Dissociation between blood pressure and heart rate response to hypoxia after bilateral carotid body removal in men with systolic heart failure

Niewiński, Piotr; Janczak, Dariusz; Ruciński, Artur; Tubek, Stanisław; Engelman, Zoar J.; Jaźwiec, Przemysław; Banasiak, Waldemar; Sobotka, Paul; Hart, Emma C J; Paton, Julian F. R.; Ponikowski, Piotr

doi:10.1113/expphysiol.2013.075580

Cited by 56 publications

(74 citation statements)

References 48 publications

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“…In contrast to scBRS, we observed an almost absent HVR with a non-significant blunting of the heart rate response to hypoxia in resected patients (Figure 1). These data are in agreement with findings from Niewinski and colleagues, who have shown carotid body resection in heart failure patients 8 significantly blunts the ventilatory response, but not the heart rate response, to hypoxia. It is likely the response to hypoxia is mediated by multiple chemoreceptive sites; whereas the carotid bodies play a role in the ventilatory response to hypoxia, it appears the heart rate response may be mediated by another site (e.g.…”

Section: Discussionsupporting

confidence: 93%

Effect of Bilateral Carotid Body Resection on Cardiac Baroreflex Control of Blood Pressure During Hypoglycemia

et al. 2015

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Hypoglycemia results in a reduction in cardiac baroreflex sensitivity and a shift in the baroreflex working range to higher heart rates. This effect is mediated in part by the carotid chemoreceptors. Therefore, we hypothesized hypoglycemia-mediated changes in baroreflex control of heart rate would be blunted in carotid body resected patients when compared with healthy controls. Five patients with bilateral carotid body resection for glomus tumors and ten healthy controls completed a 180-minute hyperinsulinemic, hypoglycemic (~3.3 mmol.L−1) clamp. Changes in heart rate, blood pressure, and spontaneous cardiac baroreflex sensitivity were assessed. Baseline baroreflex sensitivity was not different between groups (p>0.05). Hypoglycemia resulted in a reduction in baroreflex sensitivity in both groups (Main effect of time, p<0.01) and responses were lower in resected patients when compared with controls (Main effect of group, p<0.05). Hypoglycemia resulted in large reductions in systolic (−17±7 mmHg) and mean (−14±5 mmHg) blood pressure in resected patients that were not observed in controls (Interaction of group and time, p<0.05). Despite lower blood pressures, increases in heart rate with hypoglycemia were blunted in resected patients (Interaction of group and time, p<0.01). Major novel findings from this study demonstrate that intact carotid chemoreceptors are essential for increasing heart rate and maintaining arterial blood pressure during hypoglycemia in humans. These data support a contribution of the carotid chemoreceptors to blood pressure control and highlight the potential widespread effects of carotid body resection in humans.

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Section: Discussionsupporting

confidence: 93%

Effect of Bilateral Carotid Body Resection on Cardiac Baroreflex Control of Blood Pressure During Hypoglycemia

et al. 2015

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“…Moreover, CB removal in heart failure patients did not modify the heart chronotropic response, suggesting other peripheral chemoreceptors, may be involved in this response to hypoxia (Niewiński et al . ). As a whole, data reflect that CB dysfunction is implicated in the pathophysiology of various human cardiovascular diseases through the modulation of the SNS.…”

Section: Epidemiology Of Metabolic Diseasesmentioning

confidence: 97%

“…These preclinical results are supported by recent data obtained in patients (Niewiński et al . , ) showing that unilateral CB removal in a patient with chronic heart failure resulted in a decrease in peripheral chemosensitivity, which was accompanied by improvements in autonomic function, cardiac function, exercise capacity and reduced resting ventilation (Niewiński et al . ).…”

Section: Epidemiology Of Metabolic Diseasesmentioning

confidence: 99%

Insulin resistance: a new consequence of altered carotid body chemoreflex?

