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Coronary microcirculation and cardiovascular pathology.

The recent arrival of new techniques for exploring the coronary microcirculation has facilitated assessment of both the incidence and consequences of disorders of this network in a large number of cardiovascular diseases. The microcirculation is affected in numerous cardiomyopathies in the presence of different cardiovascular risk factors and also following cardiac transplantation. Dysfunction of the microcirculation may correspond to a reduction in the surface of the maximum section of coronary arterioles, which involves multiple mechanisms, although this phenomenon does not appear to play a role in ischaemic heart disease. Reduced coronary flow is most frequently related to vascular rarefaction of multifactorial origin, including greater or lesser degrees of intimal proliferation, perivascular fibrosis, hypertrophy of the media and extrinsic compression.

Cardiovascular Diseases↗

Temporal variations in testicular microcirculation.

Temporal variations in microcirculatory blood flow in the testis and blood pressure were examined in intact, pentobarbital-anesthetized rats with a two-channel laser Doppler flowmeter. The laser Doppler probes that measure local blood flow in a tissue volume of about 2 mm3 were placed either over the mid portion of the left and right testes or on the right testes 1 cm apart. Testicular microcirculation was characterized by a prominent vasomotion with a frequency of 5.3+/-1.4 cycles per minute and with an amplitude of 73+/-32% (mean +/- SD) of the mean. In addition to this large and rapid variation in local blood flow, there were also major variations from minute to minute in the average blood flow, vasomotion frequency, and vasomotion amplitude at 40 and 53 minutes. Such variations in local blood flow, vasomotion frequency, and vasomotion amplitude were correlated with each other at two different sites on the same testis (r(s) = 0.39, r(s) = 0.82, r(s) = 0.64, respectively, P < 0.001), and they were all correlated with systemic blood pressure (r(s) 0.41, r(s) = 0.61, r(s) = 0.32, respectively, P < 0.001). Minute-to-minute variations in local blood flow, vasomotion frequency, and vasomotion amplitude were also correlated between the right and left testes (r(s) = 0.58, r(s) = 0.75, r(s) = 0.57, respectively, P < 0.001). There are substantial temporal variations in testicular microcirculation. These variations are to some extent related to temporal changes in systemic blood pressure, but changes in the ultralocal environment are probably more important. The functional significance of, and the factors responsible for, local variations in testicular microcirculation remain to be elucidated.

Activity Cycles↗

A web-based research tool for functional genomics of the microcirculation: the leukocyte adhesion cascade.

OBJECTIVE: Currently, microvascular data are almost exclusively deposited in scholarly journals. With the increasing availability of molecular data and the construction of genomic databases, a need arises to organize physiological data in a more accessible format. The microcirculation is a functional system that spans all organ systems and shares certain characteristics of organization with metabolic pathways, which have successfully been organized around genomic information for several prokaryotes. Here, we present a web-based research and teaching tool (http:@hsc.Virginia.EDU/medicine/basic-sci/biomed/l ey/) that covers a small aspect of microcirculatory physiology, the leukocyte adhesion cascade. METHODS: Currently, the site is organized in a flat-text mode with hypertext links to GenBank, Medline, and online journals where available. RESULTS: The web-based research and education tool is useful for graduate student education, and as a research resource for genetic researchers interested in gene function and for physiologists and biomedical engineers interested in the molecular basis of the leukocyte adhesion cascade. Our effort is intended to be a beginning toward a distributed database for the microcirculation (microcirculation physiome. see http://www.bme.jhu.edu/news/microphys). CONCLUSIONS: We invite all microvascular researchers to provide annotations and comments to make the research and teaching tool more useful to the scientific community.

Algorithms↗

Reproducible assessment of vaginal and rectal mucosal and skin blood flow: laser doppler fluximetry of the pelvic microcirculation.

