Beetroot juice, exercise, and cardiovascular function in women planning to conceive

OBJECTIVE: Prepregnancy optimization of cardiovascular function may reduce the risk of pre-eclampsia. We aimed to assess the feasibility and effect of preconception cardiovascular monitoring, exercise, and beetroot juice on cardiovascular parameters in women planning to conceive. DESIGN AND METHOD: Prospective single-site, open-label, randomized controlled trial. Thirty-two women, aged 18-45 years, were allocated into one of four arms (1 : 1 : 1 : 1): exercise, beetroot juice, exercise plus beetroot juice and no intervention for 12 weeks. Blood pressure (BP) was measured at home daily. Cardiac output (CO) and total peripheral resistance (TPR) were assessed via bio-impedance. RESULTS: Twenty-nine out of 32 (91%) participants completed the study. Adherence to daily BP and weight measurements were 81 and 78%, respectively (n = 29). Eight out of 15 (53%) of participants did not drink all the provided beetroot juice because of forgetfulness and taste. After 12 weeks, exercise was associated with a reduction in standing TPR (-278 ± 0.272 dynes s cm-5, P < 0.05), and an increase in standing CO (+0.88 ± 0.71 l/min, P < 0.05). Exercise and beetroot juice together was associated with a reduction in standing DBP ( 7 ± 6 mmHg, P < 0.05), and an increase in standing CO (+0.49 ± 0.66 l/min, P < 0.05). The control group showed a reduction in standing TPR ( 313 ± 387 dynes s cm-5) and standing DBP ( 8 ± 5mmHg). All groups gained weight. CONCLUSION: Exercise and beetroot juice in combination showed a signal towards improving cardiovascular parameters. The control group showed improvements, indicating that home measurement devices and regular recording of parameters are interventions in themselves. Nevertheless, interventions before pregnancy to improve cardiovascular parameters may alter the occurrence of hypertensive conditions during pregnancy and require further investigation in adequately powered studies

The role of epoxyeicosatrienoic acids in the cardiovascular system.

There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of cardiovascular risk factors. This review discusses the current knowledge on the role of EETs in endothelium-dependent control of vascular tone in the healthy and in subjects with cardiovascular risk factors, and considers the pharmacological potential of targeting this pathway.Dr. Lucy Yang is funded by the Wellcome Trust TMAT programme, the Sackler fellowship, and Clare College Research Expenses Fund. Professor Ian Wilkinson and Dr. Joseph Cheriyan are both funded by the Cambridge Biomedical Research Centre. Professor Ian Wilkinson and Dr. Carmel McEniery are both funded by the British Heart Foundation.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/bcp.1260

Change in maternal cardiac output from preconception to mid-pregnancy is associated with birth weight in healthy pregnancies.

OBJECTIVE: Birth weight (BW) is thought to be determined by maternal health and genetic, nutritional and placental factors, the latter being influenced by anatomical development and perfusion. Maternal cardiovascular changes contribute to uteroplacental perfusion; however, they have not yet been investigated in relation to fetal growth or BW. Our aim was to explore the relationship between maternal cardiovascular adaptation, fetal growth and BW in healthy pregnancies. METHODS: This was a longitudinal prospective study of women planning to conceive a pregnancy. Maternal cardiac output (CO), cardiac index (CI), pulse-wave velocity, aortic augmentation index, central blood pressure and peripheral vascular resistance were assessed prior to pregnancy and at 6, 23 and 33 weeks' gestation. Fetal growth was assessed using serial ultrasound measurements of biometry. RESULTS: In total, 143 women volunteered to participate and were eligible for study inclusion. A total of 101 women conceived within 18 months and there were 64 live births with normal pregnancy outcome. There were positive correlations between BW and the pregnancy-induced changes in CO (ρ = 0.4, P = 0.004), CI (ρ = 0.3, P = 0.02) and peripheral vascular resistance (ρ = 0.3, P = 0.02). There were significant associations between second-to-third-trimester fetal weight gain and the prepregnancy-to-second-trimester increase in CO (Δ, 0.8 ± 1.2 L/min; ρ = 0.3, P = 0.02) and CI (Δ, 0.4 ± 0.6 L/min/m2 ; ρ = 0.3, P = 0.04) and reduction in aortic augmentation index (Δ, -10 ± 9%; ρ = -0.3, P = 0.04). CONCLUSIONS: In healthy pregnancy, incremental changes in maternal CO in early pregnancy are associated with third-trimester fetal growth and BW. It is plausible that this association is causative as the changes predate third-trimester fetal growth and eventual BW. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd

Review of the Techniques Used for Investigating the Role Elastin and Collagen Play in Arterial Wall Mechanics

This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI 10.1109/RBME.2020.3005448, IEEE Reviews in Biomedical Engineering. This work is licensed under a Creative Commons Attribution 4.0 License.The arterial wall is characterised by a complex microstructure that impacts the mechanical properties of the vascular tissue. The main components consist in collagen and elastin fibres, proteoglycans, Vascular Smooth Muscle Cells (VSMCs) and ground matrix. While VSMCs play a key role in the active mechanical response of arteries, collagen and elastin determine the passive mechanics. Several experimental methods have been designed to investigate the role of these structural proteins in determining the passive mechanics of the arterial wall. Microscopy imaging of load-free or fixed samples provides useful information on the structure-function coupling of the vascular tissue, and mechanical testing provides information on the mechanical role of collagen and elastin networks. However, when these techniques are used separately, they fail to provide a full picture of the arterial micromechanics. More recently, advances in imaging techniques have allowed combining both methods, thus dynamically imaging the sample while loaded in a pseudo-physiological way, and overcoming the limitation of using either of the two methods separately. The present review aims at describing the techniques currently available to researchers for the investigation of the arterial wall micromechanics. This review also aims to elucidate the current understanding of arterial mechanics and identify some research gaps.Addenbrookes Hospita

First In human study of a novel biased apelin receptor ligand, MM54, a G-alpha(i) agonist/beta-arrestin antagonist

Introduction: The peptide apelin acts via G proteins to cause beneficial vasodilation and potent positive inotropy to ameliorate pulmonary arterial hypertension in humans and animal models. Apelin is internalised via β-arrestin. In contrast, with loss of endogenous apelin, its receptor acts as a mechanosensor, stimulating β-arrestin to induce detrimental cardiac hypertrophy. Our aim was to characterise the action of our apelin ligand, MM54 that in cell based assays blocks β-arrestin but activates the Gαi protein pathway, in this first in human study. Method: Competition binding in human heart (n=3) used [I125] [Pyr1]apelin-13 (0.1nmol/L). β-arrestin recruitment, receptor internalization and forskolin-induced cAMP inhibition were measured in CHO-K1 cells expressing human apelin receptor. Forearm blood flow was measured in 9 volunteers using venous occlusion plethysmography at baseline and at 4 incremental doses (1, 10, 30, 100 nmol/min) of MM54, each for eight minutes. The Aellig hand vein technique was used to measure the effect of 3 incremental doses (3, 30, 300 nmol/min) of MM54 for 15 min on veins pre-constricted with noradrenaline in 6 individuals compared with 8 controls. Data are mean+SEM, n≥3. Results: MM54 had an affinity of pKi = 6.50±0.03. In β-arrestin (pKB 6.93±0.15) and receptor internalization assays (pKB 5.89±0.06) MM54 was an antagonist, but activated the G protein pathway (pD2±SEM 5.86+0.23). At the highest concentration (100 nmol/min), MM54 caused a significant absolute increase in forearm blood flow compared to control arm, representing a 76 % change from baseline (P<0.01, ANOVA with repeated measures with Dunnett’s post hoc analysis on untransformed data). In the hand vein, MM54 caused a significant concentration dependent dilatation in veins over the concentration range tested, with the highest dose causing 57% reversal (P<0.01). Conclusion: At the cellular level, the results suggest MM54 induced a different conformation in the receptor compared with the native peptide apelin, resulting in a biased profile of activating the G protein pathway but blocking β-arrestin. In agreement in clinical studies, in both the arterial and venous circulation, MM54 induced vasodilatation that is thought to be mediated by the G protein pathway

