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Peripheral chemoreceptors’ (PCh) hyperactivity increases sympathetic tone. An augmented acute ventilatory response to hypoxia, being a marker of PCh oversensitivity, was also identified as a marker of poor prognosis in HF. However, not much is known about the tonic (chronic) influence of PCh on cardio-respiratory parameters. In our study 30 HF patients and 30 healthy individuals were exposed to 100% oxygen for 1 min during which minute ventilation and hemodynamic parameters were non-invasively recorded. Systemic vascular resistance (SVR) and mean arterial pressure (MAP) responses to acute hyperoxia differed substantially between HF and control. In HF hyperoxia caused a significant drop in SVR in early stages with subsequent normalization, while increase in SVR was observed in controls. MAP increased in controls, but remained unchanged in HF. Bilateral carotid bodies excision performed in two HF subjects changed the response to hyperoxia towards the course seen in healthy individuals. These differences may be explained by the domination of early vascular reaction to hyperoxia in HF by vasodilation due to the inhibition of augmented tonic activity of PCh. Otherwise, in healthy subjects the vasoconstrictive action of oxygen remains unopposed. The magnitude of SVR change during acute hyperoxia may be used as a novel method for tonic PCh activity assessment.

Understanding of heart failure (HF) has evolved from a simple hemodynamic problem through a neurohormonally and proinflammatory-driven syndrome to a complex multiorgan dysfunction accompanied by inadequate energy handling. This article discusses the most important clinical aspects of advanced HF pathophysiology. It presents the concept of neurohormonal activation and its deleterious effect on cardiovascular system and reflex control. The current theories regarding the role of inflammation, cytokine activation, and myocardial remodeling in HF progression are presented. Advanced HF is a multiorgan syndrome with interplay between cardiovascular system and other organs. The role of iron deficiency is also discussed.

Key points Five years after bilateral carotid body resection (bCBR) performed in four patients, the absence of the hypoxic ventilatory response persisted, suggesting no compensatory regrowth. Breathing hypoxic gas mixtures (15% and 12%) results in a lower (by ∼10%) minimal blood oxygen saturation ( S p O 2 ) in bCBR patients compared to heart failure subjects (CHF) with intact peripheral chemoreceptors. After bCBR, patients were characterized by a greater short-term variability in S p O 2 during mild hypoxia in comparison to the CHF group. The ventilatory response to hypercapnia was preserved following bCBR and was sufficient to maintain minimal S p O 2 at levels comparable to controls when combined with hypoxia. Bilateral CBR - a novel treatment modality for sympathetically mediated diseases - should be used with caution due to the risk of significant desaturation even during mild hypoxia equivalent to that experienced during long-haul air travel and high altitude. Abstract Carotid body resection has been proposed as a novel treatment for sympathetically mediated diseases but the safety of bilateral carotid body resection (bCBR) for blood oxygenation during hypoxic stress (long-haul flights or high altitude) remains uncertain. Also unknown is whether central ventilatory drive is sufficient to maintain adequate oxygen saturation when exposed to hypercapnia with concomitant hypoxia. Thus, we administered: 15% O2 , 12% O2 , 5% CO2 /12% O2 and 5% CO2 /95% O2 to a group of four patients with congestive heart failure (65 ± 2.9 years) in whom bCBR was performed 5 years earlier. Ventilatory, haemodynamic and blood oxygen saturation ( S p O 2 ) responses were recorded non-invasively and compared to control groups with intact peripheral chemoreceptors (both healthy and heart failure patients). First, we confirmed that the ventilatory response to hypoxia was eliminated in patients with bCBR, although the increase in cardiac output was preserved. Second, administration of hypoxic gas mixtures resulted in a larger decrease in S p O 2 and greater short-term variability of the S p O 2 leading to a lower minimal S p O 2 for both hypoxia levels in the bCBR group compared to heart failure controls (82.5 ± 1.2% vs. 91.6 ± 2.3% for 15% O2 and 73.8 ± 4.0% vs. 83.7 ± 3.1% for 12% O2 ). Third, in bCBR patients the ventilatory response to hypercapnia was present and sufficient to maintain a minimal S p O 2 at a level comparable to heart failure controls following administration of 5% CO2 /12% O2 (88.7 ± 4.2% vs. 91.1 ± 2.8%). We conclude that bCBR carries a risk of significant oxygen desaturation even during mild hypoxia. Despite preservation of central chemosensitivity, future studies should focus on unilateral CBR or on pharmacological modulation of peripheral chemosensitivity.

Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance (p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia (p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO2 comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO2 on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO2 during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO2 was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO2, whereas PChT predicts an improvement in V˙E/V˙CO2 after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.

Background Pacemaker (PM) implantation may cause acute emotional distress leading to takotsubo syndrome (TTS). Frailty and cognitive impairment are known to influence outcomes after surgical procedures. It is unclear whether they may also predispose to TTS following PM implantation. Methods We identified nine cases (81 ± 6 years) of TTS following PM implantation that took place between 2013 and 2017 in one high volume implantation center. TTS was diagnosed based on typical echocardiographic appearance with resolution over time and (in cases where deemed necessary) normal coronary angiography. The TTS cases were compared with 30 consecutive cases of PM implantation (75 ± 9 years), which were not complicated by TTS (control group). Frailty was assessed using retrospective Risk Analysis Index (RAI-A). Pacing parameters were analyzed during PM implantation and after 1 month. Results Cognitive impairment was more prevalent (67% vs 10%, P = .0005), and RAI-A index was significantly higher in the TTS group compared to the control group (26 ± 13.7 vs 13.1 ± 9.8, P = .008). Perioperative right ventricular threshold was significantly higher in patients with TTS comparing to controls (0.99 ± 0.43 V vs 0.74 ± 0.20 V, P = .04). The magnitude of decrease in right ventricular threshold between implantation and 1 month follow-up was greater in TTS patients compared to controls (-0.41 ± 0.29 V vs -0.15 ± 0.38 V, P = .049). Conclusions TTS is a rare complication of PM implantation. Patients with cognitive impairment and frailty are at risk of TTS. Right ventricular pacing threshold is acutely affected by TTS and improves over time.

OBJECTIVES We evaluated the prognostic value of cardiac baroreflex sensitivity (BRS) in contemporary, optimally treated patients with mild-to-moderate heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS Data from 97 patients with HFrEF (left ventricular ejection fraction 32 ± 6%, all receiving angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker, 85% receiving aldosterone antagonist) were analysed retrospectively. All patients underwent standard clinical assessment, cardiopulmonary exercise testing and BRS evaluation with three methods: the phenylephrine (BRS-Phe), the sequence (BRS-Seq) and the controlled breathing (BRS-CtrBr) method. Data on 5-year all-cause mortality and appropriate and documented implantable cardioverter-defibrillator (ICD) discharges were collected. During a mean follow-up of 53 ± 15 months, the composite endpoint of all-cause death and appropriate and documented ICD discharge occurred in 31 (32%) patients. BRS measures assessed using all three methods were not related to survival in univariate Cox proportional hazards analyses (all P >0.25). There were also no differences in survival between low vs. preserved BRS groups, irrespective of the method used for BRS assessment (all P ≥0.15). BRS-Phe correlated with several clinically important variables (including left ventricular ejection fraction: rS = 0.27, and peak oxygen consumption: rS = 0.32, both P

