Intron 4 polymorphism of the endothelial nitric oxide synthase (eNOS) gene is associated with decreased NO production in a mercury-exposed population

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a potent vasodilator and plays a prominent role in regulating the cardiovascular system. Decreased basal NO release may predispose to cardiovascular diseases. Evidence suggests that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene may regulate eNOS expression. On the other hand, some recent reports strongly suggest an association between methylmercury (MeHg) exposures and altered NO synthesis. In the present study, we investigate the contribution of the 27-pb tandem repeat polymorphism on nitric oxide production, which could enhance susceptibility to cardiovascular disease in the MeHg-exposed study population. Two-hundred-two participants (98 men and 104 women), all chronically exposed to MeHg through fish consumption were examined. Mean blood Hg concentration and nitrite plasma concentration were 50.5 +/- 35.4 mu g/L and 251.4 +/- 106.3 nM, respectively. Mean systolic and diastolic blood pressure were 120.1 +/- 19.4 mm Hg and 72.0 +/- 10.6 mm Hg, respectively. Mean body mass index was 24.5 +/- 4.3 kg/m(2) and the mean heart rate was 69.8 +/- 11.8 bpm. There were no significant differences in age, arterial blood pressure, body mass index or cardiac frequency between genotype groups (all P>0.05). However, we observed different nitrite concentrations in the genotypes groups, with lower nitrite levels for the 4a4a genotype carriers. Age, gender and the presence of intron 4 polymorphism contributed to nitrite reduction as a result of blood Hg concentration. Taken together, our results show that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene increases susceptibility to cardiovascular diseases after MeHg exposure by modulating nitric oxide levels. (C) 2011 Elsevier B.V. All rights reserved.

Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias

FUNDAMENTO: A redução da frequência cardíaca (FC) na angiografia por tomografia das artérias coronarianas (ATCCor) é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M), e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D). Pressão arterial (PA) e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame). A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição). Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D). CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

Flexibility and modeling in business processes: a multi-dimensional relationship

Over the last few years, Business Process Management (BPM) has achieved increasing popularity and dissemination. An analysis of the underlying assumptions of BPM shows that it pursues two apparently contradicting goals: on the one hand it aims at formalising work practices into business process models; on the other hand, it intends to confer flexibility to the organization - i.e. to maintain its ability to respond to new and unforeseen situations. This paper analyses the relationship between formalisation and flexibility in business process modelling by means of an empirical case study of a BPM project in an aircraft maintenance company. A qualitative approach is adopted based on the Actor-Network Theory. The paper offers two major contributions: (a) it illustrates the sociotechnical complexity involved in BPM initiatives; (b) it points towards a multidimensional understanding of the relation between formalization and flexibility in BPM projects.

Acute exercise adjustments of cardiovascular autonomic control in diabetic rats

Introduction: We evaluated the role of cardiovascular autonomic changes in hemodynamics at rest and in response to exercise in streptozotocin-induced diabetic rats. Methods: Male Wistar rats were divided into nondiabetic (ND, n = 8) and diabetic (D, n = 8) groups. Arterial pressure signals were recorded in the basal state and after atropine or propranolol injections at rest, during exercise and during recovery. Results: At rest, vagal tonus was reduced in D (37 +/- 3 bpm) in comparison with the ND group (61 +/- 9 bpm). Heart rate during exercise was lower in D in relation to ND rats associated with reduced vagal withdrawal in the D group. The D rats had an increase in vagal tonus in the recovery period (49 +/- 6 bpm). Conclusions: Exercise-induced hemodynamic adjustment impairment in diabetic rats was associated with reduced cardiac vagal control. The vagal dysfunction was attenuated after aerobic exercise, reinforcing the positive role of this approach in the management of cardiovascular risk in diabetics. Muscle Nerve 46: 96101, 2012

