Non-invasive study of intracranial pressure in pre- and post-chemotherapy patients for the treatment of breast neoplasia / Estudo não-invasivo da pressão intracraniana pré e pós-quimioterapia em pacientes em tratamento para câncer de mama

INTRODUCTION: Breast cancer is the most common type among women and brings to them significant organic changes. A new intracranial pressure monitorization method consists of an external system of sensors that detects micrometric deformations on the cranial bones and transmits, in real-time, electrical signals that are visualized on a monitor. OBJECTIVE: To identify changes in intracranial pressure due to chemotherapy connections through non-invasive methodology. METHODS: The present study was conducted at Hospital Santa Casa de Misericordia in the city of Ponta Grossa, PR, Brazil in 2017. The variables P2/P1 ratio (ICP morphological evaluation), laboratory parameters, comorbidities, and clinical aspects of the volunteers were evaluated. The vascular toxicity of chemotherapy often causes endothelial dysfunction, resulting in a loss of vasodilation effects and suppresses anti-inflammatory and vascular repair functions. RESULTS: The values of the P2/P1 ratio before and after chemotherapy were also compared between groups. A statistically significant difference was observed in the pre chemotherapy P2/P1 values compared to the post-chemotherapy values. CONCLUSION: Variations in ICP may occur in cancer patients. Further studies are necessary to evaluate if this change may contribute to the chemotherapy side effects occurrence.

INTRODUÇÃO: O câncer de mama é o tipo mais comum entre as mulheres e traz para elas significativas alterações orgânicas. Um novo método de monitoramento da pressão intracraniana consiste em um sistema externo de sensores que detecta deformações micrométricas nos ossos cranianos e transmite, em tempo real, sinais elétricos que são visualizados em um monitor. OBJETIVO: Identificar alterações na pressão intracraniana devido às conexões de quimioterapia por meio de metodologia não invasiva. MÉTODOS: O presente estudo foi realizado no Hospital Santa Casa de Misericórdia da cidade de Ponta Grossa, PR, Brasil, em 2017. Foram avaliadas as variáveis relação P2/P1 (avaliação morfológica da PIC), parâmetros laboratoriais, comorbidades e aspectos clínicos dos voluntários. A toxicidade vascular da quimioterapia frequentemente causa disfunção endotelial, resultando na perda dos efeitos vasodilatadores e suprime as funções anti-inflamatórias e de reparo vascular. RESULTADOS: Os valores da relação P2/P1 antes e após a quimioterapia também foram comparados entre os grupos. Uma diferença estatisticamente significativa foi observada nos valores de P2/P1 pré-quimioterapia em comparação com os valores pós-quimioterapia. CONCLUSÃO: Variações na PIC podem ocorrer em pacientes com câncer. Mais estudos são necessários para avaliar se essa alteração pode contribuir para a ocorrência dos efeitos colaterais da quimioterapia.

Prognostic Importance of Pulmonary Arterial Capacitance in Acute Decompensated Heart Failure With Preserved Ejection Fraction.

Background Although the prognostic importance of pulmonary arterial capacitance (PAC; stroke volume/pulmonary arterial pulse pressure) has been elucidated in heart failure with reduced ejection fraction, whether its significance in patients suffering from heart failure with preserved ejection fraction is not known. We aimed to examine the association of PAC with outcomes in inpatients with heart failure with preserved ejection fraction. Methods and Results We prospectively studied 705 patients (median age, 83 years; 55% women) registered in PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction). We investigated the association of echocardiographic PAC at discharge with the primary end point of all-cause death or heart failure rehospitalization with a mean follow-up of 384 days. We further tested the acceptability of the prognostic significance of PAC in a subgroup of patients (167/705 patients; median age, 81 years; 53% women) in whom PAC was assessed by right heart catheterization. The median echocardiographic PAC was 2.52 mL/mm Hg, with a quartile range of 1.78 to 3.32 mL/mm Hg. Univariable and multivariable Cox regression testing revealed that echocardiographic PAC was associated with the primary end point (unadjusted hazard ratio, 0.82; 95% CI, 0.72-0.92; P=0.001; adjusted hazard ratio, 0.86; 95% CI, 0.74-0.99; P=0.035, respectively). Univariable Cox regression testing revealed that PAC assessed by right heart catheterization (median calculated PAC, 2.82 mL/mm Hg) was also associated with the primary end point (unadjusted HR, 0.70; 95% CI, 0.52-0.91; P=0.005). Conclusions A prospective cohort study revealed that impaired PAC diagnosed with both echocardiography and right heart catheterization was associated with adverse outcomes in inpatients with heart failure with preserved ejection fraction. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

