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PubMed1983

New embolization method using estrogen: effect of estrogen on microcirculation.

To ascertain the mechanism of action of estrogen administered by a new embolization method, developed by the authors as a treatment method for dural arteriovenous malformations, conjugated estrogens were injected into the mesenteric artery of rabbits, and microcirculatory changes in the dominant areas were studied biomicroscopically. Conjugated estrogen induced sludging and stasis in the microcirculation, approximately in proportion to the concentration and dose.

Animals↗

PubMed1996

Antithrombotic effect of topically applied 3-oxa-methano-prostaglandin I1 in the microcirculation and antiplatelet functions of its active form.

The antithrombotic effect of topical application of the 3-oxa-methano-prostaglandin (PG) I1 analog, SM-10902 in the microcirculation and in vitro antiplatelet functions of its active form SM-10906 were estimated in comparison with PGI2 and PGE1. In rat platelets, SM-10906 evoked accumulation of intracellular cyclic adenosine 3',5'-monophosphate, and exhibited antiaggregatory and disaggregatory activities, which were all enhanced by the phosphodiesterase inhibitor theophylline. Additionally, SM-10906 was shown to inhibit platelet adhesion to collagen in human platelet-rich plasma. PGI2 and PGE1 also showed in vitro antiplatelet effects in the order of PGI2 > SM-10906 > or = PGE1. SM-10902 exhibited a dose-dependent anti-thrombotic effect in the guinea pig mesenteric arteriole by a topical application, and this activity might be exerted by the antiplatelet functions of SM-10906. Although SM-10906, PGI2 and PGE1 also showed the antithrombotic effects, SM-10902 was the most potent. In conclusion, the present studies indicate that an external topical preparation of SM-10902 may be useful for the therapy of peripheral circulatory insufficiency.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMedDate not supplied

Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L-arginine.

Hypercholesterolaemia impairs endothelial function, possibly by interference with the intracellular formation of endothelium-derived relaxing factor from its precursor L-arginine. Whether L-arginine reverses hypercholesterolaemia-induced endothelial dysfunction in the coronary circulation was thus investigated. Epicardial artery cross-sectional area and coronary blood flow velocity were measured in 8 hypercholesterolaemic patients (mean serum cholesterol 7.8 [SE 0.3] mmol/l) and 7 age-matched controls before and after graded intracoronary infusions of the endothelium-dependent agent acetylcholine (0.036, 0.36, 3.6 micrograms/min). The effect of intracoronary infusion of L-arginine (160 mumol/min via the guiding catheter) on these measurements was then examined. In controls, acetylcholine induced a moderate dose-dependent constriction of the epicardial artery segment of the left anterior descending artery and increased coronary blood flow (by 239% [SE 57] at the highest dose). In patients with hypercholesterolaemia, the vasoconstrictive effect of acetylcholine on epicardial segments was similar to that in controls, but the increase in coronary blood flow with acetylcholine was significantly attenuated (highest dose: 61%, p less than 0.02 vs controls). L-arginine restored the acetylcholine-induced increase in blood flow in patients with hypercholesterolaemia (198% [61] vs baseline) but did not affect coronary blood flow in controls. The findings suggest that hypercholesterolaemia impairs endothelium-dependent dilatation of the coronary microcirculation and that this impairment can be restored by short-term administration of L-arginine. The possibility that L-arginine might form the basis of treatment for coronary endothelial abnormalities induced by hypercholesterolaemia could be worth investigating.

Acetylcholine↗

PubMed1988

Fringe mode transmittance laser Doppler microscope anemometer: its adaptation for measurement in the microcirculation.

Blood flow analysis in the microcirculation requires accurate measurement of velocity, volume flow and shear-rate versus shear-stress relationships. The resolution of most anemometers is too limited to obtain useful measurements, especially near the blood vessel wall and at branches and bifurcations. To make such measurements possible with a noninvasive, high resolution, accurate technique, we have developed a fringe mode, transmittance laser Doppler microscope anemometer (LDMA). This system has an intrinsically high spatial resolution (10 x 12 microns), and does not require a high concentration (10(6)/cm3) of scatters or red blood cells (RBC) as in our application. Preliminary measurements of water flow in a rectangular channel were conducted to ascertain the reliability and accuracy of velocity measurements using the LDMA. Velocity profiles were then measured by the LDMA system in arterioles 38-135 microns in diameter, in the transparent, everted cheek pouch of the anaesthetized hamster. The extremely high resolution of the optical system, and the ultra-fine traversing mechanism of the microscope stage, made velocity readings larger than 0.02 mm/s with accuracy and reproducibility better than 1%, possible near the wall to within 7-10 microns.

