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Changes in Central 24-h Ambulatory Blood Pressure and Hemodynamics 12 Months After Bariatric Surgery: the BARIHTA Study.
Oliveras, A, Goday, A, Sans, L, Arias, CE, Vazquez, S, Benaiges, D, Ramon, JM, Pascual, J
Obesity surgery. 2020;(1):195-205
Abstract
BACKGROUND Weight loss is associated to blood pressure (BP) reduction in obese patients. There is no information on central 24-h BP changes after bariatric surgery (BS). METHODS AND RESULTS In this study, we analyzed changes in 24-h BP 12 months following BS, with intermediate evaluations at 1, 3, and 6 months, in severely obese adults. The primary endpoint was aortic (central) 24-h systolic BP changes. Circadian BP patterns and hypertension resolution were also assessed. As secondary endpoints, we analyze changes in central 24-h diastolic BP as well as in all office and ambulatory peripheral BP parameters. Obese adults scheduled for BS as routine clinical care were recruited. We included 62 patients (39% with hypertension, 77% women, body mass index, 42.6 ± 5.5 kg/m2). Reduction in body weight was mean (IQR) 30.5% (26.2-34.4) 1 year after BS. Mean (95% CI) change in central 24-h systolic BP was - 3.1 mmHg (- 5.5 to - 0.7), p = 0.01 after adjustment for age, sex, and baseline hypertensive status. BP parameter changes were different between normotensives and hypertensives. Mean (95% CI) change in central 24-h systolic BP was - 5.2 mmHg (- 7.7 to - 2.7), p < 0.001, in normotensives and - 0.5 mmHg (- 5.1 to 4.0), p = 0.818, in hypertensives. There was a remission of hypertension in 48% of patients. Most patients had a reduced dipping pattern, similarly at baseline and 12 months after BS. CONCLUSIONS Among patients with severe obesity, there was a substantial central 24-h systolic BP decrease 12 months following BS. Importantly, this change was observed in those patients with normal BP at baseline. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03115502.
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Pharmacokinetic and haemodynamic interactions between amlodipine and losartan in human beings.
Park, JW, Kim, KA, Il Kim, Y, Park, JY
Basic & clinical pharmacology & toxicology. 2019;(4):345-352
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Abstract
The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUCτ , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUCτ , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUCτ , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.
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Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects.
Cecchetti, L, Lettieri, G, Handjaras, G, Leo, A, Ricciardi, E, Pietrini, P, Pellegrini, S, ,
Neural plasticity. 2019;:6874805
Abstract
Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0.05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0.0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.
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Changes of Blood Pressure and Hemodynamic Parameters after Oral Magnesium Supplementation in Patients with Essential Hypertension-An Intervention Study.
Banjanin, N, Belojevic, G
Nutrients. 2018;(5)
Abstract
The objective of this study was to examine the changes of blood pressure and hemodynamic parameters after oral magnesium supplementation in patients with essential hypertension. The single-arm non-blinded intervention study comprised 48 patients (19 men; 29 women) whose antihypertensive therapy was not changed for at least one month. The participants were asked to consume (daily at home) 300 mg of oral magnesium-oxide supplementation product for one month and to have their blood pressure and hemodynamic parameters (thoracic fluid content, stroke volume, stroke index, cardiac output, cardiac index, acceleration index, left cardiac work index and systemic vascular resistance index, heart rate) measured in the hospital before and after the intervention. Measurements were performed with impedance cardiography. After magnesium supplementation, systolic and diastolic pressures were significantly decreased (mean ± standard deviation (SD)/mmHg/from 139.7 ± 15.0 to 130.8 ± 13.4 and from 88.0 ± 10.4 to 82.2 ± 9.0, respectively; both p < 0.001). The two significant hemodynamic changes were the decrease of systemic vascular resistance index (dyn s m²/cm⁵) and left cardiac work index (kg m/m²)/mean ± SD from 2319.3 ± 753.3 to 2083.0 ± 526.9 and from 4.8 ± 1.4 to 4.4 ± 0.9, respectively; both p < 0.05). The observed hemodynamic changes may explain lowering blood pressure after magnesium supplementation.
