Effects of phosphodiesterase 5 inhibition on cardiovascular function in resistant hypertension: A systematic review.

Approximately 12-18% of hypertensive patients are diagnosed with resistant hypertension (RH). The risk of having worse cardiovascular outcomes is twice higher in those patients. The low effectiveness of conventional antihypertensive drugs in RH emphasizes the need to evaluate complementary drug therapies to achieve blood pressure (BP) control. Previous studies have demonstrated that phosphodiesterase 5 (PDE-5) inhibitors improve hemodynamics and reduce BP on essential hypertension. So, the authors aimed to summarize current clinical trials-based evidence published concerning the use of PDE-5 inhibitors on BP, cardiovascular function, and hemodynamics of patients with RH. We searched MEDLINE, EMBASE, LILACS, ClinicalTrials.gov, and WHO International Clinical Trials Registry databases on May 15th, 2020 using pre-defined search terms. Two independent reviewers assessed and extracted data from clinical trials that evaluated the effect of PDE-5 inhibitors on BP. We have included five articles in this systematic review. Four of them developed a single-day protocol, while one has developed a 14-day study. The main findings indicate that PDE-5 inhibitors ameliorate BP, vascular hemodynamics, and diastolic function parameters. Some data demonstrated improvement of endothelial function, but it was not a consensus. The side effects seemed to be limited and well-tolerated. In brief, our systematic review highlights the potential of PDE-5 inhibitors as a therapeutic alternative in addition to the multiple-drug regime for RH. Larger studies are still needed to determine whether the beneficial effects of PDE-5 inhibitors on RH would be maintained with chronic administration.

Molecular mechanisms underlying fructose-induced cardiovascular disease: exercise, metabolic pathways and microRNAs.

NEW FINDINGS: What is the central question of this study? What are the mechanisms underlying the cardiac protective effect of aerobic training in the progression of a high fructose-induced cardiometabolic disease in Wistar rats? What is the main finding and its importance? At the onset of cardiovascular disease, aerobic training activates the p-p70S6K, ERK and IRß-PI3K-AKT pathways, without changing the miR-126 and miR-195 levels, thereby providing evidence that aerobic training modulates the insulin signalling pathway. These data contribute to the understanding of the molecular cardiac changes that are associated with physiological left ventricular hypertrophy during the development of a cardiovascular disease. ABSTRACT: During the onset of cardiovascular disease (CVD), disturbances in myocardial vascularization, cell proliferation and protein expression are observed. Aerobic training prevents CVD, but the underlying mechanisms behind left ventricle (LV) hypertrophy are not fully elucidated. The aim of this study was to investigate the mechanisms by which aerobic training protects the heart from LV hypertrophy during the onset of fructose-induced cardiometabolic disease. Male Wistar rats were allocated to four groups (n = 8/group): control sedentary (C), control training (CT), fructose sedentary (F) and fructose training (FT). The C and CT groups received drinking water, and the F and FT groups received d-fructose (10% in water). After 2 weeks, the CT and FT rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min/day, 4 days/week). After 10 weeks, LV morphological remodelling, cardiomyocyte apoptosis, microRNAs and the insulin signalling pathway were investigated. The F group had systemic cardiometabolic alterations, which were normalised by aerobic training. The LV weight increased in the FT group, myocardium vascularisation decreased in the F group, and the cardiomyocyte area increased in the CT, F and FT groups. Regarding protein expression, total insulin receptor ß-subunit (IRß) decreased in the F group; phospho (p)-IRß and phosphoinositide 3-kinase (PI3K) increased in the FT group; total-AKT and p-AKT increased in all of the groups; p-p70S6 kinase (p70S6K) protein was higher in the CT group; and p-extracellular signal-regulated kinase (ERK) increased in the CT and FT groups. MiR-126, miR-195 and cardiomyocyte apoptosis did not differ among the groups. Aerobic training activates p-p70S6K and p-ERK, and during the onset of a CVD, it can activate the IRß-PI3K-AKT pathway.

Chemotherapy acutely impairs neurovascular and hemodynamic responses in women with breast cancer.

The purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Sixteen women (age: 47.0 ± 2.0 yr; body mass index: 24.2 ± 1.5 kg/m) with stage II-III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m2) and CY (600 mg/m2) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (microneurography), calf blood flow (CBF; plethysmography) and calf vascular conductance (CVC), heart rate (HR; electrocardiography), and beat-to-beat blood pressure (BP; finger plethysmography) were measured at rest before, during, and after each session. Venous blood samples (5 ml) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs; flow cytometry), a surrogate marker for endothelial damage. MSNA and BP responses were increased (P < 0.001), whereas CBF and CVC responses were decreased (P < 0.001), during and after CHT session when compared with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT (P = 0.03, CHT vs. SL session). No difference in HR response was observed (P > 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions. NEW & NOTEWORTHY It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure.

Oscillatory shear stress induces hemostatic imbalance in healthy men.

INTRODUCTION: In vitro and animal model studies have demonstrated that oscillatory shear can trigger vascular hemostasis and remodeling. However, the roles of hemodynamic forces in vascular human biology are not well understood. This study aimed to determine the effects of increasing oscillatory shear stress (OSS) on coagulation/fibrinolysis factors and matrix metalloproteinase-9 activity in healthy subjects. MATERIALS AND METHODS: Ten healthy males (35 ±â€¯7 years) underwent a 30-minute dominant forearm cuff occlusion (75 mm Hg) to exacerbate OSS in the brachial artery. Blood flow was quantified (Doppler ultrasound), and plasma samples were obtained from both arms at rest and during the last 30 s of cuff occlusion on the dominant arm. A proximal cuff (40 mm Hg, close to axilla) was also occluded to facilitate venous blood biomarker trapping. RESULTS: The retrograde shear rate and oscillatory shear index were increased and the mean shear rate, mean blood velocity, and mean blood flow were decreased in the cuffed arm (p < 0.05 vs. baseline and non-cuffed arm). Cuff occlusion induced increases in platelet microparticle release (p = 0.05 vs. baseline), prothrombin time (p < 0.05 vs. baseline and non-cuffed arm), tissue plasminogen activator (p < 0.01 vs. baseline and non-cuffed arm), plasminogen activator inhibitor-1 (p < 0.02 vs. baseline and non-cuffed arm), and matrix metalloproteinase-9 activity (p = 0.01 vs. baseline). No significant changes were found in the non-cuffed arm throughout the protocol. CONCLUSIONS: Exacerbation of OSS induced in vivo disturbances in platelet microparticle release, coagulation-fibrinolysis, and matrix metalloproteinase-9 activity in healthy individuals. These are potential mechanisms involved in OSS-mediated endothelial dysfunction.

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment. OBJECTIVE: To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay. RESULTS: The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (p sex < 0.01). CONCLUSIONS: Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome / Diferenças na Proteína C Reativa Ultrassensível associado ao gênero em Indivíduos com Fatores de Risco da Síndrome Metabólica

Abstract Background: Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment. Objective: To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay. Results: The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (psex < 0.01). Conclusions: Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.