ACE inhibitor and angiotensin receptor-II antagonist prescribing and hospital admissions with acute kidney injury: A longitudinal ecological study

This is the final version. Available from the publisher via the DOI in this record.Background: ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing. Methods and Findings: English NHS prescribing data for ACE-I/ARA prescriptions were matched at the level of the general practice to numbers of hospital admissions with a primary diagnosis of AKI. Numbers of prescriptions were weighted for the demographic characteristics of general practices by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units (ASTRO-PUs). We performed a mixed-effect Poisson regression to model the number of admissions for AKI occurring in each practice for each of 4 years from 1/4/2007. From 2007/8-2010/11, crude AKI admission rates increased from 0.38 to 0.57 per 1000 patients (51.6% increase), and national annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 to 0.234 (15.8% increase). There was strong evidence (p<0.001) that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates. The increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1% (rate ratio = 1.051 for a 0.03 per ASTRO-PU increase in annual prescribing rate, 95%CI 1.047-1.055). Using the regression model we predict that 1,636 (95%CI 1,540-1,780) AKI admissions would have been avoided if prescribing rates were at the 2007/8 level, equivalent to 14.8% of the total increase in AKI admissions. Conclusion: In this ecological analysis, up to 15% of the increase in AKI admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE-I and ARAs. However, these findings are limited by the lack of patient level data such as indication for prescribing and patient characteristics. © 2013 Tomlinson et al.Cambridge Biomedical Research InstituteBritish Heart Foundatio

Stiffening and ventricular-arterial interaction in the ascending aorta using Magnetic Resonance Imaging: Ageing effects in healthy humans

2018 The Author(s). Objectives: The aim of this study was to investigate the effect of age and sex on nPWV and ndI in the ascending aorta of healthy humans. Background: Local pulse wave velocity (nPWV) and wave intensity (ndI) in the human ascending aorta have not been studied adequately, due to the need for invasive pressure measurements. However, a recently developed technique made the non-invasive determination of nPWV and ndI possible using measurements of flow velocity and arterial diameter. Methods: Diameter and flow velocity were measured at the level of the ascending aorta in 144 healthy subjects (aged 20-77 years, 66 male), using magnetic resonance imaging. nPWV, ndI parameters; forward (FCW); backward (BCW) compression waves, forward decompression wave (FDW), local aortic distensibility (nDs) and reflection index (nRI) were calculated. Results: nPWV increased significantly with age from 4.7±0.3 m/s for those 20-30 years to 6.4±0.2 m/s for those 70-80 years (P<0.001) and did not differ between sexes. nDs decreased with age (5.3±0.5 vs. 2.6±0.2 10-5 1/Pa, P<0.001) and nRI increased with age (0.17±0.03 vs. 0.39±0.06, P<0.01) for those 20-30 and 70-80 years, respectively. FCW, BCW and FDW decreased significantly with age by 86.3%, 71.3% and 74.2%, respectively (P<0.001), all compared to the lowest age-band. Conclusions: In healthy humans, ageing results in stiffer ascending aorta, with increase in nPWV and decrease in nDs. A decrease in FCW and FDW indicates decline in left ventricular early and late systolic functions with age in healthy humans with no differences between sexes. nRI is more sensitive than BCW in establishing the effects of ageing on reflected waves measured in the ascending aorta

Towards the non-invasive determination of arterial wall distensible properties: new approach using old formulae

Addenbrook’s Hospital; Brunel University London