Publications by authors named "Gavin Lambert"

240 Publications

Lowering blood pressure by changing lifestyle through a motivational education program: a cluster randomized controlled trial study protocol.

Trials 2021 Jul 8;22(1):438. Epub 2021 Jul 8.

School of Health Sciences, Swinburne University of Technology, Hawthorn, VIC, 3122, Australia.

Background: High blood pressure is an independent risk factor of cardiovascular disease (CVD) and is a major cause of disability and death. Managing a healthy lifestyle has been shown to reduce blood pressure and improve health outcomes. We aim to investigate the effectiveness of a lifestyle modification intervention program for lowering blood pressure in a rural area of Bangladesh.

Methods: A single-center cluster randomized controlled trial (RCT). The study will be conducted for 6 months, a total of 300 participants of age 30 to 75 years with 150 adults in each of the intervention and the control arms. The intervention arm will involve the delivery of a blended learning education program on lifestyle changes for the management of high blood pressure. The education program comprises evidence-based information with pictures, fact sheets, and published literature about the effects of high blood pressure on CVD development, increased physical activity, and the role of a healthy diet in blood pressure management. The control group involves providing information booklets and general advice at the baseline data collection point. The primary outcome will be the absolute difference in clinic SBP and DBP. Secondary outcomes include the difference in the percentage of people adopting regular exercise habits, cessation of smoking and reducing sodium chloride intake, health literacy of all participants, and the perceived barriers and enablers to adopt behavior changes by collecting qualitative data. Analyses will include analysis of covariance to report the mean difference in blood pressure between the control and the intervention group and the difference in change in blood pressure due to the intervention.

Discussion: The study will assess the effects of physical activity and lifestyle modification in controlling high blood pressure. This study will develop new evidence as to whether a simple lifestyle program implemented in a rural region of a low- and middle-income country will improve blood pressure parameters for people with different chronic diseases by engaging community people.

Trial Registration: ClinicalTrials.gov NCT04505150 . Registered on 7 August 2020.
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http://dx.doi.org/10.1186/s13063-021-05379-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264477PMC
July 2021

Characteristics and physiological basis of falls in ventricular outputs after immediate cord clamping at delivery in preterm fetal lambs.

J Physiol 2021 Aug 3;599(15):3755-3770. Epub 2021 Jul 3.

Iverson Health Innovations Research Institute, Swinburne University of Technology, Hawthorn, Victoria, Australia.

Key Points: Controversy exists about the physiological mechanism(s) underlying decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, the four major determinants of ventricular output (afterload, preload, heart rate and contractility) were measured concurrently in fetal lambs at 15 s intervals over a 2 min period after cord clamping and before ventilation following delivery. After cord clamping, right (but not left) ventricular output fell by 20% in the initial 30 s, due to increased afterload associated with higher arterial blood pressures, but both outputs then halved over 45 s, due to a falling heart rate and deteriorating ventricular contractility accompanying rapid declines in arterial oxygenation to asphyxial levels. Ventricular outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in ventricular contractility accompanying asphyxia-induced surges in circulating catecholamines. These findings provide a physiological basis for the clinical recommendation that effective ventilation should occur within 60 s after immediate cord clamping.

Abstract: Controversy exists about the physiological mechanism(s) underlying large decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, anaesthetized preterm fetal lambs (127(1)d, n = 12) were instrumented with flow probes and catheters in major central arteries, and a left ventricular (LV) micromanometer-conductance catheter. Following immediate cord clamping at delivery, haemodynamics, LV and right ventricular (RV) outputs, and LV contractility were measured at 15 s intervals during a 2 min non-ventilatory period, with aortic blood gases and circulating catecholamine (noradrenaline and adrenaline) concentrations measured at 30 s intervals. After cord clamping, (1) RV (but not LV) output fell by 20% in the initial 30 s, due to a reduced stroke volume associated with increased arterial blood pressures, (2) both outputs then halved over the next 45 s, associated with falls in heart rate, arterial blood pressures and ventricular contractility accompanying a rapid decline in arterial oxygenation to asphyxial levels, (3) reduced outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in blood pressures and ventricular contractility accompanying exponential surges in circulating catecholamines. These findings are consistent with a time-dependent decline of ventricular outputs after immediate cord clamping, which comprised (1) an initial, minor fall in RV output related to altered loading conditions, (2) ensuing large decreases in both LV and RV outputs related to the combination of bradycardia and ventricular dysfunction during emergence of an asphyxial state, and (3) subsequent stabilization of reduced LV and RV outputs during ongoing asphyxia, supported by cardiovascular stimulatory effects of marked sympathoadrenal activation.
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http://dx.doi.org/10.1113/JP281693DOI Listing
August 2021

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-A Condition Associated with Heightened Sympathetic Activation.

Int J Mol Sci 2021 Apr 19;22(8). Epub 2021 Apr 19.

Dobney Hypertension Centre, School of Medicine-Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.
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http://dx.doi.org/10.3390/ijms22084241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073135PMC
April 2021

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study.

Biology (Basel) 2021 Feb 18;10(2). Epub 2021 Feb 18.

Hypertension in Africa Research Team (HART), North-West University, Potchefstroom 2520, South Africa.

Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer's disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer's and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 ± 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitive); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitive control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitive control and neuronal glia injury (Adjusted R 0.30; ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitive, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke.
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http://dx.doi.org/10.3390/biology10020162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922484PMC
February 2021

Plasma lipocalin-2/NGAL is stable over 12 weeks and is not modulated by exercise or dieting.

Sci Rep 2021 Feb 18;11(1):4056. Epub 2021 Feb 18.

Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, 25 Rainforest Walk, Melbourne, Clayton, VIC, 3800, Australia.

Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18-55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise.
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http://dx.doi.org/10.1038/s41598-021-83472-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893047PMC
February 2021

Does autonomic nervous system dysfunction influence cardiovascular disease risk in young adults with intellectual disability?

Am J Physiol Heart Circ Physiol 2021 02 31;320(2):H891-H900. Epub 2020 Dec 31.

Iverson Health Innovation Research Institute and School of Health Sciences, Faculty of Health, Arts and Design, Swinburne University of Technology, Hawthorn, Victoria, Australia.

People with intellectual disability (ID) experience cardiometabolic-related morbidity and mortality. However, it has been suggested that this population presents and lives with underestimated cardiovascular risk factors at a younger age, hence affecting their overall health and quality of life and contributing to early mortality. We assessed autonomic nervous system function in subjects with ID ( = 39), aged 18-45 yr, through measures of sudomotor function, heart rate and systolic blood pressure variability, and cardiac baroreflex function. Traditional clinical cardiovascular measurements and a biochemical analysis were also undertaken. We found that young adults with ID presented with sudomotor dysfunction, impaired cardiac baroreflex sensitivity, and systolic blood pressure variability, when compared with age-matched control subjects ( = 38). Reduced hand and feet electrochemical skin conductance and asymmetry were significantly associated with having a moderate-profound ID. Autonomic dysfunction in individuals with ID persisted after controlling for age, sex, and other metabolic parameters. Subjects in the ID group also showed significantly increased blood pressure, body mass index, and waist/hip circumference ratio, as well as increased plasma hemoglobin A1c and high-sensitivity C-reactive protein levels. We conclude that autonomic dysfunction is present in young adults with ID and is more marked in those with more severe disability. These finding have important implications in developing preventative strategies to reduce the risk of cardiovascular disease in people with ID. Adults with intellectual disability experience higher risk of premature death than the general population. Our investigation highlights increased cardiovascular risk markers and autonomic dysfunction in young adults with intellectual disability compared with control adults. Autonomic dysfunction was more marked in those with a more severe disability but independent of cardiovascular parameters. Assessment of autonomic nervous system (ANS) function may provide insight into the mechanisms of cardiometabolic disease development and progression in young adults with intellectual disability.
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http://dx.doi.org/10.1152/ajpheart.00807.2020DOI Listing
February 2021

The adrenal medulla in cardiovascular medicine: an untold story.

J Hypertens 2021 May;39(5):819-829

Baker Heart and Diabetes Institute, Melbourne, Victoria.

Unlike noradrenaline, the sympathetic neurotransmitter which overflows to the circulation, adrenaline (ADR) is a secreted hormone, with a low plasma concentration, and plasma concentration for biological action a log order lower than that of noradrenaline. The venous drainage of the left adrenal medulla into the left renal vein does expose this vein to uniquely high plasma ADR concentrations and possible risk of thrombosis at high rates of ADR secretion. There is typically a different timeframe for adrenal medullary and sympathetic nervous system responses: ADR release is short term in contrast with sympathetic activation persisting for years in heart failure and hypertension. The historic view of Walter Cannon, subject to recent review, that the sympathoadrenal system is a unified biological system, was deconstructed further with demonstration of frequent mismatching of adrenal medullary and sympathetic nervous responses. Under gravity stimulation with standing, there is prompt sympathetic activation without ADR release. In many diseases, notably obesity, hypertension, heart failure and depressive illness, an activated sympathetic nervous system and silent adrenal medulla coexist. The therapeutic corollary of this is that ADR blockade is much less commonly needed clinically than pharmacological antagonism of the sympathetic nervous system.
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http://dx.doi.org/10.1097/HJH.0000000000002748DOI Listing
May 2021

Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.

Cardiovasc J Afr 2021 Jan-Feb 23;32(1):5-16. Epub 2020 Oct 26.

Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.

Objectives: Low or high sympatho-adrenal-medullary axis (SAM) and hypothalamic-pituitary-adrenal axis (HPA) dysregulation reflect chronic stress. Retinal vessel dynamics may relate to SAM, HPA activity and stroke risk. Our objectives were therefore to assess the relationships between retinal vessel, SAM and HPA responses, and to determine stroke risk.

Methods: A prospective bi-ethnic gender cohort ( = 275, 45 ± 9 years) was included. Urine/serum/saliva samples for SAM [norepinephrine:creatinine ratio (u-NE)] and HPA [adrenocorticotrophic hormone (ACTH), cortisol] were obtained at baseline, three-year follow up and upon flicker light-induced provocation. Diastolic ocular perfusion pressure was measured as a marker of hypo-perfusion. Retinal arterial narrowing and venous widening calibres were quantified from digital images in the mydriatic eye. A validated stress and stroke risk score was applied.

Results: An interaction term was fitted for venous dilation in u-NE tertiles (p ≤ 0.05) and not in u-NE median/quartiles/quintiles. Independent of race or gender, tertile 1 (low u-NE) had a 112% increase in u-NE, decreases in cortisol, and no changes in ACTH over three years (positive feedback). Tertile 3 (high u-NE) contradictorily had decreases in u-NE and cortisol, and increases in ACTH (negative feedback). In tertile 1, reduced arterial dilation, and faster arterial vasoconstriction and narrowing were related to higher SAM activity and hypo-perfusion ( ≤ 0.05), whereas delayed venous dilation, recovery and widening were related to cortisol hypo-secretion ( ≤ 0.05). In tertile 1, delayed venous recovery responses predicted stress and stroke risk [odds ratio 4.8 (1.2-19.6); = 0.03]. These associations were not found in u-NE tertiles 2 and 3.

