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Sympathetic Nerve Activity Efferent Drive and Beta-Blocker Treatment - Effect of Interaction in Systolic Heart Failure.
Joho, S, Akabane, T, Ushijima, R, Hirai, T, Kinugawa, K
Circulation journal : official journal of the Japanese Circulation Society. 2016;(10):2149-54
Abstract
BACKGROUND Although both β-blocker dose (BBD) and sympathetic activity efferent drive are associated with prognosis in chronic heart failure (HF), little is known about the prognostic value of the interaction between them. METHODS AND RESULTS Potential prognostic variables including resting muscle sympathetic nerve activity (MSNA) were investigated in 133 patients with HF (ejection fraction [EF] <0.45). BBD was normalized to therapeutically equivalent doses of carvedilol. Primary cardiovascular endpoints included cardiovascular death and HF hospitalization. Predictors for outcomes were assessed on univariate, multivariate, and Kaplan-Meier analysis. EF was followed for 9 months after MSNA measurement in 102 patients. During the 1,419±824-day follow-up period, 24 patients died (sudden death, n=10; progressive HF, n=14). On multivariate Cox proportional hazard analysis, higher MSNA (P=0.037; HR, 2.01) and lower BBD (<5.0 mg/day; P=0.041; HR, 1.94) were independent predictors of cardiovascular events. Patients were divided into higher MSNA (≥64 bursts/100 beats) and lower MSNA groups. Although lower BBD remained an independent predictor in patients with higher MSNA, BBD was not statistically significant in patients with lower MSNA on univariate analysis. Additionally, there was a lower EF change in patients with lower BBD and higher MSNA. CONCLUSIONS Higher BBD might be necessary to avoid cardiovascular events in HF patients with central sympathetic overactivation. (Circ J 2016; 80: 2149-2154).
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Differential effects of enalapril-felodipine versus enalapril-lercanidipine combination drug treatment on sympathetic nerve traffic and metabolic profile in obesity-related hypertension.
Seravalle, G, Brambilla, G, Pizzalla, DP, Casati, A, Riva, M, Cuspidi, C, Bombelli, M, Mancia, G, Grassi, G
Journal of the American Society of Hypertension : JASH. 2016;(3):244-51
Abstract
Scanty information is available on the effects of combination drug treatment based on an ACE inhibitor and a calcium channel blocker on the neurometabolic alterations characterizing obesity-related hypertension (OHT). After 2-week run-in with enalapril (20 mg), 36 OHTs were randomized according to a double-blind crossover design to a combination therapy with either lercanidipine 10 mg (L) or felodipine extended release 5 mg (F), each lasting 8 weeks. Measurements included clinic and ambulatory blood pressure (BP) and heart rate, homeostasis model assessment index, plasma norepinephrine, and muscle sympathetic nerve activity. Patients with uncontrolled BP were then uptitrated to 20 mg/d (L) and 10 mg/d (F) combined with enalapril 20 mg, respectively, for further 8 weeks. For similar BP reductions, enalapril-lercanidipine (EL) caused norepinephrine and MSNA increases significantly less pronounced than those seen with enalapril-felodipine, the lesser sympathoexcitation observed with EL being coupled with a significant improvement in homeostasis model assessment index. This was the case also when L and F were uptitrated in the combination. In OHT, at variance from enalapril-felodipine, EL combination is almost entirely devoid of any major sympathoexcitatory effect and is associated with an improvement in insulin sensitivity.
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Effects of mildly increasing dialysis sodium removal on renin and sympathetic system in hemodialysis patients.
Shen, Y, Sun, F, Liu, J, Ma, L, Huang, J, Zhou, Y, Liu, W
Chinese medical journal. 2014;(14):2628-31
Abstract
BACKGROUND It has been argued that the benefits of reducing sodium loading may be offset by increased activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system. This study aimed to investigate the long-term effects of an increase in dialysis sodium removal on circulating RAAS and sympathetic system in hypertensive hemodialysis (HD) patients with "normal" post-HD volume status. METHODS Thirty hypertensive HD patients were enrolled in this pilot trial. After one month period of dialysis with standard dialysate sodium of 138 mmol/L, the patients were followed up for a four months period with dialysate sodium set at 136 mmol/L, without changes in instructions regarding dietary sodium control. During the period of study, the dry weight was adjusted monthly under the guidance of bioimpedance spectroscopy to maintain post-HD volume status in a steady state; 44-hour ambulatory blood pressure, plasma renin, angiotensin II (Ang II), aldosterone, and norepinephrine (NE) were measured. RESULTS After four months of HD with low dialysate sodium of 136 mmol/L, 44-hour systolic and diastolic blood pressures (BPs) were significantly lower (-10 and -6 mmHg), in the absence of changes in antihypertensive medications. No significant changes were observed in plasma renin, Ang II, aldosterone, and NE concentrations. The post-HD volume parameters were kept constant. CONCLUSION Mildly increasing dialysis sodium removal over 4 months can significantly improve BP control and does not activate circulating RAAS and sympathetic nervous system in hypertensive HD patients.
