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1.
Am J Physiol Heart Circ Physiol ; 320(3): H1055-H1065, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33449849

RESUMO

Pannexin 1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo. We hypothesized that Panx1 channels and associated ATP export contribute to hypoxic vasodilation, a mechanism that facilitates the matching of oxygen delivery to metabolic demand of tissue. Male and female mice devoid of Panx1 (Panx1-/-) and wild-type controls (WT) were anesthetized, mechanically ventilated, and instrumented with a carotid artery catheter or femoral artery flow transducer for hemodynamic and plasma ATP monitoring during inhalation of 21% (normoxia) or 10% oxygen (hypoxia). ATP export from WT vs. Panx1-/-erythrocytes (RBC) was determined ex vivo via tonometer experimentation across progressive deoxygenation. Mean arterial pressure (MAP) was similar in Panx1-/- (n = 6) and WT (n = 6) mice in normoxia, but the decrease in MAP in hypoxia seen in WT was attenuated in Panx1-/- mice (-16 ± 9% vs. -2 ± 8%; P < 0.05). Hindlimb blood flow (HBF) was significantly lower in Panx1-/- (n = 6) vs. WT (n = 6) basally, and increased in WT but not Panx1-/- mice during hypoxia (8 ± 6% vs. -10 ± 13%; P < 0.05). Estimation of hindlimb vascular conductance using data from the MAP and HBF experiments showed an average response of 28% for WT vs. -9% for Panx1-/- mice. Mean venous plasma ATP during hypoxia was 57% lower in Panx1-/- (n = 6) vs. WT mice (n = 6; P < 0.05). Mean hypoxia-induced ATP export from RBCs from Panx1-/- mice (n = 8) was 82% lower than that from WT (n = 8; P < 0.05). Panx1 channels participate in hemodynamic responses consistent with hypoxic vasodilation by regulating hypoxia-sensitive extracellular ATP levels in blood.NEW & NOTEWORTHY Export of vasodilator ATP from red blood cells requires pannexin 1. Blood plasma ATP elevations in response to hypoxia in mice require pannexin 1. Hemodynamic responses to hypoxia are accompanied by increased plasma ATP in mice in vivo and require pannexin 1.


Assuntos
Trifosfato de Adenosina/sangue , Conexinas/sangue , Eritrócitos/metabolismo , Hemodinâmica , Membro Posterior/irrigação sanguínea , Hipóxia/sangue , Proteínas do Tecido Nervoso/sangue , Oxigênio/sangue , Animais , Pressão Arterial , Conexinas/deficiência , Conexinas/genética , Modelos Animais de Doenças , Feminino , Frequência Cardíaca , Hiperemia/sangue , Hiperemia/genética , Hiperemia/fisiopatologia , Hipotensão/sangue , Hipotensão/genética , Hipotensão/fisiopatologia , Hipóxia/genética , Hipóxia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Fluxo Sanguíneo Regional , Vasodilatação
2.
Clin Appl Thromb Hemost ; 27: 1076029620984546, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33448867

RESUMO

In patients with von Willebrand disease (vWD) the interest in age-related comorbidities has grown, because the life expectancy of these patients has increased. The research question of this study was whether patients with vWD show a different endothelial function compared to the general population. A total of 37 patients with type 1 (n = 23), type 2 (n = 10) and type 3 (n = 4) vWD, 14 controls and 38 patients with coronary artery disease (CAD) were included in this study. Five markers of endothelial dysfunction (MOED) were determined. Moreover, the endothelial function was examined using the Itamar Endo-PAT. The reactive hyperemia index (RHI) was calculated from the results. The markers soluble intercellular adhesion molecule-1 (p = 0.171), P-Selectin (p = 0.512), interleukin-6 (p = 0.734) and monocyte chemoattractant protein-1 (p = 0.761) showed higher levels in patients with vWD, but were not significantly different compared to the control group. RHI was impaired in CAD-patients (1.855), whereas vWD patients had mean results of 1.870 and controls 2.112 (p = 0.367). In this study, the endothelial function measurements of patients with von Willebrand disease were not significantly different compared to healthy controls.


