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Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function.
Laurila, S, Rebelos, E, Lahesmaa, M, Sun, L, Schnabl, K, Peltomaa, TM, Klén, R, U-Din, M, Honka, MJ, Eskola, O, et al
American journal of physiology. Endocrinology and metabolism. 2022;(1):E54-E62
Abstract
The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography. Kidney function was measured with [18F]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared with placebo (secretin vs. placebo, means ± SD, 15.5 ± 7.4 vs. 9.7 ± 4.9 μmol/100 g/min, 95% confidence interval (CI) [2.2, 9.4], P = 0.004). Secretin also increased [18F]FDG renal clearance (44.5 ± 5.4 vs. 39.5 ± 8.5 mL/min, 95%CI [1.9, 8.1], P = 0.004), and eGFR was significantly increased from baseline after secretin, compared with placebo (17.8 ± 9.8 vs. 6.0 ± 5.2 ΔmL/min/1.73 m2, 95%CI [6.0, 17.6], P = 0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure.NEW & NOTEWORTHY Secretin increases myocardial glucose uptake compared with placebo, supporting a previously proposed inotropic effect. Secretin also increased renal filtration rate.
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Transcutaneous electrical nerve stimulation attenuates cardiac sympathetic drive in heart failure: a 123MIBG myocardial scintigraphy randomized controlled trial.
Campos, MO, Nóbrega, ACL, Miranda, SM, Ribeiro, ML, Guerra, TRB, Braghirolli, AMS, Mesquita, CT, Fernandes, IA
American journal of physiology. Heart and circulatory physiology. 2019;(2):H226-H233
Abstract
Cardiac sympathetic overdrive provides inotropic support to the failing heart. However, as myocardial insult evolves, this compensatory response impairs contractile function and constitutes an independent mortality predictor and a primary target in the treatment of heart failure (HF). In this prospective, randomized, double-blind, controlled crossover trial, we proposed cervicothoracic transcutaneous electrical nerve stimulation (CTENS) as a nonpharmacological therapy on cardiac sympathetic activity in patients with HF. Seventeen patients with HF were randomly assigned to an in-home CTENS (30 min twice daily, 80-Hz frequency, and 150-μs pulse duration) or a control intervention (Sham) for 14 consecutive days. Following a 60-day washout phase, patients were crossed over to the opposite intervention. The heart-to-mediastinum ratio (HMR) and washout rate (WR) (indexes of sympathetic innervation density and activity from planar 123iodo-metaiodobenzylguanidine myocardial scintigraphy images, respectively), as well as blood pressure (BP) and heart rate (HR), were quantified before and after each intervention. HMR, BP, and HR did not change throughout the study. Nonetheless, CTENS reduced WR (CTENS -4 ± 10 vs. Sham +5 ± 15%, P = 0.03) when compared with Sham. When allocated in two independent groups, preserved (PCSI, HMR > 1.6, n = 10) and impaired cardiac sympathetic innervation (ICSI, HRM ≤1.6, n = 7), PCSI patients showed an important attenuation of WR (-11 ± 9 vs. Sham +8 ± 19%, P = 0.007) after CTENS. Nonetheless, neither Sham nor CTENS evoked changes in WR of the ICSI patients (P > 0.05). These findings indicate that CTENS attenuates the cardiac sympathetic overdrive in patients with HF and a preserved innervation constitutes an essential factor for this beneficial neuromodulatory impact. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Identifier: NCT03354689. NEW & NOTEWORTHY We found that short-term cervicothoracic transcutaneous electrical nerve stimulation (CTENS) attenuates cardiac sympathetic overdrive in patients with heart failure and a preserved autonomic innervation may constitute an essential factor to maximize this beneficial neuromodulatory effect. CTENS then emerges as an alternative noninvasive and nonpharmacological strategy to attenuate exaggerated cardiac sympathetic drive in patients with heart failure.
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The Effect of Marine n-3 Polyunsaturated Fatty Acids on Heart Rate Variability in Renal Transplant Recipients: A Randomized Controlled Trial.
