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Microvascular Dysfunction (microvascular + dysfunction)
Selected AbstractsMechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular diseaseACTA PHYSIOLOGICA, Issue 1 2010D. Lominadze Abstract Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content. [source] Increased strength of erythrocyte aggregates in blood of patients with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2009Nitsan Maharshak MD Abstract Background: Increased strength of red blood cell (RBC) aggregates are present during the acute inflammatory response and contribute to erythrocyte aggregation and may lead to microvascular dysfunction. Inflammatory bowel diseases (IBDs) are characterized by damage to the bowel wall. This damage may be at least partially attributed to microvascular ischemia caused by enhanced erythrocyte aggregation. The aim of this study was to evaluate the strength of RBC aggregates in the blood of patients with IBD. Methods: The strengths of RBC aggregates were characterized by integrative RBC aggregation parameters, determined by measuring of RBC aggregation as a function of shear stress. The results are represented as the area under the curve (AUC) of aggregate size plotted against shear stress. For each patient, dynamic aggregation and disaggregation of RBC were recorded and analyzed according to the RBC aggregate size distribution at the different shear stresses. Aggregation indices were correlated with disease activity and inflammatory biomarkers. Results: We examined 53 IBD patients and 63 controls. IBD patients had significantly elevated concentrations of inflammation-sensitive proteins and aggregation parameters. The strength of large aggregates, represented by AUC for large fraction aggregates, among patients (15.2 ± 18.6) was double that of controls (7 ± 10.9) (P = 0.006). The strength of large aggregates correlated with disease activity (r = 0.340; P < 0.001) with concentration of fibrinogen (r = 0.575; P < 0.001) and with concentration of high sensitivity C-reactive protein (r = 0.386; P < 0.001). Conclusions: The strength of RBC aggregates is increased in patients with IBD and correlates with the intensity of the acute phase response. This could contribute to bowel damage in these diseases. (Inflamm Bowel Dis 2009) [source] Role of endothelin in endotoxin-induced hepatic microvascular dysfunction in rats fed chronically with ethanolJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2001Yoshinori Horie Abstract Background: We examined the role of endothelin in endotoxin-induced hepatic microcirculatory disturbance in pair-fed rats given a liquid diet containing ethanol or isocaloric control. Methods and Results: One lobe of the liver was observed with the use of an intravital microscope. Erythrocytes (RBCs) labeled with fluorescein isothiocyanate (FITC) were injected, and the flow velocity of the FITC-RBCs in the sinusoids was measured with an off-line velocimeter. The flow velocity decreased 30 min after 1 mg/kg of lipopolysaccharide (LPS) was administered to the controls, and portal pressure (PP) was increased at 60 min. In ethanol-fed rats, however, both the flow velocity and PP increased in the early phase (at 10 min), and in the late phase, flow velocity decreased and PP increased more than in the controls. The LPS-induced decrease in flow velocity was blunted, when BQ-123, an antagonist of endothelin receptor subtype A, was infused into ethanol-fed rats, and BQ-123 also attenuated the change in PP. The plasma endothelin levels in both systemic and portal blood of the ethanol-fed rats were higher than in the controls. Conclusions: These results suggest that endothelin plays a role in the LPS-induced hepatic microcirculatory disturbance, especially in alcohol-fed animals. [source] The Prognostic Value of Combined Fractional Flow Reserve and TIMI Frame Count Measurements in Patients with Stable Angina Pectoris and Acute Coronary SyndromeJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2010ALI M. ESEN M.D. Background:,The aim of this study was to evaluate the prognostic value of different fractional flow reserve (FFR) cutoff values and corrected thrombolysis in myocardial infarction frame (TIMI) count (CTFC) measurements in a series of consecutive patients with moderate coronary lesions, including patients with unstable angina, myocardial infarction, and/or positive noninvasive functional test findings. Methods:,We included 162 consecutive coronary patients in whom revascularization of a moderate coronary lesion was deferred based on a FFR value ,0.75. Patients were divided according to the results of the intracoronary pressure and flow measurements into four groups: group A: 0.75 , FFR , 0.85 and CTFC > 28 (n=22), group B: 0.75 , FFR , 0.85 and CTFC , 28 (n = 55), group