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Hemodynamic and perceptual responses to blood flow-restricted exercise among patients undergoing dialysis.
Clarkson, MJ, Brumby, C, Fraser, SF, McMahon, LP, Bennett, PN, Warmington, SA
American journal of physiology. Renal physiology. 2020;(3):F843-F850
Abstract
End-stage kidney disease is associated with reduced exercise capacity, muscle atrophy, and impaired muscle function. While these may be improved with exercise, single modalities of exercise do not traditionally elicit improvements across all required physiological domains. Blood flow-restricted exercise may improve all of these physiological domains with low intensities traditionally considered insufficient for these adaptions. Investigation of this technique appeals, but is yet to be evaluated, in patients undergoing dialysis. With the use of a progressive crossover design, 10 satellite patients undergoing hemodialysis underwent three exercise conditions over 2 wk: two bouts (10 min) of unrestricted cycling during two consecutive hemodialysis sessions (condition 1), two bouts of cycling with blood flow restriction while off hemodialysis on 2 separate days (condition 2), and two bouts of cycling with blood flow restriction during two hemodialysis sessions (condition 3). Outcomes included hemodynamic responses (heart rate and blood pressure) throughout all sessions, participant-perceived exertion and discomfort on a Borg scale, and evaluation of ultrafiltration rates and dialysis adequacy (Kt/V) obtained post hoc. Hemodynamic responses were consistent regardless of condition. Significant increases in heart rate, systolic blood pressure, and mean arterial blood pressure (P < 0.05) were observed postexercise followed by a reduction in blood pressures during the 60-min recovery (12, 5, and 11 mmHg for systolic, diastolic, and mean arterial pressures, respectively). Blood pressures returned to predialysis ranges following the recovery period. Blood flow restriction did not affect ultrafiltration achieved or Kt/V. Hemodynamic safety and tolerability of blood flow restriction during aerobic exercise on hemodialysis is comparable to standard aerobic exercise.
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Effects of a Short-Term Recreational Team Handball-Based Programme on Physical Fitness and Cardiovascular and Metabolic Health of 33-55-Year-Old Men: A Pilot Study.
Póvoas, SCA, Castagna, C, Resende, C, Coelho, EF, Silva, P, Santos, R, Pereira, R, Krustrup, P
BioMed research international. 2018;:4109796
Abstract
Recreational team handball is an intermittent high-intensity exercise mode with physiological demands in the range of those found to enhance health and physical fitness of sedentary adults. We examined the effects of a short-term team handball-based training programme on physical fitness and metabolic and cardiovascular health of sedentary 33-55-year-old former male team handball players. Twenty-four participants were divided into team handball (THG; n=15) and control groups (CG; n=9) and evaluated at baseline and postintervention. During 12 weeks, THG performed 2-3 60-min recreational team handball matches weekly (average: 2.2 ± 0.7), and CG maintained an inactive lifestyle. Average heart rate (HR) during matches was 80 ± 7%HRmax, with peak values of 91 ± 6%HRmax. A time-by-group interaction was shown in aerobic performance (p=0.016), postural balance (p=0.019), maximum oxygen uptake (VO2max) (p=0.023), resting HR (p<0.001), high-density lipoprotein (HDL) cholesterol (p=0.048), and fasting blood glucose (p=0.052) in favor of THG. THG improved aerobic performance (80%, p<0.001), VO2max (14%, p<0.001), and postural balance (27%, p=0.018). Decreases in resting HR (16%, p<0.001) and fasting blood glucose (7%, p=0.015) and increases in HDL cholesterol (11%, p=0.002) were found in THG. Recreational team handball practice shows positive physical fitness and health-related adaptations, with high attendance, which may contribute to the reduction of the risk of developing lifestyle diseases.
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QT Interval Shortening With Isavuconazole: In Vitro and In Vivo Effects on Cardiac Repolarization.
Keirns, J, Desai, A, Kowalski, D, Lademacher, C, Mujais, S, Parker, B, Schneidkraut, MJ, Townsend, R, Wojtkowski, T, Yamazaki, T, et al
Clinical pharmacology and therapeutics. 2017;(6):782-790
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Abstract
The effects of isavuconazole (active moiety of isavuconazonium sulfate) on cardiac ion channels in vitro and cardiac repolarization clinically were assessed in a phase I, randomized, double-blind study in healthy individuals who received isavuconazole (after 2-day loading dose), at therapeutic or supratherapeutic doses daily for 11 days, moxifloxacin (400 mg q.d.), or placebo. A post-hoc analysis of the phase III SECURE trial assessed effects on cardiac safety. L-type Ca2+ channels were most sensitive to inhibition by isavuconazole. The 50% inhibitory concentrations for ion channels were higher than maximum serum concentrations of nonprotein-bound isavuconazole in vivo. In the phase I study (n = 161), isavuconazole shortened the QT interval in a dose- and plasma concentration-related manner. There were no serious treatment-emergent adverse events; palpitations and tachycardia were observed in placebo and supratherapeutic isavuconazole groups; no cardiac safety signals were detected in the SECURE study (n = 257). Isavuconazole was associated with a shortened cardiac QT interval.
