osmotic water flow occurs through molecular water channels, termed "aquaporin-1." This causes an inequality between 1 - sigma and the sieving coefficient for small solutes, which is a key feature of the "three-pore model" of peritoneal transport. The peritoneal interstitium, coupled in series with the capillary walls, markedly modifies small-solute transport and makes large-solute transport asymmetric. Thus, although severely restricted in the blood-to-peritoneal direction, the absorption of large solutes from the peritoneal cavity occurs at a high clearance rate ( approximately 1 mL/min), largely independent of molecular radius. True absorption of macromolecules to the blood via lymphatics, however, seems to be occurring at a rate of approximately 0.2 mL/min. Several controversial issues regarding transcapillary and transperitoneal exchange mechanisms are discussed in this paper.

Aquaporins↗

PubMed2001

Age-dependent changes in the postnatal intestinal microcirculation.

Significant changes occur in intestinal hemodynamics during the transition from fetal to newborn life and then again during the first postnatal month. Most importantly, basal vascular resistance substantially decreases following birth. It then decreases further between postnatal days 1 and 3, plateaus, and then begins a slow, progressive increase between postnatal days 12 and 30. The basal rate of intestinal blood flow mirrors the changes in vascular resistance in an inverse manner. The postnatal changes in vascular resistance appear to be mediated, in large part, by an increase in the constitutive and stimulated production of nitric oxide. Most importantly, the diameter of terminal mesenteric arteries (150-300 microm diameter) in newborn (i.e., 1 day old) swine is determined by three intrinsic vascular control systems: endothelial production of nitric oxide and endothelin, and the inherent myogenic response of vascular smooth muscle. In contrast, these vessels in older subjects (i.e., 35 days old) are primarily passive in nature and fail to demonstrate significant diameter change in response to blockade of endogenous nitric oxide production or endothelin receptors, or applied perturbations of pressure or flow rate. The circulatory physiology of the perinatal and newborn intestine is exceptional when compared to the adult condition inasmuch as several hemodynamic variables change quite dramatically between fetal and neonatal life and during the first postnatal month. The unique hemodynamic conditions that characterize the perinatal and newborn intestine appear to be part of the overall physiological transition that occurs as the fetus, once born, replaces the placenta with his gastrointestinal tract to obtain nutrition. The goal of this review is to describe the circulatory physiology of the perinatal and newborn intestine, with a particular emphasis on those portions of the intestinal microcirculation that have thus far been studied. First, however, it is important to discuss the age-dependent changes that occur within the intestinal circulation during perinatal and early newborn life.

Age Factors↗

PubMed1996

Skin microcirculation of the foot in diabetic neuropathy.

1. In the feet of patients with diabetic neuropathy, total skin blood flow is increased due to an increased shunt flow. The question is, does this increased anastomotic shunt flow lead to either under- or overperfused nutritive capillaries. 2. To solve this question, skin microcirculation tests of the left big toe were performed in 20 healthy control subjects and in 40 insulin-dependent diabetic patients without macroangiopathy, 20 without and 20 with neuropathy. Skin temperature measurements and laser Doppler fluxmetry were performed to record mainly shunt flow and capillaroscopy to study nailfold capillary blood flow. 3. The insulin-dependent diabetic patients with neuropathy had a higher baseline skin temperature (mean +/- SEM; 30.0 +/- 0.6 degrees C) and laser Doppler fluxmetry [26.2 +/- 2.2 perfusion units (pu)] than patients without neuropathy (27.2 +/- 0.8 degrees C, P < 0.01; 16.1 +/- 2.0 pu, P < 0.01) and healthy control subjects (27.9 +/- 0.7 degrees C, P < 0.05; 18.6 +/- 2.8 pu, P < 0.05). Sympathetic stimulation (inspiratory gasp) resulted in a smaller laser Doppler fluxmetry decrease in the neuropathic patients (31.4 +/- 4.6%) compared with non-neuropathic patients (48.2 +/- 5.1%, P < 0.05) and control subjects (49.0 +/- 3.8%, P < 0.05), while no difference between the three groups was seen in the laser Doppler fluxmetry decrease during a postural vasoconstriction test. The number of visible capillaries was highest in the neuropathic patients (10.2 +/- 0.6/0.5 mm2), when compared with non-neuropathic patients (8.7 +/- 1.2/0.5 mm2, P < 0.05) and control subjects (8.3 +/- 0.3/0.5 mm2, P < 0.001). Capillary blood-cell velocity was significantly higher in the neuropathic patients (0.32 +/- 0.05 mm/s) compared with non-neuropathic patients (0.23 +/- 0.03 mm/s, P < 0.05) and control subjects (0.23 +/- 0.02 mm/s, P < 0.01). 4. We conclude that there is an overperfused nutritive capillary circulation in the feet of patients with diabetic neuropathy. This is in contradiction to the capillary steal phenomenon and favours the hyperdynamic hypothesis to explain the decreased healing potential in diabetic neuropathic foot ulceration.