Assuntos
Endotélio Vascular/fisiopatologia , Doenças de von Willebrand/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CCL2/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Hiperemia/sangue , Hiperemia/fisiopatologia , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Doença de von Willebrand Tipo 1/sangue , Doença de von Willebrand Tipo 1/fisiopatologia , Doença de von Willebrand Tipo 2/sangue , Doença de von Willebrand Tipo 2/fisiopatologia , Doença de von Willebrand Tipo 3/sangue , Doença de von Willebrand Tipo 3/fisiopatologia , Doenças de von Willebrand/sangue
3.
Int Heart J ; 61(5): 984-992, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921665

RESUMO

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.


Assuntos
Benzobromarona/uso terapêutico , Endotélio Vascular/fisiopatologia , Febuxostat/uso terapêutico , Hiperemia/fisiopatologia , Hiperuricemia/tratamento farmacológico , Uricosúricos/uso terapêutico , Adiponectina/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Estudos Cross-Over , Feminino , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Resultado do Tratamento , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores
4.
Am J Physiol Heart Circ Physiol ; 319(4): H797-H807, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32822215

RESUMO

Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory responses to handgrip exercise in patients with T2DM as well as vasoconstriction to selective α-agonist infusion. Forearm blood flow (FBF) and vascular conductance (FVC) were examined in patients with T2DM (n = 30) as well as nondiabetic controls (n = 15) with similar age (59 ± 9 vs. 60 ± 9 yr, P = 0.69) and body mass index (31.4 ± 5.2 vs. 29.5 ± 4.6 kg/m2, P = 0.48). Intra-arterial infusion of phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were used to induce vasoconstriction: [(FVCwith drug - FVCpredrug)/FVCpredrug × 100%]. Subjects completed rest and dynamic handgrip exercise (20% of maximum) trials per α-agonist. Patients with T2DM had smaller increases (Δ from rest) in FBF (147 ± 71 vs. 199 ± 63 ml/min) and FVC (126 ± 58 vs. 176 ± 50 ml·min-1·100 mmHg-1, P < 0.01 for both) during exercise compared with controls, respectively. During exercise, patients with T2DM had greater α1- (-16.9 ± 5.9 vs. -11.3 ± 3.8%) and α2-mediated vasoconstriction (-23.5 ± 7.1 vs. -19.0 ± 6.5%, P < 0.05 for both) versus controls. The magnitude of sympatholysis (Δ in %vasoconstriction between exercise and rest) for PE was lower (worse) in patients with T2DM versus controls (14.9 ± 12.2 vs. 23.1 ± 8.1%, P < 0.05) whereas groups were similar during DEX trials (24.6 ± 12.3 vs. 27.6 ± 13.4%, P = 0.47). Our data suggest patients with T2DM have attenuated hyperemic and vasodilatory responses to exercise, which could be attributable to greater α1-mediated vasoconstriction in contracting skeletal muscle.NEW & NOTEWORTHY Findings presented in this article are the first to show patients with type 2 diabetes mellitus have blunted hyperemic and vasodilatory responses to dynamic handgrip exercise. Moreover, we illustrate greater α1-adrenergic-mediated vasoconstriction may contribute to our initial observations. Collectively, these data suggest patients with type 2 diabetes may have impaired functional sympatholysis, which can contribute to their reduced exercise capacity.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Diabetes Mellitus Tipo 2/fisiopatologia , Contração Muscular , Músculo Esquelético/irrigação sanguínea , Fenilefrina/administração & dosagem , Vasoconstrição/efeitos dos fármacos , Idoso , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Antebraço , Humanos , Hiperemia/metabolismo , Hiperemia/fisiopatologia , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
5.
J Interv Cardiol ; 2020: 4829647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508541

RESUMO

Background: The index of microcirculatory resistance is an invasive measure of coronary microvascular function that has to be calculated during maximal hyperemia, classically achieved with intravenous adenosine (IV). The aim of this study was to evaluate the use of intracoronary (IC) adenosine for the calculation of IMR. Methods and Results: 31 patients with stable coronary artery disease were included in the study. Coronary pressure and thermodilution measurements were obtained at rest and during maximal hyperemia using a pressure-temperature sensor-tipped coronary guidewire. Duplicate measurements were performed using first IC and then IV adenosine. Dispersion of transit times was comparable for IC and IV adenosine. IMR values based on IC vs IV adenosine showed a high level of agreement and an intraclass correlation coefficient of 0.90. Applying an upper normal limit of 25, misclassification of IMR using IC adenosine was seen in just one patient in whom IC adenosine resulted in a lower value. A simplified procedure based on a single bolus dose of saline did not change the level of agreement or the rate of misclassification. Conclusions: We found an excellent agreement between IMR values measured during hyperemia induced by IC as compared to IV adenosine. The use of IC adenosine may facilitate invasive assessment of microvascular function and is potentially time- and cost-saving with less patient discomfort as compared to IV infusion. The trail is registered with NCT03369184.