Conclusions: In response to low norepinephrine, a reflex increase in SAM activity occurred, enhancing arterial vasoconstriction and hypo-perfusion. Concomitant HPA dysregulation attenuated retinal vein vasoactivity and tone, reflecting delayed vein recovery responses and non-adaptation to stress. These constrained vein recovery responses are indicative of increased chronic stress and stroke risk.
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http://dx.doi.org/10.5830/CVJA-2020-031DOI Listing
October 2020

Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans.

Metabolites 2020 Sep 28;10(10). Epub 2020 Sep 28.

Metabolic and Vascular Physiology Laboratory, Baker Heart and Diabetes Institute, Melbourne 3004, Australia.

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species-in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via F-fluorodeoxyglucose ([F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.
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http://dx.doi.org/10.3390/metabo10100388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601733PMC
September 2020

Contribution of the Renal Nerves to Hypertension in a Rabbit Model of Chronic Kidney Disease.

Hypertension 2020 11 8;76(5):1470-1479. Epub 2020 Sep 8.

From the Neuropharmacology Laboratory (Y.S., S.L.B., C.G., K.L., K.L.J., G.A.H.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Overactivity of the sympathetic nervous system and high blood pressure are implicated in the development and progression of chronic kidney disease (CKD) and independently predict cardiovascular events in end-stage renal disease. To assess the role of renal nerves, we determined whether renal denervation (RDN) altered the hypertension and sympathoexcitation associated with a rabbit model of CKD. The model involves glomerular layer lesioning and uninephrectomy, resulting in renal function reduced by one-third and diuresis. After 3-week CKD, blood pressure was 13±2 mm Hg higher than at baseline (<0.001), and compared with sham control rabbits, renal sympathetic nerve activity was 1.2±0.5 normalized units greater (=0.01). The depressor response to ganglion blockade was also +8.0±3 mm Hg greater, but total norepinephrine spillover was 8.7±3.7 ng/min lower (both <0.05). RDN CKD rabbits only increased blood pressure by 8.0±1.5 mm Hg. Renal sympathetic activity, the response to ganglion blockade and diuresis were similar to sham denervated rabbits (non-CKD). CKD rabbits had intact renal sympathetic baroreflex gain and range, as well as normal sympathetic responses to airjet stress. However, hypoxia-induced sympathoexcitation was reduced by -9±0.4 normalized units. RDN did not alter the sympathetic response to hypoxia or airjet stress. CKD increased oxidative stress markers Nox5 and MCP-1 (monocyte chemoattractant protein-1) in the kidney, but RDN had no effect on these measures. Thus, RDN is an effective treatment for hypertension in this model of CKD without further impairing renal function or altering the normal sympathetic reflex responses to various environmental stimuli.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15769DOI Listing
November 2020

May Measurement Month 2018: an analysis of blood pressure screening results from Australia.

Eur Heart J Suppl 2020 Aug 28;22(Suppl H):H17-H19. Epub 2020 Aug 28.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, University of Western Australia, Level 3, MRF Building, Rear 50 Murray St, Perth, WA, 6000, Australia.

May Measurement Month (MMM), originally initiated as a temporary solution to address the lack of blood pressure (BP) screening programs worldwide, emerged as an effective annual campaign to increase the awareness of hypertension. MMM18, a cross-sectional survey of volunteers aged ≥18 years was carried out during May 2018 predominantly in capital cities across Australia following the standard MMM protocol. Blood pressure screening along with additional information including anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors were collected from 3 352 individuals across Australia. After multiple imputation, 1 026 (30.6%) adult Australians had hypertension. Of the 2 936 individuals not on antihypertensive treatment, 610 (20.8%) were hypertensive, and 237 (57.1%) of the 416 individuals receiving antihypertensive treatment had uncontrolled BP. In line with MMM17 results and other previous surveys, MMM18 revealed that close to one-third of the screened population (30.6%) had hypertension, 57.1% of individuals treated with BP-lowering medication remained uncontrolled indicating suboptimal management of the condition in the majority of patients. Most importantly, only 49.0% of those with hypertension were aware of their elevated BP, highlighting lack of awareness of elevated BP in nearly half of the affected population. Elevated BP was directly associated with alcohol consumption, overweight, and obesity. Our findings demonstrate the need for (i) continued efforts to increase BP awareness in the population, (ii) optimization of BP management strategies, and (iii) tackling some of the major contributors to BP elevation, including alcohol consumption and obesity.
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http://dx.doi.org/10.1093/eurheartj/suaa018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455264PMC
August 2020

Does moxonidine reduce Achilles tendon or musculoskeletal pain in women with polycystic ovarian syndrome? A secondary analysis of a randomised controlled trial.

BMC Endocr Disord 2020 Aug 26;20(1):131. Epub 2020 Aug 26.

University of Canberra Research Institute for Sport and Exercise (UCRISE), Canberra, ACT, Australia.

Background: Sympathetic activity and insulin resistance have recently been linked with chronic tendon and musculoskeletal pain. Polycystic ovarian syndrome is linked with insulin resistance and increased sympathetic drive and was therefore an appropriate condition to study the effects of modulating sympathetic activity on Achilles tendon and musculoskeletal symptoms.

Methods: A secondary analysis of a double-blinded, randomised controlled trial on women with polycystic ovarian syndrome was conducted. Participants received 12 weeks of moxonidine (n = 14) or placebo (n = 18). Musculoskeletal symptom and Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaires were distributed, and ultrasound tissue characterisation quantified tendon structure at 0 and 12 weeks. 2-way ANOVA was used for multiple comparisons.