Capillaries↗

PubMed1998

Skin microcirculation in patients with type I diabetes with and without neuropathy after neurovascular stimulation.

1. Neurovascular inflammation is impaired in patients suffering from diabetic neuropathy. The aim of our study was to evaluate the distribution of nutritive and total skin blood flow in diabetic patients with and without neuropathy after neurovascular stimulation with acetylcholine. 2. Twenty patients with Type I diabetes, 10 with and 10 without neuropathy, and 10 age-matched non-diabetic control subjects, underwent microvascular investigations before and after neurovascular stimulation by intracutaneous application of acetylcholine. The capillary blood cell velocity in the nailfold of the hallux was measured by videophotometric capillaroscopy, and the total skin microcirculation in the same area by laser Doppler flowmetry. 3. The increase in total skin blood flow was significantly impaired in the group of neuropathic diabetic patients compared with the non-neuropathic diabetic patients (17.5 +/- 8.3 versus 51.0 +/- 16.2; P < 0.05) and the non-diabetic subjects (17.5 +/- 8.3 versus 67.8 +/- 19.7; P < 0.01). The increase in capillary blood flow was not significantly impaired in Type I diabetes patients with neuropathy. 4. The ratio between capillary blood flow and total skin perfusion decreased significantly in the control group (from 0.82 +/- 0.15 to 0.47 +/- 0.11; P < 0.05) and in the Type I diabetes patients without neuropathy (from 0.79 +/- 0.12 to 0.43 +/- 0.12; P < 0.05), whereas the decrease in the neuropathic group was statistically insignificant (from 1.05 +/- 0.19 to 0.72 +/- 0.16). 5. Diminished total skin perfusion in the foot after intracutaneous stimulation with acetylcholine in Type I diabetes patients is associated with diabetic neuropathy, indicating a disturbance in the neurovascular reflex arc. This impaired neurovascular response is caused by a diminished total and subpapillary blood flow and not by a diminished nutritive capillary flow. There is no evidence of a diminished nutritive capillary blood flow during neurogenic inflammation in Type I diabetes patients suffering from diabetic neuropathy.

Acetylcholine↗

PubMed2005

Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis.

IPC (ischaemic preconditioning) may protect the steatotic liver, which is particularly susceptible to I/R (ischaemia/reperfusion) injury. Hepatic steatosis was induced in Sprague-Dawley rats with a high-cholesterol (2%) diet for 12 weeks after which rats were subjected to I/R (ischaemia/reperfusion; 45 min of lobar ischaemia followed by 2 h of reperfusion). Rats were divided into three study groups (n=6 each) receiving: (i) sham laparotomy alone, (ii) I/R, and (iii) IPC (5 min of ischaemia, followed by 10 min of reperfusion) before I/R. Hepatic extra- and intra-cellular oxygenation and HM (hepatic microcirculation) were measured with near-infrared spectroscopy and laser Doppler flowmetry respectively. Plasma liver enzymes and hepatic tissue ATP were measured as markers of liver injury. Histology showed moderate-grade steatosis in the livers. At the end of 2 h of reperfusion, I/R significantly decreased extra- and intra-cellular oxygenation concomitant with a failure of recovery of HM (21.1+/-14.4% of baseline; P<0.001 compared with sham animals). IPC increased intracellular oxygenation (redox state of the copper centre of cytochrome oxidase; P<0.05 compared with rats receiving I/R alone) and flow in HM (70.9+/-17.1% of baseline; P<0.001 compared with rats receiving I/R alone). Hepatocellular injury was significantly reduced with IPC compared with I/R injury alone (alanine aminotransferase, 474.8+/-122.3 compared with 5436.3+/-984.7 units/l respectively; P<0.01; aspartate aminotransferase, 630.8+/-76.9 compared with 3166.3+/-379.6 units/l respectively; P<0.01]. In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis. These data may have important clinical implications in liver surgery and transplantation.