Animals↗

PubMed1993

Foot microcirculation and blood rheology in diabetes.

Diabetes mellitus is associated with circulatory abnormalities. The blood flow in the skin of the dorsum of the foot and haemorheological variables were measured in 36 subjects. They were divided into three equal groups of diabetic patients: those with neuropathy, and both age and sex matched non-diabetic subjects; all were characterized by age, duration of diabetes and blood biochemistry. High and low shear rate blood viscosities were measured; aggregation was characterized using a Myrerene Aggregometer. The microcirculation in the skin of the dorsum of the foot was measured using a laser Doppler flowmeter. Measurements were made at room temperature with the subjects supine with the leg horizontal, and then with the lower leg vertical; the measurements were repeated at 42 degrees C. Both diabetic groups had significantly increased low shear whole blood viscosity compared with normal subjects. The aggregation index was significantly greater in diabetic neuropaths than normal subjects. There were significant differences in the depth of vasomotor activity between the three groups, with the diabetic neuropaths commonly showing no motor activity at room temperature. The only significant correlations were between equilibrium laser Doppler values with the limb horizontal and both the low and high shear whole blood viscosities.

Blood Viscosity↗

PubMed1981

Response of the soft tissue microcirculation to prostacyclin infusion.

We studied the effect of prostacyclin infusion on the soft tissue microcirculation. We used lymph flow QL and the lymph/plasma L/P protein ratio to reflect transvascular fluid flux and changes in microvascular hydrostatic pressure, Pmv. Unanesthetized sheep with prefemoral lymph fistulae were infused with PGI2 (0.2 microgram/kg/min) for two hours. Changes in QL and L/P were compared to animals in which Pmv was increased by volume loading. During PGI2, QL was significantly increased, as was cardiac output while mean aortic pressure decreased. The L/P ratio did not decrease to the degree seen with a comparable increase in QL, due to an increase in Pmv. The increase in QL was most likely due to an increase in microvascular surface area. QL remained significantly increased for several hours after infusion and L/P decreased to the same degree as seen with an increase in Pmv. This indicates that Pmv is increased for several hours in soft tissue after infusion, due to a relative increase in venous resistance probably secondary to activation of the renin-angiotensin system.

Animals↗

PubMed1996

Vasomotor and permeability effects of bradykinin in the cerebral microcirculation.

All components of an intracerebral kallikrein-kinin system have been described. Thus, bradykinin (BK) acting from the parenchymal site as well as from the blood site may influence cerebral microcirculation. BK is a potent dilator of extra- and intraparenchymal cerebral arteries when acting from the perivascular site. The vasomotor effect of BK is mediated by B2 receptors which appear to be located at the abluminal membrane of the endothelial cell. The effect of BK is mediated by NO. prostanoids, free radicals, H2O2 or leukotrienes depending on the animal species and on the location of the artery. Selective opening of the blood-brain barrier for small tracers (Na(+)-fluorescein; MW, 376) has been found in cats during cortical superfusion or intraarterial application of BK. This leakage is mediated by B2 receptors located at the luminal and abluminal membrane of the endothelial cells. Formation of brain edema has been found after ventriculo-cisternal perfusion or interstitial infusion of BK. This can be explained by increase of vascular permeability and cerebral blood flow due to arterial dilation thus enhancing driving forces for the extravasation. An increase of the BK concentration in the interstitial space of the brain up to concentrations which induce extravasation, dilatation and oedema formation has been found under several pathological conditions. Thus, BK may be involved in oedema formation after cold lesion, concussive brain injury, traumatic spinal cord and ischemic brain injury. The mediator role of BK in brain edema is further supported by therapeutic results. Brain swelling due to cold lesion or ischemia could be diminished by treatment with kallikrein-inhibitors. Similarly, dilatation of cerebral arterioles after concussive brain injury was reduced by blockade of B2 receptors. Thus, all criteria favour BK as one mediator of vasogenic oedema.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Regulation of the cerebral microcirculation during neural activity: is nitric oxide the missing link?