Background Clinical and prognostic consequences of enhanced central chemosensitivity in the contemporary optimally treated patients with chronic heart failure (CHF) are unknown. Methods and Results We studied central chemosensitivity (defined as hypercapnic ventilatory response [HCVR; L/min/mmHg]) in 161 CHF patients (mean left ventricular ejection fraction [LVEF] 31 ± 6%, all receiving a combination of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker) and 55 sex- and age-matched healthy controls. HCVR did not differ between CHF patients and controls (median 0.63 vs 0.57 L/min −1 /mmHg −1 , P = .76). When the CHF patients were divided into tertiles according to their HCVR values, there were no significant differences in clinical characteristics (except for ischemic etiology, which was more frequent in those with the highest HCVR), results of the cardiopulmonary exercise testing, and indices of heart rate variability. During the follow-up (median 28 months, range 1–48 months, ≥15 months in all survivors), 21 patients died. HCVR was not related to survival in the Cox proportional hazards analysis. Conclusions Central chemosensitivity is not enhanced in contemporary, optimally treated CHF patients and its assessment does not provide significant clinical or prognostic information.

We present our Generative Enhanced Model (GEM) that we used to create samples awarded the first prize on the FEVER 2.0 Breakers Task. GEM is the extended language model developed upon GPT-2 architecture. The addition of novel target vocabulary input to the already existing context input enabled controlled text generation. The training procedure resulted in creating a model that inherited the knowledge of pretrained GPT-2, and therefore was ready to generate natural-like English sentences in the task domain with some additional control. As a result, GEM generated malicious claims that mixed facts from various articles, so it became difficult to classify their truthfulness.

The article describes our submission to SemEval 2019 Task 8 on Fact-Checking in Community Forums. The systems under discussion participated in Subtask A: decide whether a question asks for factual information, opinion/advice or is just socializing. Our primary submission was ranked as the second one among all participants in the official evaluation phase. The article presents our primary solution: Deeply Regularized Residual Neural Network (DRR NN) with Universal Sentence Encoder embeddings. This is followed by a description of two contrastive solutions based on ensemble methods.

Background Seat belt use is the single most effective means of reducing fatal injuries in road traffic accidents. The presence of a cardiac implantable electronic device (CIED) might influence seat belt-related behaviors due to the physical proximity of the seat belt and left subclavian area in which the device is usually implanted. Understanding the underlying mechanisms of improper seat belt use may improve safety of these patients. Methods We performed a prospective study using a structured questionnaire with 120 CIED recipients (age, 63.9 ± 10.9 years) attending a pacing outpatient clinic. All study participants were active drivers and predominantly male. The majority of patients (79%) had undergone high-energy device implantation. Results We found that 18% of study participants do not fasten seat belts on a regular basis or use the seat belt in an atypical fashion (such as under the armpit). Moderate or high level of discomfort from the interaction between seat belt and CIED was present in 27%, while more than half (51%) were afraid of seat belt-induced CIED damage. In multifactorial analysis, we found the following independent predictors of improper seat belt use: (1) at least moderate level of discomfort at the CIED site (P = 0.02); (2) fear of CIED damage (P = 0.009); and (3) irregular seat belt use prior to CIED implantation (P = 0.037). Conclusions Improper seat belt-related behaviors are common in CIED recipients. They arise from previous habits and from CIED-related physical and psychological factors. Patients' education regarding the importance and safety of proper seat belt use is a priority.

Aims Augmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CBs), characterize patients with systolic heart failure and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CBs in these patients can be performed safely to decrease sympathetic tone. Methods and results We studied 10 male patients with systolic heart failure (age, 59 ± 3 years; LVEF, 27 ± 7%) who underwent unilateral right-sided CB resection (four patients) or bilateral CB resection (six patients). Primary endpoints of the study were changes in muscle sympathetic nerve activity (MSNA) and peripheral chemosensitivity measured as ventilatory response to hypoxia from baseline to 1 month post-CB resection. Safety analysis included analysis of arterial blood gas and oxygenation at night through 2 months post-procedure and adverse events assessed up to 12 months. At the 1-month visit, CB resection was associated with a significant decrease both in MSNA (86.6 ± 3.1 vs. 79.7 ± 4.2 bursts/100 beats, P = 0.03) and in peripheral chemosensitivity (1.35 ± 0.19 vs. 0.41 ± 0.17 L/min/SpO2, P = 0.005). It also resulted in improved exercise tolerance. Amongst some patients with bilateral CB resection, there was a trend towards worsening of oxygen saturation at night, which in one case required therapy with non-invasive ventilation. Conclusion We present first-in-man evidence that CB resection in patients with systolic heart failure is associated with a decrease in sympathetic activity. A bilateral procedure may carry a risk of worsening oxygenation at night. CB modulation constitutes an interesting research avenue, but careful consideration of the balance between safety and efficacy is necessary before further clinical trials.