Resumo Fundamento: A síndrome metabólica (SM) está associada a um maior risco de mortalidade por todas as causas. A proteína C reativa ultrassensível (PCRus) é um marcador prototípico de inflamação que está geralmente aumentado na SM. Mulheres com doenças relacionadas à SM apresentam níveis mais elevados de PCRus quando comparadas com homens com doenças relacionadas à SM, sugerindo diferenças associados ao gênero nos marcadores inflamatórios. No entanto, não é claro se os níveis séricos de PCRus já estão aumentados em homens e/ou mulheres com fatores de risco da SM, sem doenças pré-estabelecidas ou sob tratamento farmacológico. Objetivo: Determinar o impacto do número de fatores de risco da SM sobre os níveis séricos de PCRus em mulheres e homens. Métodos: Cento e dezoito pacientes (70 homens e 48 mulheres; 36±1 anos) foram divididos em quatro grupos de acordo com o número de fatores de risco da SM: grupo saudável (CT; sem fatores de risco), SM ≤ 2, SM = 3 e SM ≥ 4. Após 12 horas de jejum, amostras de sangue foram coletadas para determinação de variáveis bioquímicas e níveis de PCRus, analisada pelo método imunoturbidimétrico. Resultados: Os grupos com fatores de risco da SM apresentaram níveis séricos mais elevados de PCRus quando comparados com o grupo CT (p < 0,02). Não foram observadas diferenças nos níveis de PCRus entre os grupos com fatores de risco da SM (p > 0,05). O melhor modelo de regressão linear para explicar a associação entre fatores de risco da SM com níveis de PCRus foram a circunferência da cintura e os níveis de HDL-colesterol (r = 0,40, p < 0,01). Mulheres com fatores de risco da SM apresentaram valores mais elevados de PCRus quando comparadas com homens (psexo < 0,01). Conclusões: Apesar da ausência de doenças pré-estabelecidas e tratamento farmacológico, os indivíduos com fatores de risco da SM já apresentaram aumento nos níveis de PCRus, que foram significativamente mais elevados nas mulheres do que nos homens em condições semelhantes.

Efficacy and effectiveness trials have different goals, use different tools, and generate different messages.

The discussion about the optimal design of clinical trials reflects the perspectives of theory-based scientists and practice-based clinicians. Scientists compare the theory with published results. They observe a continuum from explanatory to pragmatic trials. Clinicians compare the problem they want to solve by completing a clinical trial with the results they can read in the literature. They observe a mixture of what they want and what they get. None of them can solve the problem without the support of the other. Here, we summarize the results of discussions with scientists and clinicians. All participants were interested to understand and analyze the arguments of the other side. As a result of this process, we conclude that scientists tell what they see, a continuum from clear explanatory to clear pragmatic trials. Clinicians tell what they want to see, a clear explanatory trial to describe the expected effects under ideal study conditions and a clear pragmatic trial to describe the observed effects under real-world conditions. Following this discussion, the solution was not too difficult. When we accept what we see, we will not get what we want. If we discuss a necessary change of management, we will end up with the conclusion that two types of studies are necessary to demonstrate efficacy and effectiveness. Efficacy can be demonstrated in an explanatory, ie, a randomized controlled trial (RCT) completed under ideal study conditions. Effectiveness can be demonstrated in an observational, ie, a pragmatic controlled trial (PCT) completed under real-world conditions. It is impossible to design a trial which can detect efficacy and effectiveness simultaneously. The RCTs describe what we may expect in health care, while the PCTs describe what we really observe.

Mobilization of endothelial progenitor cells with exercise in healthy individuals: a systematic review.

Physical exercise mobilizes endothelial progenitor cells (EPCs) to peripheral blood. However, this effect seems to depend on exercise characteristics, such as duration and intensity. The aim of this systematic review was to verify the impact of a single bout of aerobic exercise on the mobilization of EPCs in healthy individuals, and the potential mechanisms involved. The bibliographic search was conducted on the following electronic databases in May 2011: SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus and Medline. Of the 178 articles initially identified, 12 met the inclusion criteria and were classified regarding quality according to the PEDro scale. The magnitude and duration of the EPC mobilization response were higher after long/ultralong duration exercises, and they are correlated with vascular endothelial growth factor (VEGF) plasma levels. The EPC mobilization peak in response to a maximal or submaximal single bout of exercise lasting up to one hour occurs immediately after the exercise or within the first hour after it. One possible mechanism is nitric oxide (NO) bioavailability. The individuals' age and exercise intensity seem to interfere with the EPC mobilization response. Long/ultralong duration exercises promote more pronounced EPC mobilization as compared with maximal or submaximal exercises. The mechanisms involve VEGF release in long/ultralong duration exercises and NO bioavailability in maximal or submaximal exercises lasting less than one hour.

