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microvascular resistance

Brian S Ko, James D Cameron, Ravi K Munnur, Dennis T L Wong, Yasuko Fujisawa, Takuya Sakaguchi, Kenji Hirohata, Jacqui Hislop-Jambrich, Shinichiro Fujimoto, Kazuhisa Takamura, Marcus Crossett, Michael Leung, Ahilan Kuganesan, Yuvaraj Malaiapan, Arthur Nasis, John Troupis, Ian T Meredith, Sujith K Seneviratne
OBJECTIVES: This study describes the feasibility and accuracy of a novel computed tomography (CT) fractional flow reserve (FFR) technique based on alternative boundary conditions. BACKGROUND: Techniques used to compute FFR based on images acquired from coronary computed tomography angiography (CTA) are described. Boundary conditions were typically determined by allometric scaling laws and assumptions regarding microvascular resistance. Alternatively, boundary conditions can be derived from the structural deformation of coronary lumen and aorta, although its accuracy remains unknown...
October 14, 2016: JACC. Cardiovascular Imaging
Manjit Kaur, Raj K S Badhan
Clinical translation of BCRP inhibitors have failed due to neurotoxicity and novel approaches are required to identify suitable modulators of BCRP to enhance CNS drug delivery. In this study we examine 18 compounds, primarily phytochemicals, as potential novel modulators of AhR-mediated regulation of BCRP expression and function in immortalised and primary porcine brain microvascular endothelial cells as a mechanism to enhance CNS drug delivery. The majority of modulators possessed a cellular viability IC50 > 100µM in both cell systems...
October 19, 2016: Brain Research
Yingying Liu, Shanshan Fang, Qiushi Sun, Bo Liu
Glioblastoma is one of the most vascular brain tumour and highly resistant to current therapy. Targeting both glioblastoma cells and angiogenesis may present an effective therapeutic strategy for glioblastoma. In our work, we show that an anthelmintic drug, ivermectin, is active against glioblastoma cells in vitro and in vivo, and also targets angiogenesis. Ivermectin significantly inhibits growth and anchorage-independent colony formation in U87 and T98G glioblastoma cells. It induces apoptosis in these cells through a caspase-dependent manner...
October 19, 2016: Biochemical and Biophysical Research Communications
Chloe Y Y Cheung, Elaine Y L Hui, Chi-Ho Lee, Kelvin H M Kwok, Rita A Gangwani, Kenneth K W Li, Jeffrey C W Chan, Yu-Cho Woo, Wing-Sun Chow, Michele M A Yuen, Rachel L C Wong, Carol H Y Fong, Aimin Xu, David S H Wong, Pak-Chung Sham, Karen S L Lam
Purpose: Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes (T2DM). Genome-wide association studies (GWAS) had identified novel DR-susceptibility genetic variants in various populations. We examined the associations of these DR-associated single nucleotide polymorphisms (SNPs) with severe DR in a Chinese T2DM cohort. Methods: Cross-sectional case-control studies on sight-threatening DR (STDR) and proliferative DR (PDR) were performed...
October 1, 2016: Investigative Ophthalmology & Visual Science
Walter H Reinhart
The hematocrit (Hct) determines the oxygen carrying capacity of blood, but also increases blood viscosity and thus flow resistance. From this dual role the concept of an optimum Hct for tissue oxygenation has been derived. Viscometric studies using the ratio Hct/blood viscosity at high shear rate showed an optimum Hct of 50-60% for red blood cell (RBC) suspensions in plasma. For the perfusion of an artificial microvascular network with 5-70μm channels the optimum Hct was 60-70% for high driving pressures. With lower shear rates or driving pressures the optimum Hct shifted towards lower values...
October 21, 2016: Clinical Hemorheology and Microcirculation
Maria das Graças Coelho de Souza, Luiz Guilherme Kraemer-Aguiar, Eliete Bouskela
Obesity is a crescent epidemic in the world, affecting more than half a billion of adults worldwide. Obesity is associated to main cardiovascular risk factors, such as insulin resistance, type 2 diabetes mellitus, high blood pressure and dyslipidemia. The excessive adiposity causes a dysregulation of adipokines secretion by adipose tissue, upregulating the expression of pro-inflammatory adipokines and downregulating the anti-inflammatory ones. This scenario contributes for the appearance of atherosclerosis...