Lilleberg, HS, Cichosz, SL, Svensson, M, Christensen, JH, Fleischer, J, Eide, I, Jenssen, T
Nutrients. 2019;(12)
Abstract
Resting heart rate (rHR) and heart rate variability (HRV) are non-invasive measurements that predict the risk of sudden cardiac death (SCD). Marine n-3 polyunsaturated fatty acid (PUFA) supplementation may decrease rHR, increase HRV, and reduce the risk of SCD. To date, no studies have investigated the effect of marine n-3 PUFA on HRV in renal transplant recipients. In a randomized controlled trial, 132 renal transplant recipients were randomized to receive either three 1 g capsules of marine n-3 PUFA, each containing 460 mg/g EPA and 380 mg/g DHA, or control (olive oil) for 44 weeks. HRV was calculated in the time and frequency domains during a conventional cardiovascular reflex test (response to standing, deep breathing, and Valsalva maneuver) and during 2 min of resting in the supine position. There was no significant effect of marine n-3 PUFA supplementation on time-domain HRV compared with controls. rHR decreased 3.1 bpm (± 13.1) for patients receiving marine n-3 PUFA compared to 0.8 (± 11.0) in controls (p = 0.28). In the frequency domain HRV analyses, there was a significant change in response to standing in both high and low frequency measures, 2.9 (p = 0.04, 95% CI (1.1;8)) and 2.7 (p = 0.04, 95% CI (1.1;6.5)), respectively. In conclusion, 44 weeks of supplemental marine n-3 PUFAs in renal transplant recipients significantly improved the cardiac autonomic function, assessed by measuring HRV during conventional cardiovascular reflex tests.
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Examining the Associations between Walk Score, Perceived Built Environment, and Physical Activity Behaviors among Women Participating in a Community-Randomized Lifestyle Change Intervention Trial: Strong Hearts, Healthy Communities.
Lo, BK, Graham, ML, Folta, SC, Paul, LC, Strogatz, D, Nelson, ME, Parry, SA, Carfagno, ME, Wing, D, Higgins, M, et al
International journal of environmental research and public health. 2019;(5)
Abstract
Little is known about the relationship between perceived and objective measures of the built environment and physical activity behavior among rural populations. Within the context of a lifestyle-change intervention trial for rural women, Strong Hearts, Healthy Communities (SHHC), we examined: (1) if Walk Score (WS), an objective built environment measure, was associated with perceived built environment (PBE); (2) if WS and PBE were associated with moderate-to-vigorous physical activity (MVPA); and (3) if MVPA changes were modified by WS and/or PBE. Accelerometers and questionnaires were used to collect MVPA and PBE. Bivariate analyses and linear mixed models were used for statistical analyses. We found that WS was positively associated with perceived proximity to destinations (p < 0.001) and street shoulder availability (p = 0.001). MVPA was generally not associated with WS or PBE. Compared to controls, intervention group participants increased MVPA if they lived in communities with the lowest WS (WS = 0), fewer perceived walkable destinations, or extremely safe perceived traffic (all p < 0.05). Findings suggest that WS appears to be a relevant indicator of walkable amenities in rural towns; results also suggest that the SHHC intervention likely helped rural women with the greatest dearth of built environment assets to improve MVPA.
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Assessment of Myocardial CZT SPECT Recording in a Forward-Leaning Bikerlike Position.
Perrin, M, Roch, V, Claudin, M, Verger, A, Boutley, H, Karcher, G, Baumann, C, Veran, N, Marie, PY, Imbert, L
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;(6):824-829
Abstract
This prospective randomized study assessed myocardial perfusion imaging with the high-sensitivity D.SPECT cadmium-zinc-telluride camera in a forward-leaning bikerlike position, which may potentially lower diaphragmatic attenuation and reduce breathing-related cardiac motion, in a manner comparable to the prone position proposed with other SPECT cameras. Methods: Patients referred for a stress-rest 99mTc-sestamibi protocol and positioned in the biker position, with the chest leaning forward on the D.SPECT camera-head at 35° from vertical, had an additional resting D.SPECT recording in the supine position (n = 40) or in the sitting position with the back rearward at 30° from vertical (n = 40). Segments with attenuation artifacts were defined as those with less than 65% uptake but with strictly normal contractility at gated SPECT and no defect reversibility from stress images. Results: The biker position was associated with lower heart-to-detector distances than the supine or sitting positions (both P < 0.001); lower cardiac motion amplitudes, assessed on panograms, than the supine position (P < 0.001); and fewer segments with attenuation artifacts than the supine position (on average, 1.10 ± 1.01 vs. 1.90 ± 1.74, P = 0.010) or the sitting position (0.75 ± 0.93 vs. 1.38 ± 1.60, P = 0.011). Conclusion: Myocardial perfusion images from D.SPECT are enhanced for patients positioned in a forward-leaning bikerlike position comparatively to sitting or supine positions, with a notably lower rate of attenuation artifacts.