Pelvic venous congestion is a common cause of chronic pelvic pain in women of reproductive age. Although this condition represents a functional disturbance of the pelvic circulation which is related to the menstrual cycle, its aetiology remains unknown. Indirect techniques demonstrate that the vasoconstrictive reflex response of the microcirculation of the foot to a rise in venous pressure is attenuated throughout the menstrual cycle. We wished to develop a simple and non-invasive direct measure of pelvic blood flow to aid diagnosis of this condition. Laser doppler blood flux measurements of the skin of the big toe and of the vaginal and rectal mucosa in the follicular and luteal phases of the menstrual cycle in 12 healthy asymptomatic premenopausal women (mean age 30 years) with regular cycles and in four healthy asymptomatic postmenopausal women (mean age 59 years) were carried out both in the supine position and in response to 40 degrees head-up tilt. The coefficient of variation of resting vaginal flux was lower for measurements in postmenopausal women (0.04) and in premenopausal women in the follicular phase (0. 07) compared with those in the luteal phase (0.16). At rest, vaginal blood flow was higher than rectal and skin flux in both premenopausal and postmenopausal women. In the follicular phase a decrease in flow was observed in response to head-up tilt in the skin (-32.0%), vagina (-34.3%) and rectum (-9.4%). In the luteal phase this reflex was attenuated at these three sites (-8.6%, +6.7% and +7.4% respectively). There were no significant reflex changes in postmenopausal women. Thus laser doppler fluximetry is a reproducible method for comparing the flux of blood in the microcirculation of the skin and of the vaginal and rectal mucosa. The skin is the least sensitive site for testing vascular reactivity in response to cyclical changes. The vaginal and rectal microcirculations are the most sensitive sites for testing visceral cyclical reactivity, and have the advantage of direct anatomical relevance. The follicular phase of the menstrual cycle is associated with greatest vascular reactivity and is the most appropriate phase during which to test for abnormal vascular responses.

Adult↗

[An experimental study on promoting reconstruction of microcirculation of the ischemic skin flap with basic fibroblast growth factor].

OBJECTIVE: This study was to determine whether the basic fibroblast growth factor (bFGF) could promote reconstruction of microcirculation in the ischemic portion of a random skin flap. METHODS: Five methods were used in the experiment: measurement of the survival area of the skin flap; light and electron microscopic studies; immunohistochemical observation of the endothelial cell and microvessel image analysis technology (IAT). RESULT: The survival area and microvessels in the skin flap were significantly increased in the treated group. The results indicate that bFGF can stimulate the proliferation and differentiation of endothelial cells in vivo and promote the microcirculation of the ischemic flap. CONCLUSION: bFGF could promote reconstruction of microcirculation of the ischemic skin flap.

Animals↗

The microcirculation and inflammation: site of action for glucocorticoids.

The glucocorticoid hormones and their synthetic derivatives are potent suppressors of inflammatory and allergic pathologies. Their widespread efficacy is the result of multiple modes of action occurring predominantly at the level of the microcirculation. Indeed the glucocorticoids interfere with the function of all of the cellular components of the microcirculation associated with an inflammatory response. These agents inhibit vasodilatation of the arteriolar and capillary beds. therefore preventing the increase in blood flow that characterizes the initial stages of the inflammatory response. They also prevent increases in vascular permeability in the capillary and post-capillary venule, thereby reducing exudate formation. Finally, the glucocorticoids potently suppress leukocyte emigration across post-capillary venules. However, this promiscuity of the glucocorticoids to act at multiple sites also endows this class of (drugs with major side effects associated with chronic treatment. We propose that one way to progress forward is to understand better the effects of glucocorticoids within the microcirculation. This may aid identification of specific molecular sites of action and therefore the development of novel glucocorticoid molecules with fewer side effects.

Animals↗

[Microcirculation in the skin of the upper extremities in type 1 diabetics using the laser doppler method].

BACKGROUND: Diabetic microangiopathy is a very frequent complication of both types of diabetes mellitus. Detection of early microcirculation impairment may identify patients at high risk of severe complications and may have a great value for prevention of these complications. The aim of the study was to evaluate the skin microcirculation in upper extremities in Type 1 diabetic patients and in healthy volunteers with laser Doppler technique. Parameters of microcirculation were compared between these two groups and with diabetes control expressed by glycated hemoglobin, fructosamin and fasting glycaemia. Relationship between perfusion parameters, the age of patients and the duration of diabetes was analysed as well. METHODS AND RESULTS: Thirty-eight Type 1 diabetic patients (18 men, 20 women) and twenty-six healthy persons (16 men, 10 women) were evaluated in this study. Differences of high statistical significance in many parameters of perfusion were found between these groups. A significant negative relationship was found between the percentage perfusion increase during postocclusive hyperaemia in forearm and HbA1c and fructosamine (r = -0.52, p < 0.001 and r = -0.47, p < 0.01, respectively), between percentage perfusion increase during local hypertermia and HbA1c (r = -0.47, p < 0.001). Negative correlation was also found between maximal perfusion during postocclusive hyperaemia in finger and fructosamine (r = -0.4, p < 0.01) and between the same parameter in forearm and fasting glycaemia (r = -0.62, p < 0.001). Skin perfusion was independent on age and duration of diabetes. CONCLUSIONS: Significant differences between diabetic patients and healthy controls and a relationship between perfusion parameters and compensated diabetes status were described in the current study. Laser Doppler fluxmetry is a non-invasive method comfortable for patients and it can be used for detection of microangiopathy in diabetology.