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L/T-type calcium channel blocker reduces non-Gaussianity of heart rate variability in chronic kidney disease patients under preceding treatment with ARB.
Fukuda, M, Ogiyama, Y, Sato, R, Miura, T, Fukuta, H, Mizuno, M, Kiyono, K, Yamamoto, Y, Hayano, J, Ohte, N
Journal of the renin-angiotensin-aldosterone system : JRAAS. 2016;(2):1470320316643905
Abstract
INTRODUCTION Increased sympathetic nerve activity has been suggested in patients with chronic kidney disease (CKD). Pathologic sympathetic activity can alter heart rate variability (HRV), and the altered HRV has prognostic importance, so that reducing sympathetic activity may be an important strategy. Novel nonlinear HRVs, including deceleration capacity (DC), have greater predictive power for mortality. We have recently proposed an increase in a non-Gaussianity index of HRV, λ(25s), which indicates the probability of volcanic heart rate deviations of departure from each standard deviation level, as a marker of sympathetic cardiac overdrive. L/T-type calcium channel blocker (L/T-CCB), azelnidipine, decreases sympathetic nerve activity in experimental and clinical studies. METHODS In 43 hypertensive patients with CKD under treatment with an angiotensin receptor blocker (ARB), we investigated whether 8-week add-on L/T-CCB treatment could restore HRV. RESULTS Means of all normal-to-normal intervals over 24 h (p<0.0001) and DC (p=0.002) increased, and λ(25s) (p=0.001) decreased regardless of gender, age, renal function or blood pressure, while no significant changes were observed in the other HRVs. CONCLUSIONS Reduction of λ(25s) is useful to assess the effect of sympathoinhibitory treatment. Further studies are needed to investigate if the restoration of HRV is directly associated with the improvement of prognosis in patients with CKD.
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Cardiovascular response to short-term fasting in menstrual phases in young women: an observational study.
Ohara, K, Okita, Y, Kouda, K, Mase, T, Miyawaki, C, Nakamura, H
BMC women's health. 2015;:67
Abstract
BACKGROUND Menstrual cycle-related symptoms are an important health issue for many women, and some may affect cardiac autonomic regulation. In the present study, we evaluated the cardiovascular and physiological stress response to 12-h short-term fasting in the menstrual phases of healthy young women. METHODS We performed a randomized crossover study. Subjects were seven female university students (age: 22.3 ± 1.0 years). The experiments comprised four sessions: meal intake in the follicular phase, meal intake in the luteal phase, fasting in the follicular phase, and fasting in the luteal phase. All subjects participated in a total of four experimental sessions during two successive phases (follicular and luteal phase in the same menstrual cycle, or luteal phase and follicular phase in the next menstrual cycle) according to a randomized crossover design. R-R intervals were continuously recorded before and after meals, and power spectral analysis of heart rate variability was performed. Other physiological data were obtained before and 20, 40, 60, and 80 min after meal intake or after the corresponding time point of meal intake (fasting in the follicular or luteal phase). RESULTS Heart rate decreased during fasting in the follicular and luteal phases. High frequency power increased during fasting in the follicular and luteal phases. In addition, salivary cortisol concentrations decreased during fasting in the luteal phase. CONCLUSIONS In the present study, short-term fasting resulted in higher parasympathetic activity and lower cortisol levels in the luteal phase in these young women. These results indicate a possibility to produce an anti-stress effect in the luteal phase, which may reduce menstrual symptoms.
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Cardiovascular safety of anagrelide in healthy subjects: effects of caffeine and food intake on pharmacokinetics and adverse reactions.