Although the mechanisms regulating the cerebral microcirculation during neural activity have been the subject of inquiry for a century or more, the mediators responsible for the changes in cerebral blood flow still remain to be clearly identified. The discovery that nitric oxide, a powerful cerebrovasodilator, is produced by active neurons has led to the hypothesis that this agent could be the long-sought mediator 'coupling' brain activity to cerebral blood flow. This hypothesis is supported by recent experimental data suggesting that nitric oxide participates in the maintenance of resting cerebral blood flow and in the cerebrovasodilatation elicited by increased neural activity. In this article, this evidence is critically reviewed and discussed in the context of general principles of cerebrovascular regulation.

Animals↗

PubMedDate not supplied

Met-enkephalin-induced vasoconstriction in the microcirculation of rat striated muscle.

Sprague-Dawley rats were anesthetized with pentobarbital (50 mg/kg) and the arterioles of the cremaster muscle were observed using television microscopy. Methionine (Met)-enkephalin was added to give bath concentrations of 10(-11) to 10(-7) M. Met-enkephalin caused a decrease in the diameter of first-order (127 +/- 7 microns), second-order (57 +/- 7 microns), and third-order (18 +/- 2 microns) arterioles, with the third-order arterioles showing the greatest reactivity. The effects of Met-enkephalin were attenuated by the opiate antagonist, naloxone, by the alpha-adrenergic receptor antagonists, phentolamine and prazosin, and by chemical sympathectomy with 6-hydroxydopamine. These results suggest that Met-enkephalin causes vasoconstriction in the striated muscle microcirculation by stimulating norepinephrine release from local nerve terminals.

Animals↗

PubMed1994

Chemically modified heparin improves hepatocellular function, cardiac output, and microcirculation after trauma-hemorrhage and resuscitation.

BACKGROUND: Although heparinization before hemorrhagic shock improves tissue perfusion and organ function, the anticoagulant properties of conventional heparin preclude its clinical use. The purpose of this study was to determine whether chemically modified heparin (CMH), which does not have any significant anticoagulant activity, produces any beneficial effects on hepatocellular and cardiovascular function and microcirculation after trauma-hemorrhage and resuscitation. METHODS: After induction of tissue trauma (that is, laparotomy), rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleedout volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with three times the volume of shed blood with RL over 45 minutes, followed by two times RL and CMH (7 mg/kg body wt; approximately 10% of the anticoagulant activity of conventional heparin), conventional heparin (7 mg/kg), or normal saline solution over 60 minutes. Hepatocellular function, cardiac output, and microvascular blood flow were determined thereafter. RESULTS: The results indicate that hepatocellular function, cardiac output, and microvascular blood flow in the liver, kidney, spleen, and small intestine decreased markedly after trauma-hemorrhage and resuscitation. Infusion of CMH or conventional heparin during resuscitation, however, restored or significantly improved the mentioned parameters. CONCLUSIONS: Because CMH does not have any significant anticoagulant properties and because it restores or significantly improves hepatocellular function, cardiac output, and tissue perfusion, this agent appears to be a useful adjunct in the treatment of trauma and hemorrhagic shock, even in the absence of blood resuscitation.

Animals↗

PubMed1983

Microcirculation in hypertrophic burn scars.

Using the technique of capillary microscopy the microcirculation of post burn hypertrophic scars and grafts, at varying stages of maturity, have been documented. Sympathetic innervation of larger vessels beneath and within the scarred tissues could be found only in fully-matured scars, suggesting a link between the processes of scar reinnervation and maturation.

Adrenergic Fibers↗

PubMed1995

The impact of chronic reduced microcirculation on tissue function and on neoplastic promotion.

I hypothesize that chronic reduced microcirculation, even limited to micro areas of tissue, may lead to respiratory deficiencies, to a proliferation of simplified cells as a result of a lack of energy, and to defects in immune control. In these situations, reduce resistance and specific hypofunction might occur in organs (should the entire organ be involved) and cell alterations might come about, as several authors have described experiments in conditions of hypoanoxia. The mutated cells, possibly in these areas as well, could more easily emerge as neoplasia because they are removed from immune control and surrounded by a terrain of reduced resistance. Infant leukaemias would be easier to control than adult forms because it is harder for antineoplastics to reach the latter's site of origin.

Adult↗

PubMed1994

Living isolated cells from inner ear vessels: a new approach for studying the regulation of cochlear microcirculation and vascular permeability.