Extracardiac Abnormalities of Preload Reserve: Mechanisms Underlying Exercise Limitation in Heart Failure with Preserved Ejection Fraction, Autonomic Dysfunction, and Liver Disease.

While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.

Prognostic Value of Preoperative Pulmonary Arterial Capacitance for Patients Undergoing Aortic Valve Replacement for Severe Aortic Valve Stenosis.

BACKGROUND: Pulmonary arterial capacitance (PAC) is a determinant of right ventricular afterload and a strong independent predictor of unfavorable outcomes in advanced heart failure (HF) with pulmonary hypertension (PH). We aimed to test the hypothesis that preoperative PAC may affect postoperative clinical outcomes in patients undergoing aortic valve replacement (AVR) for severe aortic valve stenosis (AS), even in the absence of PH.Methods and Results:We studied 116 patients who underwent AVR for severe AS between January 2005 and December 2017. Right heart catheterization was performed for all patients prior to surgery. PAC and pulmonary vascular resistance (PVR) fit well to a hyperbolic relationship (PAC=0.23/PVR, R2=0.73). PAC also showed an inverse relationship with pulmonary capillary wedge pressure (PCWP) (r=-0.15) and mean pulmonary arterial pressure (r=-0.29) and provided a stronger prediction of death or HF admission than PCWP or PVR (area under the ROC curve of 0.74 vs. 0.40 and 0.41, respectively, P=0.002). During a median follow-up of 36 months, PAC (hazard ratio, 0.48; 95% confidence interval, 0.30-0.78; P=0.003) was an independent predictor of death or hospitalization for HF. CONCLUSIONS: In these patients undergoing AVR for severe AS, even in the absence of PH, preoperative reduced PAC was independently associated with adverse surgical outcomes. It seems that preoperative PAC has potential as an independent predictor of long-term prognosis after AVR for severe AS.

Pulmonary arterial compliance is a useful predictor of pulmonary vascular disease in congenital heart disease.

Histopathological assessment of the pulmonary arteries is crucial to determine the surgical indications in patients with congenital heart disease (CHD) and intractable pulmonary vascular disease (PVD). We aimed to clarify whether pulmonary hemodynamic parameters can predict PVD in patients with CHD and pulmonary arterial hypertension (PAH) We performed histopathological evaluations of lung specimens and cardiac catheterizations in 27 patients with CHD-PAH. We divided these patients into the patients with and without PVD, and compared pulmonary hemodynamic parameters including pulmonary arterial compliance (Cp) between two groups. Age at lung biopsy was 4 (2-7) months. There were 16 patients with trisomy 21. Cardiac diagnosis included ventricular septal defect in 16, atrial septal defect in 5, atrioventricular septal defect in 4, and others in 2. There were 11 patients with histopathologically proven PVD (Heath-Edwards classification grade ≥ 3 in 5; the index of PVD ≥ 1.1 in 3; extremely thickened media in 6; hypoplasia of the pulmonary arteries in 3). Cp in the patients with PVD was significantly lower than that in patients without PVD (0.99 [0.74-1.42] vs 1.56 [1.45-1.88], p = 0.0047), although there was no significant difference in the ratio of systemic to pulmonary blood flow, pulmonary arterial pressure, and resistance between two groups. A Cp cutoff value of < 1.22 ml/mmHg m2 as a predictor of PVD yielded a sensitivity and a specificity of 93% and 64%, respectively. Pulmonary arterial compliance can be a predictor of PVD among patients with CHD-PAH.

Progestin enhances vasoconstrictor responses in postmenopausal women receiving estrogen replacement therapy.