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The impact of torasemide on haemodynamic and neurohormonal stress, and cardiac remodelling in heart failure - TORNADO: a study protocol for a randomized controlled trial.
Balsam, P, Ozierański, K, Tymińska, A, Główczyńska, R, Peller, M, Fojt, A, Cacko, A, Sieradzki, B, Bakuła, E, Markulis, M, et al
Trials. 2017;(1):36
Abstract
BACKGROUND Approximately 50% of heart failure patients are readmitted to hospital within 6 months, owing to deterioration of their condition. Thus, symptomatic treatment of heart failure requires significant improvement. The aim of this study is to compare the effects of torasemide and furosemide on biochemical parameters of haemodynamic and neurohormonal compensation, myocardial remodelling, clinical outcomes and quality of life in patients with chronic heart failure. METHODS This is a multicentre, randomized, open, blinded endpoint phase-IV trial. The study includes 120 heart failure patients in NYHA (New York Heart Association) functional class II-IV, treated with optimal heart failure therapy, with indications for use of loop diuretics. At enrolment, patients are stable, with a fixed dose of loop diuretics. Patients are randomized to treatment with furosemide or torasemide (randomization 1:1). After randomization, the current fixed dose of furosemide is continued or is replaced by an equipotential dose of torasemide (4:1). The study consists of two control visits (3 and 6 months after enrolment) with minimal follow-up of 6 months. Assessment involves clinical examination, Quality of Life Questionnaire, laboratory tests, echocardiography, electrocardiography, 24 h Holter-electrocardiography monitoring, 6 -min walk test and assessment of fluid retention. Any need for dose adjustment is assessed during the observation. The primary objective is to compare the effects of torasemide and furosemide on clinical and biochemical parameters of haemodynamic and neurohormonal compensation and myocardial remodelling. Secondary objectives include monitoring of: changes in signs and symptoms of heart failure, NYHA functional class, quality of life, dosage changes, rate of readmissions and mortality. DISCUSSION Despite decades of the diuretic's history, knowledge about diuretic therapy is still unsatisfactory. The most widely used diuretic, furosemide, has a stormy pharmacokinetics and pharmacodynamics, and is associated with a high risk of mortality and hospitalization for worsening heart failure. Reports are very encouraging and suggest beneficial effects of torasemide. Hence, there is a need for further studies of the overall effect of torasemide, compared with furosemide. This can translate into improved quality of life and better prognosis of patients with heart failure. TRIAL REGISTRATION ClinicalTrials.gov, NCT01942109 . Registered on 24 August 2013.
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Evolution of Hemodynamic and Functional Human Kidney Graft Dose Response to Dopamine Using an Implantable Doppler Device.
Bataille, A, Payen, D, Villiers, S, Chazalet, JJ, Jacob, L
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2016;(2):176-83
Abstract
OBJECTIVES The relation between dopamine infusion and renal hemodynamics and function has not been studied in renal allografts during early recovery. We analyzed the dose response of dopamine infusion on renal blood flow and function in human kidney transplant recipients at reperfusion and during early graft recovery. MATERIALS AND METHODS Phasic and mean renal blood flow was measured by the pulsed Doppler technique using implantable Doppler microprobes in contact with the graft artery. Systemic and renal parameters were recorded on dopamine infusion (0, 3, 5, and 10 μg·kg⁻¹·min⁻¹) immediately after transplant (day 0) in 13 patients and at day 6 in 7/13 patients with early graft recovery. Results are expressed as median and interquartile range between the 25th and 75th percentiles. RESULTS At day 0, 3 μg·kg⁻¹·min⁻¹) dopamine did not increase mean renal blood flow over baseline (580 mL/min [219-663 mL/min] vs 542 mL/min [207-686 mL/min]; P = .84). There was an absence of effect with higher dopamine doses, whereas cardiac output, heart rate, and systolic and mean arterial pressure were significantly increased. Urinary sodium excretion, creatinine clearance, and urine output increased dose dependently, with a positive correlation between the increase in urine output and mean arterial pressure (r = 0.48, P < .001). At day 6, 3 μg·kg⁻¹·min⁻¹ dopamine increased mean renal blood flow over baseline (318 mL/min [234-897 mL/min] vs 191 mL/min [173-706 mL/min]; P = .016), with no further increase at higher doses. CONCLUSIONS Immediately after transplant, kidney grafts with ischemic-reperfusion injury are fully dilated and do not respond to dopamine. The specific renal effects observed are due to systemic hemodynamic status. Vascular responsiveness to a "renal dopamine dose" returns on graft recovery.