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Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients-a description of the DAPACARD study.
Åkerblom, A, Oldgren, J, Latva-Rasku, A, Johansson, L, Lisovskaja, V, Karlsson, C, Oscarsson, J, Nuutila, P
Upsala journal of medical sciences. 2019;(1):59-64
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Abstract
BACKGROUND Diabetes increases the risk for cardiovascular (CV) events. It has recently been shown that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to a reduction in CV outcomes in patients with type 2 diabetes mellitus (T2DM), including mortality and heart failure hospitalization. The exact mechanisms of how SGLT2 inhibitors lead to this CV risk reduction remain incompletely understood. The study of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency and myocardial contractile work in type 2 diabetes patients (DAPACARD) (NCT03387683) explores the possible effects of dapagliflozin, an SGLT2 inhibitor, on cardiac work, metabolism, and biomarker levels. METHODS DAPACARD is an international, randomized, double-blind trial that aims to examine the effects of dapagliflozin versus matching placebo in 52 patients with T2DM that are on stable metformin therapy prior to and during the 6 weeks of treatment. The primary efficacy endpoint is change in global longitudinal strain of the left ventricle (GLSLV) measured with magnetic resonance imaging (MRI) between baseline (pre-treatment) and end of study (on-treatment). The secondary endpoint is the corresponding change in myocardial efficiency measured as external left ventricular work divided by total left ventricular work, which is estimated using [11C]-acetate clearance using positron emission tomography (PET). CONCLUSION The DAPACARD study is an extensive investigation of cardiac function and metabolism, by advanced imaging with PET and MRI, as well as biomarkers, performed in order to further explore how the SGLT2 inhibitor dapagliflozin could influence cardiovascular outcomes in patients with T2DM.
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The effect of acute and 7-days dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with chronic obstructive pulmonary disease.
Beijers, RJHCG, Huysmans, SMD, van de Bool, C, Kingma, BRM, Verdijk, LB, van Loon, LJC, Meex, SJR, Gosker, HR, Schols, AMWJ
Clinical nutrition (Edinburgh, Scotland). 2018;(6 Pt A):1852-1861
Abstract
BACKGROUND & AIMS Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD. METHODS This double-blind, randomized cross-over placebo controlled trial included 20 mild-to-moderate COPD patients (66.6 ± 7.5 years) with moderate exercise impairments and decreased mechanical efficiency, normal BMI (26 ± 3 kg/m2) but high prevalence of abdominal obesity (83.3%). Subjects were randomly allocated to the treatment order of 7 days sodium nitrate ingestion (∼8 mmol/day) and 7 days placebo (NaCl solution) or vice versa, separated by a washout period. Before (Day-1) and after (Day-7) both intervention periods resting metabolic rate and the metabolic response during submaximal cycle ergometry, cycling endurance time, plasma nitrate and nitrite levels, cardiac plasma biomarkers (e.g. cardiac troponin T, Nt-proBNP and creatinine kinase) and blood pressure were measured. Subsequently, gross, net and delta mechanical efficiency were calculated. RESULTS Plasma nitrate and nitrite concentrations increased at Day-1 and Day-7 after sodium nitrate but not after placebo ingestion. Systolic and diastolic blood pressure did not change following nitrate ingestion. Furthermore, no differences were observed in gross, net, and delta mechanical efficiency during submaximal exercise, cycling endurance time and cardiac biomarkers between nitrate and placebo on Day-1 and Day-7. Meta-analysis of all available studies in COPD also showed no beneficial effect of beetroot juice on systolic and diastolic blood pressure. CONCLUSION Acute as well as 7-days sodium nitrate supplementation does not modulate mechanical efficiency, blood pressure or cardiac biomarkers in mild-to-moderate COPD patients.
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Alterations in dietary sodium intake affect cardiovagal baroreflex sensitivity.