Clinical and experimental evidence suggests that the cardioprotective effect of estrogen replacement is due to effects both on scrum lipids and on blood vessels. Current practice includes the use of a progestin in combination with estrogen if the patient still has her uterus: however, little is known about the effects of combination therapy on vascular reactivity. We therefore studied the effects of estrogen alone and with added progestin on forearm vascular resistance at rest, during reactive hyperemia, and after cold pressor stimulation using plethysmography in six healthy, postmenopausal women. Measurements were made before therapy: after giving conjugated estrogen i.v.; followed by a daily oral dose of 0.625 mg for 21 days; and sequentially after the addition of 10 mg of medroxyprogesterone acetate (MPA) for 10 days. Mean blood pressure did not change significantly. After 21 days of estrogen therapy, forearm blood flow, resting vascular resistance, and resistance after cold pressor stimulation did not change significantly. However, after addition of MPA, resting forearm vascular resistance rose significantly from baseline: 25.7 ±â€Š2.7 U (SE) versus 38.3 ±â€Š2.5 (p = 0.004). In addition, forearm vascular resistance rose to a higher level after cold pressor stimulus during combination therapy (32.3 ±â€Š5.9 vs. 58.4 ±â€Š5.7; p = 0.0057) than after estrogen replacement alone (32.3 ±â€Š5.9 vs. 37.7 ±â€Š5.3; p = NS). We conclude that combination hormone replacement therapy results in higher resting vascular resistance and increased pressor responsiveness than does estrogen replacement therapy alone.

Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

Condutância vascular aumentada em indivíduos fisicamente ativos filhos de hipertensos / Vascular conductance increased in physically active children of hypertensive individuals

Objetivou-se testar a hipótese de que a prática regular de exercício físico melhora a função vascular de filhos de hipertensos em repouso. Foram avaliados 13 indivíduos fisicamente ativos filhos de hipertensos (FHA) e 22 indivíduos sedentários filhos de hipertensos (FHS), pareados por idade (22,5±2,9 vs. 23,8±2,7 anos, p=0,18) e IMC (23,8±1,9 vs. 23,0±3,0 kg/m², p=0,45). Foram registrados, simultaneamente, a frequência cardíaca, a pressão arterial, minuto a minuto (método oscilométrico ­ DIXTAL 2022®) e o fluxo sanguíneo do antebraço (pletismografia de oclusão venosa ­ Hokanson®), continuamente, durante 3 minutos em repouso. A função vascular foi avaliada por meio da condutância vascular do antebraço, calculada pela divisão do fluxo sanguíneo do antebraço pela pressão arterial média e multiplicada por 100. Foi adotado significância de p≤0,05. Como resultados, em condições basais, os grupos FHA e FHS foram semelhantes para pressão arterial sistólica (124 ± 9 vs. 121 ± 11 mmHg, p=0,42), diastólica (64 ± 5 vs. 64 ± 5 mmHg, p=0,94), média (84 ± 6 vs. 83 ± 7 mmHg, p=0,71) e fluxo sanguíneo do antebraço (3,6 ± 1,1 vs. 2,9 ± 0,9 ml/min/100ml, p=0,06). Mas, o grupo FHA apresentou menor valor de frequência cardíaca de repouso (61 ± 7 vs. 70 ± 8 bpm, p<0,01) e maior condutância vascular do antebraço (4,3 ± 1,3 vs. 3,4 ± 1,0 unidades, p=0,05). Conclui-se que indivíduos fisicamente ativos filhos de hipertensos apresentam melhor função vascular em situação de repouso.