Stimulation of peripheral chemoreceptors by acute hypoxia causes an increase in minute ventilation (VI), heart rate (HR) and arterial blood pressure (BP). However, the contribution of particular chemosensory areas - carotid (CB) vs. aortic bodies - to this response in humans remains unknown. We performed a blinded, randomized and placebo controlled study in 11 conscious patients (9 men, 2 women) undergoing common carotid artery angiography. Doses of adenosine ranging from 4 to 512 μg or placebo solution of matching volume were administered in randomized order via a diagnostic catheter located in a common carotid artery. Separately, ventilatory and hemodynamic responses to systemic hypoxia were also assessed. Direct excitation of a CB with intra-arterial adenosine increased VI, systolic BP, mean BP and decreased HR. No responses in these variables were seen after injections of placebo. The magnitude of the ventilatory and hemodynamic responses depended on both the dose of adenosine used and on the level of chemosensitivity as determined by the ventilatory response to hypoxia. Percutaneous radio-frequency ablation of the CB abolished the adenosine evoked respiratory response and partially depressed the cardiovascular response in one participant. Our study confirms the excitatory role of purines in CB physiology in humans and suggests that adenosine may be used for selective stimulation and assessment of CB activity. The trial is registered at ClinicalTrials.gov NCT01939912. This article is protected by copyright. All rights reserved

Augmented sensitivity of peripheral chemoreceptors (PChS) is a common finding in systolic heart failure (HF). It is related to lower left ventricle systolic function, higher plasma concentrations of natriuretic peptides, worse exercise tolerance and greater prevalence of atrial fibrillation compared to patients with normal PChS. The magnitude of ventilatory response to the activation of peripheral chemoreceptors is proportional to the level of heart rate (tachycardia) and blood pressure (hypertension) responses. All these responses can be measured non-invasively in a safe and reproducible fashion using different methods employing either hypoxia or hypercapnia. Current interventions aimed at modulation of peripheral chemoreceptors in HF are focused on carotid bodies (CBs). There is a clear link between afferent signalling from CBs and sympathetic overactivity, which remains the priority target of modern HF treatment. However, CB modulation therapies may face several potential obstacles: (1) As evidenced by HF trials, an excessive inhibition of sympathetic system may be harmful. (2) Proximity of critical anatomical structures (important vessels and nerves) makes surgical and transcutaneous interventions on CB technically demanding. (3) Co-existence of atherosclerosis in the area of carotid artery bifurcation increases the risk of central embolic events related to CB modulation. (4) The relative contribution of CBs vs. aortic bodies to sympathetic activation in HF patients is unclear. (5) Choosing optimal candidates for CB modulation from the population of HF patients may be problematic. (6) There is a risk of nocturnal hypoxia following CB ablation - mostly after bilateral procedures and in patients with concomitant obstructive sleep apnoea.

From the physiological point of view, carotid bodies are mainly responsible for the ventilatory response to hypoxia; however, they also take part in the regulation of sympathetic tone. According to preclinical data, these structures likely contribute to the development and progression of sympathetically mediated diseases. Moreover, carotid body deactivation in animal models improved blood pressure control in hypertension and reduced mortality in heart failure, along with reducing sympathetic activity. On this basis, two first-in-man studies have been recently performed to investigate the safety and feasibility of such an approach in humans. In this review we summarise the current knowledge regarding the function of carotid bodies, the prevalence of their abnormalities, and the consequences of their excision in human hypertension and heart failure.