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Effect of acute nitrate ingestion on central hemodynamic load in hypoxia.
Lefferts, WK, Hughes, WE, Heffernan, KS
Nitric oxide : biology and chemistry. 2016;:49-55
Abstract
UNLABELLED Acute hypoxia results in local vasodilation that may temporarily unload the left ventricle (LV) through nitric oxide (NO)-mediated mechanisms. Whether increasing NO levels augments LV unloading and improves ventricular-vascular coupling in hypoxia remains unknown. PURPOSE Investigate the effect of acute nitrate ingestion on central hemodynamic load in hypoxia. METHODS 20 Healthy men (23 ± 3 yrs, BMI 24.6 ± 2.8 kg m(-2)) consumed 70 mL of either a) 0.45 g nitrate (NIT) or b) an inert placebo (PLA) prior to 105 min of normobaric hypoxia (11.6 ± 0.1%) in this randomized, double-blind, crossover-design study. Wave reflection index (RIX; ratio of forward to reflected wave pressure), augmentation index (AIX75) and pulse wave velocity were calculated as measures of wave reflection magnitude and aortic stiffness, respectively, from the aortic blood pressure (BP) waveform. LV wasted pressure effort (WPE) was calculated as an index of LV work due to wave reflections. Subendocardial viability ratio (SEVR) was assessed a measure of myocardial O2 supply/demand ratio. RESULTS Aortic diastolic BP decreased in hypoxia compared to normoxia (p < 0.05). Aortic RIX, AIX75, and LV WPE significantly decreased in hypoxia compared to normoxia (p < 0.05). Aortic systolic BP, SEVR, and PWV were unaffected by hypoxia (p > 0.05). Compared to placebo, nitrate ingestion did not significantly alter central hemodynamics in hypoxia (p > 0.05). CONCLUSIONS Acute hypoxic exposure unloads the LV (WPE, AIX75, and RIX) without disturbing myocardial O2 supply-demand ratio (SEVR). Reductions in LV work with hypoxia are likely due to reductions in pressure from wave reflections as hypoxia had negligible effects on aortic stiffness. Nitrate ingestion did not affect the central hemodynamic response to acute systemic hypoxia.
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Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites.
Rincón, D, Vaquero, J, Hernando, A, Galindo, E, Ripoll, C, Puerto, M, Salcedo, M, Francés, R, Matilla, A, Catalina, MV, et al
Liver international : official journal of the International Association for the Study of the Liver. 2014;(10):1504-12
Abstract
BACKGROUND & AIMS The modulation of gut flora constitutes a therapeutic tool in patients with liver disease, but some of its modalities require further investigation. Here, we evaluated the effects of probiotics on the hepatic and systemic haemodynamic alterations of advanced liver disease. METHODS Seventeen patients with cirrhosis and ascites were prospectively included, five of whom abandoned this study prematurely. Hepatic and systemic haemodynamic evaluations were performed at baseline and after 6 weeks of receiving an oral VSL#3 probiotic preparation. Peripheral blood analyses included the evaluation of cytokines (TNF-alpha, IL-1beta, IL-6), bacterial translocation [bacterial DNA and lipopolysaccharide-binding protein (LBP)] and nitric oxide end-products (NOx). RESULTS In 12 patients completing this study, the oral administration of VSL#3 resulted in reductions of the hepatic venous pressure gradient (HVPG, P < 0.001), cardiac index and heart rate (both P < 0.01) and in increases of the systemic vascular resistance (P < 0.05) and mean arterial pressure (P = 0.06). HVPG decreased at least 10% from baseline in eight patients (67%). Serum sodium increased in most patients (P < 0.01). All these changes were unrelated to the detection of bacterial DNA or to the levels of LBP, pro-inflammatory cytokines or NOx. No significant adverse effects were observed. CONCLUSION Administration of the probiotic mixture VSL#3 improved the hepatic and systemic haemodynamics and serum sodium levels in patients with cirrhosis. Our results identify major effects of probiotics in liver disease and provide the rationale for assessing their therapeutic potential against the progression of portal hypertension and its complications in future clinical trials.