C: 0.85 < FFR and CTFC > 28 (n = 19), and group D: 0.85 < FFR and CTFC , 28 (n = 66). Adverse cardiac events and the presence of angina were evaluated at follow-up. Results:,At a mean follow-up of 18 ± 10 months, cardiac event rate in patients with 0.75 , FFR , 0.85 and FFR > 0.85 were 22% and 9%, respectively (P = 0.026) and also, a trend was observed toward a higher cardiac event rate in case of an abnormal CTFC (CTFC > 28) compared to a normal CTFC (24% vs 12%, P = 0.066). Furthermore, a significantly higher cardiac event rate was observed when group A was compared to group D (31.8% vs 7.6%, respectively, P = 0.004). Conclusion:,Patients with potential microvascular dysfunction and borderline FFR values should be interpreted with caution, and management strategies should be guided not only by pressure measurement, but also by possibly supplementary clinical risk stratification and noninvasive tests. (J Interven Cardiol 2010;23:421,428) [source] Experimental Models To Investigate Inflammatory Processes in Chronic Venous InsufficiencyMICROCIRCULATION, Issue S1 2000RONALD J. KORTHUIS ABSTRACT Chronic venous insufficiency (CVI) is characterized by leukocyte adhesion and infiltration, venous hypertension and dilatation, and valvular dysfunction. The fact that activated white cells can direct a powerful cytotoxic arsenal at parenchymal cells following their extravasation into the tissues led to the original proposal that leukocytes may play a causative role in the pathogenesis of venous disease. A large body of subsequent work indicates that white blood cells are indeed activated in CVI. However, identification of the factors responsible for initiating leukosequestration and activation in such disorders and determination of whether these activated cells then contribute to the progression of venous disease have been hampered by the lack of appropriate animal models that accurately mimic the human condition. Tantalizing evidence suggesting that cyclical periods of ischemia and reperfusion (I/R) may occur in diseased regions of the skin is beginning to accumulate. As is the case with CVI, leukocyte infiltration is a prominent feature in I/R and activated neutrophils play a causative role in the reperfusion component of tissue injury via the targeted release of reactive oxygen metabolites and hydrolytic enzymes. In light of these considerations, many investigators have suggested that examining the mechanisms of I/R injury in skin and skeletal muscle, where ischemia is produced by arterial occlusion, may provide a relevant model for studying the pathogenesis of CVI. Others have suggested that venous occlusion may represent a more appropriate model, as this approach also produces the venous hypertension that is characteristic of the disease. The purpose of this review is to summarize the evidence pointing to the involvement of I/R and venous hypertension as causative factors in CVI-induced leukocyte recruitment. In addition, we will describe the evidence in favor of the view that white blood cells contribute to the pathogenesis of CVI. Finally, we will describe several different experimental models that have been used to examine the role of I/R-induced microvascular dysfunction as it may pertain to the development of CVI, together with a discussion of the relative advantages and limitations of the various models. [source] Microvascular Perfusion and Transport in the Diabetic HeartMICROCIRCULATION, Issue 3 2000PAUL F. McDONAGH ABSTRACT Diabetes is a chronic disease of metabolic dysfunction that is increasing worldwide. The hyperglycemia associated with diabetes causes significant protein alterations and an oxidative stress. In the heart, all cell types are affected by diabetes; the myocyte, the vasculature and the blood cells. Four out of five diabetics die from ischemic heart disease and stroke, suggesting that the diabetic is quite vulnerable to ischemic injury. It is important to understand the pathophysiologic changes that occur in the diabetic heart in order to develop thoughtful treatments to limit this serious complication. This review focuses on the anatomical and functional alterations that occur in the diabetic circulation of the heart, with emphasis on the coronary microcirculation. Coronary microvascular dysfunction combined with blood cellular alterations are presented to explain the amplified oxidative stress that occurs in the diabetic heart under ischemic conditions. [source] Impairment of Coronary Microvascular Function in Patients with Neurally Mediated SyncopePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2p1 2003JAW-WEN CHEN CHEN, J.