Babcock, MC, Brian, MS, Watso, JC, Edwards, DG, Stocker, SD, Wenner, MM, Farquhar, WB
American journal of physiology. Regulatory, integrative and comparative physiology. 2018;(4):R688-R695
Abstract
High dietary sodium intake has been linked to alterations in neurally mediated cardiovascular function, but the effects of high sodium on cardiovagal baroreflex sensitivity (cBRS) in healthy adults are unknown. The purpose of this study was to determine whether high dietary sodium alters cBRS and heart rate variability (HRV) and whether acute intravenous sodium loading similarly alters cBRS and HRV. High dietary sodium (300 mmol/day, 7 days) was compared with low dietary sodium (20 mmol/day, 7 days; randomized) in 14 participants (38 ± 4 yr old, 23 ± 1 kg/m2 body mass index, 7 women). Acute sodium loading was achieved via a 23-min intravenous hypertonic saline infusion (HSI) in 14 participants (22 ± 1 yr old, 23 ± 1 kg/m2 body mass index, 7 women). During both protocols, participants were supine for 5 min during measurement of beat-to-beat blood pressure (photoplethysmography) and R-R interval (ECG). cBRS was evaluated using the sequence method. Root mean square of successive differences in R-R interval (RMSSD) was used as an index of HRV. Serum sodium (137.4 ± 0.7 vs. 139.9 ± 0.5 meq/l, P < 0.05), plasma osmolality (285 ± 1 vs. 289 ± 1 mosmol/kgH2O, P < 0.05), cBRS (18 ± 2 vs. 26 ± 3 ms/mmHg, P < 0.05), and RMSSD (62 ± 6 vs. 79 ± 10 ms, P < 0.05) were increased following high-sodium diet intake compared with low-sodium diet intake. HSI increased serum sodium (138.1 ± 0.4 vs. 141.1 ± 0.5 meq/l, P < 0.05) and plasma osmolality (286 ± 1 vs. 290 ± 1 mosmol/kgH2O, P < 0.05) but did not change cBRS (26 ± 5 vs. 25 ± 3 ms/mmHg, P = 0.73) and RMSSD (63 ± 9 vs. 63 ± 8 ms, P = 0.99). These data suggest that alterations in dietary sodium intake alter cBRS and HRV but that acute intravenous sodium loading does not alter these indexes of autonomic cardiovascular regulation.
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Impact of an exercise training program on cardiac neuronal function in heart failure patients on optimal medical therapy : A randomized Iodine-123 metaiodobenzylguanidine scintigraphy study.
Valborgland, T, Isaksen, K, Munk, PS, Grabowski, ZP, Larsen, AI
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2018;(4):1164-1171
Abstract
BACKGROUND The syndrome of heart failure (HF) is characterized by left ventricular dysfunction and a compensatory chronic over activation of the sympathetic nervous system. We wanted to investigate if the beneficial effects of exercise training (ET) in HF patients on optimal medical therapy (OMT) are associated with alterations in cardiac sympathetic activity. METHODS Cardiac sympathetic activity was evaluated at baseline and after 12 weeks using metaiodobenzylguanidine scintigraphy in 23 patients with stable HF participating in the SmartEx trial. Patients with HF in New York Heart Association class II or III and left ventricular ejection fraction <35 % were randomized to three different ET groups. RESULTS We found no statistically significant changes in cardiac sympathetic activity after 12 weeks of ET. Heart to mediastinum (H/M) ratio at 15 minutes (0.00174 ± 0.0841, P = 0.922), H/M ratio at 4 hours (-0.00565 ± 0.1163, P = 0.818) and washout ratio (WR) (-1.2666 ± 16.5412, P = 0.717). A further group-wise analysis of the three ET groups did not show any difference between the groups. CONCLUSION A 12-week ET program did not alter the abnormal cardiac sympathetic activity in stable HF patients on modern OMT.
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Inorganic nitrate supplementation attenuates peripheral chemoreflex sensitivity but does not improve cardiovagal baroreflex sensitivity in older adults.
Bock, JM, Ueda, K, Schneider, AC, Hughes, WE, Limberg, JK, Bryan, NS, Casey, DP
American journal of physiology. Heart and circulatory physiology. 2018;(1):H45-H51
Abstract
Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min-1·%[Formula: see text]-1, P = 0.01) versus BRP (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min-1·%[Formula: see text]-1, P = 0.80), with no differences in heart rate responsiveness (BRA: from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min-1·%[Formula: see text]-1, BRP: from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min-1·%[Formula: see text]-1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.