Martínez-Sellés, M, Datino, T, Figueiras-Graillet, L, Gama, JG, Jones, C, Franklin, R, Fernández-Avilés, F
Clinical drug investigation. 2013;(1):45-54
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BACKGROUND Essential thrombocythaemia (ET) is a rare clonal myeloproliferative disorder characterized by a sustained elevation in platelet count and megakaryocyte hyperplasia. Anagrelide is used in the treatment of ET, where it has been shown to reduce platelet count. Anagrelide is metabolized by cytochrome P450 (CYP) 1A2, and previous studies of the effect of food on the bioavailability and pharmacokinetics of anagrelide were conducted prior to the identification of the active metabolite, 3-hydroxyanagrelide. OBJECTIVES The objectives of this study were to determine the effect of food and caffeine on the pharmacokinetics of anagrelide and its active metabolite, 3-hydroxyanagrelide, to monitor electrocardiogram (ECG) parameters following drug administration, and to document the relationship between palpitations, ECG changes and caffeine intake METHODS Thirty-five healthy subjects who received 1 mg of anagrelide following either a 10-h fast or within 30 min of a standardized breakfast, including two cups of coffee, were studied. RESULTS Time to maximum (peak) plasma concentration (C(max)) of anagrelide was 4.0 h in the fed and 1.5 h in the fasted group (p < 0.05); similar results were observed for 3-hydroxyanagrelide. The mean C(max) of anagrelide was 4.45 ± 2.32 ng/mL and 5.08 ± 2.99 ng/mL in the fed/caffeine and fasted groups, respectively; peak concentrations were higher for 3-hydroxyanagrelide in both the fed/caffeine and fasted groups. The most frequent adverse events (AEs) were headache (60 %) and palpitations (40 %). There were no serious AEs and all ECGs were normal, although significant reductions in PR interval, QRS length and QT interval were observed in both groups. Heart rate increased after anagrelide administration in both fed/caffeine and fasted states (p < 0.01); however, increased heart rate was significantly more frequent in the fed/caffeine state than in the fasted state (p < 0.001 for heart rate increase in the first hour after drug administration). There was a trend towards a greater heart rate increase in subjects reporting palpitations than in those without (mean heart rate ± SD at 1 h: 10.1 ± 6.4 vs. 8.0 ± 8.4 beats/min [p = 0.35]; at 4 h: 12.7 ± 7.5 vs. 9.1 ± 8.8 beats/min [p = 0.10], respectively). CONCLUSION We conclude that food/caffeine delayed absorption of anagrelide. Anagrelide was generally well tolerated and had small effects on ECG parameters and heart rate. Caffeine may be implicated in a higher increase in heart rate and increased frequency of palpitations observed following administration of anagrelide with food/caffeine versus fasting.
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Impact of endogenous and exogenous insulin on basal energy expenditure in patients with type 2 diabetes under standard treatment.
Ikeda, K, Fujimoto, S, Goto, M, Yamada, C, Hamasaki, A, Shide, K, Kawamura, T, Inagaki, N
The American journal of clinical nutrition. 2011;(6):1513-8
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BACKGROUND Factors that affect resting energy expenditure or basal energy expenditure (BEE) in patients with type 2 diabetes under standard treatment have not been evaluated in detail. OBJECTIVE We determined the clinical factors that affected BEE in addition to body composition in patients with type 2 diabetes under standard treatment. DESIGN BEE was measured by using indirect calorimetry under a strict basal condition in 58 Japanese patients with type 2 diabetes after >7 d as inpatients under management of diabetes with medical nutrition therapy and medications. Insulin secretion was measured with a glucagon test. Stepwise regression was applied to explore determinants of BEE. RESULTS In the stepwise estimation, insulin secretion (P = 0.015), insulin therapy (P = 0.012), and pulse rate (P = 0.011) were selected in addition to fat-free mass (FFM) (P < 0.001) and fat mass (P = 0.006) as significant independent determinants of BEE. Standardized partial regression coefficients of the additional 3 factors were -0.16, -0.15, and 0.15, respectively, whereas those for FFM and fat mass were 0.82 and 0.19, respectively. The additional 3 factors explained another 3.9% of the variability of BEE, and the adjusted coefficient of determination was 83.4%. Age, sex, other medications, and parameters of glycemic control were not significant determinants beyond the combined contribution of body composition, endogenous and exogenous insulin, and pulse rate. CONCLUSION Endogenous insulin secretion and exogenous insulin administered in treatment have significant independent effects in the lowering of BEE in patients with diabetes under standard management with medical nutrition therapy and medications.
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Effects of landiolol, an ultra-short-acting beta1-selective blocker, on electrical storm refractory to class III antiarrhythmic drugs.
Miwa, Y, Ikeda, T, Mera, H, Miyakoshi, M, Hoshida, K, Yanagisawa, R, Ishiguro, H, Tsukada, T, Abe, A, Yusu, S, et al
Circulation journal : official journal of the Japanese Circulation Society. 2010;(5):856-63
Abstract
BACKGROUND Occasionally it is difficult to inhibit electrical storm (ES) with standard pharmacological treatment. In the present study the effect of landiolol, an ultra-short-acting beta(1)-selective blocker, on ES refractory to class III antiarrhythmic drugs was evaluated. METHODS AND RESULTS The study group comprised 42 consecutive patients who developed ES for which intravenous class III antiarrhythmic drugs, such as amiodarone and nifekalant, were ineffective. Landiolol was administered intravenously with an initial dose of 2.5 microg x kg(-1) x min(-1), which was doubled if it was ineffective, up to a maximum dose of 80 microg x kg(-1) x min(-1). Landiolol inhibited ES in 33 patients (79%) at a mean dose of 7.5+/-12.2 microg x kg(-1) x min(-1). All patients in whom landiolol was ineffective died of arrhythmia. Of the 33 patients in whom landiolol was effective, 25 survived and were discharged (60% of all patients). Landiolol significantly decreased heart rate (P<0.0001), but did not affect blood pressure. Landiolol was not discontinued for adverse effects in any of the responders. Age, APACHE II score, and pH of arterial blood gas differed significantly between the responders and nonresponders. CONCLUSIONS Landiolol is useful as a life-saving drug for class III antiarrhythmic drug-resistant ES. The main mechanism of ES refractory to class III antiarrhythmic drugs could be abnormal automaticity but not reentry.