Results: There was no difference in mean change in musculoskeletal symptoms (- 0.6 ± 1.7 vs - 0.4 ± 1.8, p = 0.69) or VISA-A (moxonidine - 0.2 ± 8.8 vs placebo + 4.2 ± 14.6, p = 0.24) attributable to the intervention. There was no difference in any measures of Achilles structure. Moxonidine did not reduce sympathetic drive when compared to placebo.

Conclusions: This was the first study to investigate the effects of blocking sympathetic drive on musculoskeletal and Achilles tendon symptoms in a metabolically diverse population. While the study was limited by small sample size and lack of sympathetic modulation, moxonidine did not change tendon pain/structure or musculoskeletal symptoms.

Trial Registration: ClinicalTrials.gov, NCT01504321 . Registered 5 January 2012.
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http://dx.doi.org/10.1186/s12902-020-00610-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449016PMC
August 2020

Differential sympathetic response to lesion-induced chronic kidney disease in rabbits.

Kidney Int 2020 10 25;98(4):906-917. Epub 2020 Apr 25.

Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Pharmacology, Monash University, Melbourne, Victoria, Australia. Electronic address:

Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6 of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-β, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.
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http://dx.doi.org/10.1016/j.kint.2020.03.039DOI Listing
October 2020

Fitness, Strength and Body Composition during Weight Loss in Women with Clinically Severe Obesity: A Randomised Clinical Trial.

Obes Facts 2020 23;13(4):307-321. Epub 2020 Jul 23.

Clinical Obesity Research Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Introduction: To determine whether combined exercise training with an energy-restricted diet leads to improved physical fitness and body composition when compared to energy restriction alone in free-living premenopausal women with clinically severe obesity.

Methods: Sixty premenopausal women (BMI of 40.4 ± 6.7) were randomised to energy restriction only (ER) or to exercise plus energy restriction (EXER) for 12 months. Body composition and fitness were measured at baseline, 3, 6 and 12 months.

Results: VO2 peak improved more for EXER compared to ER at 3 (mean difference ± SEM 2.5 ± 0.9 mL ∙ kg-1 ∙ min-1, p = 0.006) and 6 (3.1 ± 1.2 mL ∙ kg-1 ∙ min-1, p = 0.007) but not 12 months (2.3 ± 1.6 mL ∙ kg-1 ∙ min-1, p = 0.15). Muscle strength improved more for EXER compared to ER at all time points. No differences between groups for lean mass were observed at 12 months.

Conclusion: Combining exercise training with an energy-restricted diet did not lead to greater aerobic power, total body mass, fat mass or limit lean body mass loss at 12 months when compared to energy restriction alone for premenopausal women with clinically severe obesity in free-living situations. Future research should aim to determine an effective lifestyle approach which can be applied in the community setting for this high-risk group.
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http://dx.doi.org/10.1159/000506643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588734PMC
April 2021

Neural suppression of miRNA-181a in the kidney elevates renin expression and exacerbates hypertension in Schlager mice.

Hypertens Res 2020 11 19;43(11):1152-1164. Epub 2020 May 19.

Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

BPH/2J mice are a genetic model of hypertension with overactivity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS). BPH/2J display higher renal renin mRNA and low levels of its negative regulator microRNA-181a (miR-181a). We hypothesise that high renal SNS activity may reduce miR-181a expression, which contributes to elevated RAS activity and hypertension in BPH/2J. Our aim was to determine whether in vivo administration of a renal-specific miR-181a mimic or whether renal denervation could increase renal miR-181a abundance to reduce renal renin mRNA, RAS activity and hypertension in BPH/2J mice. Blood pressure (BP) in BPH/2J and normotensive BPN/3J mice was measured via radiotelemetry probes. Mice were administered miR-181a mimic or a negative control (1-25 nmol, i.v., n = 6-10) with BP measured for 48 h after each dose or they underwent renal denervation or sham surgery (n = 7-9). Injection of 5-25 nmol miR-181a mimic reduced BP in BPH/2J mice after 36-48 h (-5.3 ± 1.8, -6.1 ± 1.9 mmHg, respectively, P < 0.016). Treatment resulted in lower renal renin and inflammatory marker (TLR4) mRNA levels in BPH/2J. The mimic abolished the hypotensive effect of blocking the RAS with enalaprilat (P < 0.01). No differences between mimic or vehicle were observed in BPN/3J mice except for a higher level of renal angiotensinogen in the mimic-treated mice. Renal miR-181a levels that were lower in sham BPH/2J mice were greater following renal denervation and were thus similar to those of BPN/3J. Our findings suggest that the reduced renal miR-181a may partially contribute to the elevated BP in BPH/2J mice, through an interaction between the renal sympathetic nerves and miR-181a regulation of the RAS.
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http://dx.doi.org/10.1038/s41440-020-0453-xDOI Listing
November 2020

Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes.

Diabetologia 2020 07 5;63(7):1424-1434. Epub 2020 May 5.

Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, Melbourne, VIC, 3004, Australia.

Aims/hypothesis: We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits.

Methods: Diabetes was induced by alloxan, and RSNA, mean arterial pressure (MAP) and heart rate were measured before and after 1 week of treatment with empagliflozin, insulin, the diuretic acetazolamide or the ACE inhibitor perindopril, or no treatment, in conscious rabbits.

Results: Four weeks after alloxan administration, blood glucose was threefold and MAP 9% higher than non-diabetic controls (p < 0.05). One week of treatment with empagliflozin produced a stable fall in blood glucose (-43%) and increased water intake (+49%) but did not change RSNA, MAP or heart rate compared with untreated diabetic rabbits. The maximum RSNA to hypotension was augmented by 75% (p < 0.01) in diabetic rabbits but the heart rate baroreflex was unaltered. Empagliflozin and acetazolamide reduced the augmentation of the RSNA baroreflex (p < 0.05) to be similar to the non-diabetic group. Noradrenaline (norepinephrine) spillover was similar in untreated diabetic and non-diabetic rabbits but twofold greater in empagliflozin- and acetazolamide-treated rabbits (p < 0.05).

