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p53 Immunoreactivity, Ki-67 expression, and microcirculation patterns in melanoma of the iris, ciliary body, and choroid.

PURPOSE: The major role of p53 is to modulate cell proliferation, but recently, it has been found that p53 also modulates angiogenesis through several pathways. Because both cellular proliferation and microcirculation patterns are important prognostic markers in uveal melanoma, we tested the relationships between p53 expression, the expression of the cell proliferation marker Ki-67, and the presence of various microcirculation patterns in uveal melanoma. METHODS: Immunostaining of p53 and Ki-67 using the bp53.12 and the MIB-1 antibodies, respectively, were preformed in 98 uveal melanomas (18 melanomas confined to the iris, 30 ciliary body melanomas, and 50 choroidal melanomas). Percent of p53 positive cells, and the mean MIB-1 positive cell count per high power field were calculated in each section by two observers. Microcirculation patterns were assessed in adjacent PAS stained sections. RESULTS: p53 immunoreactivity was found in 14 of the 98 melanomas. High proliferative activity and epithelioid cell type were associated with p53 immunoreactivity. However, p53 immunoreactivity was not associated with any of the microcirculation patterns or with tumor location. CONCLUSIONS: The findings suggest that alterations in p53 expression are associated with the expression of the cellular proliferation marker, Ki-67, but are not associated with the presence of microcirculation patterns.

Ciliary Body↗

Dynamics of skin microcirculation in humans.

The human cutaneous microcirculation has so far been studied by rather crude methods, such as plethysmography and 133Xn clearance. New sophisticated and noninvasive techniques are now available, with which the microcirculation of the skin can be continuously studied and measured for hours. With two such methods, i.e., Laser-Doppler flowmetry and dynamic capillaroscopy, fast dynamic fluctuations of the microcirculation can be followed. Under resting conditions, the total skin flow of a small area (1-2 mm2) varies consistently with time. These variations are caused by the arterial pulse, but also by active vasomotion with a frequency of about 4-8 cycles/min. These fluctuations can also be seen in single skin capillaries, but with a somewhat faster frequency: 6-10 cycles/min. The reaction of the cutaneous microcirculation to provocation tests, such as postocclusive reactive hyperemia response and venous occlusion (50 mm Hg), can also be studied. The time to peak during postocclusive reactive hyperemia is very consistent. In response to venous congestion, capillary flow rate falls drastically, whereas Laser-Doppler flow is much less dramatically reduced. These discrepancies suggest that the Laser-Doppler flowmeter records blood flow in skin vessels in addition to the superficial, nutritional capillaries. The dynamic pattern of the skin microcirculation is altered in patients with hypertension, diabetes, and obstructive arterial disease.

Blood Flow Velocity↗

Assessment of microcirculation of an axial skin flap using indocyanine green fluorescence angiography.

In many cases the complexities of skin-flap microcirculation are difficult to assess despite all the subjective and objective examination techniques available today. Adequate microcirculation is essential for tissue viability, so any method employed for studying microcirculation should provide as accurate an assessment of the prevailing conditions as possible. Of all the clinical methods, the fluorescence technique using the dye sodium fluorescein has so far provided the most reliable results. However, the pharmacokinetic properties of this tracer have prevented the technique from becoming established in clinical practice. The fluorescent dye indocyanine green (Cardio Green), on the other hand, has far more favorable pharmacokinetics. In an experimental animal model, the fluorescence technique using indocyanine green (indocyanine green angiography, ICGA) was used to study postoperative changes in the microcirculation of a skin flap. On the day of operation, indocyanine green angiography revealed a state of hemodynamic imbalance for which the organism was able to compensate in the postoperative phase with the aid of humoral, physical, and metabolic factors. With indocyanine green angiography it was possible to quantify objectively the new hemodynamic equilibrium. Basically, microcirculation may be quantified in temporal and spatial terms. The significant objectivity of indocyanine green angiography and short intervals between each examination favor its possible and meaningful use in clinical practice and give cause for continuing studies.

Angiography↗

Choroidal melanoma microcirculation with confocal indocyanine green angiography before and 1 year after radiation brachytherapy.