Assuntos
Adenosina/farmacologia , Doença da Artéria Coronariana , Circulação Coronária , Injeções Intra-Arteriais/métodos , Microcirculação , Resistência Vascular , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Hiperemia/induzido quimicamente , Hiperemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Vasodilatadores/farmacologia
6.
Cardiovasc Diabetol ; 19(1): 82, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534580

RESUMO

BACKGROUND: Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients. METHODS: Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI < 1.67 was considered to indicate peripheral endothelial dysfunction (PED). RESULTS: In total, 149 subjects were included (mean age, 61.8 ± 9.2 years; duration of diabetes was 12 years). During the follow-up period (median, 49.7 months), of the 149 subjects, primary outcomes were detected in 12 (1 [2.3%] and 11 [10.5%] of those without and with PED, respectively). The presence of PED in baseline measurements significantly increased both primary and secondary outcomes, following adjustment for age, sex, hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, baseline estimated glomerular filtration rate, overt proteinuria, duration of diabetes, premedical history of ischemic events, anti-platelet agents, and smoking history (hazard ratio [HR]: 10.95; 95% confidence interval CI 1.00-119.91 for the primary outcome; HR, 4.12; 95% CI 1.37-12.41 for secondary outcome). In addition, PED could predict secondary outcomes independent of the risk score according to the American College of Cardiology/American Heart Association (HR: 3.24; 95% CI 1.14-9.17). CONCLUSIONS: PED can independently predict future cardiovascular events among diabetic patients with albuminuria.


Assuntos
Albuminúria/epidemiologia , Nefropatias Diabéticas/epidemiologia , Endotélio Vascular/fisiopatologia , Doença Arterial Periférica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Idoso , Albuminúria/diagnóstico , Albuminúria/mortalidade , Albuminúria/terapia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Manometria , Pessoa de Meia-Idade , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/terapia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Seul/epidemiologia , Fatores de Tempo
7.
PLoS One ; 15(5): e0233484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470022

RESUMO

BACKGROUND: Measurement of the reactive hyperemia index (RHI) using peripheral arterial tonometry (PAT) has shown benefits in the evaluation of vascular endothelial function and prediction of cardiovascular disease prognosis. Thus, it is important to examine the factors that promote the RHI. In this study, we aimed to investigate the effect of molecular hydrogen (H2) on reactive hyperemia-PAT of the small arteries of fingers in healthy people. METHODS: To determine the efficacy of H2 for improving peripheral vascular endothelial function, water containing high H2 concentrations was administered to participants, and the Ln_RHI was measured in the finger vasculature. Sixty-eight volunteers were randomly divided into two groups: a placebo group (n = 34) that drank molecular nitrogen (N2)-containing water and a high H2 group (n = 34) that drank high H2 water (containing 7 ppm of H2: 3.5 mg H2 in 500-mL water). The Ln_RHI was measured before ingesting the placebo or high H2 water, 1 h and 24 h after the first ingestion, and 14 days after daily ingestion of high H2 water or the placebo. The mixed effects model for repeated measures was used in data analysis. RESULTS: The high H2 group had a significantly greater improvement in Ln_RHI than the placebo group. Ln_RHI improved by 22.2% (p<0.05) at 24 h after the first ingestion of high H2 water and by 25.4% (p<0.05) after the daily consumption of high H2 water for 2 weeks. CONCLUSIONS: Daily consumption of high H2 water improved the endothelial function of the arteries or arterioles assessed by the PAT test. The results suggest that the continuous consumption of high H2 water contributes to improved cardiovascular health.