Conclusions/interpretation: As empagliflozin can restore diabetes-induced augmented sympathetic reflexes, this may be beneficial in diabetic patients. A similar action of the diuretic acetazolamide suggests that the mechanism may involve increased sodium and water excretion. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05145-0DOI Listing
July 2020

The Relationship between Vitamin D Metabolites and Androgens in Women with Polycystic Ovary Syndrome.

Nutrients 2020 Apr 26;12(5). Epub 2020 Apr 26.

Department of Medicine, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton 3168, Australia.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with hyperandrogenism present in up to 90% of affected women. Some evidence suggests a link between vitamin D deficiency and PCOS features via insulin resistance and inflammation. Our aim was to explore the relationship between biochemical markers of vitamin D status and androgens in women with PCOS. This cross-sectional study used bio-banked samples from 46 pre-menopausal women with PCOS (mean ± SD: age 30 ± 6 years; BMI 29 ± 6 kg/m). We measured 25-hydroxyvitamin D (25[OH]D), vitamin D-binding protein (DBP), total testosterone, sex hormone-binding globulin (SHBG), and calculated the free androgen index (FAI) and bioavailable and free 25(OH)D. Fasting glucose and insulin were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) and body fat percentage was determined via dual energy x-ray absorptiometry. High-sensitivity C-reactive protein (hs-CRP) was measured as a marker of inflammation. DBP was positively associated with total 25(OH)D and expectedly, negatively associated with free 25(OH)D. There were no associations between vitamin D metabolites and total testosterone, SHBG or FAI, even after adjusting for age, body fat percentage, HOMA-IR and hs-CRP. We found no associations between vitamin D metabolites and androgens in women with PCOS. Studies that have identified a vitamin D-androgen link have largely relied on methodology with numerous pitfalls; future studies should exclusively use gold-standard measures to confirm these findings in this population.
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http://dx.doi.org/10.3390/nu12051219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282251PMC
April 2020

White Coat Hypertension-A Case for Assessing Vascular Age?

Am J Hypertens 2020 07;33(7):599-601

Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, Australia.

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http://dx.doi.org/10.1093/ajh/hpaa061DOI Listing
July 2020

Evaluation of elevated heart rate as a sympathetic nervous system biomarker in essential hypertension.

J Hypertens 2020 08;38(8):1488-1495

Baker Heart and Diabetes Institute.

Background: There is a need for an easily accessible biomarker of sympathetic nervous activation in essential hypertension, but none exists. Heart rate (HR) has been suggested, but requires validation, now doubly important as an elevated HR in hypertension has emerged as an independent cardiovascular risk factor.

Methods: Isotope dilution methodology was used to measure total and regional noradrenaline spillover and adrenaline secretion rates in 30 patients with unmedicated essential hypertension and in a comparator group of 48 healthy participants with normal blood pressure. The particular interest was in the relationship of measured HR to cardiac noradrenaline spillover, the measure of cardiac sympathetic activity.

Results: Sympathetic activation was present in the patients with essential hypertension, evident in significantly increased mean cardiac, renal and total noradrenaline spillover rates. Adrenaline secretion was normal. HR in hypertension correlated directly with cardiac noradrenaline spillover (r = 0.82, P = 9.3 × 10), but not with renal noradrenaline spillover or adrenaline secretion. 67% of the variance in HR was attributable to differences in cardiac sympathetic activity. Among hypertensive patients there was no internal correlation between cardiac noradrenaline spillover, renal noradrenaline spillover and adrenaline secretion; the sympathetic activation commonly was not 'global'. In healthy participants HR did not correlate with measures of sympathetic activity or adrenaline secretion.

Conclusion: When sympathetic activation exists in essential hypertension it is differentiated, not necessarily involving all sympathetic outflows. An elevated HR proved to be a biomarker of cardiac sympathetic activation but not activation of the renal sympathetic outflow. Identifying activation of the cardiac sympathetic outflow as the prime mechanism of hypertension tachycardia is relevant to therapies which should now be considered to minimize cardiovascular risk in this clinical setting. Is an elevated HR a valid biomarker of sympathetic activation in essential hypertension? Yes, but only for the cardiac sympathetic outflow. The unavoidable principle is that regional differentiation of sympathetic responses in essential hypertension means that no simple test can ever represent each and every sympathetic outflow.
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http://dx.doi.org/10.1097/HJH.0000000000002407DOI Listing
August 2020

Deficiency of Prebiotic Fiber and Insufficient Signaling Through Gut Metabolite-Sensing Receptors Leads to Cardiovascular Disease.

Circulation 2020 04 25;141(17):1393-1403. Epub 2020 Feb 25.

Heart Failure Research Group (D.M.K., W.A.S., H.A.J., D.H., B.G., A.F., F.Z.M.), Baker Heart and Diabetes Institute, Melbourne, Australia.

Background: High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Among key Western lifestyle factors, a diet poor in fiber is associated with prevalence of high BP. The impact of lack of prebiotic fiber and the associated mechanisms that lead to higher BP are unknown. Here we show that lack of prebiotic dietary fiber leads to the development of a hypertensinogenic gut microbiota, hypertension and its complications, and demonstrate a role for G-protein coupled-receptors (GPCRs) that sense gut metabolites.

