Suppressing Sympathetic Activation in Congestive Heart Failure

Manolis, Athanasios; Olympios, Christoforos; Sifaki, Maria; Handanis, S.; Bresnahan, Margaret; Gavras, Irène; Gavras, Haralambos

doi:10.1161/01.hyp.26.5.719

Cited by 71 publications

(40 citation statements)

References 31 publications

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“…Therefore, any method of inhibiting this enhanced sympathetic drive might be an effective therapy for HF. The beneficial effects of sympathoinhibitory drugs in the treatment of HF are consistent with this contention (25). The source/cause for the increased sympathoexcitation associated with HF is not entirely clear.…”

supporting

confidence: 52%

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Zheng

Liu

Sharma

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Zheng H, Liu X, Sharma NM, Patel KP. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of ␤-adrenoceptors. Am J Physiol Heart Circ Physiol 311: H337-H346, 2016. First published June 10, 2016; doi:10.1152/ajpheart.00999.2015.-Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area Ͼ30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) Ͼ20 mmHg. ␤ 1-and ␤2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of ␤ 1-adrenoceptor (by 47%) and ␤2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 g/kg)-induced increase in ϩdP/dt (by 71%) and ϪdP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts ␤-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. renal nerve; sympathetic nerve activity; cardiac function; heart failure NEW & NOTEWORTHYThis study shows in a comprehensive way that renal denervation initiated after a period of chronic heart failure enhances cardiac contractility and the responsiveness of hearts to isoproterenol stimulation, and these effects are due in part to renal denervation-induced increase in ␤-adrenoceptor protein and function.WORLDWIDE, MORE THAN 100 MILLION people are afflicted with chronic heart failure (HF), imposing a significant burden on the health care systems throughout the world. Chronic overactivation of the sympathetic nervous system is one of the major pathophysiological soliloquy abnormalities leading to the progression of chronic HF (28,29,48). Activation of sympathetic outflow is initially a hemodynamic adaptation to compensate for decreased cardiac function and output. This adaptation also includes an increase in Na ϩ and fluid retention and activation of the renin-angiotensin-aldosterone system (11, 34). Additional adverse effects of elevated sympathetic drive directed toward the heart have been shown to result in the desensitization or downreg...

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supporting

confidence: 52%

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Zheng

Liu

Sharma

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…In this respect, the reader should note that alpha-adrenergic blockade decreases pulmonary extravascular leakage in the setting of experimental haemorrhage [137] f) diuresis [138] in the setting of ascites [139−141], cardiac failure [142] and critical care [143] g) lowered pro-inflammatory IL6 [144], increased anti-inflammatory IL10 [145] The use of SV in the setting of early severe diffuse ARDS remains seldom used [39,40]. This lack of enthusiasm may be related to the absence of epidemiological data: a) clearly, the mode of ventilation was selected appropriately, e.g., [21], with a reduction in CCU stay.…”

Section: Sedationmentioning

confidence: 99%

Early severe acute respiratory distress syndrome: What’s going on? Part II: controlled vs. spontaneous ventilation?