Adult↗

[Microcirculation bed in chronic uremia].

Microcirculation of the bulbar conjunctiva and nailbed was studied in 120 patients with chronic renal failure (CRF) and its complications. Peritoneal, pleural and pericardial circulation was investigated in 15 dogs with experimental chronic uremia. It was found that the degree and frequency of microcirculatory disorders in chronic uremia correlate with the stage of CRF and diseases causing CRF. The presence of cardiac insufficiency aggravated CRF. Clinical, morphological, light and electron microscopic examinations of microcirculation in CRF revealed alterations in all the regions of microcirculation. Additional data on etiopathogenesis of cardiovascular disorders in CRF were obtained basing on the changes in peritoneal, pleural and pericardial microvessels in the experimental model of chronic uremia.

Adolescent↗

[Extracardiac effect of nitroglycerin in chronic ischemic heart disease according to the study of microcirculation].

Study of the dynamics of circulation in the microvessels of the eye conjunctiva under the effect of nitroglycerin in 50 patients with chronic ischemic heart disease showed short-lived dilatation of the postcapillaries and venules in most of them. Simultaneous fall in venous pressure may be evidence of a diminution of the venous tonus with a tendency to the storage of blood in the microcirculation system. The encountered shifts in the systemic hemodynamics may possibly be due to the reaction of the microcirculation channel, the labile character of which in the various "micro-areas" of the conjunctiva testifies to the complex reorganization of microcirculation under the effect of nitroglycerin.

Adult↗

[Features of microcirculation in the liver during anaphylactic shock].

Microcirculation in the liver was studied in rats and dogs with anaphylactic shock. Injection of a reacting dose of the horse serum led to elevation of systemic arterial pressure by an average of 20 mm Hg; there also occurred spasm of the sinusoids, hepatic venules and an acceleration of blood flow in them With the following blood pressure reduction to 60-40 mm Hg there was blood congestion in the vessels, retarded circulation, intravascular aggregation of the blood formed elements, hemorrhages and ischemic changes. Restoration of systemic arterial pressure and of microcirculation occurred in parallel; no complete normalization of microcirculation in the liver ensued, yet.

Anaphylaxis↗

Experimental study on liver microcirculation disturbance following transplantation and the protective effect of prostaglandin E1 in the rat.

OBJECTIVE: To determine the effect of PGE1 on liver microcirculation disturbance following orthotopic liver transplantation in rats. METHODS: Forty male adult Wistar rats were divided randomly into 3 groups. Eight transplantations were established in both the experimental and control group, while in the sham group, the liver was dissected like in the experimental group, but no resection was performed. In the experimental group, PGE1(0.5 microgram/kg.min-1) was injected intravenously into the donor before the operation, and added (1 mg/L) to the flush and preservation fluid, while PGE1 was replaced by normal saline in the control group. Confocal laser scan microscopy, biochemical test, and optical and electronic microscopy were used. RESULTS: In the control group the reperfusion state was poor, leukocyte infiltration appeared in the center of lobule, and transaminase rose after transplantation. In the experimental group distinctive improvement was seen as compared with the control group (P < 0.05). Histological findings showed progressive degeneration and necrosis following transplantation in the control group, while in the experimental group the histological changes were improved to some degree by the use of PGE1. CONCLUSIONS: In liver transplantation, ischemic reperfusion damage may lead to hepatic microcirculation disturbance, which is the major cause of graft failure. Infusing PGE1 into the donor intravenously before ischemia and adding PGE1 to the cold storage fluid could improve hepatic microcirculation, and thus reducing ischemic reperfusion damage in liver transplantation.

Alprostadil↗

[Diabetic arteriopathy. Microcirculation, an inevitable therapeutic objective].