Pilates in Heart Failure Patients: A Randomized Controlled Pilot Trial

Background: Conventional cardiac rehabilitation program consist of 15 min of warm-up, 30 min of aerobic exercise and followed by 15 min calisthenics exercise. The Pilates method has been increasingly applied for its therapeutic benefits, however little scientific evidence supports or rebukes its use as a treatment in patients with heart failure (HF). Purpose: Investigate the effects of Pilates on exercise capacity variables in HF. Methods: Sixteen pts with HF, left ventricular ejection fraction 27 +/- 14%, NYHA class III were randomly assigned to conventional cardiac rehabilitation program (n = 8) or mat Pilates training (n = 8) for 16 weeks of 30 min of aerobic exercise followed by 20 min of the specific program. Results: At 16 weeks, pts in the mat Pilates group and conventional group showed significantly increase on exercise time 11.9 +/- 2.5 to 17.8 +/- 4 and 11.7 +/- 3.9 to 14.2 +/- 4 min, respectively. However, only the Pilates group increased significantly the ventilation (from 56 +/- 20 to 69 +/- 17 L/min, P= 0.02), peak VO2 (from 20.9 +/- 6 to 24.8 +/- 6 mL/kg/min, P= 0.01), and O-2 pulse (from 11.9 +/- 2 to 13.8 +/- 3 mL/bpm, P= 0.003). The Pilates group showed significantly increase in peak VO2 when compared with conventional group (24.8 +/- 6 vs. 18.3 +/- 4, P= 0.02). Conclusions: The result suggests that the Pilates method may be a beneficial adjunctive treatment that enhances functional capacity in patients with HF who are already receiving standard medical therapy.

Physiological responses and rate of perceived exertion in Brazilian jiu-jitsu athletes

In this study, the physiological responses and rate of perceived exertion in Brazilian jiu-jitsu fighters submitted to a combat simulation were investigated. Venous blood samples and heart rate were taken from twelve male Brazilian jiu-jitsu athletes (27.1+/-2.7 yrs, 75.4+/-8.8 kg, 174.9+/-4.4 cm, 9.2+/-2.4% fat), at rest, after a warm-up (ten minutes), immediately after the fight simulation (seven minutes) and after recovery (fourteen minutes). After the combat the rate of perceived exertion was collected. The combat of the Brazilian jiu-jitsu fighters did not change blood concentrations of glucose, triglycerides, total cholesterol, low density lipoprotein and very low density lipoprotein, ureia and ammonia. However, blood levels of high density lipoprotein were significantly higher post-fight (before: 43.0+/-6.9 mg/dL, after: 45.1+/-8.0 mg/dL) and stayed at high levels during the recovery period (43.6+/-8.1 mg/dL) compared to the rest values (40.0+/-6.6 mg/dL). The fight did not cause changes in the concentrations of the cell damage markers of creatine kinase, aspartate aminotransferase and creatinine. However, blood concentrations of the alanine aminotransferase (before: 16.1+/-7.1 U/L, after: 18.6+/-7.1 U/L) and lactate dehydrogenase (before: 491.5+/-177.6 U/L, after: 542.6+/-141.4 U/L) enzymes were elevated after the fight. Heart rate (before: 122+/-25 bpm, after: 165+/-17 bpm) and lactate (before: 2.5+/-1.2 mmol/L, after: 11.9+/-5.8 mmol/L) increased significantly with the completion of combat. Despite this, the athletes rated the fight as being light or somewhat hard (12+/-2). These results showed that muscle glycogen is not the only substrate used in Brazilian jiu-jitsu fights, since there are indications of activation of the glycolytic, lipolytic and proteolytic pathways. Furthermore, the athletes rated the combats as being light or somewhat hard although muscle damage markers were generated.

Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 +/- 2 versus PE: 111 +/- 3 mmHg) and HR (R: 290 +/- 7 versus PE:328 +/- 10 bpm) reductions and BR dysfunction (R: -0.70 +/- 0.06 versus PE:-1.21 +/- 0.09 bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes.