PURPOSE: The authors previously demonstrated that confocal indocyanine green (ICG) angiography is capable of imaging the microcirculation of choroidal melanomas. The purpose of this study is to report their observations regarding the response of the microcirculation using confocal ICG at 1 year after radiation brachytherapy. METHODS: Thirteen patients with unilateral choroidal melanoma were examined once before and several times up to 1 year after radiation brachytherapy (Iodine-125 or Ruthenium-106 plaque). At each visit, a complete ophthalmologic examination including standardized echography and fluorescein and ICG angiography was obtained, the latter using a confocal scanning laser ophthalmoscope. RESULTS: In 10 patients (77%), the tumor microcirculation changed considerably within 1 year after treatment. Distortion, thickening, thinning, and complete obliteration of vessels could be observed. In the other 3 patients (23%), no changes in the microcirculation were noticed within the observation period. CONCLUSIONS: Follow-up with confocal ICG of choroidal melanomas after treatment with local radiation brachytherapy allows for visualization of the microcirculation reaction following radiation brachytherapy. This provides the clinician with additional information for the posttreatment monitoring of these patients. Confocal ICG might also be a useful tool to monitor the effects of future antiangiogenesis-based tumor therapies in choroidal melanomas.

Adult↗

Orthogonal polarization spectral imaging as a tool for the assessment of hepatic microcirculation: a validation study.

BACKGROUND: Quantitative analysis of liver microcirculation using intravital fluorescence microscopy in animals has increased our knowledge about ischemia-reperfusion injury. However, because of the size of the instrumentation and the necessity of fluochromes for contrast enhancement, human liver microcirculation cannot be observed. Orthogonal Polarization Spectral (OPS) imaging is a recently introduced technique that can be used to visualize the microcirculation without the need for fluorescent dyes. It is a small, hand-held device and could potentially be used to study the microcirculation of the human liver in a clinical setting. However, before implementation into clinical use its ability to quantitatively measure microcirculatory parameters must be validated. METHODS: The livers of Spraque-Dawley rats (n=9) were exteriorized, and images were obtained using OPS imaging and intravital fluorescence microscopy of the identical microvascular regions before and after the induction of a 20-min warm lobar ischemia. Images were videotaped for later computer-assisted off-line analysis. RESULTS: OPS imaging can be used to accurately quantify the sinusoidal perfusion rate, vessel diameter, and venular red blood cell velocity. Correlation parameters were significant and Bland-Altman analyses showed good agreement for data obtained from the two methods at baseline as well as during reperfusion. CONCLUSION: OPS imaging can be used to quantitatively measure microcirculatory parameters in the rat liver under both physiological and pathophysiological conditions. Thus, OPS imaging has the potential to be used to make quantitative measurements of the microcirculation in the human liver.

Animals↗

How monitoring of the microcirculation may help us at the bedside.

PURPOSE OF REVIEW: Recent technologic developments have allowed the direct visualization of the microcirculation at the bedside. The present review explores how the monitoring of microcirculation can help in clinical practice. RECENT FINDINGS: Using orthogonal polarization spectral (OPS) imaging techniques, various investigators have reported microcirculatory alterations in critically ill patients and especially in patients with severe sepsis and septic shock. These alterations include a decrease in vessel density and an increased proportion of nonperfused or intermittently perfused capillaries. The persistence of these alterations is associated with the development of organ failure and death. Several therapeutic interventions, including vasoactive agents, fluid resuscitation, and activated protein C, can affect the microcirculation. Vasoactive agents have variable effects but vasodilatory agents seem very promising. Unfortunately, although many animal studies have investigated the effects of many of these interventions, human data are limited. SUMMARY: Microcirculation plays an important role in the pathogenesis of shock and organ dysfunction, especially in sepsis. Monitoring microcirculation at the bedside may be used to assess severity of the disease and to predict outcome, but in the absence of sufficient data regarding the effects of therapeutic interventions it cannot yet be used to guide therapy, even though this approach is promising.

Belgium↗

Biological effect of far-infrared therapy on increasing skin microcirculation in rats.