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The effects of the L/N-type calcium channel blocker (cilnidipine) on sympathetic hyperactive morning hypertension: results from ACHIEVE-ONE.
Kario, K, Ando, S, Kido, H, Nariyama, J, Takiuchi, S, Yagi, T, Shimizu, T, Eguchi, K, Ohno, M, Kinoshita, O, et al
Journal of clinical hypertension (Greenwich, Conn.). 2013;(2):133-42
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Abstract
The Ambulatory Blood Pressure Control and Home Blood Pressure (Morning and Evening) Lowering By N-Channel Blocker Cilnidipine (ACHIEVE-ONE) trial is a large-scale clinical study on blood pressure (BP) and pulse rate (PR) in the real world with use of cilnidipine, a unique L/N-type Ca channel blocker, possessing a suppressive action on increased sympathetic activity in patients with essential hypertension. The effects of cilnidipine on morning hypertension were examined. The authors examined 2319 patients treated with cilnidipine for 12 weeks. Clinic systolic BP (SBP) decreased by 19.6 mm Hg from 155.0 mm Hg, whereas morning SBP decreased by 17.0 mm Hg from 152.9 mm Hg after 12-week cilnidipine treatment. Cilnidipine reduced both morning SBP and PR more markedly in patients with higher baseline morning SBP (-3.2 mm Hg and -1.3 beats per minute in the first quartile of morning SBP, -30.9 mm Hg and -3.2 beats per minute in the fourth quartile), and also reduced both morning PR and SBP more markedly in patients with higher baseline morning PR (0.6 beats per minute and -15.6 mm Hg in <70 beats per minute, and -9.7 beats per minute and -20.2 mm Hg in ≥85 beats per minute). Cilnidipine significantly reduced BP and PR in hypertensive patients at the clinic and at home, especially with higher BP and PR in the morning.
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L/T-type and L/N-type calcium-channel blockers attenuate cardiac sympathetic nerve activity in patients with hypertension.
Ogura, C, Ono, K, Miyamoto, S, Ikai, A, Mitani, S, Sugimoto, N, Tanaka, S, Fujita, M
Blood pressure. 2012;(6):367-71
Abstract
Sympathetic nerve activity is augmented by calcium-channel blocker treatment as a result of decreased blood pressure. Dihydropyridine calcium-channel blockers are divided into three different types. The purpose of the present study was to investigate whether treatment effects on hemodynamics, cardiac autonomic nerve activity and plasma norepinephrine levels differ among amlodipine (L type), efonidipine (L + T type) and cilnidipine (L + N type). We enrolled 14 hypertensive patients (seven males, seven females, 70 ± 6 years old) undergoing a monotherapy of amlodipine, efonidipine or cilnidipine into this prospective, open-labeled, randomized, crossover study. At baseline and every 6 months of the treatment period, we repeated the evaluation of hemodynamics, spectral analysis of heart rate variability and plasma norepinephrine levels. Blood pressure and pulse rate were comparable among the three treatments. The low-frequency (LF)/high-frequency (HF) power ratio, an index of cardiac sympathovagal balance, was significantly lower with efonidipine and cilnidipine than with amlodipine, while the HF/total power ratio, an index of cardiac vagal activity, revealed the opposite results. There was no significant correlation between the LF/HF ratio and plasma norepinephrine levels. Antihypertensive monotherapy with efonidipine or cilnidipine attenuates cardiac sympathetic nerve activity more effectively than amlodipine monotherapy.
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Cardiac sympathetic reserve and response to cardiac resynchronization therapy.