Mobilização de células progenitoras endoteliais com o exercício em sadios: uma revisão sistemática / Mobilization of endothelial progenitor cells with exercise in healthy individuals: a systematic review / Movilización de células progenitoras endoteliales con el ejercicio en sanos: una revisión sistemática

O exercício físico mobiliza Células Progenitoras Endoteliais (CPE) para o sangue periférico. Entretanto, esse efeito parece depender de características do exercício, como duração e intensidade. O objetivo do presente trabalho foi verificar, por meio de revisão sistemática, o impacto de uma única sessão de exercício aeróbico sobre a mobilização de CPE em indivíduos sadios e os potenciais mecanismos envolvidos. A busca bibliográfica foi realizada nas bases de dados eletrônicas SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus e Medline, em maio de 2011. Dos 178 estudos inicialmente identificados, 12 atenderam aos critérios de inclusão e foram classificados quanto à qualidade mediante critérios da escala PEDro. A magnitude e a duração da resposta de mobilização das CPE foram maiores após a realização de exercícios de longa/ultralonga duração e estão correlacionadas com níveis plasmáticos de fator de crescimento endotélio vascular (VEGF). O pico de mobilização dessas células em resposta a uma sessão de exercício máximo ou submáximo, com duração de até uma hora, ocorre no período imediatamente após o esforço até uma hora após sua interrupção. Um possível mecanismo é a biodisponibilidade do Óxido Nítrico (NO). A idade dos indivíduos e a intensidade do exercício parecem interferir na resposta de mobilização das CPE. Exercícios de longa/ultralonga duração promovem mobilização mais acentuada das CPE quando comparados a exercícios máximos ou submáximos. Os mecanismos envolvem a liberação do VEGF em exercícios de longa/ultralonga duração e a biodisponibilidade de NO em exercícios máximo e submáximo com até uma hora de duração.

Physical exercise mobilizes endothelial progenitor cells (EPCs) to peripheral blood. However, this effect seems to depend on exercise characteristics, such as duration and intensity. The aim of this systematic review was to verify the impact of a single bout of aerobic exercise on the mobilization of EPCs in healthy individuals, and the potential mechanisms involved. The bibliographic search was conducted on the following electronic databases in May 2011: SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus and Medline. Of the 178 articles initially identified, 12 met the inclusion criteria and were classified regarding quality according to the PEDro scale. The magnitude and duration of the EPC mobilization response were higher after long/ultralong duration exercises, and they are correlated with vascular endothelial growth factor (VEGF) plasma levels. The EPC mobilization peak in response to a maximal or submaximal single bout of exercise lasting up to one hour occurs immediately after the exercise or within the first hour after it. One possible mechanism is nitric oxide (NO) bioavailability. The individuals' age and exercise intensity seem to interfere with the EPC mobilization response. Long/ultralong duration exercises promote more pronounced EPC mobilization as compared with maximal or submaximal exercises. The mechanisms involve VEGF release in long/ultralong duration exercises and NO bioavailability in maximal or submaximal exercises lasting less than one hour.

El ejercicio físico moviliza Células Progenitoras Endoteliales (CPE) hacia la sangre periférica. Entre tanto, ese efecto parece depender de características del ejercicio, como duración e intensidad. El objetivo de este estudio fue verificar, por medio de revisión sistemática, el impacto de una única sesión de ejercicio aeróbico sobre la Movilización de CPE en individuos sanos y los potenciales mecanismos envueltos. La búsqueda bibliográfica fue realizada en las bases de datos electrónicas SciELO, LILACS, Cochrane, ClinicalTrials.gov, SPORTDiscus y Medline, en mayo de 2011. De los 178 estudios inicialmente identificados, 12 respondieron a los criterios de inclusión y fueron clasificados en cuanto a la calidad mediante criterios de la escala PEDro. La magnitud y la duración de la respuesta de Movilización de las CPE fueron mayores después de la realización de ejercicios de larga/ultra larga duración y están correlacionadas con niveles plasmáticos de factor de crecimiento endotelio vascular (VEGF). El pico de Movilización de esas células en respuesta a una sesión de ejercicio máximo o submáximo, con duración de hasta una hora, ocurre en el período inmediatamente después del esfuerzo y hasta una hora después de su interrupción. Un posible mecanismo es la biodisponibilidad del Óxido Nítrico (NO). La edad de los individuos y la intensidad del ejercicio parecen interferir en la respuesta de Movilización de las CPE. Ejercicios de larga/ultra larga duración promueven Movilización más acentuada de las CPE cuando son comparados a ejercicios máximos o submáximos. Los mecanismos envuelven la liberación del VEGF en ejercicios de larga/ultra larga duración y la biodisponibilidad de NO en ejercicios máximo y submáximo con hasta una hora de duración.