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Myocardial FFA metabolism during rest and atrial pacing in humans.
Bergman, BC, Tsvetkova, T, Lowes, B, Wolfel, EE
American journal of physiology. Endocrinology and metabolism. 2009;(2):E358-66
Abstract
There is limited in vivo data in humans evaluating myocardial fat utilization during increased heart work. This study was done to determine myocardial free fatty acid (FFA) metabolism during rest and atrial pacing, which increases cardiac work without changing arterial substrate concentration. We studied seven healthy men and women (age = 49.7 +/- 3.9 yr, BMI = 23.4 +/- 1.1 kg/m(2), Vo(2max) = 35.5 +/- 3.0 ml.kg(-1).min(-1), ejection fraction = 68 +/- 3%). After 3 days of dietary control, coronary sinus, femoral arterial and venous, and peripheral venous catheters were placed. Subjects received [(13)C]bicarbonate followed by a continuous infusion of [1-(13)C]palmitate through the end of the study. Arterial and coronary sinus blood sampling and measurements of resting coronary sinus blood flow were made during rest and atrial pacing to 120 beats/min. MVo(2) increased (P < 0.05) from rest to atrial pacing. Coronary sinus FFA concentration was significantly lower than arterial through rest and atrial pacing (P = 0.007). Isotopically measured myocardial palmitate uptake increased significantly from rest to atrial pacing (P = 0.03). Approximately one-third of palmitate delivery was extracted by the myocardium during rest and atrial pacing. Myocardial V(13)CO(2) production and palmitate oxidation increased significantly from rest (P < 0.01) to atrial pacing. Net glycerol balance was significantly greater than zero during rest (P = 0.04) but not different from zero during atrial pacing (P = 0.13). These data suggest that myocardial lipid uptake and oxidation increase with greater heart work during atrial pacing, with a similar relative proportion of fat oxidation to total myocardial energy expenditure.
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Magnesium sulfate versus placebo for paroxysmal atrial fibrillation: a randomized clinical trial.
Chu, K, Evans, R, Emerson, G, Greenslade, J, Brown, A
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2009;(4):295-300
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OBJECTIVES The objective was to investigate the efficacy of magnesium sulfate (MgSO4) in decreasing the ventricular rate in emergency department (ED) patients presenting with new-onset, rapid atrial fibrillation (AF). METHODS A double-blinded, placebo-controlled randomized clinical trial was conducted in an adult university hospital. Patients aged > or =18 years with AF onset of less than 48 hours and a sustained ventricular rate of >100 beats/min were randomized to either intravenous (IV) MgSO4 10 mmol or normal saline (NSal). Rhythm and instantaneous heart rate as measured by the monitor were recorded at baseline and every 15 minutes for 2 hours after starting the trial drug. Heart rate and rhythm were compared at 2 hours. A multilevel modeling analysis was performed to adjust for differences in baseline heart rate and any additional treatment and to examine changes in heart rate over time. RESULTS Twenty-four patients were randomized to MgSO4 and 24 to NSal. Baseline heart rate was lower in the MgSO4 group (mean +/- standard deviation [+/-SD] = 125 +/- 24 vs. 140 +/- 21 beats/min]. One and 3 patients in the MgSO4 and NSal groups, respectively, were given another antiarrhythmic or were electrically cardioverted within 2 hours after starting the trial drug. Heart rate (mean +/- SD) at 2 hours in both MgSO4 (116 +/- 30 beats/min) and NSal groups (114 +/- 31 beats/min) decreased below their respective baseline levels. However, the rate of heart rate decrease across time did not differ between groups (p = 0.124). The proportion of patients who converted to sinus rhythm 2 hours post-trial drug did not differ (MgSO4 8.7% vs. NSal 25.0%, p = 0.25). CONCLUSIONS This study was unable to demonstrate a difference between IV MgSO4 10 mmol and saline placebo for reducing heart rate or conversion to sinus rhythm at 2 hours posttreatment in ED patients with AF of less than 48 hours duration.