BACKGROUND/PURPOSE: Insufficient microcirculation of skin leads to acute and chronic tissue ischemia in cases of trauma, reconstructive surgery, diabetes mellitus and peripheral arterial occlusive disease. The autonomic nervous system and nitric oxide (NO) play important roles in maintaining blood perfusion of the skin. Far-infrared (FIR) therapy provides low energy of light emitted from an artificial radiator and has been used to treat many vascular-related disorders. Nevertheless, the mechanisms through which FIR works remain unclear. The present study aims to test the hypothesis that the effect of FIR is through increasing skin microcirculation by a mechanism other than its thermal effect. METHODS: Sixty rats were used in the present study. A WS TY301 FIR emitter was placed 20 cm above the rats. Skin temperature and blood flow were continuously measured by a K-type thermocouple. Under laboratory control, the abdominal skin temperature steadily increased from 38-39 degrees C, and was kept at constant temperature. Skin microcirculation was measured with a continuous laser Doppler flowmeter. RESULTS: There was no significant change of skin blood flow during FIR treatment. Skin blood flow increased significantly soon after the removal of the FIR emitter. The stimulating effect on skin blood flow was more significant in the rats treated with FIR for 45 min and could be sustained as long as 60 min. These findings suggested a non-thermic biological effect of FIR on skin microcirculation. The promotive effect of FIR on increasing skin blood flow was not influenced by pretreatment of APP (atropine, propranolol and phentolamine), but was suppressed by pretreatment with NG-nitro-L-arginine methyl ester (an endothelial nitric oxide synthase inhibitor). CONCLUSION: In conclusion, FIR therapy exerts a NO-related biological effect to increase skin microcirculation in rats. This might bring into perspective the clinical application of FIR to treat ischemic disease by augmenting L-arginine/NO pathway.

Animals↗

The organization of the salivary gland microcirculation.

1. The microvasculature of the rabbit submandibular salivary gland has been investigated employing in vivo microscopy, blood flow measurements, latex casts, microsphere injections and examination of fixed sections of the gland.2. Two principal microcirculations were distinguished in the living gland, one supplying the acini and the other the intralobular ducts. Parasympathetic nerve stimulation (2, 5 or 10 sec(-1)) elicited different responses in each of the two microcirculations. Flow in the capillaries around the acini slowed initially before increasing. In contrast, flow in the intralobular duct capillaries increased soon after beginning stimulation.3. In some experiments both whole gland flow and microvascular flow were monitored simultaneously. Whole gland flow increased at the same time as flow in the acinar capillaries was decreasing and as flow in the intralobular duct capillaries increased. Flow in acinar capillaries increased about 5 sec after glandular flow started to increase.4. These observations could be explained if either the vascular beds of the acini and the intralobular ducts were arranged in parallel or if arteriovenous anastomoses were to shunt the acinar circulation. No such anastomoses were found in latex casts made of the gland vasculature, and microspheres injected into the artery supplying the gland were not found in the venous effluent.5. The intraglandular distribution of microspheres was measured in histological sections of the injected glands to give an estimate of the distribution of blood flow between the duct and acinar microcirculations. At rest and during maintained stimulation about 55% of the blood flow passed through the intralobular duct microcirculations, whilst during this initial 15 sec of stimulation this proportion was increased to over 70%. This finding is consistent with a parallel arrangement of the two microcirculations.6. The conclusions drawn from these observations are that the duct and acinar microcirculations are arranged in parallel, that there are differences in the way the vasodilatation is mediated in these circulations, and that arterio-venous anastomoses play no significant role in this gland.

Animals↗

Strict control of glycaemia: effects on blood flow in the large retinal vessels and in the macular microcirculation.

