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The effect of glycoprotein IIb/IIIa receptor inhibitor on the microcirculation in patients undergoing high-risk coronary stenting; a prospective, randomized study.

OBJECTIVES: We evaluated the effect of the glycoprotein IIb/IIIa inhibitor, tirofiban, on the microcirculation measured by Doppler coronary flow reserve (CFR) in patients undergoing high-risk coronary stenting. BACKGROUND: The mechanisms by which glycoprotein IIb/IIIa inhibitors benefit patients undergoing high-risk angioplasty are not fully understood. This may be due to prevention of distal embolization of the coronary clot at the site of angioplasty. METHODS: Thirty two consecutive patients with acute coronary syndrome within 72 hours or with high-risk angiographic features were randomized into 2 groups. Group A (n = 17) received tirofiban (10 microg/kg bolus followed 0.15 microg/kg/min). Group B (n = 15) received placebo bolus and infusion. Coronary flow reserve was measured by Doppler wire technique at baseline, post balloon angioplasty and post-stenting. Platelet aggregation was measured at baseline, 10 minutes, 6 hours and 12 hours post bolus. RESULTS: There was no significant difference in CFR between the groups at baseline and after balloon angioplasty. Post-stenting CFR, however, was significantly higher in the group pretreated with tirofiban (2.94 vs. 2.25, p = 0.014). The inhibition of platelet aggregation was 94% at 10 minutes, 97% at 6 hours and 94% at 12 hours in the tirofiban group. CONCLUSION: In patients undergoing high-risk coronary stenting, tirofiban protects and improves the microcirculation measured by Doppler wire technique. This may be due to prevention of distal embolization of clot by tirofiban and explain the clinical benefit.

Aged↗

Effects of vacuum compression therapy on skin microcirculation in patients suffering from lower limb ischaemia.

BACKGROUND: We investigated the short-term effect of vacuum compression (VC) treatment on skin microcirculatory perfusion in the foot of patients with lower limb ischaemia and healthy controls. PATIENTS AND METHODS: Ten patients with intermittent claudication or rest pain and 5 healthy controls underwent vacuum-compression treatment for half an hour. The leg was positioned in an air-tight plexiglass cylinder in which hypobaric (-115 mm Hg) and hyperbaric (75 mm Hg) pressure could be generated alternately, in order to improve peripheral circulation. The effect on skin microcirculation was investigated using nailfold capillary microscopy (measuring nutritive perfusion), laser Doppler fluxmetry (LDF) (total skin perfusion) and transcutaneous oxygen tension measurements (TcpO2). RESULTS: A few patients experienced ischaemic symptoms during VC, probably because the leg was pinched off through inflation of the cuff. In both patients and controls capillary microscopic parameters did not change significantly. In some cases, microcirculatory perfusion decreased because the leg had cooled during the treatment. Application of a heating matrass annihilated this effect. Only in the patient group a few LDF- and TcpO2 parameters improved slightly, but significantly. CONCLUSION: Vacuum-compression therapy only slightly improves total skin perfusion and oxygenation, but not the nutritive microcirculation, being an essential factor in the occurrence of ischaemic symptoms. We therefore conclude that this instrument in its present form is not an aid in the treatment of lower limb ischaemia.

Aged↗

Leucocyte interactions with the mouse cremaster muscle microcirculation in vivo in response to tumour-conditioned medium.

Leucocyte interactions with the cremaster muscle microcirculation in vivo were investigated in response to culture medium conditioned with different cell types in 25 adult male Swiss mice. Animals were divided into five groups. Three groups received ex vivo fluorescently labelled lymphokine activated killer (LAK) cells systemically and had either tumour (murine melanoma K1735)-conditioned medium (TCM), fibroblast (murine 3T3)-conditioned medium (FCM) or fresh culture medium administered topically to the cremaster muscle. In the two remaining groups, the host leucocytes were labelled fluorescently by systemic administration of acridine red, and either TCM or FCM was applied topically to the cremaster muscle. There was an immediate but transient increase in the frequency of rolling and adherent LAK cells, and a subsequent (90-120 min later) increase in rolling and adherent host leucocytes, demonstrating temporal differences in the response to topical administration of TCM. These increases in contact with the vascular endothelium occurred in all vessel types, venules, arterioles and capillaries, with the greatest response observed in the venules. The FCM and normal culture medium did not affect the distribution and localization of either LAK cells or host leucocytes. These data suggest that there are one or more soluble tumour-specific chemoattractants for leucocytes present in the conditioned medium. The mouse cremaster muscle microcirculation is therefore a useful model to investigate the mechanism of leucocyte-endothelium interactions in tumour biology.