Computerized cardiotocography in pregnancies complicated by maternal asthma

Objective: The aim of the present study was to investigate the FHR parameters in term pregnancies complicated by asthma. Study design: prospective cross-sectional study performed between July 2008 and November 2009. Twenty-one singleton pregnancy between 36 and 40 weeks gestation with diagnosis of maternal asthma and no current use of oral corticosteroids were compared with 30 pregnancies without morbidities at the same gestational age. The computerized cardiotocography (System 8002, Sonicaid) was performed and 30 min analysis was studied. Statistical analysis included Student's t-test or Mann-Whitney U test for comparisons between groups. Categorical data were compared using the chi(2)-test or Fisher's exact test. Results: There were no significant differences in FHR parameters analyzed by computerized cardiotocography: basal FHR (p = 0.80), number of accelerations >10 bpm (p = 0.08) or >15 bpm (p = 0.20), duration of high episodes (p = 0.70), duration of low episodes (p = 0.46) and STV (p = 0.66). Asthmatic mothers presented mean number of fetal movement per hour significantly lower than control group (34.6 +/- 28.2 vs. 60.6 +/- 43.1, p = 0.02). Conclusion: Computerized cardiotocography demonstrates no association between the abnormal parameters of FHR and maternal asthma in term pregnancies. Maternal asthma was associated with less fetal movements per hour, suggesting further studies on the counting of fetal movements in pregnant women with asthma.

Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure

Inoue BH, dos Santos L, Pessoa TD, Antonio EL, Pacheco BPM, Savignano FA, Carraro-Lacroix LR, Tucci PJF, Malnic G, Girardi ACC. Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure. Am J Physiol Regul Integr Comp Physiol 302: R166-R174, 2012. First published October 26, 2011; doi:10.1152/ajpregu.00127.2011.-Heart failure (HF) is associated with a reduced effective circulating volume that drives sodium and water retention and extracellular volume expansion. We therefore hypothesized that Na(+)/H(+) exchanger isoform 3 (NHE3), the major apical transcellular pathway for sodium reabsorption in the proximal tubule, is upregulated in an experimental model of HF. HF was induced in male rats by left ventricle radiofrequency ablation. Sham-operated rats (sham) were used as controls. At 6 wk after surgery, HF rats exhibited cardiac dysfunction with a dramatic increase in left ventricular end-diastolic pressure. By means of stationary in vivo microperfusion and pH-dependent sodium uptake, we demonstrated that NHE3 transport activity was significantly higher in the proximal tubule of HF compared with sham rats. Increased NHE3 activity was paralleled by increased renal cortical NHE3 expression at both protein and mRNA levels. In addition, the baseline PKA-dependent NHE3 phosphorylation at serine 552 was reduced in renal cortical membranes of rats with HF. Collectively, these results suggest that NHE3 is upregulated in the proximal tubule of HF rats by transcriptional, translational, and posttranslational mechanisms. Enhanced NHE3-mediated sodium reabsorption in the proximal tubule may contribute to extracellular volume expansion and edema, the hallmark feature of HF. Moreover, our study emphasizes the importance of undertaking a cardiorenal approach to contain progression of cardiac disease.

Experimental gestational hypothyroidism evokes hypertension in adult offspring rats

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n = 13) or water-treated dams (OWTD, n = 13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 +/- 2.0 vs 108.8 +/- 3.0 mm Hg, p<0.001), SAP (157.3 +/- 2.9 vs 135.7 +/- 4.5 mm Hg, p<0.001) and DAP (109.7 +/- 1.9 vs 88.4 +/- 2.6 mm Hg, p<0.001) when compared to OWED, and had lower HR (355.1 +/- 8.9 vs 386.8 +/- 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 +/- 0.8 vs 4.0 +/- 0.6 mm Hg-2, p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

Glutamatergic neurotransmission in the hypothalamus PVN on heart rate variability in exercise trained rats