AIMS: The purpose of this study was to investigate the effect of instituting strict diabetic glycaemic control on the retinal macular microcirculation and to compare this effect with that observed in the main retinal veins. METHODS: In 28 insulin dependent diabetic patients with poor glycaemic control a regimen of strict diabetic control, consisting of four daily insulin injections was instituted and maintained for 6 months. Retinal haemodynamics were investigated in the macular microcirculation by the blue field simulation technique and in the major retinal veins by a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography. Progression of diabetic retinopathy was assessed from fundus photographs taken at baseline and at the end of the study. RESULTS: Institution of strict diabetic control resulted in a significant increase in leucocyte velocity in the macular circulation (p = 0.013). No significant difference in this increase was observed between eyes that showed progression (n = 8) and no progression (n = 20) of retinopathy during the study. Significant correlations were found between relative changes over time of blood flow measured in the main retinal veins and relative changes of leucocyte velocity determined in the macular microcirculation at 2 months (p = 0.008) and 6 months (p = 0.001) but not at 5 days (p = 0.49). In the eight eyes that showed progression of retinopathy, the product of leucocyte velocity and density at baseline was significantly higher than normal (p < 0.05). During the length of this study, this product was also significantly higher in the eight eyes that showed retinopathy progression than in the 20 eyes that did not show progression (p = 0.005). CONCLUSION: Our results suggest that increased flow in the macular microcirculation may be associated with progression of retinopathy, thus supporting the hypothesis that increased blood flow may play a role in the development of diabetic microangiopathy. Although there are correlations between the changes detected in the macular microcirculation and those measured in the main retinal vessels, there are also differences which need to be further investigated in order to better understand pathogenetic mechanisms.

Adolescent↗

Effects of percutaneous transluminal angioplasty on skin microcirculation in patients with disabling peripheral arterial occlusive disease.

Percutaneous transluminal angioplasty (PTA) provokes a huge trauma to the arterial wall and potentially liberates fragments of atherosclerotic material that may impair the microcirculation downstream. Incidence and clinical relevance of such embolisms are not known. This study was aimed at investigating the changes of the skin microcirculation in patients with peripheral arterial occlusive disease undergoing PTA of the lower limbs. Pedal transcutaneous oxygen tension (tcpO2) and nailfold skin microcirculation were measured in 21 patients with disabling peripheral arterial occlusive disease before and after PTA. Sixteen matched patients undergoing arteriography alone were used as controls. The skin microcirculation was investigated at the nailfold of the great toe by the combination of laser Doppler fluxmetry and dynamic capillaroscopy. PTA was successful in all patients. The tcpO2 decreased immediately after PTA (delta tcpO2 = -5 mm Hg; p < 0.004), whereas it tended to increase (delta tcpO2 = 1 mm Hg; NS) following arteriography as compared with baseline values. By contrast, blood flow increased in both groups, predominantly for the total circulation in the PTA group and for nutritional circulation (p < 0.0017) in the arteriography group, respectively. Consequently, the 'nutritional index', i.e., the index of nutritional versus total microcirculation, was decreased following PTA, particularly following mechanical recanalization (p < 0.02), but did not change in the controls. The changes of this 'nutritional index' and those of the tcpO2 were positively correlated (r = 0.4, p = 0.023).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Advances in microcirculation network evaluation: an update.

Many methods are available today for clinical evaluation of the blood supply to an extremity or part of an extremity, some of which are excellent for determining the presence and severity of arterial and venous disorders. These methods, however, do not give any information on the microvascular status of the diseased areas. This is particularly true for the skin circulation, which has a rather complex vascular network with nutritional and thermoregulatory vessels, arteriovenous shunts, etc. The most useful method for clinical evaluation of the skin capillary circulation is vital capillary microscopy. The skin capillaries in an area with a reduced microcirculation change in structure, and it is possible to evaluate the viability of the skin by microscopic studies of these capillary changes. Both morphology and blood flow can be investigated. By using different intravital fluorescent dyes, e.g. sodium fluorescein and indocyanine green, the microvascular dynamics, flow distribution and microvascular permeability can also be studied. The total skin microcirculation can be evaluated by Laser Doppler fluxmetry, which measures primarily the blood flow in the thermoregulatory vascular bed, i.e. the subpapillary arterial and venous plexa. It is easy to use in clinical practice, but interpretation of the results can sometimes be difficult. Measuring transcutaneous oxygen tension has for many years been used in clinical routine to evaluate the viability of skin in patients with vascular disorders. It has recently been shown that inhalation of oxygen may induce vasoconstriction in healthy subjects and in patients with moderate arterial insufficiency, but an increase of the skin microcirculation in areas of severe ischaemia. By using different combinations of the above mentioned microcirculatory techniques, valuable information can be gained regarding pathophysiological phenomena of the microcirculation in many diseases, e.g. vascular disorders, collagenosis. Raynaud's phenomenon, diabetes and hypertension. Using techniques for both macro- and microcirculation is also of great importance for evaluating the effect of therapeutic procedures in several of these disorders.

