Clinical characteristics of chronic heart failure patients with an augmented peripheral chemoreflex

Chua, Tuan Peng; Ponikowski, Piotr; Webb-Peploe, Katharine; Harrington, Derek; Anker, Stefan D.; Piepoli, Massimo F; Coats, Andrew J.S.

doi:10.1093/oxfordjournals.eurheartj.a015269

Cited by 105 publications

(112 citation statements)

References 29 publications

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“…3,4 Augmented peripheral chemoreceptor sensitivity in HF has also been described, which may also underlie the augmented central sympathetic outflow. 5,6 In healthy humans, hypoxia leads to increased blood flow directed to skeletal muscle, and this vasodilatation is mediated by NO release. 7 In a recent study, we reported that, paradoxically, the peripheral chemoreceptor stimulation resulted in skeletal muscle vasoconstriction in HF patients.…”

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Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

et al. 2012

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Abstract-We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O 2 and 90% N 2 ). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N G -monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012;60:669-676.) • Online Data Supplement Key Words: heart failure � chemoreceptors � vasodilation � sympathetic nervous system � endothelium R esting sympathetic nerve activity is increased in patients with chronic systolic heart failure (HF), and patients with the greatest sympathetic activation have the highest mortality.1,2 Many potential mechanisms underlying the sympathetic excitation in HF have been proposed, including blunted baroreceptor control of central sympathetic outflow.3,4 Augmented peripheral chemoreceptor sensitivity in HF has also been described, which may also underlie the augmented central sympathetic outflow. 5,6 In healthy humans, hypoxia leads to increased blood flow directed to skeletal muscle, and this vasodilatation is mediated by NO release. 7 In a recent study, we reported that, paradoxically, the peripheral chemoreceptor stimulation resulted in skeletal muscle vasoconstriction in HF patients. 6 This unexpected vascular response led us to hypothesize that either the exaggerated sympathetic outflow attributable to chemoreceptor stimulation or the blunted endothelially mediated vasodilatation results in this muscle vasoconstriction during hypoxia in HF patients. In the present study, we describe muscle blood flow responses during peripheral chemoreceptor stimulation with local blockade of postsynaptic ␣-adrenergic receptors and in association with blockade of endothelial NO production in patients with severe HF and in healthy controls. In addition, we describe the effects of vitamin C, an antioxidant, alone, and an ant...

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Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

et al. 2012

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“…By contrast, other groups ,Ponikowski & Banasiak, 2001,Ciarka et al 2006 have found an enhanced ventilatory response to hypoxia in CHF patients, particularly those in more severe stages of heart failure. In addition, heightened peripheral chemoreflex function correlates significantly with the enhanced ventilatory response to exercise and dyspnea observed in these patients (Chua et al 1997,Ciarka et al 2006). …”

Section: Chemoreflex Control Of Sympathetic Function In Heart Failurementioning

confidence: 91%

Carotid body function in heart failure

Schultz

2007

Respiratory Physiology & Neurobiology

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In this review, we summarize the present state of knowledge of the functional characteristics of the carotid body (CB) chemoreflex with respect to control of sympathetic nerve activity (SNA) in chronic heart failure (CHF). Evidence from both CHF patients and animal models of CHF has clearly established that the CB chemoreflex is enhanced in CHF and contributes to the tonic elevation in SNA. This adaptive change derives from altered function at the level of both the afferent and central nervous system (CNS) pathways of the reflex arc. At the level of the CB, an elevation in basal afferent discharge occurs under normoxic conditions in CHF rabbits, and the discharge responsiveness to hypoxia is enhanced. Outward voltage-gated K + currents (I K ) are suppressed in CB glomus cells from CHF rabbits, and their sensitivity to hypoxic inhibition is enhanced. These changes in I K derive partly from downregulation of nitric oxide synthase (NOS) / NO signaling and upregulation of angiotensin II (Ang II) / Ang II receptor (AT 1 R) signaling in glomus cells. At the level of the CNS, interactions of the enhanced input from CB chemoreceptors with altered input from baroreceptor and cardiac afferent pathways and from central Ang II further enhance sympathetic drive. In addition, impaired function of NO in the paraventricular nucleus of the hypothalamus participates in the increased SNA response to CB chemoreceptor activation. These results underscore the principle that multiple mechanisms involving Ang II and NO at the level of both the CB and CNS represent complementary and perhaps redundant adaptive mechanisms to enhance CB chemoreflex function in CHF.

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“…6 -9 The cause of the heightened sympathetic drive is not known. Possible mechanisms include impaired inhibitory cardiac and arterial baroreflex function, 9,10 abnormalities in central neural control, 1 and augmented sympathetic excitatory chemoreceptor [11][12][13][14][15] and somatic reflexes. 1,16 The role of chemoreflex mechanisms in heart failure has recently received considerable attention.…”

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“…1,16 The role of chemoreflex mechanisms in heart failure has recently received considerable attention. [11][12][13][14]17,18 Chemoreflexes are the dominant control mechanisms regulating ventilatory responses to changes in arterial oxygen and CO 2 content. 19 -22 The peripheral chemoreceptors, located in the carotid bodies, respond primarily to hypoxia.…”

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Enhanced Sympathetic and Ventilatory Responses to Central Chemoreflex Activation in Heart Failure

et al. 1999

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Background-Sympathetic activation and respiratory abnormalities may each be implicated in the pathophysiology of congestive heart failure (CHF). Chemoreflexes are an important mechanism regulating both sympathetic drive and breathing. We therefore tested the hypothesis that chemoreflex function is altered in CHF. Methods and Results-We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypoxia, hypercapnia, and the cold pressor test in 9 patients with CHF and 9 control subjects matched for age and body mass index. Baseline muscle sympathetic nerve activity (MSNA) was higher in the patients with CHF compared with control subjects (47Ϯ8 versus 23Ϯ3 bursts per minute, PϽ0.01). During hypercapnia, patients with CHF had greater increases in minute ventilation (6.7Ϯ1.4 versus 2.7Ϯ0.9 L/min, Pϭ0.03) and heart rate (7.0Ϯ2.1 versus 0.6Ϯ1.2 bpm, Pϭ0.02). Despite higher ventilation, which inhibits sympathetic activity, the MSNA increase in patients with CHF was also greater than that in control subjects (58Ϯ12% versus 21Ϯ9%, Pϭ0.03). Ventilatory, autonomic, and blood pressure responses to hypoxia and the cold pressor test in CHF patients were not different from those in control subjects. Conclusions-Chronic heart failure is characterized by a selective potentiation of ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia. (Circulation. 1999;100:262-267.)

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Clinical characteristics of chronic heart failure patients with an augmented peripheral chemoreflex

Cited by 105 publications

References 29 publications

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

Carotid body function in heart failure

Enhanced Sympathetic and Ventilatory Responses to Central Chemoreflex Activation in Heart Failure

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