The spiral modiolar artery with its proximal branches and the microvessels in the spiral ligament and the stria vascularis were microdissected from the guinea pig cochlea. After incubation with proteolytic and collagenolytic enzymes the mixed cell suspension was fractionated by gradient centrifugation. The cells migrated according to their buoyant densities into the fractions of 1.04 g/ml (endothelial cells), 1.06 g/ml (vascular smooth muscle cells obtained from the spiral modiolar artery; strial pericytes) and 1.08 g/ml (pericytes obtained from the spiral ligament). To test for viability cells were loaded with a fluorescent vital stain (BCECF-AM); for identification, cell-specific stains were used. Identity of endothelial cells (ECs) was confirmed using acetylated low density lipoprotein fluorescently labeled with dioctadecyl-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL). Pericytes were identified immunofluorescently using the method according to Nayak et al. (1988). Vascular smooth muscle cells were stained for F-actin with rhodamin-phalloidin. This in vitro technique may open new approaches to study local factors involved in microcirculation and vessel permeability of various cochlear vascular beds.

Actins↗

PubMed1995

Bioelectric and microcirculation cutaneous sensors for the study of vigilance and emotional response during tasks and tests.

Bioelectronic phenomena related to the activity of the Autonomic Nervous System (ANS) activity mainly take place in the deep part of the brain where they are difficult to record. The hand skin, being richly innervated by sympathetic efferent fibres, offers an interface from which relevant ANS-related signals can be recorded. Two non-invasive bioelectronic measurements (skin resistance and potential) reflecting the activity of the ANS were performed at the skin surface. These measurements were complemented by thermovascular (skin microcirculation and skin temperature) and cardiorespiratory (instantaneous heart rate and instantaneous respiratory frequency) measurements. The bioelectric measurements were performed using noninvasive Ag/AgCl electrodes. Non-metallic NASICON (Na Super Ionic Conductor) electrodes were tested and compared with traditional electrodes for the optimization of bioelectric measurements. Signal analysis and data processing was accomplished by means of original indices on a specially designed PC-based software. The methodology was used to evaluate vigilance level, mental workload, and emotional response during tasks (sporting activity, mental calculation, olfactive stimuli) and in critical situations (car crash avoidance).

Accidents, Traffic↗

PubMedDate not supplied

Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in hamster cheek pouch microcirculation.

The effects of Vaccinium myrtillus anthocyanosides (VMA) on ischaemia reperfusion injury were investigated in the hamster cheek pouch microcirculation. Ischaemia was induced by clamping the cheek pouch for 30 min followed by 30 min of reperfusion. The microvasculature was visualized by a fluorescence technique. VMA [10 mg (100 g body weight)-1] were orally administered for 2 and 4 weeks. The number of adhering leukocytes to venular vessel walls, the perfused capillary length, the increase in permeability, the arteriolar diameter changes were determined. Ischaemia and reperfusion were associated with increased number of leukocytes sticking to venules, decreased number of perfused capillaries, and increased permeability. VMA decreased the number of leukocytes sticking to the venular wall and preserved the capillary perfusion; the increase in permeability was significantly reduced after reperfusion. VMA saved the arteriolar tone and induced the appearance of rhythmic diameter changes of arterioles. These results demonstrate the ability of Vaccinium myrtillus anthocyanosides to reduce microvascular impairments due to ischaemia reperfusion injury, with preservation of endothelium, attenuation of leukocyte adhesion and improvement of capillary perfusion.

Animals↗

PubMed1993

Relaxation responses of the coronary microcirculation after cardiopulmonary bypass and ischemic arrest with cardioplegia: implications for the treatment of postoperative coronary spasm.

Coronary arteriolar spasm may occur following cardiopulmonary bypass and ischemic arrest, resulting in impaired cardiac function. Because myocardial perfusion is principally regulated by the microcirculation, the in vitro effects of various clinically used vasodilating drugs on porcine coronary microvessels less than 200 microns in diameter were examined following cardioplegic arrest and reperfusion. After 1 hour of ischemic arrest using either crystalloid or blood cardioplegia solutions followed by 1 hour of reperfusion, microvessels were studied in a pressurized (40 mmHg), no-flow state, and imaged with a video tracking device. Vessels were preconstricted by 30% to 60% of their resting diameter using acetylcholine, and various vasodilatory agents were applied extraluminally. Responses to the beta-adrenergic receptor agonist isoproterenol and the nitrovasodilator sodium nitroprusside were minimally altered by either cardioplegia solution as compared to control. In contrast, relaxation responses to both the calcium channel antagonist nifedipine and nitroglycerin were diminished after ischemic arrest and reperfusion. Relaxation responses were similar with crystalloid or blood cardioplegia for all drugs tested. Despite its somewhat attenuated response, nifedipine remained the most potent vasodilator of those studied. It is concluded that (1) following ischemic arrest with either crystalloid or blood cardioplegia solutions, responses to sodium nitroprusside and isoproterenol were minimally altered, while responses to nifedipine and nitroglycerin were attenuated; (2) relaxation responses of coronary arterioles were not significantly different with either blood or crystalloid cardioplegia; and (3) despite a slightly decreased response after cardioplegia, nifedipine was the most potent vasodilator of coronary arterioles, and may be the best choice for treating postoperative coronary arteriolar spasm.