October 18, 2016: Clinical Hemorheology and Microcirculation
Matthias Jacob, Daniel Chappell, Bernhard F Becker
Oxygen delivery to cells is the basic prerequisite of life. Within the human body, an ingenious oxygen delivery system, comprising steps of convection and diffusion from the upper airways via the lungs and the cardiovascular system to the microvascular area, bridges the gap between oxygen in the outside airspace and the interstitial space around the cells. However, the complexity of this evolutionary development makes us prone to pathophysiological problems. While those problems related to respiration and macrohemodynamics have already been successfully addressed by modern medicine, the pathophysiology of the microcirculation is still often a closed book in daily practice...
October 21, 2016: Critical Care: the Official Journal of the Critical Care Forum
Esther Peters, Bülent Ergin, Asli Kandil, Ebru Gurel-Gurevin, Andrea van Elsas, Rosalinde Masereeuw, Peter Pickkers, Can Ince
Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n=18) were subjected to renal ischemia (30min) and reperfusion (I/R), or sham-operated...
October 16, 2016: Toxicology and Applied Pharmacology
Ben Clark, Sarah Withers, Anthony Heagerty
OBJECTIVE: Resistance arteries significantly contribute to peripheral vascular resistance, and also determine insulin-sensitivity by controlling blood flow to skeletal muscle. Increased microvascular tone therefore facilitates the development of hypertension and insulin-resistance. Surrounding most blood vessels, perivascular adipose tissue (PVAT) exerts a vasorelaxant 'anti-contractile' effect. Few studies on skeletal muscle resistance arteries have investigated this vasorelaxant effect and the role of insulin...
September 2016: Journal of Hypertension
Leroy L Cooper, Gary F Mitchell
BACKGROUND: Aortic stiffness is associated with cardiovascular and cerebrovascular events and cognitive decline. This mini-review focuses on relations of aortic stiffness with microvascular dysfunction and discusses the contribution of abnormal pulsatile hemodynamics to cerebrovascular damage and cognitive decline. We also provide a rationale for considering aortic stiffness as a putative and important contributor to memory impairment in older individuals. SUMMARY: Aging is associated with stiffening of the aorta but not the muscular arteries, which reduces wave reflection and increases the transmission of pulsatility into the periphery...
September 2016: Pulse (Basel, Switzerland)
Sebastian Völz, Sara Svedlund, Bert Andersson, Gan Li-Ming, Bengt Rundqvist
Resistant hypertension is associated with increased risk for cardiovascular events. Coronary flow reserve (CFR) is impaired in patients with hypertension and an independent predictor of cardiac mortality. However, there are no published data on CFR in the subset of treatment-resistant hypertension. The aim of this study was to assess CFR in patients with resistant hypertension. Twenty-five consecutive patients with primary resistant hypertension, scheduled for renal denervation, 25 matched patients with controlled hypertension, and 25 healthy controls underwent transthoracic colour Doppler echocardiography at rest and during adenosine infusion...
October 17, 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Shyanne Page, Alli Munsell, Abraham J Al-Ahmad
BACKGROUND: Cerebral hypoxia/ischemia (H/I) is an important stress factor involved in the disruption of the blood-brain barrier (BBB) following stroke injury, yet the cellular and molecular mechanisms on how the human BBB responds to such injury remains unclear. In this study, we investigated the cellular response of the human BBB to chemical and environmental H/I in vitro. METHODS: In this study, we used immortalized hCMEC/D3 and IMR90 stem-cell derived human brain microvascular endothelial cell lines (IMR90-derived BMECs)...
October 11, 2016: Fluids and Barriers of the CNS
Onur Kilic, David Pamies, Emily Lavell, Paula Schiapparelli, Yun Feng, Thomas Hartung, Anna Bal-Price, Helena T Hogberg, Alfredo Quinones-Hinojosa, Hugo Guerrero-Cazares, Andre Levchenko
Migration of neural progenitors in the complex tissue environment of the central nervous system is not well understood. Progress in this area has the potential to drive breakthroughs in neuroregenerative therapies, brain cancer treatments, and neurodevelopmental studies. To a large extent, advances have been limited due to a lack of controlled environments recapitulating characteristics of the central nervous system milieu. Reductionist cell culture models are frequently too simplistic, and physiologically more relevant approaches such as ex vivo brain slices or in situ experiments provide little control and make information extraction difficult...
