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1.
Evaluation of systemic microvascular reactivity in adults with congenital heart disease.
Marino, P, de Oliveira Lopes, G, Pereira Borges, J, Carolina Terra Cola, M, Arkader Kopiler, D, Tibirica, E
Congenital heart disease. 2018;(6):978-987
Abstract
OBJECTIVE Adults with congenital heart disease share some features with those with chronic heart failure. Although microvascular endothelial dysfunction has been described in chronic heart failure, evaluation of the microcirculation in adults with congenital heart disease is lacking. The present study aimed to investigate systemic microvascular reactivity in adults with congenital heart disease. INTERVENTIONS The patients initially underwent cardiopulmonary exercise testing. Then, the cutaneous microvascular reactivity was evaluated in these patients using a laser speckle contrast imaging system coupled with skin iontophoresis of endothelial-dependent (acetylcholine) or -independent (sodium nitroprusside) vasodilators and postocclusive reactive hyperemia (PORH) and compared with healthy controls matched for age and sex. RESULTS Thirty-one patients and 29 healthy controls were evaluated. The basal microvascular flow (P < .0001) and area under the curve in response to acetylcholine (P < .0001) were higher in the patients than in the healthy volunteers. The increase in cutaneous vascular conductance in response to sodium nitroprusside was reduced in the patients compared to the healthy volunteers (P = .0031). No difference in the microvascular response was observed during postocclusive reactive hyperemia. The basal microvascular flow of patients with peak oxygen consumption below 16.0 mL kg-1 min-1 was superior to that of patients with values greater than 16.0 mL kg-1 min-1 (P = .0046). CONCLUSIONS Adults with congenital heart disease present a higher baseline cutaneous microvascular blood flow than healthy controls and do not present systemic microvascular endothelial dysfunction. Nevertheless, endothelium-independent microvascular reactivity is blunted, suggesting an altered vascular smooth muscle response or vascular structural alterations. Finally, patients with a lower functional capacity presented a greater microvascular basal blood flow than subjects with a higher functional capacity.
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2.
Microvascular Vasodilator Plasticity After Acute Exercise.
Robinson, AT, Fancher, IS, Mahmoud, AM, Phillips, SA
Exercise and sport sciences reviews. 2018;(1):48-55
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Abstract
Endothelium-dependent vasodilation is reduced after acute exercise or after high intraluminal pressure in isolated arterioles from sedentary adults but not in arterioles from regular exercisers. The preserved vasodilation in arterioles from exercisers is hydrogen peroxide (H2O2) dependent, whereas resting dilation is nitric oxide (NO) dependent. We hypothesize chronic exercise elicits adaptations allowing for maintained vasodilation when NO bioavailability is reduced.
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Acute effects of diets rich in almonds and walnuts on endothelial function.
Bhardwaj, R, Dod, H, Sandhu, MS, Bedi, R, Dod, S, Konat, G, Chopra, HK, Sharma, R, Jain, AC, Nanda, N
Indian heart journal. 2018;(4):497-501
Abstract
OBJECTIVE Omega-3 fatty acids, especially alpha-linolenic acid (ALA), which are present in nuts may reduce cardiovascular disease (CVD) risk, by changing vascular inflammation and improving endothelial dysfunction. The objective of the study was to evaluate the acute effects of two different diets, one containing walnuts and the other almonds on endothelial function. METHODS Twenty-seven overweight volunteers underwent a randomized 2-period, crossover, controlled intervention study. The subjects were given either walnut or almond diets which varied in monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content. The walnut diet provided 23.1% energy from PUFA and the almond diet provided 7.6% energy from PUFA. Endothelial function was assessed physiologically by flow-mediated dilation (FMD) and biochemically by sVCAM (soluble vascular cell adhesion molecules). RESULTS The walnut diet significantly improved FMD (p=0.004) and decreased sVCAM (p=0.009) whereas the almond diet tended to improve FMD (p=0.06) and significantly decreased sVCAM (p=0.004). CONCLUSION Both walnut and almond diets improved FMD and sVCAM and there was no significant difference in physiological and biochemical markers between the two diets.
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Brachial Artery Flow-mediated Dilatation and Carotid Intima-Media Thickness in Children With Idiopathic Nephrotic Syndrome.