Methods: One hundred seventy-nine mice including C57BL/6J, gnotobiotic C57BL/6J, and knockout strains for GPR41, GPR43, GPR109A, and GPR43/109A were included. C57BL/6J mice were implanted with minipumps containing saline or a slow-pressor dose of angiotensin II (0.25 mg·kg·d). Mice were fed diets lacking prebiotic fiber with or without addition of gut metabolites called short-chain fatty acids ([SCFA)] produced during fermentation of prebiotic fiber in the large intestine), or high prebiotic fiber diets. Cardiac histology and function, BP, sodium and potassium excretion, gut microbiome, flow cytometry, catecholamines and methylation-wide changes were determined.

Results: Lack of prebiotic fiber predisposed mice to hypertension in the presence of a mild hypertensive stimulus, with resultant pathological cardiac remodeling. Transfer of a hypertensinogenic microbiota to gnotobiotic mice recapitulated the prebiotic-deprived hypertensive phenotype, including cardiac manifestations. Reintroduction of SCFAs to fiber-depleted mice had protective effects on the development of hypertension, cardiac hypertrophy, and fibrosis. The cardioprotective effect of SCFAs were mediated via the cognate SCFA receptors GPR43/GPR109A, and modulated L-3,4-dihydroxyphenylalanine levels and the abundance of T regulatory cells regulated by DNA methylation.

Conclusions: The detrimental effects of low fiber Westernized diets may underlie hypertension, through deficient SCFA production and GPR43/109A signaling. Maintaining a healthy, SCFA-producing microbiota is important for cardiovascular health.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043081DOI Listing
April 2020

Sedentary Behavior and Public Health: Integrating the Evidence and Identifying Potential Solutions.

Annu Rev Public Health 2020 04 8;41:265-287. Epub 2020 Jan 8.

Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; email:

In developed and developing countries, social, economic, and environmental transitions have led to physical inactivity and large amounts of time spent sitting. Research is now unraveling the adverse public health consequences of too much sitting. We describe improvements in device-based measurement that are providing new insights into sedentary behavior and health. We consider the implications of research linking evidence from epidemiology and behavioral science with mechanistic insights into the underlying biology of sitting time. Such evidence has led to new sedentary behavior guidelines and initiatives. We highlight ways that this emerging knowledge base can inform public health strategy: First, we consider epidemiologic and experimental evidence on the health consequences of sedentary behavior; second, we describe solutions-focused research from initiatives in workplaces and schools. To inform a broad public health strategy, researchers need to pursue evidence-informed collaborations with occupational health, education, and other sectors.
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http://dx.doi.org/10.1146/annurev-publhealth-040119-094201DOI Listing
April 2020

Ambulatory blood pressure monitoring and morning surge in blood pressure in adult black and white South Africans.

J Clin Hypertens (Greenwich) 2020 01 25;22(1):21-28. Epub 2019 Nov 25.

Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.

We examined whether there were differences in the circadian variation in blood pressure and the morning surge in blood pressure between black and white Africans. Clinic and ambulatory blood pressure data obtained from the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study was examined (n = 406; 49% black African). Ambulatory blood pressure readings were fitted to a six-parameter double logistic equation to determine the power and rate of the morning surge in blood pressure. Multiple linear regression analysis was used to examine differences in blood pressure between black and white participants. Clinic and ambulatory blood pressure were higher in black participants throughout the day and night. In those taking medications, blood pressure was less well controlled in black subjects. Despite the higher systolic blood pressure, the day-night difference estimated by the logistic function was similar in black and white participants. However, the rate of rise and power in the morning surge in blood pressure was lower in black participants. We conclude that black participants of the SABPA study present with higher blood pressure throughout the day and night but have a lower power of the morning surge in blood pressure due to a slower morning rate of increase. Moreover, they had an increased prevalence of undiagnosed hypertension and, in those taking medication, were less likely to have their blood pressure controlled than their white counterparts.
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http://dx.doi.org/10.1111/jch.13740DOI Listing
January 2020

Effect of Salt Supplementation on Sympathetic Activity and Endothelial Function in Salt-Sensitive Type 2 Diabetes.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.

Context: Lower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D).

Objective: To determine whether sympathetic nervous system (SNS) activation and endothelial dysfunction contribute to these observations, we examined the effect of salt supplementation on these systems in people with T2D with habitual low sodium. We hypothesized that salt supplementation would lower SNS activity and improve endothelial function compared to placebo.

Design: We conducted a randomized, double-blinded, placebo-controlled crossover trial.

Setting: The study took place in a tertiary referral diabetes outpatient clinic.

Participants: Twenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included.

Intervention: Salt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered.

Main Outcome Measures: The primary outcome of SNS activity and endothelial function was assessed as follows: Microneurography assessed muscle sympathetic nerve activity (MSNA), pulse amplitude tonometry assessed endothelial function via reactive hyperemic index (RHI), and arterial stiffness was assessed via augmentation index (AI). Secondary outcomes included cardiac baroreflex, serum aldosterone, ambulatory blood pressure monitoring (ABPM), heart rate variability (HRV), and salt sensitivity.

Results: Compared to placebo, salt supplementation increased MSNA (burst frequency P = .047, burst incidence P = .016); however, RHI (P = .24), AI (P = .201), ABPM (systolic P = .09, diastolic P = .14), and HRV were unaffected. Salt supplementation improved baroreflex (slope P = .026) and lowered aldosterone (P = .004), and in salt-resistant individuals there was a trend toward improved RHI (P = .07).

Conclusions: In people with T2D and low habitual sodium intake, salt supplementation increased SNS activity without altering endothelial function or blood pressure but improved baroreflex function, a predictor of cardiac mortality. Salt-resistant individuals trended toward improved endothelial function with salt supplementation.
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http://dx.doi.org/10.1210/clinem/dgz219DOI Listing
April 2020

The influence of hospital location and 'level of care' on continuing professional development.