Animals↗

Comparative effects of L-NOARG and L-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation.

1. The effects of N omega-nitro-L-arginine (L-NOARG) and N omega-nitro-L-arginine methyl ester (L-NAME) on diaphragmatic microcirculation in male Sprague-Dawley rats were assessed under basal conditions and after acetylcholine (ACh) stimulation. In addition, L-arginine (L-arg) was used with the aim of preventing L-NOARG and L-NAME from inhibiting ACh-induced vasodilatation, in order to explore the possibility that L-NOARG is not only a nitric oxide (NO) synthase inhibitor but also a muscarinic receptor antagonist. 2. Male Sprague-Dawley rats were anaesthetized with urethane and mechanically ventilated. The left hemi-diaphragm of each rat was prepared and microvascular blood flow was recorded during continuous superfusion with bicarbonate-buffered prewarmed Ringer solution by using laser-Doppler flowmetry. The drugs were topically applied to the surface of the hemi-diaphragm. 3. Baseline microvascular blood flow was unaffected after 15 min superfusion with any one of the following agents: L-NOARG (0.1 mM). L-NAME (0.1 mM), L-arg (10 mM). 4. ACh (0.03 mM, 0.1 mM and 0.3 mM) elicited a significant increase of microvascular blood flow (171 +/- 16%, 214 +/- 55%, and 323 +/- 68% of baseline values, respectively), via interaction with the muscarinic receptor, for the vasodilator response was severely inhibited by 15 min superfusion with atropine (0.3 mM). 5. Following 15 min superfusion with either of the L-arg analogues (0.1 mM), the ACh-induced vasodilator response was significantly inhibited. Pretreatment with L-arg (10 mM) for 5 min, followed by co-administration of L-arg (10 mM) and L-NOARG (0.1 mM) for another 15 min significantly prevented the inhibitory effect of L-NOARG or ACh-induced vasodilatation. However, a similar pretreatment schedule with L-arg failed to prevent L-NAME from exerting its inhibitory effect. 6. Neither of the L-arg analogues potentiated sodium nitroprusside (10 microM and 30 microM)-induced vasodilatation. However, adenosine (0.1 mM)-induced vasodilatation was slightly but significantly attenuated by either L-NOARG (0.1 mM) or L-NAME (0.1 mM), an effect which was prevented by L-arg (10 mM). 7. In conclusion, an increase in endothelium-dependent blood flow stimulated by ACh may occur in diaphragmatic microcirculation of anaesthetized rats independently of low baseline NO activity. The results also suggest that L-NAME has muscarinic receptor antagonist action in addition to its ability to inhibit NO synthase. Thus, we suggest that L-NAME should not be used as a specific NO synthase inhibitor in the rat diaphragm in situations in which there is potential for muscarinic receptors to be stimulated.

Acetylcholine↗

The involvement of ATP-sensitive potassium channels in beta 2-adrenoceptor agonist-induced vasodilatation on rat diaphragmatic microcirculation.

1. The effects of glibenclamide (GLB), a blocker of ATP-sensitive potassium (KATP) channels, on diaphragmatic microcirculation in male Sprague-Dawley rats were assessed under basal conditions and after beta 2-adrenoceptor-agonist stimulation. In addition, forskolin was used to bypass beta-adrenoceptors and GTP-binding proteins (G-protein) to explore the possible mechanism of GLB effects. For comparison, the relationships between KATP channel activity and cyclic GMP-mediated vasodilator responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were also assessed. 2. Male Sprague-Dawley rats were anaesthetized with urethane and mechanically ventilated. The left hemi-diaphragm of each rat was prepared and microvascular blood flow (QLDF) was recorded with laser-Doppler flowmetry during continuous superfusion with bicarbonate-buffered, prewarmed Ringer solution. The drugs were topically applied to the surface of the hemi-diaphragm. 3. Salbutamol (0.32-32 microM), terbutaline (0.32 microM-0.32 microM) and forskolin (0.32-10 microM) each elicited a concentration-dependent increase in QLDF. 4. Baseline microvascular blood flow was unaffected by a 30 min suffusion of 1 microM GLB (295 +/- 51 mV vs 325 +/- 62 mV. P = 0.738). 5. The vasodilator response elicited by salbutamol (0.32 microM, 1 microM and 3.2 microM and 10 microM), was significantly attenuated by a 30 min superfusion with 1 microM GLB; this salbutamol-induced vasodilatation was mediated via an interaction with beta-adrenoceptor receptors, as in other experiments it was greatly inhibited by 30-min superfusion with propranolol (10 microM). 6. Similarly, following 30-min superfusion with GLB (1 microM), the terbutaline (1 microM, 3.2 microM and 10 microM)-induced vasodilator response was almost abolished and the vasodilator responses induced by incremental concentrations of forskolin (0.32 microM, 1 microM and 3.2 microM) were also significantly attenuated. 7. Cromakalim (1.5 microM, 3 microM and 3.2 microM) produced an increase of QLDF in a dose-dependent manner, which was virtually abolished by GLB (1 microM). In contrast, the vasodilator responses induced by acetylcholine (32 microM, 0.1 mM, and 0.32 mM) or sodium nitroprusside (3.2 microM, 10 microM and 20 microM) were independent of GLB (1 microM). 8. In conclusion, KATP channels may be functional, but tonically inactive in the resting diaphragmatic microcirculation and the vasodilator effect of beta 2-adrenoceptor agonists may be partly mediated by KATP channels; the activation of KATP channels may involve the accumulation of cyclic AMP in vascular smooth muscle cells.