Cha, YM, Chareonthaitawee, P, Dong, YX, Kemp, BJ, Oh, JK, Miyazaki, C, Hayes, DL, Rea, RF, Asirvatham, SJ, Webster, TL, et al
Circulation. Heart failure. 2011;(3):339-44
Abstract
BACKGROUND The objective of the present study was to investigate the effect of cardiac resynchronization therapy (CRT) on cardiac autonomic function. METHODS AND RESULTS This prospective study included 45 consecutive patients with heart failure who received CRT devices with defibrillator and 20 age-matched, healthy control subjects. At baseline and 3 months and 6 months after CRT, we assessed New York Heart Association (NYHA) class, 6-minute walk distance, plasma sympathetic biomarker nerve growth factor, echocardiography, heart rate variability and cardiac presynaptic sympathetic function determined by iodine 123 metaiodobenzylguanidine scintigraphy. After CRT, NYHA class improved by 1 class (P<0.001), and left ventricular ejection fraction increased by 8% (P<0.001). Along with improvement in the standard deviation of all normal-to-normal R-R intervals (85.63±31.66 ms versus 114.79±38.99 ms; P=0.004) and the standard deviation of the averaged normal-to-normal R-R intervals (82.62±23.03 ms versus 100.50±34.87 ms; P=0.004), the delayed heart/mediastinum (H/M) ratio increased (1.82 [0.58] versus 1.97 [0.59]; P=0.03), whereas the mean (SD) H/M washout rate was reduced (48% [19%] versus 37% [22%]; P=0.01). Twenty-two of 45 study patients responded to CRT, with a reduction of left ventricular end-systolic volume index >15%. Compared with nonresponders, responders had a higher delayed H/M ratio (2.11 versus 1.48; P=0.003) and lower H/M washout rate (37% versus 62%; P=0.003) at baseline. CONCLUSIONS CRT improved sympathetic function. Cardiac sympathetic reserve may be a marker for the reversibility of failing myocardial function.
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Influence of high- and low-carbohydrate diet following glycogen-depleting exercise on heart rate variability and plasma catecholamines.
Lima-Silva, AE, Bertuzzi, R, Dalquano, E, Nogueira, M, Casarini, D, Kiss, MA, Ugrinowitsch, C, Pires, FO
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2010;(4):541-7
Abstract
The purpose of this study was to investigate the effects of a short-term low- or high-carbohydrate (CHO) diet consumed after exercise on sympathetic nervous system activity. Twelve healthy males underwent a progressive incremental test; a control measurement of plasma catecholamines and heart rate variability (HRV); an exercise protocol to reduce endogenous CHO stores; a low- or high-CHO diet (counterbalanced order) consumed for 2 days, beginning immediately after the exercise protocol; and a second resting plasma catecholamine and HRV measurement. The exercise and diet protocols and the second round of measurements were performed again after a 1-week washout period. The mean (+/-SD) values of the standard deviation of R-R intervals were similar between conditions (control, 899.0+/-146.1 ms; low-CHO diet, 876.8+/-115.8 ms; and high-CHO diet, 878.7+/-127.7 ms). The absolute high- and low-frequency (HF and LF, respectively) densities of the HRV power spectrum were also not different between conditions. However, normalized HF and LF (i.e., relative to the total power spectrum) were lower and higher, respectively, in the low-CHO diet than in the control diet (mean+/-SD, 17+/-9 normalized units (NU) and 83+/-9 NU vs. 27+/-11 NU and 73+/-17 NU, respectively; p<0.05). The LF/HF ratio was higher with the low-CHO diet than with the control diet (mean+/-SD, 7.2+/-6.2 and 4.2+/-3.2, respectively; p<0.05). The mean values of plasma catecholamines were not different between diets. These results suggest that the autonomic control of the heart rate was modified after a short-term low-CHO diet, but plasma catecholamine levels were not altered.
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Levosimedan improves hemodynamics functions without sympathetic activation in severe heart failure patients: direct evidence from sympathetic neural recording.
Despas, F, Trouillet, C, Franchitto, N, Labrunee, M, Galinier, M, Senard, JM, Pathak, A
Acute cardiac care. 2010;(1):25-30
Abstract
Levosimendan is a new inodilatory agent with calcium sensitizing activity. A major concern regarding the use of inotropic agent in heart failure is their effect on the sympathetic tone. This effect could explain increase in short term mortality with other inotropes. We aimed to assess the effect of levosimendan on sympathetic tone measured directly by microneurogra-phy. In a group of acute decompensated heart failure patients, we assessed cardiac performance by digital plethysmography measurement. Sympathetic tone was assessed through recording of muscle sympathetic nerve activity (MSNA) by micro-neurography. Recording were done blindly, for each patient after dobutamine perfusion was stopped (baseline) and 48 h after levosimendan infusion. Clinical, biological and morphological data were collected. We compared cardiac parameters and MSNA before and after administration of levosimendan. 13 patients were recruited (48 +/- 3.6 years). Systolic blood pressure and rate pressure product (mmHg x Beat/min) decreased significantly after levosimendan infusion (P< 0.05). Cardiac output and stroke volume were significantly increased after levosimendan infusion (P< 0.05). A significant decrease of MSNA activity is observed after levosimendan infusion (P< 0.01). Levosimendan induced improvement of cardiac performance, associated with a decreased in MSNA. This study show for the first time that levosimendan has no direct detrimental effect on the sympathetic nervous system.