BACKGROUND The clinical significance of the carotid body (CB) has been increasing. Currently, research connected with the CB is focused on establishing the significance of chronically increased activity of the CB in the progression of heart failure and in the genesis of hypertension. Moreover, it has been suggested that cardiac hypertrophy may be associated with an increase in CB volume. OBJECTIVES The aim of study was to assess the quality of imaging the CB by following the standard protocol for computed tomography angiography (CTA) of the carotid arteries. MATERIAL AND METHODS The analysis includes 50 consecutive CTA examinations of the carotid arteries. A retrospective assessment of the quality of imaging both the right and left CB (rCB and lCB) was carried out for all the CTA examinations of the carotid arteries. RESULTS The rCB was exposed in 62% and the lCB in 56% of the CTA examinations. None of the CTA examinations analyzed resulted in good or very good quality visualization of the CB. Only 22% of the CTA examinations provided a medium quality rCB image. An even lower ratio of medium-quality visualizations of the lCB was noted: only 14% of the analyzed examinations. In the male sample group, the CB was exposed significantly more often than in the female group. CONCLUSIONS The standard protocol for CTA examinations of the carotid arteries appears to be insufficient for use in assessing the CB.

Objective The study aimed: (i) to characterize reflex responses from peripheral and central chemoreceptors in different age groups of healthy men (

Enhanced peripheral chemosensitivity (PChS) is a common finding in congestive heart failure (CHF). Although initially it may be regarded as a compensatory mechanism to maintain adequate oxygenation and tissue perfusion, importantly it also contributes to disease progression. The magnitude of PChS is related to the severity of CHF but does not depend on its etiology. Numerous methodologies have been developed to assess PChS reliably; however, only two methods based on acute hypoxia have proven to be clinically and prognostically useful. The pathophysiology behind increased PChS is complex and involves disturbances in regional blood flow, gaseous neurotransmission, redox processes, and angiotensin signaling. Augmented PChS is believed to translate into sympathetic overactivity, decreased barosensitivity, reduced exercise tolerance, more arrhythmic events, and poor outcomes. In this review, we present current knowledge regarding the pathophysiology of peripheral chemoreflex, available methods for assessment, and clinical significance of increased PChS.

Key points Low-dose dopamine reduces the ventilatory response to acute hypoxia both in animal and in human studies. In this study we show that low-dose dopamine also attenuates the haemodynamic responses (tachycardia, hypertension) to acute hypoxia in healthy humans. Moreover, we found that dopamine withdrawal results in a temporary increase in minute ventilation. The magnitude of the increase in minute ventilation after dopamine withdrawal correlates with the degree of ventilatory response to acute hypoxia and depends on the duration of dopamine administration. Dopamine may provide a novel method for assessing differences in the level of peripheral chemoreceptor activity, which has important clinical implications given the recently reported pathological role of the carotid body in cardiovascular diseases in animals and humans. Abstract Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function.

New Findings What is the central question of this study? Carotid body denervation removes the ventilatory response to acute hypoxia, although haemodynamic responses to acute hypoxia after carotid body removal have not been described conclusively in humans. What is the main finding and its importance? Carotid body removal results in dissociation of heart rate and blood pressure responses to hypoxia in human subjects. While the heart rate response (tachycardia) is maintained, there is a significant attenuation of the blood pressure response (hypertension), which indicates the existence of different sensory afferent pathways in the haemodynamic response to hypoxia that has important clinical implications for this novel therapeutic modality. While the ventilatory response to hypoxia is known to be mediated by the carotid bodies, the origin of the haemodynamic alterations evoked by hypoxia is less certain. Bilateral carotid body removal (CBR) performed to treat congestive heart failure may serve as a model to improve our understanding of haemodynamic responses to hypoxia in humans. We studied six congestive heart failure patients before and 1 month after CBR [median (interquartile range): age, 58.5 (56–61) years old; and ejection fraction, 32 (25–34)%]. Peripheral chemosensitivity (hypoxic ventilatory response) was equated to the slope relating lowest oxygen saturation to highest minute ventilation following exposures to hypoxia. Likewise, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) slopes were calculated as slopes relating the lowest oxygen saturations to the highest SBP, DBP and HR responses. We found that CBR reduces the hypoxic ventilatory response (∆91%, P