Arterial Occlusive Diseases↗

Differential aspects of endothelial function of the coronary microcirculation considering myocardial virus persistence, endothelial activation, and myocardial leukocyte infiltrates.

BACKGROUND: Viral cardiomyopathy resulting from myocardial virus persistence can be associated with inflammatory immune responses that involve the myocardium and coronary blood vessels. The aim of this study was to investigate the differential impact of myocardial virus persistence and inflammation on endothelial function of the coronary microcirculation. METHODS AND RESULTS: In 71 patients with nonischemic cardiomyopathy, myocardial biopsies were examined for virus persistence (by polymerase chain reaction) and inflammation (by immunohistology). Endothelial function of the coronary microcirculation was examined during heart catheterization by measuring diameter (by quantitative coronary angiography) and velocity changes (by intracoronary Doppler) of the left anterior descending artery in response to acetylcholine. Coronary blood flow (CBF) was calculated. Endothelium-independent vasoreactivity to adenosine was assessed. Mean age of the patients (37 men, 34 women) was 43+/-13 years; mean ejection fraction was 64+/-11%. In 43 patients, adenovirus, enterovirus, parvovirus, or HHV-6 was detected; 28 had no virus. Endothelial function of the coronary microcirculation was significantly impaired in patients with myocardial virus persistence (V) compared with patients without virus (Co) (DeltaCBF-V, 22+/-86%; DeltaCBF-Co, 110+/-113%; P=0.001), which was confirmed in 51 patients with myocardial inflammation (MC) (32 with virus, 19 with no virus) (DeltaCBF-MC-V, 12+/-89%; DeltaCBF-MC-Co, 81+/-109%; P=0.034) and in 20 patients with normal immunohistology of the myocardial biopsies (Co) (11 with virus, 9 with no virus) (DeltaCBF-Co-V, 51+/-72%; DeltaCBF-Co-Co, 175+/-97%; P=0.006). Endothelial function of the coronary microcirculation was also significantly impaired in patients with myocardial inflammation/endothelial activation compared with patients without inflammatory immune response. Endothelium-independent vasodilation was not influenced significantly. CONCLUSIONS: Myocardial virus persistence and myocardial inflammation/endothelial activation are associated with endothelial dysfunction of the coronary microcirculation. Endothelial dysfunction in patients with myocardial virus persistence can occur independently of myocardial inflammation/endothelial activation but is more pronounced in patients with concurrent inflammation.

Adult↗

Effects of oxygen inhalation on skin microcirculation in patients with peripheral arterial occlusive disease.

BACKGROUND: Oxygen administration is currently used in clinical medicine to improve peripheral oxygen delivery to tissues threatened by ischemia. However, conflicting results have been reported on the effects of oxygen in ischemic areas. This study was aimed at investigating the effects of 40% oxygen inhalation on the skin microcirculation in the feet of patients with peripheral arterial occlusive disease (PAOD). METHODS AND RESULTS: Transcutaneous oxygen tension (tc PO2) was measured on the dorsal skin of the foot, and the nailfold microcirculation was investigated by a combination of laser Doppler flowmetry (LDF) and dynamic capillaroscopy (CBV) in the great toes of 17 legs of 11 patients, with 13 legs of eight normal subjects as a control group. Inhalation of oxygen induced a significant decrease of both the total (delta LDF, -307%, p less than 0.02) and nutritional (delta CBV, -17%, p less 0.002) skin microcirculation in normal legs compared with baseline values. A similar response was observed in 10 legs of patients who showed a significant increase of the tc PO2 (greater than or equal to 10 mm Hg) (delta LDF, -14%, NS; delta CBV, -13%, p less than 0.005). By contrast, both the total (+21%, p less than 0.03) and nutritional (+52%, p less than 0.05) circulation significantly increased in the seven legs without significant tc PO2 increase. In addition, the flow motion, which was impaired in the patients, was significantly (p less than 0.05) improved by oxygen inhalation. CONCLUSIONS: Inhalation of 40% oxygen induces a vasoconstriction in the skin microcirculation of toes of the normal subjects and patients with moderate PAOD but induces an increase of the skin microcirculation in patients with severe PAOD.