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Effects of short-term hypocaloric diet on sympatho-vagal interaction assessed by spectral analysis of heart rate and blood pressure variability during stress tests in obese hypertensive patients.
Ashida, T, Ono, C, Sugiyama, T
Hypertension research : official journal of the Japanese Society of Hypertension. 2007;(12):1199-203
Abstract
We examined the effects of a short-term low-calorie diet on the activity of the autonomic nervous system during stress tests in obese patients with hypertension by analysis of heart rate and blood pressure variability. Eighteen obese inpatients with essential hypertension were given a regular-calorie diet (1,600 kcal, NaCl 7 g) for 4 days, and then a low-calorie diet (1,100 kcal, NaCl 7 g) for 11 days. During both the regular-calorie diet and low-calorie diet, power spectral analysis of heart rate and blood pressure variability at rest and during mental arithmetic test, deep breathing test, isometric handgrip test or cold pressor test was performed. Body weight and 24-h ambulatory blood pressure were significantly lower during the low-calorie diet than during the regular-calorie diet. Systolic and diastolic blood pressure significantly increased over the handgrip test and cold pressor test during both diets. The low frequency component (LF) of systolic blood pressure, a marker of sympathetic activity to the vasculature, during the deep breathing test and cold pressor test were significantly lower on the low-calorie diet than the regular-calorie diet. The blood leptin concentration was also significantly lower on the low-calorie diet than the regular-calorie diet. The decrease in body weight was positively correlated with the decrease in blood leptin concentration. The LF/high frequency component (HF) ratio of the RR interval at rest on the regular-calorie diet was negatively correlated with the decrease in blood leptin concentration. These results suggest that the autonomic nervous function assessed by analysis of heart rate and blood pressure variability during stress tests may be improved by weight loss due to a short-term low-calorie diet in obese patients with hypertension.
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10.
Differential effects of metaboreceptor and chemoreceptor activation on sympathetic and cardiac baroreflex control following exercise in hypoxia in human.
Gujic, M, Laude, D, Houssière, A, Beloka, S, Argacha, JF, Adamopoulos, D, Xhaët, O, Elghozi, JL, van de Borne, P
The Journal of physiology. 2007;(Pt 1):165-74
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Abstract
Muscle metaboreceptors and peripheral chemoreceptors exert differential effects on the cardiorespiratory and autonomic responses following hypoxic exercise. Whether these effects are accompanied by specific changes in sympathetic and cardiac baroreflex control is not known. Sympathetic and cardiac baroreflex functions were assessed by intravenous nitroprusside and phenylephrine boluses in 15 young male subjects. Recordings were performed in random order, under locally circulatory arrested conditions, during: (1) rest and normoxia (no metaboreflex and no chemoreflex activation); (2) normoxic post-handgrip exercise at 30% of maximum voluntary contraction (metaboreflex activation without chemoreflex activation); (3) hypoxia without handgrip (10% O2 in N2, chemoreflex activation without metaboreflex activation); and (4) post-handgrip exercise in hypoxia (chemoreflex and metaboreflex activation). When compared with normoxic rest (-42 +/- 7% muscle sympathetic nerve activity (MSNA) mmHg(-1)), sympathetic baroreflex sensitivity did not change during normoxic post-exercise ischaemia (PEI; -53 +/- 9% MSNA mmHg(-1), P = 0.5) and increased during resting hypoxia (-68 +/- 5% MSNA mmHg(-1), P < 0.01). Sympathetic baroreflex sensitivity decreased during PEI in hypoxia (-35 +/- 6% MSNA mmHg(-1), P < 0.001 versus hypoxia without exercise; P = 0.16 versus normoxic PEI). Conversely, when compared with normoxic rest (11.1 +/- 1.7 ms mmHg(-1)), cardiac baroreflex sensitivity did not change during normoxic PEI (8.3 +/- 1.3 ms mmHg(-1), P = 0.09), but decreased during resting hypoxia (7.3 +/- 0.8 ms mmHg(-1), P < 0.05). Cardiac baroreflex sensitivity was lowest during PEI in hypoxia (4.3 +/- 1 ms mmHg(-1), P < 0.01 versus hypoxia without exercise; P < 0.001 versus normoxic exercise). The metaboreceptors and chemoreceptors exert differential effects on sympathetic and cardiac baroreflex function. Metaboreceptor activation is the major determinant of sympathetic baroreflex sensitivity, when these receptors are stimulated in the presence of hypoxia.