Assuntos
Endotélio Vascular/fisiologia , Hidrogênio/administração & dosagem , Hiperemia/etiologia , Adulto , Fatores Biológicos/agonistas , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Feminino , Dedos/irrigação sanguínea , Voluntários Saudáveis , Humanos , Hiperemia/fisiopatologia , Masculino , Manometria/métodos , Pessoa de Meia-Idade , Modelos Cardiovasculares , Óxido Nítrico/agonistas , Óxido Nítrico/fisiologia , Fatores de Risco , Água/análise
8.
Am J Physiol Heart Circ Physiol ; 318(6): H1371-H1378, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330091

RESUMO

Microvascular dysfunction often precedes other age-related macrovascular conditions and predicts future cardiovascular risk. Sirtuin 1 (Sirt1) has recently emerged as a protein that protects the vasculature and reduces the risk of cardiovascular diseases. We tested the hypothesis that lower Sirt1 during childhood is associated with a reduced microvascular function during adulthood. Thirty-four adults (34 ± 3 yr) from the Augusta Heart Study returned to participate in the present clinical observational study. Sirt1 was assessed in samples collected during both adulthood and participants' childhood (16 ± 3 yr), and data were divided based on childhood Sirt1 concentrations: <3 ng/dL (LowCS; n = 16) and ≥3 ng/dL (HighCS; n = 18). MVF was evaluated in all of the adults using laser-Doppler flowmetry coupled with three vascular reactivity tests: 1) local thermal hyperemia (LTH), 2) post-occlusive reactive hyperemia (PORH), and 3) iontophoresis of acetylcholine (ACh). The hyperemic response to LTH was significantly (P ≤ 0.044) lower in the LowCS than in the HighCS group. Similarly, the LowCS also exhibited an ameliorated (P ≤ 0.045) response to the PORH test and lower (P ≤ 0.008) vasodilation in response to iontophoresis of ACh when compared with the HighCS. Positive relationships were identified between childhood Sirt1 and all MVF reactivity tests (r≥0.367, P ≤ 0.004). Novel observations suggest that lower Sirt1 during childhood is associated with premature microvascular dysfunction in adulthood. These findings provide evidence that Sirt1 may play a critical role in microvascular function and have therapeutic potential for the prevention of age-associated vascular dysfunction in humans.NEW & NOTEWORTHY With a longitudinal cohort, novel observations from the present study demonstrate that individuals who had lower Sirt1 early in life exhibit premature microvascular dysfunction during adulthood and may be at higher risk to develop CVD. These results provide experimental evidence that Sirt1 may play an important role in microvascular function with age and represent a potential therapeutic target to prevent premature vascular dysfunction.


Assuntos
Hiperemia/fisiopatologia , Microcirculação/fisiologia , Microvasos/fisiologia , Sirtuína 1/sangue , Vasodilatação/fisiologia , Acetilcolina/farmacologia , Adolescente , Adulto , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hiperemia/sangue , Fluxometria por Laser-Doppler , Masculino , Microcirculação/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto Jovem
9.
Microvasc Res ; 130: 104008, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32330479

RESUMO

Endothelial dysfunction (ED) plays a key role in developing of cardiovascular diseases and is an important predictor of future cardiovascular events. Nevertheless, there is no established method assessing endothelial function in general population. The most popular protocol includes the ultrasound-flow-mediated-dilation, but its repeatability is operator-dependent. We intended to compare the two other operator-independent methods assessing endothelial function - the EndoPAT and Laser Doppler flowmetry (LD), and we endeavored to place them on current individual profile of biochemical cardiovascular risk and endothelial function. A total of 61 clinically healthy subjects (aged 29 ± 1y) were investigated. The blood was collected for conventional cardiovascular risk markers, the NO-pathway metabolites (ADMA, L-arginine, SDMA), oxidative-stress-markers (MDA, thiol-index) as well as endothelial and platelet activation markers (sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin, VEGF). Subsequently, all participants underwent examination by both EndoPAT and LD. There was a poor correlation between EndoPAT and LD results. No significant differences between participants with preserved and impaired endothelial function regarding endothelial activation nor cardiovascular risk markers were observed. Both methods assess endothelial function independently from the profile of endothelial pro/anti-inflammatory status and conventional risk factors, therefore further prospective studies are needed in order to verify their additional value in the cardiovascular risk stratification.