-W., et al.: Impairment of Coronary Microvascular Function in Patients with Neurally Mediated Syncope.Recent evidence suggests that myocardial ischemia may occur in patients with neurally mediated syncope and normal coronary angiograms. This study was conducted to evaluate if coronary microvascular function is impaired in such patients. Coronary hemodynamic studies and head-up tilt table tests (HUTs) were performed on 30 consecutive patients with normal coronary angiograms and recurrent syncope. Another ten subjects with atypical chest pain and no evidence of myocardial ischemia or syncope served as a control. Great cardiac vein flow (GCVF) and coronary sinus flow (CSF) were measured by the thermodilution method at baseline and after dipyridamole infusion (0.56 mg/kg IV for 4 minutes). Coronary flow reserve (CFR), derived from CSF and GCVF, was significantly lower in the 15 patients with positive HUT than in the other 15 patients with negative HUT (1.75 ± 0.48vs2.64 ± 0.8, P < 0.01and2.29 ± 0.45vs3.07 ± 0.63, P < 0.01, respectively). Ischemic-like ECG was noted during treadmill exercise test in 40% of the former and in 7% of the latter group(P = 0.01). There was no significant difference in CFR between patients with negative HUT and control subjects. Coronary microvascular function was impaired in syncopal patients with positive HUT and relatively preserved in those with negative HUT, suggesting the possible linkage between coronary microvascular dysfunction and the development of neurally mediated syncope. (PACE 2003; 26[Pt. I]:605,612) [source] Exercise prevents age-related decline in nitric-oxide-mediated vasodilator function in cutaneous microvesselsTHE JOURNAL OF PHYSIOLOGY, Issue 14 2008Mark A. Black Ageing is associated with impaired endothelium-derived nitric oxide (NO) function in human microvessels. We investigated the impact of cardiorespiratory fitness and exercise training on physiological and pharmacological NO-mediated microvascular responses in older subjects. NO-mediated vasodilatation was examined in young, older sedentary and older fit subjects who had two microdialysis fibres embedded into the skin on the ventral aspect of the forearm and laser Doppler probes placed over these sites. Both sites were then heated to 42°C, with Ringer solution infused in one probe and N -nitro- l -arginine methyl ester (l -NAME) through the second. In another study, three doses of ACh were infused in the presence or absence of l -NAME in similar subjects. The older sedentary subjects then undertook exercise training, with repeat studies at 12 and 24 weeks. The NO component of the heat-induced rise in cutaneous vascular conductance (CVC) was diminished in the older sedentary subjects after 30 min of prolonged heating at 42°C (26.9 ± 3.9%CVCmax), compared to older fit (46.2 ± 7.0%CVCmax, P < 0.05) and young subjects (41.2 ± 5.2%CVCmax, P < 0.05), whereas exercise training in the older sedentary group enhanced NO-vasodilator function in response to incremental heating (P < 0.05). Similarly, the NO contribution to ACh responses was impaired in the older sedentary versus older fit subjects (low dose 3.2 ± 1.3 versus 6.6 ± 1.3%CVCmax; mid dose 11.4 ± 2.4 versus 21.6 ± 4.5%CVCmax; high dose 35.2 ± 6.0 versus 52.6 ± 7.9%CVCmax, P < 0.05) and training reversed this (12 weeks: 13.7 ± 3.6, 28.9 ± 5.3, 56.1 ± 3.9%CVCmax, P < 0.05). These findings indicate that maintaining a high level of fitness, or undertaking exercise training, prevents age-related decline in indices of physiological and pharmacological microvascular NO-mediated vasodilator function. Since higher levels of NO confer anti-atherogenic benefit, this study has potential implications for the prevention of microvascular dysfunction in humans. [source] Reproducible microvascular dysfunction with dobutamine infusion in Takotsubo cardiomyopathy presenting with ST segment elevationCATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 5 2006Stacy D. Brewington MD Abstract Takotsubo (ampulla) cardiomyopathy, or broken heart syndrome, is an underrecognized cardiac illness that usually presents as an acute coronary syndrome in postmenopausal females. The disorder is frequently associated with episodes of mental or physical stress, implicating an abnormal cardiac response to increased catecholamines. Although death has been reported during the index event, the long-term prognosis is good with full recovery of left ventricular function. We present a case of Takotsubo cardiomyopathy mimicking anterior ST segment elevation myocardial infarction precipitated by dobutamine stress testing. Reinfusion of dobutamine in the catheterization laboratory reproduced symptoms with angiography and intravascular ultrasound supporting the theory of abnormal microvascular circulation as the etiology of Takotsubo cardiomyopathy. Acute and delayed magnetic resonance imaging demonstrated no infarction with complete recovery of ventricular function. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||