Adenosine Triphosphate↗

Application of physiological genomics to the microcirculation.

Physiological genomics represents a new challenge in the biological sciences-the quest to define the functions of thousands of genes that will emerge from the sequencing of the human genome and the genomes of other model organisms. Because the attention of the scientific community has focused on this task, new tools that will allow high-efficiency identification of gene function are being developed at remarkable speed. Physiological genomic approaches to understanding integrated systems function are now becoming widely used in many areas of biological research. The availability of genomic information across species has now revealed a striking degree of conservation of both gene order and function, allowing researchers to easily move from model organisms to man in the hunt for gene function. Physiological genomics approaches in the cardiovascular system have focused on disease-based models and the behavior of large vessels. In the microcirculation, genomic studies have largely been confined to the use of single gene knockouts or to the study of angiogenesis. This review summarizes the strategies for physiological genomics that are appropriate to the study of the microcirculation and discusses several key discoveries that have been made by using these approaches.

Animals↗

Endothelin-a receptor antagonist treatment improves the periosteal microcirculation after hindlimb ischemia and reperfusion in the rat.

OBJECTIVES: To examine the microcirculatory changes in the rat tibial periosteum after hindlimb ischemia and reperfusion and to evaluate the effects of endothelin-A (ET-A) receptor antagonist therapy in this condition. The healing and functioning of vascularized bone autografts depend mainly on the patency of the microcirculation, and the activation of ET-A receptors may be an important component of the tissue response that occurs during ischemia-reoxygenation injuries. METHODS: Wistar rats were subjected to 1 hour of hindlimb ischemia and 3 hours of reperfusion. The periosteal microcirculation was visualized by intravital fluorescence microscopy. The leukocyte rolling and adherence in the postcapillary venules and the functional capillary density of the periosteum were determined. Two separate groups were treated with the selective ET-A receptor antagonist BQ 610 or the novel ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion. RESULTS: Reperfusion was accompanied by a significant decrease in functional capillary density and by an increase in the primary and secondary leukocyte-endothelial cell interactions. ET-A receptor inhibition reduced the leukocyte rolling and firm adherence and attenuated the decrease in functional capillary density in both treated groups. CONCLUSIONS: ET-1 plays a major role in microvascular dysfunction in the periosteum during reperfusion. The ET-1-ET-A receptor system might be an important target for tissue salvage therapy in transplantation surgery.

Animals↗

Microcirculation as a target for the anti-inflammatory properties of statins.

Statins are inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a ubiquitous enzyme critical for the biosynthesis of cholesterol. Because of their cholesterol-lowering properties, statins are extensively used in medical practice, and large clinical trials have shown that statins effectively reduce cardiovascular related morbidity and mortality. In the past 5 years, an important, new concept suggesting that the cardioprotective effects of statins are not necessarily related to cholesterol-lowering actions has emerged. Indeed, in vivo findings have clearly shown that statins exert anti-inflammatory and immunomodulatory effects and that they modulate vascular remodeling under normocholesterolemic conditions. These pleiotropic properties of statins affect important molecules in vascular biology and help preserve endothelial function in acute and chronic inflammatory states of the cardiovascular system, including coronary and cerebral artery diseases, diabetes, and atherosclerosis. Emerging evidence indicates that the microcirculation is a crucial target for the pleiotropic actions of statins because of its important role in regulating blood flow, leukocyte-endothelium interactions, and vascular remodeling. Accordingly, this review focuses on the role that the microcirculation plays in the vascular protective action of statins.