The aim of this study was to test the hypothesis that regular physical exercise practice improves vascular function at rest of hypertensive parents' offspring. We evaluated 13 physically active offspring of hypertensive (FHA) parents and 22 sedentary offspring of hypertensive (FHS), matched by age (22.5 ± 2.9 vs. 23.8 ± 2.7 years, p=0.18) and BMI (23.8 ± 1.9 vs. 23.0 ± 3.0 kg/m², p=0.45). Heart rate, minute by minute, blood pressure (oscillometric method - DIXTAL 2022®), and forearm blood flow (venous occlusion plethysmography - Hokanson®) were continuously recorded for 3 minutes at rest. Vascular function was assessed by forearm vascular conductance, which was calculated by the division of forearm blood flow by mean arterial pressure, multiplied by 100. A p-value <0.05 was considered statistically significant. At rest condition, the groups were similar for systolic (124 ± 9 vs. 121 ± 11 mmHg, p=0.42), diastolic (64 ± 5 vs. 64 ± 5 mmHg, p=0.94), mean blood pressure (84 ± 6 vs. 83 ± 7 mmHg, p=0.71) and forearm blood flow (3.6 ± 1.1 vs. 2.9 ± 0.9 ml/min/100ml, p=0.06). On the other hand, FHA group showed lower resting heart rate (61 ± 7 vs. 70 ± 8 bpm, p<0,01) and higher forearm vascular conductance (4.3 ± 1.3 vs. 3.4 ± 10 units, p=0.05) than FHS group. We concluded that physically active offspring of hypertensive parents presents improved vascular function at rest in comparison with sedentary ones.

Skeletonization of Left Internal Mammary Artery in Coronary Artery Bypass Grafting.

OBJECTIVE: To compare mean per-operative flow capacity between skeletonized and pedicled left internal mammary artery (LIMA) in patients undergoing coronary artery bypass grafting (CABG) surgery. STUDY DESIGN: Randomized control trial. PLACE AND DURATION OF STUDY: Department of Cardiac Surgery, Armed Forces Institute of Cardiology and National Institute of Heart Diseases (AFIC-NIHD), Rawalpindi, Pakistan from February to August, 2013. METHODOLOGY: Patients undergoing CABG for coronary artery disease, under 80 years, excluded by the exclusion criteria; and fulfilling the inclusion criteria were randomly assigned to two groups of 70 each. One group underwent skeletonized and the other underwent pedicled technique of LIMAharvesting. Free flow was checked just before anastamosis of each LIMAto the LAD, manually in blood flow in ml per minute during cardiopulmonary bypass by allowing it to bleed into a 100 ml container over 20 seconds. Aspecialized proforma was used to record the age, gender, weight, disease, type of IMA used, and free flow of the IMA. Data was analyzed using SPSS 18. RESULTS: The mean age of the patients was 57.16 years in 40 patients, ranging from 36 to 75 years. Disease pattern analysis showed 5%, 10.7% and 84.3% single, double and triple vessel coronary artery disease, respectively. There was significantly higher free flow in the skeletonized group than the pedicled group (p=0.04). CONCLUSION: Skeletonized IMAhad superior flow to pedicled IMAin addition to its traditional proven advantages, which justifies its further use as a conduit for myocardial revascularization.

Pulmonary Vascular Capacitance is Associated with Vasoreactivity and Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension.

PURPOSE: This study aimed to identify the relationship between pulmonary vascular capacitance (PVC) and vasoreactivity in patients with idiopathic pulmonary arterial hypertension (IPAH), and the value of PVC in predicting long-term response to CCB treatment. METHODS: Pulmonary vasodilator testing with inhaling iloprost was performed in 308 newly diagnosed IPAH patients. Acute vasodilator-responsive patients accepted CCBs treatment. Patients who benefit from long-term CCB were defined as those being in World Health Organization (WHO) functional class II or I after at least 1 year on CCB monotherapy. RESULTS: PVC had significant correlations with WHO function class, 6-min walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance (r = -0.363, p < 0.001; r = 0.333, p < 0.001; r = -0.514, p < 0.001; r = -0.739, p < 0.001). Thirty-five acute vasodilator-responsive IPAH patients (11.4 %) displayed less severe disease and a higher baseline PVC (1.5 ± 0.6 vs. 1.1 ± 0.7 ml/mmHg, p = 0.003). During acute vasodilator testing, PVC increased significantly by mean of 79 ± 48 % and reached to a higher absolute value of 2.6 ± 1.5 ml/mmHg compared with non-responsive patients (1.4 ± 1.5 ml/mmHg, p < 0.001). Furthermore, PVC increased more during acute vasodilator testing in the 24 patients who benefit from long-term CCB treatment (1.4 ± 1.3 vs. 0.5 ± 0.4 ml/mmHg, p = 0.004). The OR of increased PVC during vasodilator testing for predicting patients with long-term response to CCB was 1.24 (95 % CI 1.02-1.50, p = 0.031) as assessed by multivariable logistic regression analysis. CONCLUSIONS: PVC was higher in acute vasodilator-responsive IPAH patients and may be a predictor of long-term response to CCBs therapy.