The paraventricular nucleus of hypothalamus (PVN) is a well known site of integration for autonomic and cardiovascular responses, and the glutamate neurotransmitter plays an important role. The aim of our study was to evaluate the cardiovascular parameters and autonomic modulation by means of spectral analysis after ionotropic glutamate receptor inhibition in the PVN in conscious sedentary (S) or swimming trained (ST) rats. After exercise training protocol, adult male Wistar rats, instrumented with guide cannulae to PVN and artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recording. At baseline, physical training induced a resting bradycardia (S: 379 +/- 3, ST: 349 +/- 2 bpm, P<0.05) and promoted adaptations in HRV characterized by an increase of HF in normalized values and a decrease of LF in absolute and normalized units compared with the sedentary group. Microinjection of kynurenic acid (KYNA) in the PVN of sedentary and trained rats promoted decreases in MAP and HR, but the decrease in HR was smaller in the trained animals (Delta HRS: -48 +/- 7, ST: -28 +/- 4 bpm, P<0.05). Furthermore, the differences in baseline parameters of pulse interval, found between sedentary and trained animals, disappeared after KYNA microinjection in the PVN. Our data suggest that the cardiovascular and autonomic adaptations to the heart induced by exercise training may involve glutamatergic mechanisms in the PVN. (C) 2012 Elsevier B.V. All rights reserved.

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 +/- 8.3 years old, FEV1: 49.3 +/- 19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

Genetic mapping of a new heart rate QTL on chromosome 8 of spontaneously hypertensive rats

Abstract Background Tachycardia is commonly observed in hypertensive patients, predominantly mediated by regulatory mechanisms integrated within the autonomic nervous system. The genetic loci and genes associated with increased heart rate in hypertension, however, have not yet been identified. Methods An F2 intercross of Spontaneously Hypertensive Rats (SHR) × Brown Norway (BN) linkage analysis of quantitative trait loci mapping was utilized to identify candidate genes associated with an increased heart rate in arterial hypertension. Results Basal heart rate in SHR was higher compared to that of normotensive BN rats (365 ± 3 vs. 314 ± 6 bpm, p < 0.05 for SHR and BN, respectively). A total genome scan identified one quantitative trait locus in a 6.78 cM interval on rat chromosome 8 (8q22–q24) that was responsible for elevated heart rate. This interval contained 241 genes, of which 65 are known genes. Conclusion Our data suggest that an influential genetic region located on the rat chromosome 8 contributes to the regulation of heart rate. Candidate genes that have previously been associated with tachycardia and/or hypertension were found within this QTL, strengthening our hypothesis that these genes are, potentially, associated with the increase in heart rate in a hypertension rat model.

Chest associated to motor physiotherapy improves cardiovascular variables in newborns with respiratory distress syndrome

Background We aimed to evaluate the effects of chest and motor physiotherapy treatment on hemodynamic variables in preterm newborns with respiratory distress syndrome. Methods We evaluated heart rate (HR), respiratory rate (RR), systolic (SAP), mean (MAP) and diastolic arterial pressure (DAP), temperature and oxygen saturation (SO2%) in 44 newborns with respiratory distress syndrome. We compared all variables between before physiotherapy treatment vs. after the last physiotherapy treatment. Newborns were treated during 11 days. Variables were measured 2 minutes before and 5 minutes after each physiotherapy treatment. We applied paired Student t test to compare variables between the two periods. Results HR (148.5 ± 8.5 bpm vs. 137.1 ± 6.8 bpm - p < 0.001), SAP (72.3 ± 11.3 mmHg vs. 63.6 ± 6.7 mmHg - p = 0.001) and MAP (57.5 ± 12 mmHg vs. 47.7 ± 5.8 mmHg - p = 0.001) were significantly reduced after 11 days of physiotherapy treatment compared to before the first session. There were no significant changes regarding RR, temperature, DAP and SO2%. Conclusions Chest and motor physiotherapy improved cardiovascular parameters in respiratory distress syndrome newborns.