Anti-Inflammatory Agents↗

Remodeling in the microcirculation of rat skeletal muscle during chronic ischemia.

OBJECTIVE: To establish the time course and extent of remodeling of terminal microcirculation in ischemic rat skeletal muscle during prolonged low flow that does not lead to inflammation. METHODS: One common iliac artery was ligated via laparotomy in adult Sprague-Dawley rats and extensor digitorum longus (EDL) muscles removed at intervals (1, 2, and 5 weeks) postsurgery. Serial frozen EDL sections were stained to show capillaries (alkaline phosphatase), cell proliferation (antibody to proliferating cell nuclear antigen [PCNA]), terminal microvessels (antibodies to alpha-smooth muscle actin (alpha-SMA) or endothelial nitric oxide synthase [eNOS]), and macrophages (antibodies to infiltrating and resident macrophages). Total muscle eNOS protein was quantified by standard Western blotting techniques. RESULTS: Capillary proliferation was very limited in ischemic EDLs, with a modest 12% increase in the capillary/fiber ratio after 5 weeks, preceded at 2 weeks by increased numbers of PCNA-positive nuclei at capillary sites. There was no muscle necrosis or evidence of inflammation, based on macrophage staining. The number of terminal microvessels that were positive for alpha-SMA and <10 microm in diameter was fewer in ischemic EDLs at all time points, whereas the number of larger positive vessels was unchanged. eNOS-positive vessels <10 microm in diameter were stained similarly throughout ischemic muscles as the controls, and showed a similar increase in vessel/fiber ratio as the capillaries. The total eNOS protein level was similar to that in controls in ischemic EDLs after 1 and 2 weeks, but was 28% lower after 5 weeks. CONCLUSIONS: Prolonged, moderate flow reduction to skeletal muscles does not necessarily lead to inflammation or extensive capillary growth. Based on eNOS staining, the terminal microcirculation remains intact, but the loss of alpha-SMA immunoreactivity may indicate remodeling involving the "deinvestment" of microvessels by smooth muscle.

Actins↗

Intravital fluorescence videomicroscopy to study tumor angiogenesis and microcirculation.

Angiogenesis and microcirculation play a central role in growth and metastasis of human neoplasms, and, thus, represent a major target for novel treatment strategies. Mechanistic analysis of processes involved in tumor vascularization, however, requires sophisticated in vivo experimental models and techniques. Intravital microscopy allows direct assessment of tumor angiogenesis, microcirculation and overall perfusion. Its application to the study of tumor-induced neovascularization further provides information on molecular transport and delivery, intra- and extravascular cell-to-cell and cell-to-matrix interaction, as well as tumor oxygenation and metabolism. With the recent advances in the field of bioluminescence and fluorescent reporter genes, appropriate for in vivo imaging, the intravital fluorescent microscopic approach has to be considered a powerful tool to study microvascular, cellular and molecular mechanisms of tumor growth.

Animals↗

An effective and economical solution for digitizing and analyzing video recordings of the microcirculation.

OBJECTIVE: To assemble an economical system for analysis of microcirculation movies. METHODS: Images of cremaster microvessels were recorded onto sVHS video cassettes. These recordings were digitized onto a Macintosh computer using a MiroMotion DC30 plus video compression card and Adobe Premiere software, which permits video rate (25-30 fps) capture of full-sized (768 x 576 PAL, 640 x 480 NTSC) frames. Once captured, images were analyzed using NIH Image software. RESULTS: Combination of the Macintosh computer, the MiroMotion card, and Adobe Premiere allowed capture of high-resolution images at video rate, with the only limitation to sequence length being available hard-drive space. Captured movies could be directly accessed using the freely available NIH Image software. Use of built-in analysis tools and custom-written macros greatly facilitated rapid, accurate, and reproducible analysis of parameters such as blood flow velocity, leukocyte rolling velocity, and firm adhesion. CONCLUSIONS: Low-priced hardware and software aimed at the home-video enthusiast can be combined with free image-analysis software to provide a powerful image-analysis solution for study of the microcirculation.

Animals↗

Vasomotion in rat diaphragm microcirculation at rest and during stepwise arterial pressure reduction.