Conde

Ribeiro

Melo

et al. 2016

The Journal of Physiology

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Reactive oxygen species Inflammation HyperinsulinaemiaHypercaloric diets, obesity Carotid body overactivation Insulin resistance HypertensionSympathetic nervous system activity ? Abstract Metabolic diseases affect millions of individuals across the world and represent a group of chronic diseases of very high prevalence and relatively low therapeutic success, making them suitable candidates for pathophysiological studies. The sympathetic nervous system (SNS) contributes to the regulation of energy balance and energy expenditure both in physiological and pathological states. For instance, drugs that stimulate sympathetic activity decrease food intake, increase resting metabolic rate and increase the thermogenic response to food, while Silvia Conde's research focuses on understanding the physiology of the autonomic nervous system, in particular the carotid body, and in the application of its findings to pathological states allowing the identification of molecular targets for therapy. pharmacological blockade of the SNS has opposite effects. Likewise, dysmetabolic features such as insulin resistance, dyslipidaemia and obesity are characterized by a basal overactivation of the SNS. Recently, a new line of research linking the SNS to metabolic diseases has emerged with the report that the carotid bodies (CBs) are involved in the development of insulin resistance. The CBs are arterial chemoreceptors that classically sense changes in arterial blood O 2 , CO 2 and pH levels and whose activity is known to be increased in rodent models of insulin resistance. We have shown that selective bilateral resection of the nerve of the CB, the carotid sinus nerve (CSN), totally prevents diet-induced insulin resistance, hyperglycaemia, dyslipidaemia, hypertension and sympathoadrenal overactivity. These results imply that the beneficial effects of CSN resection on insulin action and glucoregulation are modulated by target-related efferent sympathetic nerves through a reflex that is initiated in the CBs. It also highlights modulation of CB activity as a putative future therapeutic intervention for metabolic diseases. Abstract figure legend Role of the carotid body (CB) in the development of insulin resistance through an increase in sympathetic nervous system activity. Obesity and hypercaloric diets promote hyperinsulinaemia, inflammation and the increase in oxidative stress. The hyperinsulinaemia and/or inflammation and/or reactive oxygen species stimulate the CB and promote its overactivation that contributes to the excessive sympatho-excitation that originates insulin resistance and hypertension.Abbreviations CB, carotid body; CSN, carotid sinus nerve; NEFAs, non-esterified fatty acids; OSA, obstructive sleep apnoea; SNS, sympathetic nervous system.

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“…The carotid body chemoreceptors have been previously associated with the aetiology of cardiometabolic diseases both in animal models [25][26][27] and in humans [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

Sacramento

Chew²,

Melo

et al. 2018

Diabetologia

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Aims/hypothesis A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function. Herein we characterise the ability of a novel bioelectronic application, classified as kilohertz frequency alternating current (KHFAC) modulation, to suppress neural signals within the CSN of rodents. Methods Rats were fed either a chow or high-fat/high-sucrose (HFHSu) diet (60% lipid-rich diet plus 35% sucrose drinking water) over 14 weeks. Neural interfaces were bilaterally implanted in the CSNs and attached to an external pulse generator. The rats were then randomised to KHFAC or sham modulation groups. KHFAC modulation variables were defined acutely by respiratory and cardiac responses to hypoxia (10% O 2 + 90% N 2 ). Insulin sensitivity was evaluated periodically through an ITT and glucose tolerance by an OGTT. Results KHFAC modulation of the CSN, applied over 9 weeks, restored insulin sensitivity (constant of the insulin tolerance test [K ITT ] HFHSu sham, 2.56 ± 0.41% glucose/min; K ITT HFHSu KHFAC, 5.01 ± 0.52% glucose/min) and glucose tolerance (AUC HFHSu sham, 1278 ± 20.36 mmol/l × min; AUC HFHSu KHFAC, 1054.15 ± 62.64 mmol/l × min) in rat models of type 2 diabetes. Upon cessation of KHFAC, insulin resistance and glucose intolerance returned to normal values within 5 weeks. Conclusions/interpretation KHFAC modulation of the CSN improves metabolic control in rat models of type 2 diabetes. These positive outcomes have significant translational potential as a novel therapeutic modality for the purpose of treating metabolic diseases in humans.

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Dissociation between blood pressure and heart rate response to hypoxia after bilateral carotid body removal in men with systolic heart failure

Cited by 56 publications

References 48 publications

Effect of Bilateral Carotid Body Resection on Cardiac Baroreflex Control of Blood Pressure During Hypoglycemia

Effect of Bilateral Carotid Body Resection on Cardiac Baroreflex Control of Blood Pressure During Hypoglycemia

Insulin resistance: a new consequence of altered carotid body chemoreflex?

Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

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