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Two formulations of epoprostenol sodium in the treatment of pulmonary arterial hypertension: EPITOME-1 (epoprostenol for injection in pulmonary arterial hypertension), a phase IV, open-label, randomized study.
Chin, KM, Badesch, DB, Robbins, IM, Tapson, VF, Palevsky, HI, Kim, NH, Kawut, SM, Frost, A, Benton, WW, Lemarie, JC, et al
American heart journal. 2014;(2):218-225.e1
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Abstract
BACKGROUND Epoprostenol sodium with arginine-mannitol excipients (epoprostenol AM; Veletri [Actelion Pharmaceuticals Ltd, Allschwil, Switzerland]) and epoprostenol sodium with glycine-mannitol excipients (epoprostenol GM; Flolan [GlaxoSmithKline, Triangle Park, NC]) are intravenous treatments for pulmonary arterial hypertension (PAH). Epoprostenol AM contains different inactive excipients, resulting in greater stability at room temperature compared with epoprostenol GM. METHODS In this prospective, multicenter, open-label, randomized, phase IV exploratory study, epoprostenol-naïve patients in need of injectable prostanoid therapy were randomized 2:1 to open-label epoprostenol AM or epoprostenol GM. The study period was 28 days, followed by a 30-day safety follow-up. Study aims were to descriptively compare the safety, tolerability, drug metabolite levels, and treatment effects of epoprostenol AM and epoprostenol GM in PAH. Statistical analysis was descriptive only because of the exploratory nature of the study. RESULTS Thirty patients with PAH (18-70 years, 24 women, 20 idiopathic PAH) were randomized to epoprostenol AM (n = 20) or epoprostenol GM (n = 10). Most frequently reported adverse events included jaw pain, headache, nausea, and flushing. Two deaths occurred during the study period, and 1 death occurred during the 30-day safety follow-up period, all in patients receiving epoprostenol AM. All deaths were classified by the treating physician as unrelated to epoprostenol AM. The median (range) change from baseline to day 28 in 6-minute walk distance was 36 m (-127 to 210 m) and 49 m (-44 to 110 m) for the epoprostenol AM and epoprostenol GM groups, respectively. CONCLUSIONS In this randomized clinical study of epoprostenol AM in PAH, use of this novel preparation with greater room temperature stability was well tolerated.
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Combined effect of appointment telmisartan and atorvastatin on hemodynamic indicators and the indicators of lipid profile in patients with arterial hypertension combined with obesity and steatohepatitis.
Bochar, OM
Wiadomosci lekarskie (Warsaw, Poland : 1960). 2014;(2 Pt 2):157-60
Abstract
The results of investigations had showed the high efficiency of the combination of atorvastatin with telmisartan in patients with arterial hypertension combined with obesity and NAFLD. Such combined treatment had led to a significant decrease of cholesterol levels (p < 0.01), LDL cholesterol (p < 0.05) and TG (p < 0.01), helped to decrease in SBP of 159.75 ± 3,00 to 137.50 ± 1,38 mm Hg (< 0.01), DBP from 93.75 ± 1,57 to 79.25 ± 0,90 mm Hg ( < 0.001), and thus made it possible to significantly improve the health of patients and reduce the risk of cardiovascular complications. According 13C-methacetin breath test, this combination positively influences the lipid metabolism and improves the metabolic function of the liver. One of the mechanisms of action of telmisartan may be its indirect impact on adipokines system, which was demonstrated by an increase in the rate of metabolism and growth of indices of cumulative doses on 40 and 120 minutes.