Assuntos
Endotélio Vascular/fisiopatologia , Fluxometria por Laser-Doppler , Manometria , Microcirculação , Pele/irrigação sanguínea , Adulto , Idoso , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Endotélio Vascular/metabolismo , Feminino , Humanos , Hiperemia/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Procedimentos Desnecessários
10.
Circ Cardiovasc Interv ; 13(5): e007868, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32345039

RESUMO

BACKGROUND: The resting distal-to-aortic coronary pressure ratio (Pd/Pa) is a universally available, hyperemia-free physiological index of coronary stenosis. We investigated clinical outcomes according to resting Pd/Pa versus hyperemic fractional flow reserve (FFR). METHODS: From the IRIS-FFR (Interventional Cardiology Research Incooperation Society Fractional Flow Reserve) registry, 7014 lesions in 4707 patients with valid resting Pd/Pa and FFR were included in this study. The primary outcome was major adverse cardiac events (MACE; a composite of cardiac death, myocardial infarction, and repeat intervention). The MACE rate was compared among resting Pd/Pa ≤0.92 and FFR ≤0.80. A marginal Cox model accounted for correlated data in patients with multiple lesions. RESULTS: During a median follow-up of 2.0 years, 223 MACEs occurred. Resting Pd/Pa was an independent predictor for the occurrence of MACE (adjusted hazard ratio [aHR], 1.89 [95% CI, 1.32-2.71]; P=0.001) over clinical and angiographic variables. When resting Pd/Pa and FFR were added into a multivariable model, MACE was no longer significantly associated with resting Pd/Pa (aHR, 1.35 [95% CI, 0.93-1.97]; P=0.12) but remained to be associated with FFR (aHR, 2.34 [95% CI, 1.56-3.54]; P<0.001). Compared with lesions with normal value of resting Pa/Pa and FFR, lesions with abnormal values of either resting Pd/Pa (aHR, 2.12 [95% CI, 1.17-3.84]; P=0.014) or FFR (aHR, 2.32 [95% CI, 1.52-3.55]; P<0.001) or both (aHR, 2.37 [95% CI, 1.57-3.57]; P<0.001) showed a significantly increased risk of the occurrence of MACE. CONCLUSIONS: Resting Pd/Pa appeared to be a less-robust prognostic index than FFR. Resting Pd/Pa could be used as a prognostic index when hyperemic agents are contraindicated or not easily available. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01366404.


Assuntos
Aorta/fisiopatologia , Pressão Arterial , Cateterismo Cardíaco , Estenose Coronária/diagnóstico , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico , Idoso , Angiografia Coronária , Estenose Coronária/mortalidade , Estenose Coronária/fisiopatologia , Estenose Coronária/terapia , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Sistema de Registros , Reprodutibilidade dos Testes , República da Coreia , Medição de Risco , Fatores de Risco
11.
Vascular ; 28(5): 548-556, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32338153

RESUMO

BACKGROUND: Research shows impaired endothelial function in patients with vascular diseases and improved endothelial function following revascularization and medical treatment. There is, however, a dearth of data on the effects of different endovascular therapeutic strategies on endothelial function. We sought to compare the effects of two endovascular strategies of drug-coated balloons versus stenting on endothelial function. METHODS: The reactive hyperemia index, the ankle-brachial index, and the toe-brachial index were measured in patients undergoing endovascular revascularization preprocedurally and on the 90th postprocedural day. After adjusting for baseline line characteristics, reactive hyperemia index were compared between the two groups at baseline and at 90 days. RESULTS: Between January 2018 and March 2019, 86 patients were prospectively included in a non-randomized manner. Drug-coated ballooning alone was carried out on 46 patients, and bailout stenting after plain balloon angioplasty was performed on the remaining 40 patients The post-revascularization reactive hyperemia index exhibited a significant rise in both groups (1.58 ± 0.21 vs. 1.43 ± 0.20; P = 0.0001). There was no difference in the postprocedural reactive hyperemia index between the two treatment groups. Additionally, the follow-up reactive hyperemia index showed no significant change compared with the postprocedural reactive hyperemia index (1.58 ± 0.23 vs. 1.57 ± 0.22). The results of subgroup analysis between a group of clinically high-risk patients and a group of patients with complex lesions were similar to the aforementioned results. CONCLUSIONS: The reactive hyperemia index was significantly improved by endovascular therapy in our study population. However, no difference was observed between drug-coated ballooning and bare-metal stenting, which highlights the effects of vessel patency on endothelial function.