The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances.

BACKGROUND: Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume. METHODS: Cardiac output (CO) was measured using Modelflow(®) in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations. RESULTS: Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 µg ml(-1). Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased. CONCLUSIONS: An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register: NTR2486.

Abdominal Aortic Hemodynamics in Intermittent Claudication Patients at Rest and during Dynamic Pedaling Exercise.

BACKGROUND: Lower-extremity exercise has been shown to eliminate adverse hemodynamics conditions, such as low and oscillating blood flow and wall shear stress, in the abdominal aortas of healthy young and older adults. METHODS: We use cine phase-contrast magnetic resonance imaging and a custom MRI-compatible exercise cycle to quantify hemodynamic changes because of pedaling exercise in patients diagnosed with intermittent claudication. RESULTS: With only an average heart increase of 35 ± 18% and exercise workload of 36 ± 16 watts, the patients experienced approximately 3- and 6-fold increases in blood flow, and 4- and 16-fold increases in wall shear stress at the supraceliac and infrarenal aortic locations, respectively. Also, all oscillations in flow and shear stress at rest were eliminated with exercise. CONCLUSIONS: Claudication patients experience 3- to 4-fold lower oscillations in flow and shear stress at rest as compared with healthy age-matched controls, likely because of reduced distal arterial compliance as a result of distal atherosclerosis. The magnitude of flow and shear oscillatory indices may be good indicators of distal arterial compliance and health, and may provide predictive power for the efficacy of focal interventions.

Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice.

Aging leads to increased insulin resistance and arterial dysfunction, with oxidative stress playing an important role. This study explored the metabolic and arterial effects of a chronic treatment with resveratrol, an antioxidant polyphenol compound that has been shown to restore insulin sensitivity and decrease oxidative stress, in old mice with or without a high-protein diet renutrition care. High-protein diet tended to increase insulin resistance and atheromatous risk. Resveratrol improved insulin sensitivity in old mice fed standard diet by decreasing homeostasis model of assessment-insulin resistance and resistin levels. However, resveratrol did not improve insulin resistance status in old mice receiving the high-protein diet. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and diminishing aortic distensibility. In conclusion, we demonstrate that resveratrol has beneficial or deleterious effects on insulin sensitivity and arterial function, depending on nutritional status in our models.

Understanding coronary artery bypass transit time flow curves: role of bypass graft compliance.

OBJECTIVES: Low mean bypass graft flow (Q) and high pulsatility index (PI) measured by the transit time flow measurement method are not specific for anastomotic stenosis, but occur with competitive flow and poor coronary run-off. We hypothesized that graft compliance is responsible for these changes and that flow measured at the proximal end of the coronary bypass can be viewed as a sum of the graft capacitive flow and flow that passes through the distal anastomosis. METHODS: Transit time flow measurements (TTFMs) of 15 left internal thoracic artery (LITA) to LAD bypass grafts and 10 saphenous vein grafts (SVGs) to either the right coronary artery (RCA) or posterior descending artery (PDA) were analysed. The TTFM was performed on the proximal and distal end of the graft, and proximally with distal occlusion of the graft. Low mean bypass graft flow PI and diastolic filling (DF) measured distally and proximally were compared, and graft compliance was estimated. RESULTS: Diastolic filling was higher distally in every single case (LITA-LAD: distal DF 76 ± 12% vs proximal 66 ± 13%, P = 0.005; SVG-RCA/PDA: distal 72 ± 15% vs proximal 63 ± 12%, P = 0.018). There were no significant differences in Q and PI. Subtracting the distal from the proximal flow gave a result identical to the proximal TTFM in distally occluded grafts, confirming the presence of graft capacitive flow. Graft compliance estimated from the flow of distally occluded grafts was 0.99 ± 0.47 µl/mmHg for LITA grafts and 0.78 ± 0.42 µl/mmHg for SVG grafts. CONCLUSIONS: The study confirmed that the TTFM measured at the proximal end of the coronary bypass could be viewed as a sum of graft capacitive flow and the flow that passes through the distal anastomosis. Graft capacitive flow increases the systolic and decreases the diastolic TTFM when measured at the proximal end of the graft. It explains the higher DF when the TTFM is measured at the distal end of the graft and the increase in the PI at the proximal end when Q decreases. As the influence of graft capacitive flow on the PI in low Q can be eliminated by performing the TTFM at the distal end of the graft, we believe that the value of PI is clinically irrelevant.