The 894G>T endothelial nitric oxide synthase genetic polymorphism affects hemodynamic responses to mental stress performed before and after exercise.

Nitric oxide is the primary mediator of vasodilation during mental stress. Since genetic polymorphisms in the nitric oxide synthase (eNOS) gene seem to impair the production of NO, this study aimed to evaluate the effect of an exercise bout on hemodynamic responses to mental stress in subjects with the 894G>T polymorphism of eNOS. Subjects without (wild-type group; n = 16) or with (polymorphic-type group; n = 19) the 894G>T polymorphism underwent a mental stress challenge before and after a maximal cardiopulmonary exercise test. Blood pressure was measured by auscultation and forearm blood flow by venous occlusion plethysmography. The groups were similar regarding anthropometric, metabolic, resting blood pressure and exercise variables. Before exercise, systolic blood pressure response during mental stress was higher in the polymorphic-type group (∆wild-type: 8.0 ± 2.0% vs. ∆polymorphic-type: 12.5 ± 1.8%, P = 0.01), while the increase in forearm vascular conductance was similar between the groups (∆wild-type 90.8 ± 26.4% vs. ∆polymorphic-type: 86.3 ± 24.1%, P = 0.44). After exercise, the systolic blood pressure at baseline and during mental stress was lower than before exercise in the whole group (P < 0.05), but the pressure response during mental stress was still higher in the polymorphic-type group (∆wild-type: 5.8 ± 1.5% vs. ∆polymorphic-type: 10.2 ± 1.4%, P = 0.01). The increase in forearm vascular conductance was inhibited only in the polymorphic-type group (∆before exercise 86.3 ± 24.1% vs. ∆after exercise: 41.5 ± 12.6%, P = 0.04). In conclusion, these results suggest the 894G>T eNOS polymorphism is associated with altered hemodynamic responses to mental stress both before and after a single bout of dynamic exercise with potential clinical implications.

Impaired hemodynamic response to mental stress in subjects with prehypertension is improved after a single bout of maximal dynamic exercise.

INTRODUCTION: High blood pressure during mental stress in subjects with prehypertension is associated with blunted vasodilation in skeletal muscles, which might be improved by an acute bout of exercise. OBJECTIVE: To investigate the hemodynamic responses to mental stress before and after a bout of exercise in subjects with prehypertension. METHOD: Eighteen subjects with prehypertension and 16 with normotension underwent a mental stress test before and after a maximal cardiopulmonary exercise test on a treadmill. Blood pressure was measured by auscultation, and forearm blood flow was measured by venous occlusion plethysmography; from these measurements, the vascular conductance was calculated. RESULTS: Subjects with prehypertension had a higher mean blood pressure during mental stress (prehypertension 112 ± 2 vs. normotension 101 ± 3 mm Hg, p<0.05), and their vascular conductance did not increase (baseline 0.025 ± 0.004 vs. mental stress 0.022 ± 0.003 a.u., p.0.05). After the exercise bout, the mean blood pressure during mental stress was lower in subjects with prehypertension (before exercise 112 ± 2 vs. after exercise 107 ± 2 mm Hg, p<0.05), and vascular conductance increased (baseline 0.011 ± 0.001 vs. mental stress 0.024 ± 0.004 a.u., p<0.05). CONCLUSION: Subjects with prehypertension had elevated blood pressure and a blunted vasodilator response during mental stress, but their blood pressure was attenuated and their vasodilator response was normalized after a single bout of maximal dynamic exercise.