Administration, Inhalation↗

Achilles tendon and paratendon microcirculation in midportion and insertional tendinopathy in athletes.

BACKGROUND: Neovascularisation can be detected qualitatively by Power Doppler in Achilles tendinopathy. Quantitative data regarding tendon microcirculation have not been established and may be substantial. PURPOSE: To assess the microcirculation of the Achilles tendon and the paratendon in healthy volunteers as well as in athletes with either midportion or insertional tendinopathy. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: In 66 physically active volunteers, parameters of Achilles tendon and paratendon microcirculation, such as tissue oxygen saturation, relative postcapillary venous filling pressures, and microcirculatory blood flow, were determined at rest at 2-mm and 8-mm tissue depths. Forty-one patients never had Achilles pain (25 men, 27 +/- 8 years), 14 patients had insertional pain (7 men, 29 +/- 8 years), and 11 patients had midportion tendinopathy (7 men, 38 +/- 13 years, not significant). RESULTS: Achilles tendon diameter 2 cm and 6 cm proximal to the insertion was increased in symptomatic tendons. Compared with the uninvolved opposite tendon, deep microcirculatory blood flow was significantly elevated at insertional (160 +/- 79 vs 132 +/- 42, P < .05) as well as in midportion tendinopathy (150 +/- 74 vs 119 +/- 34, P < .05). The microcirculation in the uninvolved opposite tendon and the normal athlete controls were not significantly different from each other (132 +/- 42 insertional asymptomatic vs 119 +/- 34 mid-portion vs 120 +/- 48 healthy tendon). Insertional paratendon deep microcirculatory flow was elevated in all groups, whereas tissue oxygen saturation and relative postcapillary venous filling pressures were not significantly different. CONCLUSION: Microcirculatory blood flow is significantly elevated at the point of pain in insertional and midportion tendinopathy. Postcapillary venous filling pressures are increased at both the midportion Achilles tendon and the midportion paratendon, whereas tissue oxygen saturation is not different among the studied groups. We found no evidence of an abnormal microcirculation of the asymptomatic limb in Achilles tendinopathy.

Achilles Tendon↗

The microcirculation is the motor of sepsis.

Regional tissue distress caused by microcirculatory dysfunction and mitochondrial depression underlies the condition in sepsis and shock where, despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist. We have termed this condition microcirculatory and mitochondrial distress syndrome (MMDS). Orthogonal polarization spectral imaging allowed the first clinical observation of the microcirculation in human internal organs, and has identified the pivotal role of microcirculatory abnormalities in defining the severity of sepsis, a condition not revealed by systemic hemodynamic or oxygen-derived variables. Recently, sublingual sidestream dark-field (SDF) imaging has been introduced, allowing observation of the microcirculation in even greater detail. Microcirculatory recruitment is needed to ensure adequate microcirculatory perfusion and the oxygenation of tissue cells that follows. In sepsis, where inflammation-induced autoregulatory dysfunction persists and oxygen need is not matched by supply, the microcirculation can be recruited by reducing pathological shunting, promoting microcirculatory perfusion, supporting pump function, and controlling hemorheology and coagulation. Resuscitation following MMDS must include focused recruitment of hypoxic-shunted microcirculatory units and/or resuscitation of the mitochondria. A combination of agents is required for successful rescue of the microcirculation. Single compounds such as activated protein C, which acts on multiple pathways, can be expected to be beneficial in rescuing the microcirculation in sepsis.

Animals↗

Cutaneous microcirculation is not altered by a weak 50 Hz magnetic field.