The most severe stages of arteriopathy often involve multifocal macrovascular lesions leading to defective perfusion of the distal tissues and subsequent dysfunction of the microcirculation. Diabetic autonomous neuropathy facilitates and aggravates this endothelial dysfunction. Loss of vasomotricity, platelet and white cell activation, and cytokine release lead to an obstruction of the capillaries and alteration or even destruction of the endothelium. At this stage, the lesions are irreversible and tissue vitality is definitively compromised. The goal of medical treatment is to delay the development of dysfunction and subsequent destruction of the microcirculation before, during and after restoration of sufficient flow through the macrocirculation lesions by angioplasty and/or surgery. Extrapolating from in vitro and animal studies, two mediators, EDRF (NO) and prostacycline, could theoretically inactivate inappropriate activated cells and re-establish flow. Besides their vasodilator proprieties, NO and prostacycline have a synergetic inhibitory effect on platelet and leukocyte activation. The role of platelet antiaggregates and heparins in this stage of severe chronic ischemia remains to be determined. The relative failures of therapeutic drug trials conducted since the end of the eighties demonstrates the importance of intervening before the microcirulation disorders become too severe. Until new compounds are developed, therapeutic progress can be achieved by more precise and earlier detection of alterations in the microcirculation to enable optimal management of arteriopathy of the lower limbs with surgery or angioplasty.

Animals↗

Hepatic microcirculation as a morpho-functional basis for the metabolic zonation in normal and pathological rat liver.

The hepatic microcirculation is well known as a fundamental component of the liver structure, deeply involved in the zonal organization of the acinar structure. In cirrhosis, the microvascular tree shows dramatic changes that would heavily influence the development of the disease. When the cirrhosis becomes evident the result is a progressive organ failure, also in presence of only moderately decreased hepatocyte volume. The aim of this research was to compare the role of microcirculation of the hepatic zonation in normal and cirrhotic livers. Cirrhosis was experimentally induced in 36 rats following a controlled intragastric CCl4 administration. Cirrhotic and control normal livers were processed for routine light microscopy, histoenzimology, and scanning electron microscopy vascular corrosion cast. Control livers showed normal hepatic structure and microvascularization; enzymatic activities were constantly and normally distributed. In CCl4-treated animals LM showed a characteristic micronodular cirrhosis in all livers. Vascular corrosion casts under the scanning electron microscope displayed a progressive reduction of the distance between pre- and post-sinusoidal vessels and the presence of newly formed perinodular plexus. The histoenzymatic analysis demonstrated the loss of zonation in the cirrhotic parenchyma. Moreover, the sinusoid/hepatocyte ratio was significantly reduced, because of the presence of two or more hepatocyte thick laminae during the scarring development. The altered microcirculation in cirrhosis also changed the normal acinous metabolic gradient. The histoenzymatic study revealed a zonal rearrangement of the cirrhotic liver metabolic activity, that leads to a progressive hepatic failure. These data confirm the fundamental importance of the normal relationship between the hepatocyte laminae and the sinusoids for the preservation of a normal zonation which represents the basis for a normal liver function.

Animals↗

[Structure and function of pancreatic microcirculation].

To gain an insight into the relationship between structure and function in pancreatic microcirculation, observations were carried out in 9 corpse, 30 monkeys, 24 dogs, 62 Wistar rats and 24 rabbits by the use of scanning electron microscopy and light microscopy with the technique of retaining microcirculatory dynamic and tissular information in the static specimens, and/or by intravital fluorescence microscopy with FITC-labeled erythrocytes. The results showed: there were two capillary beds destined for the endocrine and exocrine parts of pancreas between the intralobular arteriole and venule; the blood of pancreatic portal circulation flowed from the endocrine to the exocrine part; each pancreatic lobule was supplied by a single centrally located intralobular artery and there was no anastomosis between the intralobular arterioles or any of their branches, so they were end arteries; the physiological blood flow was about 1.18 +/- 0.05 nl/min per capillary with stable capillary perfusion pattern; a profound decreased functional capillary density and capillary perfusion was observed in the early phase of acute pancreatitis. These results suggest that pancreatic lobule is a structured and functional basic unit of pancreatic microcirculation, insulo-acinar portal circulation represents the basic feature of the pancreatic microcirculation, and the intralobular arteriole, being an end artery, forms the anatomical basis of the pancreatic microcirculatory disturbance during acute pancreatitis.

Adult↗

[Effect of complete dentures on the blood flow and blood cell velocity of alveolar mucosal microcirculation].