Impaired hemodynamic response to mental stress in subjects with prehypertension is improved after a single bout of maximal dynamic exercise

INTRODUCTION: High blood pressure during mental stress in subjects with prehypertension is associated with blunted vasodilation in skeletal muscles, which might be improved by an acute bout of exercise. OBJECTIVE: To investigate the hemodynamic responses to mental stress before and after a bout of exercise in subjects with prehypertension. METHOD: Eighteen subjects with prehypertension and 16 with normotension underwent a mental stress test before and after a maximal cardiopulmonary exercise test on a treadmill. Blood pressure was measured by auscultation, and forearm blood flow was measured by venous occlusion plethysmography; from these measurements, the vascular conductance was calculated. RESULTS: Subjects with prehypertension had a higher mean blood pressure during mental stress (prehypertension 112±2 vs. normotension 101±3 mm Hg, p<0.05), and their vascular conductance did not increase (baseline 0.025±0.004 vs. mental stress 0.022±0.003 a.u., p.0.05). After the exercise bout, the mean blood pressure during mental stress was lower in subjects with prehypertension (before exercise 112±2 vs. after exercise 107±2 mm Hg, p<0.05), and vascular conductance increased (baseline 0.011±0.001 vs. mental stress 0.024±0.004 a.u., p<0.05). CONCLUSION: Subjects with prehypertension had elevated blood pressure and a blunted vasodilator response during mental stress, but their blood pressure was attenuated and their vasodilator response was normalized after a single bout of maximal dynamic exercise.

Intra- and inter-tester reproducibility of venous occlusion plethysmography: comparison between a manual and a semi-automatic method of blood flow analysis.

Venous occlusion plethysmography (VOP) is a valid non-invasive method to assess peripheral blood flow (BF) in humans. Our aim was to determine intra- and inter-tester reproducibility of BF analysis using a traditional manual method and a novel system, based on a semi-automatic approach. Ten healthy subjects and ten subjects with chronic heart failure (CHF) were evaluated. Blood flow was measured on the forearm at baseline and after 5 min of circulatory occlusion (reactive hyperemia (RH)). Two testers independently and blindly analyzed each VOP recording. Both methods were highly reproducible intra- and inter-testers. In addition, there was a high association between the methods, since the intraclass correlation coefficients (ICCs) for healthy subjects were 0.99, 0.99 and 0.99, and the coefficients of variation (CVs) were 1.8, 2.4 and 1.6% for baseline, RH peak and RH area under the curve, respectively. For CHF subjects, the ICCs were 0.99, 0.98 and 0.99, and the CVs were 2.9, 3.6 and 2.0%. In addition, the time spent on the semi-automatic analyses was shorter (p < 0.05). In conclusion, both methods demonstrated high intra- and inter-tester reproducibility for baseline and RH BF analysis. However, since the semi-automatic method was faster to generate the results, the present study supports its usage for the analysis of BF measured by VOP.

História familiar de Diabetes Mellitus tipo 2 e modulação autonômica cardíaca / Family history of type 2 Diabetes Mellitus and cardiac autonomic modulation

Fundamentos: Faltam evidências para identificar se a redução na função autonômica observada em indivíduos com história familiar de primeiro grau de diabetes mellitus tipo 2 (HFDM2) é uma característica primária ou uma consequência de desordens metabólicas comumente observadas nesses indivíduos. Objetivo: Investigar a influência da HFDM2 na modulação autonômica cardíaca em ausência de desordens metabólicas concomitantes. Métodos: Foram recrutados indivíduos saudáveis com HFDM2 (grupo HFDM2; n=61) e sem HFDM2 (grupo-controle; n=53). O protocolo incluiu: dosagem de glicose, insulina, colesterol total e subfrações, triglicerídeos, leptina e proteína C-reativa; e avaliação da variabilidade da frequência cardíaca (VFC) através da análise espectral de um registro de intervalos RR durante 10 minutos na posição supina. Resultados: Os indivíduos com HFDM2 apresentaram maiores valores para variáveis antropométricas e metabólicas e uma menor VFC quando comparados com o grupo-controle (p menor que 0,05)...