Assuntos
Angioplastia com Balão/instrumentação , Materiais Revestidos Biocompatíveis , Endotélio Vascular/fisiopatologia , Claudicação Intermitente/terapia , Extremidade Inferior/irrigação sanguínea , Metais , Doença Arterial Periférica/terapia , Stents , Vasodilatação , Idoso , Angioplastia com Balão/efeitos adversos , Índice Tornozelo-Braço , Feminino , Humanos , Hiperemia/fisiopatologia , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudos Prospectivos , Desenho de Prótese , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
12.
Biochem Pharmacol ; 176: 113893, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32135157

RESUMO

Post-occlusive reactive hyperemia (PORH) is a key feature of physiological vasomotion to appropriately match the supply/demand ratio of tissues. This adaptive mechanism is severely disturbed in endothelial dysfunction with a reduced flow-mediated dilation (FMD). Reduced PORH and FMD are powerful prognostic risk factors in cardiovascular diseases. While these parameters are frequently determined in human beings, comparable methods applicable to mouse models are sparse. We aimed to evaluate the applicability and accuracy of scanning laser Doppler perfusion imaging (LDPI) to measure PORH in the mouse hindlimb. Changes in mean perfusion in response to vasoactive drugs and PORH (assessed by scanning LDPI) were compared with changes in diameter and blood flow in the femoral artery, as assessed by high-resolution ultrasound. We found that the measured LDPI signal significantly correlated with changes of inflow into the femoral artery. Vasodilation induced by administration of nitroglycerine and acetylcholine increased vessel diameter, blood flow and mean perfusion, while vasoconstriction following administration of epinephrine decreased all three parameters. PORH was induced by temporal occlusion of the femoral artery with an external cuff. During occlusion, mean perfusion decreased to a condition of zero-perfusion and release of the cuff induced an immediate increase in blood flow that was followed by femoral artery dilation driving PORH/perfusion. Surgical removal of the femoral artery decreased mean perfusion to a zero-perfusion level and fully abolished PORH. Importantly, the measurement of the PORH response by scanning LDPI is highly reproducible as determined by repeated measurements and intra/interobserver variation analysis. Last, we found that the PORH response was dependent on nitric oxide synthase and cyclooxygenase and declined with age. Thus, we here provide novel and robust non-invasive methods to serially measure tissue perfusion at baseline and during physiological and pharmacological modulation of vasomotor tone in the hindlimb of mice. The application of these LDPI scanning and ultrasound-based methods may be useful for testing the effects of drugs affecting vasomotor function or future elucidation of mechanisms leading to vasomotor dysfunction in mice in vivo.


Assuntos
Hiperemia/diagnóstico por imagem , Imagem de Perfusão/métodos , Perfusão/métodos , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Endotélio/irrigação sanguínea , Endotélio/diagnóstico por imagem , Endotélio/metabolismo , Humanos , Hiperemia/diagnóstico , Hiperemia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Nitroglicerina/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
13.
Microvasc Res ; 130: 104000, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32194082

RESUMO

INTRODUCTION: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. MATERIALS AND METHODS: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (CRBC,TiVi), oxygenation (ΔCOH,TiVi) and deoxygenation (ΔCDOH,TiVi) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). RESULTS: During arterial occlusion, CRBC,TiVi remained unchanged while ΔCOH,TiVi decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, CRBC,TiVi increased to 39.2 (18.8) AU (p < 0.001), ΔCOH,TiVi increased to 38.5. During venous occlusion, CRBC,TiVi increased to 28.9 (11.2) AU (p < 0.001), ΔCOH,TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. CONCLUSION: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.


Assuntos
Hemoglobinas/metabolismo , Microcirculação , Oxiemoglobinas/metabolismo , Pele/irrigação sanguínea , Adulto , Velocidade do Fluxo Sanguíneo , Contagem de Eritrócitos , Feminino , Antebraço , Voluntários Saudáveis , Humanos , Hiperemia/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Fluxo Sanguíneo Regional , Análise Espectral , Fatores de Tempo , Adulto Jovem
14.
Int J Cardiovasc Imaging ; 36(7): 1193-1201, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32221772