The Purpose of this study was to determine the effects of complete dentures on alveolar mucosa microcirculation. The alveolar mucosal microcirculation of 17 edentulous subjects was measured by videomicroscope. The variance of the alveolar mucosa microcirculation before and after insertion of the dentures was compared. The results showed that: 7 days after wearing complete dentures, the mucosal blood flow and blood cell velocity of maxillary anterior alveolar ridge crest decreased significantly (P < 0.05), those of labial region of maxillary anterior alveolar ridge increased significantly (P < 0.05), 14 days after wearing complete dentures, the mucosal blood flow and blood cell velocity almost recovered the levels before wearing the dentures. The results can be relative to adjustment the occlusion in the early period of wearing the complete dentures and not wearing the complete dentures at night.

Adult↗

[Changes in microcirculation and selected laboratory parameters in the early stages of diabetic microangiopathy].

BACKGROUND: Early stages of diabetic microangiopathy are accompanied with dysfunction, manifested by changes of some biochemical parameters. Parallel changes were observed in microcirculation. The aim of this study was to compare microcirculation in the skin of a forearm evaluated by laser Doppler with selected laboratory markers of endothelial dysfunction in Type 1 diabetes mellitus without microangiopathy or with incipient microangiopathy. METHODS AND RESULTS: Group of 43 Type 1 diabetic patients was examined in this study. 20 of them had no signs of microangiopathy and in 23 patients a simple diabetic retinopathy (background retinopathy) was diagnosed. Control group consisted of 25 healthy persons of comparable age, sex, and body mass index. All persons involved in this study were examined by laser Doppler and by biochemical examination and the results were compared. In comparison with control group, in diabetic patients the arm occlusion significantly lowered the increase of perfusion (29 +/- 12 vs. 41 +/- 18 perfusion units (PU) p < 0.01). Similarly the perfusion velocity increase was significantly lower in diabetic patients than in healthy controls (p < 0.01). Also the velocity of the perfusion increase after the warming up was lower in the diabetic than in non-diabetic persons (p < 0.01). Such changes of perfusion or those of velocity of perfusion increase were significantly lower in diabetic patients with microangiopathy than in those without this complication. Perfusion increases after both stimuli highly correlated (r = 0.86, p < 0.001). In diabetic patients with microangiopathy significantly higher N-acetyl-beta-glucosaminidase (NAG) activities in serum and E-selection or ICAM-1 concentrations were found as compared with patients without microangiopathy, whereas plasma concentrations of tissue plasminogen activator (tPA) or inhibitor (PAI-1) were comparable with those in the control group. NAG activity inversely correlated with velocity of the perfusion increase after both the occlusion (r = -0.41, p < 0.01) and the warming (r = -0.38, p < 0.05). Similar relationship was found between tPA or E-selectin and the velocity of the perfusion increase after the occlusion (r = -0.48, p < 0.01). CONCLUSIONS: Our results confirm that biochemical parameters and microcirculation are impaired in the early stage of microangiopathy in Type 1 diabetic patients. Detailed analysis showed that both types of examination offer slightly different information on the vascular status. A long prospective study in diabetic patients without incipient vascular changes will be necessary to evaluate if biochemical or microcirculatory changes can bring an earlier information on the developing angiopathy.

Acetylglucosaminidase↗

[Changes of microcirculation in nasal mucosa during -15 degrees head-down tilt].

Changes of microcirculation in nasal mucosa in 19 young men during 2.5 h head-down -15 degrees tilt (DHT) were observed with Laser Doppler Flowmetry. The results showed that the change of microcirculation in nasal mucosa was significant, blood volume, concentration and the velocity of blood flow increased, and distinct periodical wave of microvessels appeared during HDT. The results suggest that the change of microcirculation in nasal mucosa caused by fluid shift from the lower to the upper body is one of the important factors causing stuffy nose and breathe with a little difficulty.

Aerospace Medicine↗

[Changes in the bulbar microcirculation under lateral light-color therapy in patients with glomerular nephritis].

Brain lateral light-colour stimulation-induced changes in bulbar microcirculation were studied in 47 patients (29 male and 18 female subjects) with chronic glomerulonephritis. After stimulation, a drop in arterial pressure was noted together with a decrease in red cell aggregation, dilation of arteries, increase in the number of functioning capillaries and in the velocity of microcirculation. A conclusion has been reached that the above stimulations can be an effective method for improvement of microcirculation in patients with chronic glomerulonephritis.

Adolescent↗