Adenosine Triphosphate↗

PubMed2000

The cutaneous microcirculation.

The cutaneous microcirculation is organized as two horizontal plexuses. One is situated 1-1.5 mm below the skin surface and the other is at the dermal-subcutaneous junction. Ascending arterioles and descending venules are paired as they connect the two plexuses. From the upper layer, arterial capillaries rise to form the dermal papillary loops that represent the nutritive component of the skin circulation. There are sphincter-like smooth muscle cells at the point where the ascending arterioles divide to form the arteriolar component of the upper horizontal plexus. At the dermal-subcutaneous junction, there are collecting veins with two cusped valves that are oriented to prevent the retrograde flow of blood. Laser Doppler flowmetry has demonstrated vasomotion of red cell flux localized to the sites of ascending arterioles. The simultaneous recording by laser Doppler flowmetry of red cell flux and the concentration of moving red blood cells from individual sites allows one to construct topographic maps of these two values. These two maps, based on initial studies using correlative skin biopsies, can define 1 mm3 volumes of skin that are predominantly arteriolar in composition, venular in composition, or essentially devoid of all microvascular elements. The electron and light microscopic features that define the microvascular segments, when coupled with that ability of laser Doppler flowmetry to define the predominant microvascular segments under the probe, allow one to study both the mechanisms of normal physiologic states and the pathogenetic mechanisms underlying pathologic skin disorders in which the microvasculature plays a predominant role.

Animals↗

PubMed2000

The bronchial microcirculation in asthma.

Airway wall remodelling in asthma involves a number of changes including increased vascularity, vasodilation and microvascular leakage. Evidence suggests that the number and size of bronchial vessels is increased in patients with asthma compared with normal controls. In particular, there may be increased numbers of vessels in patients with fatal asthma. Treatment with inhaled corticosteroids is now known to reduce this vascularity. Bronchial vessels may undergo proliferation in response to inflammatory stimuli. Many factors can induce angiogenesis including a range of mediators and growth factors. Others can cause a vascular response by causing vasodilation and microvascular leakage. Airway wall oedema is likely to be important in asthma but has not yet been quantified. It is thought that mast cells play a key role in modulating these vascular remodelling changes by releasing cytokines and growth factors. Many key issues remain to be resolved before we fully understand the role of the bronchial microcirculation in asthma. In the future, novel therapies may be directed towards angiogenesis, vasodilation and microvascular leakage.

Asthma↗

PubMed1999

Microcirculation in venous ulcers and the surrounding skin: findings with capillary microscopy and a laser Doppler imager.

BACKGROUND: To obtain more information about microcirculatory disturbances in venous ulcers, we studied their laser Doppler flux images and capillary densities. MATERIALS AND METHODS: On photographs of venous ulcers and the adjacent skin of 17 patients, four regions of interest were marked: one non-granulation tissue area (NGTA) within the venous ulcer, one granulation tissue area (GTA) within the ulcer, one adjacent skin area (ASA) and one distant skin area (DSA). Within these four regions the average laser Doppler area fluxes and capillary densities were determined for each patient using a laser Doppler imager and capillary microscopy respectively. RESULTS: The laser Doppler area flux (mean +/- SD in AU) was significantly lower in NGTA (1.39 +/- 1.12) than in GTA (4.06 +/- 1. 52) or DSA (3.86 +/- 1.54) (P < 0.00001). In addition, the ASA flux (1.95 +/- 1.39) was significantly lower than the GTA or DSA flux (P < 0.0001). Capillary density (capillaries per mm2) in NGTA (0.82 +/- 1.98) was significantly lower than that in GTA (6.00 +/- 2.55), ASA (13.88 +/- 5.16) or DSA (10.29 +/- 3.41) (P < 0.0001). In addition, the capillary density of ASA was significantly higher than that of GTA or DSA (P < 0.05). CONCLUSION: The four areas showed the following characteristics: NGTA, low laser Doppler area flux and lowest capillary density (possible sign of ulcer area without healing tendency); GTA, high laser Doppler area flux and second lowest capillary density (possible sign of wound healing); ASA, low laser Doppler area flux and highest capillary density (possible sign of healing process nearly completed; scar); DSA, high laser Doppler area flux and second highest number of capillaries (sign of microcirculation of chronic venous disorder).

Aged↗