Aortic elastic properties and cognitive function in elderly individuals: the Ikaria Study.

BACKGROUND: The aim of this work was to evaluate the association between aortic elastic properties and cognitive function in elderly individuals, permanent inhabitants of Ikaria Island. METHODS: In 535 individuals (75 ± 6 years, 53% males) aortic distensibility (AoD) was non-invasively calculated from the aortic diameters measured with echocardiography and brachial artery pressure using the formula by Stefanadis et al.; cognitive status was evaluated using the Mini Mental State Examination (MMSE). RESULTS: 88% of the elders had normal values of MMSE score (i.e., ≥ 24). Elders who achieved MMSE score ≥ 24 had higher values of AoD (1.90 ± 2.06 vs. 1.08 ± 1.42, p < 0.001), as well as were more physically active (85% vs. 69%, p = 0.05), had higher educational status (8.5 ± 2.8 years vs. 6 ± 2 years, p = 0.001), higher creatinine clearance levels (70 ± 21 vs. 63 ± 23, p = 0.05) and lower pulse pressure (PP) values (63 ± 16 vs. 68 ± 18, p = 0.06), as compared with those individuals with MMSE < 24. Logistic regression analysis showed that for every unit increase in AoD there was a 25% higher likelihood of having MMSE ≥ 24 (OR per 1000 × mmHg(-1) = 1.25, 95%CI 0.99-1.58), after adjustments for age, gender, current smoking, cardiovascular disease, creatinine clearance, hypertension, diabetes mellitus, obesity, physical activity status and education status. Furthermore having PP levels in the upper tertile (> 70 mmHg), increases by 55% the likelihood of having MMSE < 24 (OR for above 70 mmHg = 0.45, 95%CI 0.22, 0.92), after the same adjustments were made. CONCLUSION: Arterial aging seems to affect cognitive function; a finding that states a novel research hypothesis about the pathophysiological mechanisms of mental functioning.

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels.

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca(2+)-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca(2+)-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

The role of endothelium in the vasorelaxant effects of the essential oil of Ocimum gratissimum in aorta and mesenteric vascular bed of rats.

This study investigated the endothelium-dependent vasorelaxant effects of the essential oil of Ocimum gratissimum (EOOG) in aortas and mesenteric vascular beds isolated from rats. EOOG (3-300 µg/mL) relaxed the tonic contractions induced by phenylephrine (0.1 µmol/L) in isolated aortas in a concentration-dependent manner in both endothelium-containing and endothelium-denuded preparations. This effect was partially reversed by L-NAME (100 µmol/L) but not by indomethacin (10 µmol/L) or TEA (5 mmol/L). In mesenteric vascular beds, bolus injections of EOOG (30, 50, 100, and 300 ng) decreased the perfusion pressure induced by noradrenaline (6 µmol/L) in endothelium-intact preparations but not in those treated with deoxycholate. L-NAME (300 µmol/L) but not TEA (1 mmol/L) or indomethacin (3 µmol/L) significantly reduced the vasodilatory response to EOOG at all of the doses tested. Our data showed that EOOG exerts a dose-dependent vasodilatory response in the resistance blood vessels of rat mesenteric vascular beds and in the capacitance blood vessel, the rat aorta. This action is completely dependent on endothelial nitric oxide (NO) release in the mesenteric vascular beds but only partially dependent on NO in the aorta. These novel effects of EOOG highlight interesting differences between resistance and capacitance blood vessels.