RESUMO

Currently there is lack of data regarding the use of optical coherence tomography (OCT) to depict the hemodynamic relevance of coronary stenoses in diabetic patients. We sought to assess the diagnostic accuracy of OCT-derived morphologic assessment in identifying hemodynamically significant coronary lesions as determined by both, the resting instantaneous wave-free ratio (iFR) and the hyperemic fractional flow reserve (FFR) in diabetic patients. Diabetic patients presenting with at least one intermediate coronary lesion were prospectively and consecutively enrolled. All lesions were systematically assessed by iFR, FFR and OCT. A total of 41 intermediate lesions were analysed. Mean iFR and FFR values were 0.90 ± 0.04 and 0.81 ± 0.06, respectively (intra-class correlation coefficient 0.49; 95% CI 0.22-0.79). A moderate correlation between iFR and OCT derived minimal lumen diameter (MLD, r = 0.49) and minimal lumen area (MLA, r = 0.50) was found. Conversely, there was a poor correlation between FFR and OCT-derived MLD (r = 0.34) and MLA (r = 0.32). The diagnostic efficiency of MLA and MLD to identify iFR significant stenoses showed an AUC of 0.82 (95% CI 0.69-0.95) for MLD and 0.83 (95% CI 0.71-0.96) for MLA. A worse diagnostic efficiency was found when FFR was used as the reference with an AUC of 0.71 (95% CI 0.54-0.87) for MLD and 0.70 (95% CI 0.53-0.87). OCT-derived MLA and MLD were the strongest independent anatomic predictors of abnormal iFR and FFR values. In diabetic patients, OCT-derived MLA and MLD showed a moderate diagnostic efficiency in identifying functionally significant coronary stenoses by FFR or iFR. In diabetics, anatomic OCT measurements better predicted resting than FFR-determined physiologically significant lesions.


Assuntos
Estenose Coronária/diagnóstico por imagem , Diabetes Mellitus/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Tomografia de Coerência Óptica , Idoso , Cateterismo Cardíaco , Angiografia Coronária , Estenose Coronária/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes
16.
Am J Med Sci ; 359(4): 193-205, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32089228

RESUMO

The significance of effective renal perfusion is relatively underemphasized in the current literature. From a renal standpoint, besides optimizing cardiac output, renal perfusion should be maximized as well. Among the several additional variables of the critically ill, such as intra-abdominal pressure, the presence of venous congestion and elevated central venous pressures, airway pressures generated by mechanical ventilation do affect net renal perfusion. These forces represent both a potential danger and an ongoing opportunity to improve renal outcomes in the critically ill and an opportunity to move beyond the simplified viewpoint of optimizing volume status. Therefore, to optimize nephron-protective therapies, nephrologists and intensive care physicians should be familiar with the concept of net renal perfusion pressure. This review appraises the background literature on renal perfusion pressure, including the initial animal data and historical human studies up to the most current developments in the field, exploring potential avenues to assess and improve renal blood supply.


Assuntos
Lesão Renal Aguda/terapia , Hiperemia/fisiopatologia , Rim/irrigação sanguínea , Circulação Renal , Hemodinâmica , Humanos , Perfusão
17.
Einstein (Sao Paulo) ; 18: eAO5227, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32022106

RESUMO

OBJECTIVE: To investigate the efficacy of a behavior change program named Vida Ativa Melhorando a Saúde on cardiovascular parameters in hypertensive patients. METHODS: Ninety hypertensive patients aged over 40 years were randomly allocated to one of two groups: Vida Ativa Melhorando a Saúde or Control (n=45 respectively). Patients in the Vida Ativa Melhorando a Saúde group took part in a behavior change program aimed to encourage changes in physical activity levels and eating habits, according to the Social Cognitive Theory. The program consisted of 90-minute weekly group meetings conducted by a physical therapist and a dietitian. One chapter of the educational material (workbook) provided was discussed per meeting. Participants in the Control Group attended a single educative lecture on lifestyle changes. Brachial and central blood pressure, arterial stiffness and endothelial function parameters were measured pre- and post-intervention. RESULTS: Vida Ativa Melhorando a Saúde led to reduction of brachial (131.3±15.8mmHg to 125.1±17.3mmHg; p<0.01) and central (123.6±16.3mmHg to 119.0±20.6mmHg; p=0.02) systolic and brachial diastolic (123.6±16.3mmHg to 119.0±20.6mmHg; p<0.01) blood pressure values, and improvement of post-occlusive reactive hyperemia (from 5.7±2.5mL·100mL-1 to 6.5±2.1mL·100mL-1 tissue·min-1; p=0.04). No changes in body composition, heart rate and arterial stiffness parameters were detected in both groups (p>0.05). CONCLUSION: Vida Ativa Melhorando a Saúde program improved blood pressure and microvascular reactivity in hypertensive patients. Trial registration: ClinicalTrials.gov: NCT02257268.


Assuntos
Comportamentos Relacionados com a Saúde/fisiologia , Hipertensão/fisiopatologia , Idoso , Pressão Sanguínea/fisiologia , Composição Corporal , Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hiperemia/fisiopatologia , Hipertensão/psicologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento , Rigidez Vascular/fisiologia
18.
Eur J Ophthalmol ; 30(3): 430-438, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32064920

RESUMO

PURPOSE: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water. METHODS: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5). RESULTS: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (-3.00 s) (p = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining (p < 0.0001), Ocular Surface Disease Index (p < 0.05), and visual analog scale (p = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent. CONCLUSION: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL®, has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.