Nurse Educ Pract 2019 Nov 5;41:102634. Epub 2019 Oct 5.

Swinburne University of Technology, PO Box 218, Hawthorn, 3122, Australia. Electronic address:

Healthcare workers core skills are reinforced and knowledge of latest developments ensured by undertaking systematic continuing professional development. The current study explored the impact of health facility location and level of care provided on the continuing professional development offered to maternity services healthcare workers in Victoria, Australia. An online survey of middle to senior management staff of 71 public and private health services as well as 7 professional bodies was conducted, yielding 114 participants. Analysis was by location (metropolitan or regional/rural) and level of care provided. The findings revealed Australian Health Practitioner Regulation Agency registration is the predominant requirement to provide continuing professional development to staff. Dedicated education departments or educators are significantly underrepresented in Level 1&2 facilities, while Level 5&6 facilities are more likely to provide breastfeeding continuing professional development. Metropolitan locations provided more wide-ranging programmes compared with rural/regional locations. Key enablers are the capacity to share resources, have access to external courses and simulation equipment/centres, and the provision of relevant and timely continuing professional development programmes, indicating that 'Educational hubs' with credentialed staff working from better resourced regional facilities could deliver a complete array of CPD programmes to lower level facilities.
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http://dx.doi.org/10.1016/j.nepr.2019.102634DOI Listing
November 2019

Android Fat Deposition and Its Association With Cardiovascular Risk Factors in Overweight Young Males.

Front Physiol 2019 18;10:1162. Epub 2019 Sep 18.

Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Objective: Excess adiposity increases the risk of type-2 diabetes and cardiovascular disease development. Beyond the simple level of adiposity, the pattern of fat distribution may influence these risks. We sought to examine if higher android fat distribution was associated with different hemodynamic, metabolic or vascular profile compared to a lower accumulation of android fat deposits in young overweight males.

Methods: Forty-six participants underwent dual-energy X-ray absorptiometry and were stratified into two groups. Group 1: low level of android fat (<9.5%) and group 2: high level of android fat (>9.5%). Assessments comprised measures of plasma lipid and glucose profile, blood pressure, endothelial function [reactive hyperemia index (RHI)] and muscle sympathetic nerve activity (MSNA).

Results: There were no differences in weight, BMI, total body fat and lean mass between the two groups. Glucose tolerance and insulin resistance (fasting plasma insulin) were impaired in group 2 ( < 0.05). Levels of plasma triglycerides and 5 lipid species were higher in group 2 ( < 0.05). Endothelial function was less in group 2 (RHI: 1.64 vs. 2.26, = 0.003) and heart rate was higher (76 vs. 67 bpm, = 0.004). No difference occurred in MSNA nor blood pressure between the 2 groups.

Conclusion: Preferential fat accumulation in the android compartment is associated with increased cardiovascular and metabolic risk via alteration of endothelial function.
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http://dx.doi.org/10.3389/fphys.2019.01162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759693PMC
September 2019

#MindinBody - feasibility of vigorous exercise (Bikram yoga versus high intensity interval training) to improve persistent pain in women with a history of trauma: a pilot randomized control trial.

BMC Complement Altern Med 2019 Aug 29;19(1):234. Epub 2019 Aug 29.

Human Neurotransmitter Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.

Background: The neurobiology of persistent pain shares common underlying psychobiology with that of traumatic stress. Modern treatments for traumatic stress often involve bottom-up sensorimotor retraining/exposure therapies, where breath, movement, balance and mindfulness, are used to target underlying psychobiology. Vigorous exercise, in particular Bikram yoga, combines many of these sensorimotor/exposure therapeutic features. However, there is very little research investigating the feasibility and efficacy of such treatments for targeting the underlying psychobiology of persistent pain.

Methods: This study was a randomized controlled trail (RCT) comparing the efficacy of Bikram yoga versus high intensity interval training (HIIT), for improving persistent pain in women aged 20 to 50 years. The participants were 1:1 randomized to attend their assigned intervention, 3 times per week, for 8 weeks. The primary outcome measure was the Brief Pain Inventory (BPI) and further pain related biopsychosocial secondary outcomes, including SF-36 Medical Outcomes and heart rate variability (HRV), were also explored. Data was collected pre (t0) and post (t1) intervention via an online questionnaire and physiological testing.

Results: A total of 34 women were recruited from the community. Analyses using ANCOVA demonstrated no significant difference in BPI (severity plus interference) scores between the Bikram yoga (n = 17) and the HIIT (n = 15). Women in the Bikram yoga group demonstrated significantly improved SF-36 subscale physical functioning: [ANCOVA: F(1, 29) = 6.17, p = .019, partial eta-squared effect size (η) = .175 and mental health: F(1, 29) = 9.09, p = .005, η = .239; and increased heart rate variability (SDNN): F(1, 29) = 5.12, p = .013, η = .150, scores compared to the HIIT group. Across both groups, pain was shown to decrease, no injuries were experienced and retention rates were 94% for Bikram yoga and 75% for HIIT .

Conclusions: Bikram yoga does not appear a superior exercise compared to HIIT for persistent pain. However, imporvements in quality of life measures and indicator of better health were seen in the Bikram yoga group. The outcomes of the present study suggest vigorous exercise interventions in persistent pain cohorts are feasible.

Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12617001507370 , 26/10/2017).
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http://dx.doi.org/10.1186/s12906-019-2642-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714085PMC
August 2019

Effects of sympathetic modulation in metabolic disease.

Ann N Y Acad Sci 2019 10 19;1454(1):80-89. Epub 2019 Aug 19.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit/Medical Research Foundation, University of Western Australia, Perth, Western Australia, Australia.