The α2 isoform of the Na,K-pump is important for intercellular communication, agonist-induced contraction, and EDHF-like response in rat mesenteric arteries.

The specific role of different isoforms of the Na,K-pump in the vascular wall is still under debate. We have previously suggested that the α(2) isoform of the Na,K-pump (α(2)), Na(+), Ca(2+)-exchange (NCX), and connexin43 form a regulatory microdomain in smooth muscle cells (SMCs), which controls intercellular communication and contractile properties of the vascular wall. We have tested this hypothesis by downregulating α(2) in cultured SMCs and in small arteries with siRNA in vivo. Intercellular communication was assessed by using membrane capacitance measurements. Arteries transfected in vivo were tested for isometric and isobaric force development in vitro; [Ca(2+)](i) was measured simultaneously. Cultured rat SMCs were well-coupled electrically, but 10 µM ouabain uncoupled them. Downregulation of α(2) reduced electrical coupling between SMCs and made them insensitive to ouabain. Downregulation of α(2) in small arteries was accompanied with significant reduction in NCX expression. Acetylcholine-induced relaxation was not different between the groups, but the endothelium-dependent hyperpolarizing factor-like component of the response was significantly diminished in α(2)-downregulated arteries. Micromolar ouabain reduced in a concentration-dependent manner the amplitude of norepinephrine (NE)-induced vasomotion. Sixty percent of the α(2)-downregulated arteries did not have vasomotion, and vasomotion in the remaining 40% was ouabain insensitive. Although ouabain increased the sensitivity to NE in the control arteries, it had no effect on α(2)-downregulated arteries. In the presence of a low NE concentration the α(2)-downregulated arteries had higher [Ca(2+)](i) and tone. However, the NE EC50 was reduced under isometric conditions, and maximal contraction was reduced under isometric and isobaric conditions. The latter was caused by a reduced Ca(2+)-sensitivity. The α(2)-downregulated arteries also had reduced contraction to vasopressin, whereas the contractile response to high K(+) was not affected. Our results demonstrate the importance of α(2) for intercellular coupling in the vascular wall and its involvement in the regulation of vascular tone.

Comparison of arterial stiffness in end­stage renal disease patients treated with peritoneal dialysis or hemodialysis.

INTRODUCTION: Dialysis patients presents increased arterial stiffness. Results of available studies comparing arterial stiffness in peritoneal dialysis (PD) patients vs hemodialysis (HD) patients are inconsistent. OBJECTIVES: The aim of the study was to compare pulse wave velocity (PWV) in PD and HD patients and to compare value of measured PWV (PWV(M)) with theoretical value of this parameter (PWV(T)) calculated using formula developed by Blacher et al. From the equation it is apparent that PWV increases by 0.8 m/s for each decade of life. PATIENTS AND METHODS: Carotid-femoral PWV(M) was measured in 35 PD and 26 HD patients, using Complior device. In all patients PWV(T) was also calculated. RESULTS: The study groups did not differ significantly with respect to age, gender, and prevalence of diabetes. The value of PWV(M) (PD:12.1 ± 3.3 vs HD:12.0 ± 3.0 m/s) and PWV(T) (PD:10.0 ± 1.4 vs HD:9.9 ± 1.2 m/s) did not differ significantly between PD and HD. PWV(M) was significantly higher than PWVT in both, PD and HD patients. Diastolic blood pressure and mean arterial pressure was higher in PD patients, but systolic blood pressure and pulse pressure did not differ significantly. In PD patients a higher number of antihypertensive medications was used (3 ± 1 vs 2 ± 1;p<0.05). CONCLUSIONS: Arterial stiffness is equally high in peritoneal dialysis patients and in hemodialysis patients. Measured value of PWV in both, PD and HD patients, is significantly higher when compared with theoretical value of PWV. This finding may reflect accelerated arterial aging in patients on dialysis.