Youssef, DM, Gomaa, MA, El-Akhras, A, Tolba, SAR, Abd Allah, GM, Daoud, O, Saber, S
Iranian journal of kidney diseases. 2018;(6):331-340
Abstract
INTRODUCTION Disturbances of lipid metabolism has been reported in nephrotic syndrome (NS) and may predispose to atherosclerosis. This study aimed to investigate the correlation between cardiovascular risk factors and carotid intima-media thickness (CIMT) and brachial artery flow-mediated dilatation in patients with idiopathic NS. MATERIALS AND METHODS This case-control study included 31 patients with NS and 31 healthy individuals as the control group. All patients were subjected to full clinical examination; laboratory investigations in the form of lipid profile, kidney function tests, serum protein, serum albumin, C-reactive protein, and ferritin; carotid ultrasonography, and brachial artery flow-mediated dilatation. RESULTS Serum cholesterol, low-density lipoprotein cholesterol, and triglyceride levels was significantly higher in the case group than the control group. High-density lipoprotein cholesterol and albumin levels were significantly lower in the case group. The absolute change in brachial artery diameter was significantly lower in the case group than that of the control group. Proportionate change in brachial artery diameter was significantly lower in the case group than that of the control group. Common carotid artery CIMT in the case group was significantly higher than that of the controls. Lastly, there were significant increases in weight and body mass index in the relapse group than the remission group. CONCLUSIONS Patients with NS are more prone to atherosclerosis and vascular changes; CIMT was thicker in nephrotic children compared to the controls. The significantly abnormal values of flow-mediated dilatation in children with NS suggests an ongoing process of endothelial dysfunction.
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Effect of 6 wk of high-intensity one-legged cycling on functional sympatholysis and ATP signaling in patients with heart failure.
Munch, GW, Iepsen, UW, Ryrsø, CK, Rosenmeier, JB, Pedersen, BK, Mortensen, SP
American journal of physiology. Heart and circulatory physiology. 2018;(3):H616-H626
Abstract
Breathlessness during daily activities is the primary symptom in patients with heart failure (HF). Poor correlation between the hemodynamic parameters of left ventricular performance and perceived symptoms suggests that other factors, such as skeletal muscle function, play a role in determining exercise capacity. We investigated the effect of 6 wk of high-intensity, one-legged cycling (HIC; 8 × 4 at 90% one-legged cycling max) on 1) the ability to override sympathetic vasoconstriction (arterial infusion of tyramine) during one-legged knee-extensor exercise (KEE), 2) vascular function (arterial infusion of ACh, sodium nitroprusside, tyramine, and ATP), and 3) exercise capacity in HF patients with reduced ejection fraction ( n = 8) compared with healthy individuals ( n = 6). Arterial tyramine infusion lowered leg blood flow and leg vascular conductance at rest and during KEE before the training intervention in both groups ( P < 0.05) but not during KEE after the training intervention. There was no difference between groups. The peak vasodilatory response to ATP was blunted in HF patients ( P < 0.05), whereas there was no difference in ACh- and sodium nitroprusside-induced vasodilation between HF patients and healthy individuals. ACh-induced vasodilation increased in HF patients after the training intervention ( P < 0.05). HIC improved aerobic capacity in both groups ( P < 0.05), whereas only HF patients made improvements in the 6-min walking distance ( P < 0.05). These results suggest that exercise hyperemia and functional sympatholysis are not altered in HF patients and that functional sympatholysis is improved with HIC in both HF patients and healthy individuals. Moreover, these results suggest that the peak vasodilatory response to ATP is blunted in HF. NEW & NOTEWORTHY The ability to override sympathetic vasoconstrictor activity (by arterial tyramine infusion) during exercise is not different between heart failure patients and healthy individuals and is improved by high-intensity, one-legged cycling training. The peak vasodilatory response to ATP is reduced in heart failure patients.
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Attenuated cutaneous microvascular function in healthy young African Americans: Role of intradermal l-arginine supplementation.
Kim, K, Hurr, C, Patik, JC, Matthew Brothers, R
Microvascular research. 2018;:1-6
Abstract
It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l-arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringer's solution as a control site; 2) 20 mM NG-nitro-l-arginine (l-NAME) to inhibit NO synthase activity; 3) 10 mM l-arginine to local supplement l-arginine; or 4) a combination of 5.0 mM (S)-(2‑boronoethyl)-l-cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor-l-arginine (nor-NOHA) at a rate of 2.0 μl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ± 12 vs. AA: 62 ± 6 vs. %CVCmax; P < 0.001). This response was improved in AA at the l-arginine site (Control: 62 ± 6 vs. l-arginine: 70 ± 18%CVCmax; P < 0.05) but not in the arginase inhibited site (Control: 62 ± 6 vs. Arginase inhibited: 62 ± 13%CVCmax; P = 0.91). In addition, the AA group had an attenuated NO contribution to the plateau phase during 42 °C local heating relative to the CA group (CA: 56 ± 14 vs. AA: 44 ± 6 Δ %CVCmax; P < 0.001). These findings suggest that 1) cutaneous microvascular function in response to local heating is blunted in young AA when compared to age-matched young CA; 2) this attenuated response is partly related to decrease in NO bioavailability in young AA; and 3) a local infusion of l-arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA.
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Empagliflozin on top of metformin treatment improves arterial function in patients with type 1 diabetes mellitus.