Petitjeans

Pichot

Ghignone

et al. 2016

Anaesthesiol Intensive Ther

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The second part of this overview on early severe ARDS delineates the pros and cons of the following: a) controlled mechanical ventilation (CMV: lowered oxygen consumption and perfect patient-to-ventilator synchrony), to be used during acute cardio-ventilatory distress in order to "buy time" and correct circulatory insufficiency and metabolic defects (acidosis, etc.); b) spontaneous ventilation (SV: improved venous return, lowered intrathoracic pressure, absence of muscle atrophy). Given a stabilized early severe ARDS, as soon as the overall clinical situation improves, spontaneous ventilation will be used with the following stringent conditionalities: upfront circulatory optimization, upright positioning, lowered VO 2 , lowered acidotic and hypercapnic drives, sedation without ventilatory depression and without lowered muscular tone, as well as high PEEP (titrated on transpulmonary pressure, or as a second best: "trial"-PEEP) with spontaneous ventilation + pressure support (or newer modes of ventilation). As these propositions require evidence-based demonstration, the reader is reminded that the accepted practice remains, in 2016, controlled mechanical ventilation, muscle relaxation and prone position. Anestezjologia Intensywna Terapia 2016, tom 48, nr 5, 354-366Key words: acute respiratory distress syndrome, ARDS, severe ARDS; acute hypoxic non-hypercapnic respiratory failure; driving pressure; tidal volume, Vt, low tidal volume, ultra-low tidal volume; positive end-expiratory pressure, PEEP; transpulmonary pressure; controlled mechanical ventilation; spontaneous ventilation; spontaneous breathing; pressure support, airway pressure release ventilation; sedation, cooperative sedation; alpha-2 adrenergic agonist, clonidine, dexmedetomidineThe previous chapter overviewed, for residents rotating through the critical care unit (CCU), basic pathophysiology required to analyze early severe acute respiratory distress syndrome (ARDS). An emphasis was placed on spontaneous ventilation both in the setting of the healthy volunteer and of severe ARDS. This chapter will address the pros and cons of controlled mechanical ventilation, with the help of muscle relaxation, as opposed to the putative advantages of spontaneous ventilation. So far, spontaneous ventilation has not achieved evidence-based demonstration: thus, as in part I, conjectures are within [….], following [1]. i. MUSCLE RELAXATiON VERSUS SPONTANEOUS VENTiLATiON?When muscle relaxation is considered, the overall picture appears to be simplified with 48 h of muscle relaxation [2]. A sober interpretation may be considered. a. Muscle relaxationIn severe ARDS (P/F < 120), muscle relaxation [2] lowered the mortality (45 to 31%; difference of −32%; P = 0.04), multiple organ failure (MOF), and barotrauma and led to more ventilator-free days and identical CCU-acquired paresis. Muscle relaxation was hypothesized to minimize excessive transpulmonary pressure, patient-to-ventilator asynchrony [2], ventilator-induced lung injury (VILI), atelectrauma, overdistension,...

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“…9,10 Moxonidine is a selective imidazoline ligand that acts specifically on central nervous system receptors to decrease sympathetic outflow. 11 In preclinical studies, the antihypertensive effects of moxonidine appear to correlate with its potency at putative brain stem imidazoline sites rather than ␣ 2 -receptors.…”

Section: See P 1753mentioning

confidence: 99%

Effects of Sustained-Release Moxonidine, an Imidazoline Agonist, on Plasma Norepinephrine in Patients With Chronic Heart Failure

et al. 2002

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Background-In chronic heart failure, sympathetic activation is increased. Moxonidine acts on central nervous system receptors to decrease sympathetic activation. We investigated the dose-response relationship of a new sustained-release (SR) preparation of moxonidine and the plasma concentration of norepinephrine in patients with chronic heart failure. Methods and Results-A total of 268 patients with chronic heart failure in NYHA functional class II to IV on optimal standard therapy were randomized to placebo or 1 of 5 doses of moxonidine SR: 0.3, 0.6, 0.9, 1.2, or 1.5 mg BID. After a dose-titration phase (7 weeks), patients were followed up for another 12 weeks at their maximally tolerated dose. Blood samples for plasma norepinephrine were collected at baseline and weekly during the initial 7 weeks, at week 19, and at the end of the study. At baseline and 7 and 19 weeks, sampling was also done 4 hours after the dose. After the active phases of the study, plasma norepinephrine was evaluated for an additional 3 days. A marked, statistically significant dose-related decrease in plasma norepinephrine was observed for predose levels as well as 4 hours after the dose at week 19. At the highest dose (1.5 mg BID), the trough reduction in norepinephrine was 52%. These reductions were accompanied by a modest decrease in heart rate, a modest increase in left ventricular ejection fraction, and a dose-related increase in adverse events. Conclusions-Plasma norepinephrine was markedly reduced in a dose-related manner by moxonidine SR. This reduction was accompanied by evidence of reverse remodeling, but also by an increase in adverse events.

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Suppressing Sympathetic Activation in Congestive Heart Failure

Cited by 71 publications

References 31 publications

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Early severe acute respiratory distress syndrome: What’s going on? Part II: controlled vs. spontaneous ventilation?

Effects of Sustained-Release Moxonidine, an Imidazoline Agonist, on Plasma Norepinephrine in Patients With Chronic Heart Failure

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