Carotid Chemoreceptor Ablation Improves Survival in Heart Failure

Rio, Rodrigo Del; Marcus, Noah J.; Schultz, Harold D.

doi:10.1016/j.jacc.2013.07.079

Cited by 170 publications

(136 citation statements)

References 34 publications

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“…7,12,19,23,24 Recently, new experimental evidence has shown that the CB is involved in several sympathetic-mediated diseases. 7,[47][48][49][50][51] The selective ablation of the CB reduced BP in spontaneous hypertensive rats, 50 reduced sympathetic hyperactivation, improved survival in heart failure experimental models , 30,52 and prevented the development of hypertension and insulin resistance in rats fed with a highfat diet. 51 Thus, it is possible that the ablation of the CB will improve cardiovascular control in OSA.…”

Section: Discussionmentioning

confidence: 99%

“…13,30 In addition, intravenous infusion of phenylephrine (25 µg/kg) and sodium nitroprusside (50 µg/kg) was used to fully determine the cardiac baroreflex function.…”

Section: Baroreflex Sensitivitymentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

“…12,13,19,30 In addition, we studied the effects of the β-adrenergic and cholinergic receptors blockers on resting HR to determine the sympathovagal control to the heart.…”

Section: Cardiac Autonomic Balancementioning

confidence: 99%

“…The CB has been involved in several human sympathetic-mediated diseases, and the denervation or selective ablation of the CBs has been proposed as a feasible clinical treatment for severe and resistant hypertension in humans 49,50 and cardiovascular consequences of heart failure. 30 Thus, it is possible that the modulation of the enhanced CB function will be of therapeutic value to develop new treatments intended to improve the cardiovascular consequences of OSA.We previously reported that CIH induced local and systemic oxidative stress and that increase in reactive oxygen species in the CB is the key component on CB potentiation after CIH exposure. 7,19,24,25 We found that CIH induced a reactive oxygen species-dependent increases of tumor necrosis factor-α and interleukin-1β in the CB, suggesting that these proinflammatory cytokines may mediate the reactive oxygen species-induced CB potentiation.…”

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Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

et al. 2016

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The obstructive sleep apnea (OSA), a worldwide sleep breathing disorder that affect 9% of women and 24% of adult men, 1 is an independent risk factor for systemic hypertension and stroke and is associated with atrial arrhythmogenesis. [2][3][4][5][6] Chronic intermittent hypoxia (CIH), which is the principal feature of OSA, is considered the main factor for the hypertension.2-4,7 CIH produces autonomic dysfunction characterized by sympathetic hyperactivity, alterations of heart rate (HR) variability (HRV), and reduction of cardiac baroreflex efficiency. [8][9][10][11][12][13][14] Although the link between OSA and hypertension is well established, the mechanisms responsible for the autonomic imbalance and the hypertension are not entirely known. CIH produces oxidative stress, inflammation, and endothelial dysfunction that contribute to the hypertension. [2][3][4]7 However, a growing body of evidences suggests that the carotid body (CB), the main oxygen chemoreceptor organ, 15 plays a crucial role in the development of autonomic alterations and hypertension after CIH. Indeed, patients with OSA and animals exposed to CIH show enhanced cardiorespiratory and sympathetic responses to hypoxia, suggesting that CIH potentiates the CB-mediated chemoreflex drive. 7,13,[16][17][18][19] found that bilateral CB denervation before the CIH exposure prevents the development of the hypertension in rats. Despite this important result, the idea that the CB chemoreceptor contributes to the progression of cardiovascular pathologies associated with OSA was not seriously considered until the last decade. Indeed, in the last years, the proposal that the CB is involved in the progression of the CIH-induced hypertension received further attention . 3,4,7,18,21,22 Neural recordings of CB chemosensory activity have shown that CIH selectively Abstract-Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O 2 , 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments.In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and inc...

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Section: Discussionmentioning

confidence: 99%

“…13,30 In addition, intravenous infusion of phenylephrine (25 µg/kg) and sodium nitroprusside (50 µg/kg) was used to fully determine the cardiac baroreflex function.…”

Section: Baroreflex Sensitivitymentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

“…12,13,19,30 In addition, we studied the effects of the β-adrenergic and cholinergic receptors blockers on resting HR to determine the sympathovagal control to the heart.…”

Section: Cardiac Autonomic Balancementioning

confidence: 99%

mentioning

confidence: 99%

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Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

et al. 2016

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Closed‐loop modeling of central and intrinsic cardiac nervous system circuits underlying cardiovascular control

et al. 2023

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The baroreflex is a multi-input, multi-output physiological control system that regulates blood pressure by modulating nerve activity between the brainstem and the heart. Existing computational models of the baroreflex do not explicitly incorporate the intrinsic cardiac nervous system (ICN), which mediates central control of heart function. We developed a computational model of closed-loop cardiovascular control by integrating a network representation of the ICN within central control reflex circuits. We examined central and local contributions to the control of heart rate, ventricular functions, and respiratory sinus arrhythmia (RSA). Our simulations match the experimentally observed relationship between RSA and lung tidal volume. Our simulations predicted the relative contributions of the sensory and the motor neuron pathways to the experimentally observed changes in the heart rate. Our closed-loop cardiovascular control model is primed for evaluating bioelectronic interventions to treat heart failure and renormalize cardiovascular physiology.

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Regulation of Breathing and Autonomic Outflows by Chemoreceptors

Guyenet

2014

Comprehensive Physiology

274

293

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Lung ventilation fluctuates widely with behavior but arterial PCO2 remains stable. Under normal conditions, the chemoreflexes contribute to PaCO2 stability by producing small corrective cardiorespiratory adjustments mediated by lower brainstem circuits. Carotid body (CB) information reaches the respiratory pattern generator (RPG) via nucleus solitarius (NTS) glutamatergic neurons which also target rostral ventrolateral medulla (RVLM) presympathetic neurons thereby raising sympathetic nerve activity (SNA). Chemoreceptors also regulate presympathetic neurons and cardiovagal preganglionic neurons indirectly via inputs from the RPG. Secondary effects of chemoreceptors on the autonomic outflows result from changes in lung stretch afferent and baroreceptor activity. Central respiratory chemosensitivity is caused by direct effects of acid on neurons and indirect effects of CO2 via astrocytes. Central respiratory chemoreceptors are not definitively identified but the retrotrapezoid nucleus (RTN) is a particularly strong candidate. The absence of RTN likely causes severe central apneas in congenital central hypoventilation syndrome. Like other stressors, intense chemosensory stimuli produce arousal and activate circuits that are wake- or attention-promoting. Such pathways (e.g., locus coeruleus, raphe, and orexin system) modulate the chemoreflexes in a state-dependent manner and their activation by strong chemosensory stimuli intensifies these reflexes. In essential hypertension, obstructive sleep apnea and congestive heart failure, chronically elevated CB afferent activity contributes to raising SNA but breathing is unchanged or becomes periodic (severe CHF). Extreme CNS hypoxia produces a stereotyped cardiorespiratory response (gasping, increased SNA). The effects of these various pathologies on brainstem cardiorespiratory networks are discussed, special consideration being given to the interactions between central and peripheral chemoreflexes.

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Carotid Chemoreceptor Ablation Improves Survival in Heart Failure

Cited by 170 publications

References 34 publications

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

Closed‐loop modeling of central and intrinsic cardiac nervous system circuits underlying cardiovascular control

Regulation of Breathing and Autonomic Outflows by Chemoreceptors

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