Animals↗

PubMed2005

Effect of exogenous urotensin-II on vascular tone in skin microcirculation of patients with essential hypertension.

BACKGROUND: Plasma levels of urotensin-II (U-II) have been found to be elevated in patients with essential hypertension. However, the consequence of activation of the U-II system have not been previously determined in these patients. We therefore compared the effect of exogenous U-II administration on vascular tone in hypertensive patients (n = 13) and normotensive subjects (n = 14). METHODS: The effect of U-II on vascular tone was determined in the forearm skin microcirculation using iontophoresis to administer the drug and laser Doppler velocimetry to measure microvascular response. RESULTS: The U-II administration was associated with a dose-dependent vasodilator response from baseline in normotensive subjects (U-II 1 x 10(-12) mol/L, 609 +/- 164; U-II 1 x 10(-9) mol/L, 839 +/- 216; U-II, 1 x 10(-7) mol/L, 1249 +/- 228 arbitrary flux units; P < .0005). A dose-dependent vasoconstrictor response was observed in hypertensive patients compared to baseline (U-II 1 x 10(-12) mol/L, 60 +/- 212; U-II 1 x 10(-9) mol/L, -288 +/- 172; U-II, 1 x 10(-7) mol/L, -607 +/- 165 arbitrary flux units; P < .005). Differences in flow between the two groups were significant at the 1 x 10(-9) mol/L and 1 x 10(-7) mol/L dose levels (P < .001). In contrast, there was no significant difference in flux between baseline and U-II in either group (or between groups) when the opposite polarity was applied. CONCLUSIONS: The demonstration of opposing effects of exogenous U-II in patients with hypertension and normal subjects suggests that U-II may be contributory to the increased vascular tone of these patients.

Acetylcholine↗

PubMedDate not supplied

Microcirculation disturbances in patients with venous ulcer before and after healing as assessed by laser Doppler flux-metry.

BACKGROUND: We studied whether a characteristic pattern of laser Doppler flux (LDF) could be identified in perimalleolar skin of patients with venous ulcer before and after ulcer healing. METHODS: Nine subjects with venous ulcer that healed after conservative treatment in 1-6 months and nine healthy persons were included in the study. Microcirculation investigations of laser Doppler flux (LDF) were carried out before and after ulcer healing at rest, upon arterial occlusion, during thermal stimulation and during experimental venous hypertension. RESULTS: Resting LDF expressed as median and range (in arbitrary perfusion units) was significantly higher in patients with venous ulcer in comparison to healthy subjects: 60.6 (40.2-156.5) vs. 9.2 (6.5-19.5), p=0.008. During thermal stimulation and during postischemic reactive hyperemia, absolute values of LDF were slightly but significantly higher in patients with venous ulcer than in healthy subjects, but indices of hyperemic reactivity were very low in patients (median postischemic LDF increase to 101.8 vs. 450.0% in healthy controls, p=0.008; and thermally induced LDF increase to 125.5 vs. 881.5% in healthy controls, p=0.008. Experimental venous hypertension (cuff pressure 40 and 70 mmHg, respectively) led to an equally pronounced relative reduction of LDF in healthy persons as in patients with venous ulcer before and after ulcer healing, but the absolute values of flow remained about six to seven times higher in patients when compared to healthy subjects. Hyperemic reactivity and venoarteriolar response did not change after ulcer healing. CONCLUSIONS: Elevated basal LDF and preserved maximal LDF during reactive hyperemia were found in perimalleolar skin of patients with venous ulcers that eventually healed. The relative venoarteriolar response was preserved in spite of elevated absolute values of LDF during experimental venous hypertension. These hemodynamic characteristics remained unchanged after epithelialization of venous ulcers.

Adult↗