October 18, 2016: Lab on a Chip
Sang-Don Park, Man-Jong Lee, Yong-Soo Baek, Sung-Woo Kwon, Sung-Hee Shin, Seong-Ill Woo, Dae-Hyeok Kim, Jun Kwan, Keum-Soo Park
AIMS: Ticagrelor has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. However, the superiority of ticagrelor for preventing ischaemic damage in STEMI patients has not been proven. The aim of this trial was to assess whether ticagrelor is superior to clopidogrel in preventing microvascular injury in ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Patients with STEMI underwent prospective random assignment to receive a loading dose (LD) of clopidogrel 600 mg or ticagrelor 180 mg (1:1 ratio) before primary percutaneous coronary intervention (PCI)...
October 10, 2016: EuroIntervention
Steven F Merkel, Allison M Andrews, Evan M Lutton, Dakai Mu, Eloise Hudry, Bradley T Hyman, Casey A Maguire, Servio H Ramirez
Developing therapies for central nervous system (CNS) diseases is exceedingly difficult due to the blood-brain barrier (BBB). Notably, emerging technologies may provide promising new options for the treatment of CNS disorders. Adeno-associated virus serotype 9 (AAV9) has been shown to transduce cells in the CNS following intravascular administration in rodents, cats, pigs, and non-human primates. These results suggest that AAV9 is capable of crossing the BBB. However, mechanisms that govern AAV9 transendothelial trafficking at the BBB remain unknown...
October 8, 2016: Journal of Neurochemistry
Tobias Hilbert, Kathrin Dornbusch, Georg Baumgarten, Andreas Hoeft, Stilla Frede, Sven Klaschik
Increased pulmonary vascular resistance is a critical complication in sepsis. Toll-like receptor (TLR) as well as angiopoietin (ANG) signaling both contribute to the emergence of pulmonary arterial hypertension. We hypothesized that TLR stimulation by bacterial ligands directly affects expression and secretion of ligands and receptors of the angiopoietin/TIE axis. Microvascular endothelial (HPMEC) and smooth muscle cells (SMC) of pulmonary origin were incubated with thrombin and with ligands for TLR2, -4, -5, and -9...
October 6, 2016: Clinical and Experimental Pharmacology & Physiology
Junwei Xu, Lu Lu, Jing Lu, Jihui Xia, Hongjin Lu, Lin Yang, Wensheng Xia, Shihai Shen
BACKGROUND: Recent evidence suggests that CD200 fusion protein (CD200Fc), a CD200R1 agonist may attenuate inflammatory responses in autoimmune diseases and neuro-degeneration. While, little is known about the function of CD200Fc in cigarette smoke extract (CSE)-induced mouse Cardiac Microvascular Endothelial Cells (mCMECs). The present study was designed to elucidate the effects of CD200Fc on CSE-induced vascular endothelial barrier (VEB) dysfunction and inflammatory responses, which is a highly clinically relevant model of smoking related cardiovascular diseases...
October 3, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Valérie Julian, David Thivel, Bruno Pereira, Frédéric Costes, Ruddy Richard, Martine Duclos
OBJECTIVE: The effects of a training program (TP) on muscle microvascularization during exercise remained to be explored in adolescents with obesity. We hypothesized that a TP would lead to better microvascular adaptations to exercise in skeletal muscle. METHODS: 15 inactive adolescents followed a 12-week TP where both peripheral (muscular microvascularization) and central (cardiac) adaptations to exercise (40 min exercise set at 70% V̇O2peak) were assessed before and after intervention...
October 4, 2016: Obesity Facts
David Carrick, Caroline Haig, Jaclyn Carberry, Vannesa Teng Yue May, Peter McCartney, Paul Welsh, Nadeem Ahmed, Margaret McEntegart, Mark C Petrie, Hany Eteiba, Mitchell Lindsay, Stuart Hood, Stuart Watkins, Ahmed Mahrous, Samuli M O Rauhalammi, Ify Mordi, Ian Ford, Aleksandra Radjenovic, Naveed Sattar, Keith G Oldroyd, Colin Berry
BACKGROUND: Failed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors. METHODS: IMR (n = 288) and CFR (n = 283; mean age [SD], 60 [12] years) were measured acutely using guide wire-based thermodilution...
May 5, 2016: JCI Insight
Wen-Juan Huang, Wei-Wei Chen, Xia Zhang
Central nervous system-based cancers have a much higher mortality rate with the 2016 estimates at 6.4 for incidence and 4.3 for deaths per 100,000 individuals. Grade IV astrocytomas, known as glioblastomas are highly aggressive and show a high proliferation index, diffused infiltration, angiogenesis, microvascular proliferation and pleomorphic vessels, resistance to apoptosis, and pseudopalisading necrosis. Extensive hypoxic regions in glioblastomas contribute to the highly malignant phenotype of these tumors...
October 2016: Oncology Letters
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