The effect of haemorrhagic hypotension on the incidence, frequency and relative amplitude of vasomotion in rat diaphragm microcirculation was assessed by laser Doppler flowmetry (LDF). Graded bleeding to four hypotension levels (80, 60, 40 and 30% of the control state) were performed in 24 Sprague-Dawley rats. The incidence of vasomotion was 83% in the control state, 96% at the 80% level, 100% at the 60% level, 96% at the 40% level, and 46% at the 30% level. The median fundamental frequency of vasomotion determined manually during the control state and at the hypotension levels (in descending order) was 4.11 (range, 3.29-5.58) cycles min-1 (cpm), 4.48 (3.21-5.92) cpm, 4.20 (3.5-5.56) cpm, 4.01 (3.33-5.36) cpm, 3.71 (3.25-4.49) cpm (P < 0.01 from the fundamental frequency at 80 and 60% hypotension levels). The median relative amplitudes determined manually during the control state and descending hypotension levels were 44.5% (range, 24.9-135.9%), 69.4% (26.6-147.2%), 84.0% (40.3-177.1%) (P < 0.01 from resting and last stage of bleeding), 90.40% (26.2-189.6%) (P < 0.01 from resting and last stage of bleeding), 69.2% (35.6-93.2%). We concluded first that during the resting condition, vasomotion was frequently present in diaphragm microcirculation, which is distinct from other vascular beds of skeletal muscles. Second, the relative amplitude of vasomotion during haemorrhagic hypotension plotted against decreasing blood pressure exhibited a reverse U-shaped curve with a maximum at 40-60% of the control blood pressure, while the frequency of vasomotion remained relatively constant until the last stage of haemorrhage and centred around 3-5 cpm.

Animals↗

The behaviour of red cells in narrow tubes in vitro as a model of the microcirculation.

To investigate the behaviour of red cells in the microcirculation, we established a new capillary method using narrow fluorinated ethylenepropylene copolymer tubes with internal diameters of 12.5 and 25.0 microns. Red cell flow in the tubes under a given range of pressure was analysed through a video system connected to a microscope. The experimental condition was adjusted so that the velocity of the control normocytes would be compatible with that in corresponding vessels in vivo, 0.5-1.5 mm/s. In the 12.5 microns tube, normocytes obtained from 12 young normal volunteers ran in an axisymmetric edge-on orientation with a folded shape at higher pressures, but rolled along freely without deformation at lower pressures. Deformation during the passage of the microcytes obtained from four patients with polycythaemia vera complicated with iron-deficient microcytosis and 10 patients with iron deficiency anaemia was relatively mild, whereas that of the macrocytes obtained from eight patients with refractory anaemia was marked. Even after the screening effect at the tube entrance was taken into consideration, the velocities of both microcytes and macrocytes were found to be significantly lower than the control normocytes. Therefore this method may be a new way to investigate the flow properties of red cells in the microcirculation.

Adult↗

Acute hyperglycaemia causes severe disturbances of mesenteric microcirculation in an in vivo rat model.

BACKGROUND: Chronic hyperglycaemia in diabetes is suggested to be a major cause of diabetic angiopathy. Up until now, the effects of acutely induced hyperglycaemia in non-diabetic subjects as well as hyperglycaemic effects in early diabetes, on mesenteric microcirculation and leucocyte endothelial cell interaction have not been investigated extensively. METHODS: The aim of this study was to examine rat mesenteric microcirculatory parameters such as leucocyte adhesion, leucocyte emigration, venular shear rate and leucocyte rolling velocity using a new rat model both with continuous venous glucose infusion and with continuous arterial measurement of blood glucose concentration while observing mesenteric microcirculation with in vivo capillary microscopy in the non-diabetic and diabetic state. RESULTS: In normal non-diabetic rats, acute elevation of glucose concentration resulted in a highly significant, rapid and step-by- step enhancement of adhesion and emigration in a dose dependent manner. Leucocyte rolling velocity was reduced with rising glucose levels. Venular shear rate showed a similar reduction at all hyperglycaemic levels. In streptozotocin-induced diabetes, adhesion and emigration were significantly enhanced while shear rate and leucocyte rolling velocity were severely reduced, resembling the effects of glucose infusion experiments. Longer duration of diabetes resulted in a further enhancement of leucocyte adhesion and reduction of leucocyte rolling velocity while emigration and shear rate were not influenced by a longer period of diabetes manifestation. CONCLUSION: Experiments using different mannitol concentrations revealed that most of the observed glucose effects can be mimicked by mannitol and are therefore - at least in part - due to changes in osmolarity by yet unknown mechanisms.