Lunder, M, Janić, M, Japelj, M, Juretič, A, Janež, A, Šabovič, M
Cardiovascular diabetology. 2018;(1):153
Abstract
BACKGROUND Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We explored the possible effects of empagliflozin's effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients. METHODS Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function [brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI)], arterial stiffness [pulse wave velocity (PWV) and common carotid artery stiffness (β-stiffness)]. For statistical analysis one-way analysis of variance with Bonferroni post-test was used. RESULTS Empagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD [2.6-fold (P < 0.001) vs. 1.8-fold (P < 0.05)] and RHI [1.4-fold (P < 0.01) vs. 1.3-fold (P < 0.05)]. Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and β-stiffness compared to metformin [by 15.8% (P < 0.01) and by 36.6% (P < 0.05), respectively]. Metformin alone did not influence arterial stiffness. CONCLUSION Empagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies. Trial registration Clinical trial registration: NCT03639545.
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High-Density Lipoproteins: Effects on Vascular Function and Role in the Immune Response.
Haghikia, A, Landmesser, U
Cardiology clinics. 2018;(2):317-327
Abstract
The focus in studies of high-density lipoproteins was on their capacity to remove excess cholesterol and deliver it to the liver. Other functions and vascular effects have been described. Clinical trials and translational/genetic studies have led to a refined understanding of the role of high-density lipoprotein; it is likely not a causal cardiovascular risk factor. In healthy subjects, it limits lipid oxidation, protects endothelial cell functions/integrity, and exerts antiinflammatory/antiapoptotic effects. In patients with coronary disease or diabetes, it undergoes modifications/remodeling, resulting in dysfunctional high-density lipoprotein. We summarize recent findings about the regulation of its function and discuss the clinical implications.
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Regional myocardial function abnormalities are associated with macro- and microcirculation dysfunction in the metabolic syndrome: the RESOLVE study.
Obert, P, Walther, G, Dutheil, F, Lesourd, B, Chapier, R, Courteix, D, Vinet, A
Heart and vessels. 2018;(6):688-694
Abstract
Abnormalities in myocardial and vascular function have been reported in the metabolic syndrome (MetS), but whether these alterations are related remains poorly documented. Our aim was accordingly to investigate interrelationships between macro- and microcirculatory vasoreactivity and left ventricular (LV) myocardial function in MetS patients. Eighty-eight MetS individuals and 44 age- and gender-matched healthy controls were enrolled. LV global longitudinal strain (GLS) was measured using Vector Velocity Imaging. Endothelial-dependent and independent reactivity in macro- and microcirculatory territories was established using flow-mediated dilation and nitrate-mediated dilation of the brachial artery and cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside, respectively. Carotid intima-media thickness (cIMT) was measured according to the Mannheim consensus. Compared to controls, MetS patients presented with reduced GLS (p < 0.001) increased cIMT and impaired (p < 0.001) endothelial and smooth muscle function of the brachial artery and the forearm skin microcirculation. Highly significant relationships (p < 0.01) were noticed between GLS and vascular outcomes. In addition, cIMT (β = 0.21, p = 0.024) and microcirculatory endothelium-dependent reactivity (β = - 0.20, p = 0.035) were identified as independent predictors of GLS. In MetS, abnormalities in myocardial function and endothelial as well as smooth muscle function of small and large arteries co-exist and are closely associated. This study supports a role for microvascular dysfunction in the pathogenesis of LV myocardial dysfunction.
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How is the human umbilical artery regulated?
Lorigo, M, Mariana, M, Feiteiro, J, Cairrao, E
The journal of obstetrics and gynaecology research. 2018;(7):1193-1201
Abstract
The purpose of this review is to present an update of the main mechanisms involved in the physiological regulation of contraction and relaxation of the human umbilical artery (HUA) smooth muscle cells. A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the regulation of the HUA are presented in this article. The vascular smooth muscle is a highly specialized structure, whose main function is to regulate the vascular tonus. This is controlled by a balance between the cellular signaling pathways that mediate contraction and relaxation. The cells responsible for the contractile property of this muscle are the smooth muscle cells (SMC), and an excellent source of these cells is the HUA, involved in fetoplacental circulation. Since the umbilical blood vessels are not innervated, the HUA tonus is modulated by vasoactive substances that regulate the contractile process. The main vasoactive substances that induce contraction are serotonin, histamine, thromboxane, bradykinin, endothelin 1 and prostaglandin F2α, that are linked to the activation of proteins Gq and Gi/0 . On the other hand, the main vasorelaxation mechanisms are the activation of adenyl and guanil cyclases, potassium channels and the inhibition of calcium channels. The SMC from the HUA allow the study of different cellular mechanisms and their functions. Therefore, these cells are an important tool to study the mechanisms regulating the contractility of this artery, allowing to detect potential therapeutic targets to treat HUA disorders (gestational hypertension and pre-eclampsia).