Sympathetic overdrive contributes to the derangement of glucose metabolism evident in clinical conditions, such as obesity, metabolic syndrome, type 2 diabetes, obstructive sleep apnea, and others. Targeting the sympathetic nervous system directly therefore appears as an attractive therapeutic approach to restore impaired glucose metabolism. Indeed, lifestyle interventions, including healthier diets and exercise, have been shown to exert their beneficial effects at least in part by reducing sympathetic nervous system activity. Pharmacologic inhibition of exaggerated central sympathetic outflow has also been demonstrated to beneficially impact on body weight and glucose and lipid metabolism. More recently, catheter-based renal denervation, an intervention applied predominantly to lower elevated blood pressure in patients with resistant hypertension, revealed salutary effects on glucose metabolism. Here, we review the mechanisms that contribute to the beneficial effects of targeting the sympathetic nervous system directly and discuss how these approaches may best be embedded in routine clinical practice.
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http://dx.doi.org/10.1111/nyas.14217DOI Listing
October 2019

Competencies and skill development in maternity care services in Victoria - A qualitative study.

Nurse Educ Pract 2019 Aug 6;39:55-60. Epub 2019 Aug 6.

Faculty of Health, Art and Design, Swinburne University of Technology, Australia. Electronic address:

In healthcare, continuing professional development is provided to ensure professional standards are maintained and for clinicians to remain fit to practice. The purpose of the study was to identify potential gaps or issues with continuing professional development in maternity services through consultations with key stakeholders and, in addition, to generate possible solutions or recommendations towards the development of a state wide continuing professional development program. The data was collected through semi-structured interviews of a purposive sample between June and August 2018. A thematic analysis was undertaken. Participants included a practicing midwife, allied health practitioner (physiotherapist), manager, healthcare educator, and an outlier service worker (maternal and child health nurse). Following the thematic analysis, four main themes (education, practitioner standards, programme monitoring and resources) were identified along with nine sub-themes. The results suggest organisations need to offer explicit support for staff to access to continuing professional development. In addition, the qualifications of facilitators of continuing professional development and/or consumer education are recommended to go beyond education levels required for registration. In this respect, some organisations credentialed their educators locally in a 'train the trainer' manner however, most participants supported professional preparation for the role of educator.
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http://dx.doi.org/10.1016/j.nepr.2019.08.001DOI Listing
August 2019

Sympathetic activity in obesity: a brief review of methods and supportive data.

Ann N Y Acad Sci 2019 10 3;1454(1):56-67. Epub 2019 Jul 3.

The Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, Victoria, Australia.

The increase in the prevalence of obesity and the concomitant rise in obesity-related illness have led to substantial pressure on health care systems throughout the world. While the combination of reduced exercise, increased sedentary time, poor diet, and genetic predisposition is undoubtedly pivotal in generating obesity and increasing disease risk, a large body of work indicates that the sympathetic nervous system (SNS) contributes to obesity-related disease development and progression. In obesity, sympathetic nervous activity is regionalized, with activity in some outflows being particularly sensitive to the obese state, whereas other outflows, or responses to stimuli, may be blunted, thereby making the assessment of sympathetic nervous activation in the clinical setting difficult. Isotope dilution methods and direct nerve recording techniques have been developed and utilized in clinical research, demonstrating that in obesity there is preferential activation of the muscle vasoconstrictor and renal sympathetic outflows. With weight loss, sympathetic activity is reduced. Importantly, sympathetic nervous activity is associated with end-organ dysfunction and changes in sympathetic activation that accompany weight loss are often reflected in an improvement of end-organ function. Whether targeting the SNS directly improves obesity-related illness remains unknown, but merits further attention.
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http://dx.doi.org/10.1111/nyas.14140DOI Listing
October 2019

Neurohumoral interactions contributing to renal vasoconstriction and decreased renal blood flow in heart failure.

Am J Physiol Regul Integr Comp Physiol 2019 09 26;317(3):R386-R396. Epub 2019 Jun 26.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.

In heart failure (HF), increases in renal sympathetic nerve activity (RSNA), renal norepinephrine spillover, and renin release cause renal vasoconstriction, which may contribute to the cardiorenal syndrome. To increase our understanding of the mechanisms causing renal vasoconstriction in HF, we investigated the interactions between the increased activity of the renal nerves and the renal release of norepinephrine and renin in an ovine pacing-induced model of HF compared with healthy sheep. In addition, we determined the level of renal angiotensin type-1 receptors and the renal vascular responsiveness to stimulation of the renal nerves and α-adrenoceptors. In conscious sheep with mild HF (ejection fraction 35%-40%), renal blood flow (276 ± 13 to 185 ± 18 mL/min) and renal vascular conductance (3.8 ± 0.2 to 3.1 ± 0.2 mL·min·mmHg) were decreased compared with healthy sheep. There were increases in the burst frequency of RSNA (27%), renal norepinephrine spillover (377%), and plasma renin activity (141%), whereas the density of renal medullary angiotensin type-1 receptors decreased. In anesthetized sheep with HF, the renal vasoconstrictor responses to electrical stimulation of the renal nerves or to phenylephrine were attenuated. Irbesartan improved the responses to nerve stimulation, but not to phenylephrine, in HF and reduced the responses in normal sheep. In summary, in HF, the increases in renal norepinephrine spillover and plasma renin activity are augmented compared with the increase in RSNA. The vasoconstrictor effect of the increased renal norepinephrine and angiotensin II is offset by reduced levels of renal angiotensin type-1 receptors and reduced renal vasoconstrictor responsiveness to α-adrenoceptor stimulation.
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http://dx.doi.org/10.1152/ajpregu.00026.2019DOI Listing
September 2019
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