Acute Disease↗

Atrial natriuretic peptide, brain natriuretic peptide and c-type natriuretic peptide: effects on testicular microcirculation and immunohistochemical localization.

The effect of local injection of atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides and an ANP antagonist (HS-142-1) on testicular microcirculation and vasomotion was studied using laser Doppler flowmetry. The natriuretic peptides were also localized immunohistochemically within the testis. ANP, BNP-32, CNP-22 and CNP-53 all caused a dose-related increase in testicular blood flow. The effect of ANP was blocked by concomitant injection of the ANP antagonist. Immunoreactive (ir) CNP and ir BNP were found in Leydig cells whereas in ANP was observed in the seminiferous tubules. It is suggested that the natriuretic peptides could play a role in local regulation of the testicular microcirculation.

Animals↗

Activity of cardiopulmonary baroreceptors, peripheral resistance and cutaneous microcirculation in patients with peripheral obstructive arterial disease.

OBJECTIVES: To assess the effects of cardiopulmonary baroreceptors on the haemodynamics of the humeral and common carotid arteries in patients suffering from peripheral artery disease (PAD) and to discover whether the stimulation of these receptors modifies the cutaneous microcirculation in the forearm. DESIGN: We studied a group of patients suffering from peripheral artery disease and two groups as controls. SETTING: Patients were examined at the ambulatory for Vascular Research, Division of Vascular Medicine and Rehabilitation, University of Verona. PATIENTS: We studied 15 patients with peripheral artery disease of the lower limbs at Fontaine stage II (group C), 10 free of arterial pathologies (group B) and 10 young people (group A). MAIN OUTCOME MEASURES: We subjected the patients to passive elevation of the legs and the trunk in a horizontal position with pressure monitoring and measurement of the calibre and flow in the brachial and common carotid arteries using a colourDoppler ultrasound. We also studied the cutaneous microcirculation with laserDoppler flowmetry. RESULTS: During the test, arterial pressure and cardiac frequency remained constant in group A, systolic pressure values showed a slight, but statistically significant increase in group B, whilst the increase in systolic pressure values at this stage was marked in group C. Diastolic pressure values and cardiac frequency remained unchanged in all groups. The calibre of the humeral artery increased in the control groups. Carotid resistance was unchanged in the three groups. Humeral resistance during the test decreased in the two control groups whilst it increased in group C. The number of perfusion units felt in the control groups; no variations in group C. CONCLUSIONS: Our study demonstrates, in patients with peripheral artery disease, a reduction in the activity of the cardiopulmonary baroreceptors with an increase in the humeral resistance during the test and impairment of the mechanisms of cutaneous microcirculatory vasoregulation in the forearm.

Aged↗

Cerebral thrombosis and microcirculation of the rat during the oestrous cycle and after ovariectomy.

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

Animals↗

The single breath transfer factor (Tl,co) and the transfer coefficient (Kco): a window onto the pulmonary microcirculation.

The transfer factor, Tl,co (with the transfer coefficient, Kco, also known as the transfer factor per unit alveolar volume, [Tl/Va]), is one of the most useful clinical tests of pulmonary function, the only one which specifically focuses on pulmonary microcirculation. It was originally devised in 1909 as a physiological tool to assess the diffusive capacity of the lung as a gas exchanger. It was subsequently developed as a clinical tool, but cumbersome analytical techniques delayed its introduction into clinical medicine until 1950s. The physiology of the carbon monoxide transfer factor (also called the diffusing capacity Dl,co) is based on the Roughton-Forster equation which partitions Dl,co, a conductance, into membrane (Dm) and red cell (thetaVc) diffusion conductances. Recent work (1987-2001) suggests that 70-80% of the resistance to CO (and O2) diffusion may reside in the red cell fraction. The clinical implication is that Tl,co and Kco are 'windows' onto the pulmonary microcirculation. As regards reference values for clinical use, Tl,co depends on age, height and gender. Kco, which is actually a rate constant, is independent of gender, and is affected principally by age. A schema is presented for the clinical interpretation of Tl,co. As Tl,co is derived from the product of Kco and the accessible alveolar volume (Va), examination of these two components (Kco and Va) will usually suggest a specific pathophysiological mechanism as the explanation for a reduction in Tl,co.

Humans↗