Electromagnetic hypersensitivity (EH) is an increasing problem in modern industrial societies. As crawling sensations are frequently mentioned by EH patients alterations in cutaneous microcirculation possibly linked to exposure to magnetic fields might be involved in the development of such sensations and further dysesthesias. In seven healthy volunteers and in three persons convinced to suffer from EH the microcirculation of the right thumb was determined by laser-Doppler-flowmetry (LDF) during exposure to circularly polarized 50 Hz magnetic flux densities of 96 mT. During field exposure the LDF values remained constant. The LDF ratio "field on/field off" was found to be 1.03 +/- 0.03. In contrast, reactive hyperemia and hyperventilation caused significant changes in the LDF values of volunteers as well as of EH patients. Following arterial congestion of the forearm microcirculation of the thumb was clearly increased during reperfusion, and the LDF values were elevated up to 2.02 +/- 0.36. 10 deep breaths caused a significant decrease in the LDF values up to 0.63 +/- 0.18. In conclusion, reactive hyperemia and hyperventilation caused clear alterations of cutaneous microcirculation, whereas, 50 Hz magnetic fields had no influence on cutaneous microcirculation.

Adult↗

Role of the renal microcirculation in antihypertensive therapy.

BACKGROUND: The renal circulation plays a central role in regulating blood pressure and glomerular filtration. OBJECTIVE: To examine the effects of the various classes of antihypertensive agents on the renal microcirculation. SUMMARY: Peripheral vascular resistance is generally increased in hypertension, and the microcirculation makes the major contribution to resistance. In the kidney, the preglomerular and postglomerular vessels constrict to protect the glomerular capillary from increased hydrostatic pressure, further increasing peripheral resistance. Because the renal microcirculation adjusts to maintain glomerular filtration and blood flow, antihypertensive agents that can normalize the pressure and blood flow in these vessels may help prevent the long-term consequences of hypertension. Angiotensin-converting enzyme inhibitors directly affect preglomerular and postglomerular resistance, but they further decrease postglomerular resistance. Calcium antagonists selectively decrease preglomerular resistance. The diuretics, vasodilators, alpha blockers, and beta blockers may also cause changes in preglomerular and postglomerular resistance; however, compensatory reflex responses may mitigate their direct effects. CONCLUSION: Some antihypertensive agents have unique actions on the renal microcirculation that better maintain renal function. A basic understanding of the physiologic action of these agents on the microcirculation may help in their selection.

Antihypertensive Agents↗

Binge drinking disturbs hepatic microcirculation after transplantation: prevention with free radical scavengers.

Disturbances in hepatic microcirculation increase graft injury and failure; therefore, this study evaluates the effects of ethanol on microcirculation after liver transplantation. Donor rats were given one dose of ethanol (5 g/kg) by gavage 20 h before explantation, and grafts were stored in University of Wisconsin solution for 24 h before implantation. Acute ethanol treatment decreased 7-day survival of grafts from about 90 to 30%, increased transaminase release nearly 4-fold, and decreased bile production by 60%. Moreover, portal pressure increased significantly and liver surface oxygen tension decreased about 50%, indicating that ethanol disturbs hepatic microcirculation. Pimonidazole, a 2-nitroimidazole hypoxia marker, was given i.v. to recipients 30 min after implantation, and grafts were harvested 1 h later. Ethanol increased hepatic pimonidazole binding about 3-fold, indicating that ethanol led to hypoxia in fatty grafts. Ethanol also significantly increased free radicals in bile. Catechin (30 mg/kg i.v. upon reperfusion), a free radical scavenger, and Carolina Rinse solution, which contains several agents that inhibit free radical formation, minimized disturbances in microcirculation and prevented pimonidazole adduct formation significantly. These treatments also blunted increases in transaminase release and improved survival of fatty grafts. Destruction of Kupffer cells with GdCl(3) (20 mg/kg i.v. 24 h before explantation) or inhibition of formation of leukotrienes with MK-886 (50 microM in University of Wisconsin or rinse solution) also minimized hypoxia and improved survival after transplantation. Taken together, these results demonstrate that ethanol disturbs hepatic microcirculation, leading to graft hypoxia after transplantation, most likely by activating Kupffer cells and increasing free radical production.

Animals↗