Assuntos
Cloraminas/efeitos adversos , Doenças da Túnica Conjuntiva/tratamento farmacológico , Doenças da Córnea/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Hiperemia/tratamento farmacológico , Ubiquinona/análogos & derivados , Poluentes Químicos da Água/efeitos adversos , Administração Oftálmica , Adolescente , Adulto , Doenças da Túnica Conjuntiva/induzido quimicamente , Doenças da Túnica Conjuntiva/fisiopatologia , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/fisiopatologia , Reagentes para Ligações Cruzadas , Desinfetantes/efeitos adversos , Combinação de Medicamentos , Humanos , Hiperemia/induzido quimicamente , Hiperemia/fisiopatologia , Masculino , Soluções Oftálmicas , Concentração Osmolar , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Piscinas , Lágrimas/química , Lágrimas/fisiologia , Ubiquinona/administração & dosagem , Vitamina E/administração & dosagem , Vitaminas/administração & dosagem , Adulto Jovem
19.
Am J Physiol Regul Integr Comp Physiol ; 318(3): R605-R618, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32022580

RESUMO

Reactive hyperemia is a well-established technique for noninvasive assessment of peripheral microvascular function and a predictor of all-cause and cardiovascular morbidity and mortality. In its simplest form, reactive hyperemia represents the magnitude of limb reperfusion following a brief period of ischemia induced by arterial occlusion. Over the past two decades, investigators have employed a variety of methods, including brachial artery velocity by Doppler ultrasound, tissue reperfusion by near-infrared spectroscopy, limb distension by venous occlusion plethysmography, and peripheral artery tonometry, to measure reactive hyperemia. Regardless of the technique used to measure reactive hyperemia, blunted reactive hyperemia is believed to reflect impaired microvascular function. With the advent of several technological advancements, together with an increased interest in the microcirculation, reactive hyperemia is becoming more common as a research tool and is widely used across multiple disciplines. With this in mind, we sought to review the various methodologies commonly used to assess reactive hyperemia and current mechanistic pathways believed to contribute to reactive hyperemia and reflect on several methodological considerations.


Assuntos
Hiperemia/fisiopatologia , Isquemia/fisiopatologia , Microcirculação/fisiologia , Vasodilatação/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Braquial/fisiopatologia , Humanos
20.
J Sports Sci ; 38(7): 751-758, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32106780

RESUMO

Blood flow changes in response to exercise have been attributed, among other factors, to the effect of vasodilators factors on the microvasculature, suggesting a close relationship between small blood vessels and conducting arteries. The main purpose of this study was to determine the relationship between the changes in near infrared spectroscopy (NIRS)-derived total haemoglobin ([tHb]) and muscle oxygen saturation (SmO2) signals and femoral artery blood flow in response to resistance exercise at fast- and slow-velocity muscle contraction. The study randomised crossover design included twelve participants. NIRS and blood flow measurements were continuously monitored before, during, and 5 min after the exercise protocol. There was a significant correlation between [tHb] reperfusion slope ([tHb]slope) and peak blood flow (BFpeak) after slow- and fast-velocity muscle contraction (r = 0.83, p = 0.0008 and r = 0.72, p = 0.0080, respectively). No significant correlation existed between the SmO2 reperfusion slope (SmO2_slope) and BFpeak after both slow- and fast-velocity muscle contraction exercise (r = -0.46, p = 0.1253 and r = 0.33, p = 0.2841, respectively). This study demonstrated a strong relationship between the NIRS-derived [tHb] and Doppler ultrasound BF during the recovery period of dynamic resistance exercise at both slow- and fast-velocity contraction.


Assuntos
Hemoglobinas/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem , Oxiemoglobinas/metabolismo , Treinamento de Resistência/métodos , Espectroscopia de Luz Próxima ao Infravermelho , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos Cross-Over , Artéria Femoral/fisiologia , Humanos , Hiperemia/fisiopatologia , Microcirculação/fisiologia , Contração Muscular/fisiologia , Consumo de Oxigênio/fisiologia , Fluxo Sanguíneo Regional , Ultrassonografia Doppler
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