Aims Augmented peripheral chemoreflex response is an important mechanism in the pathophysiology of chronic heart failure (CHF). This study characterizes prevalence and clinical predictors of this phenomenon in optimally managed male CHF patients, and seeks to describe the hemodynamic consequences of chemoreceptor hypersensitivity. Methods and Results Thirty-four optimally managed CHF patients and 16 control subjects were prospectively studied. Hypoxic ventilatory response (HVR)—a measure of peripheral chemosensitivity—was calculated with the use of short nitrogen gas administrations. Systolic blood pressure (SBP) and heart rate (HR) following transient hypoxic challenges were recorded with a Nexfin monitor. Hemodynamic responses to hypoxia were expressed by the linear slopes between oxygen saturation (%) and SBP (mm Hg) or HR (beats/min). Elevated HVR was present in 15 (44%) of the CHF patients. Patients with elevated HVR exhibited higher levels of N-terminal pro–B-type natriuretic peptide, lower left ventricular ejection fraction, and higher prevalence of atrial fibrillation. CHF patients with elevated HVR had significantly greater SBP and HR responses to hypoxia than CHF patients with normal HVR. Conclusions Despite comprehensive pharmacotherapy, elevated HVR is prevalent in CHF patients, related to severity of the disease and associated with augmented hemodynamic responses to hypoxia. CHF patients with elevated HVR may be prone to unfavorable hemodynamic changes.

In humans, excitation of peripheral chemoreceptors with systemic hypoxia causes hyperventilation, hypertension and tachycardia. However, the contribution of particular chemosensory areas (carotid vs. aortic bodies) to this response is unclear. We showed that selective stimulation of the carotid body by the injection of adenosine into the carotid artery causes a dose-dependent increase in minute ventilation and blood pressure with a concomitant decrease in heart rate in conscious humans. The ventilatory response was abolished and the haemodynamic response was diminished following carotid body ablation. We found that the magnitude of adenosine evoked responses in minute ventilation and blood pressure was analogous to the responses evoked by hypoxia. By contrast, opposing heart rate responses were evoked by adenosine (bradycardia) vs. hypoxia (tachycardia). Intra-carotid adenosine administration may provide a novel method for perioperative assessment of the effectiveness of carotid body ablation, which has been recently proposed as a treatment strategy for sympathetically-mediated diseases.Stimulation of peripheral chemoreceptors by acute hypoxia causes an increase in minute ventilation (VI), heart rate (HR) and arterial blood pressure (BP). However, the contribution of particular chemosensory areas, such as carotid (CB) vs. aortic bodies, to this response in humans remains unknown. We performed a blinded, randomized and placebo-controlled study in 11 conscious patients (nine men, two women) undergoing common carotid artery angiography. Doses of adenosine ranging from 4 to 512 μg or placebo solution of a matching volume were administered in randomized order via a diagnostic catheter located in a common carotid artery. Separately, ventilatory and haemodynamic responses to systemic hypoxia were also assessed. Direct excitation of a CB with intra-arterial adenosine increased VI, systolic BP, mean BP and decreased HR. No responses in these variables were seen after injections of placebo. The magnitude of the ventilatory and haemodynamic responses depended on both the dose of adenosine used and on the level of chemosensitivity as determined by the ventilatory response to hypoxia. Percutaneous radiofrequency ablation of the CB abolished the adenosine evoked respiratory response and partially depressed the cardiovascular response in one participant. The results of the present study confirm the excitatory role of purines in CB physiology in humans and suggest that adenosine may be used for selective stimulation and assessment of CB activity. The trial is registered at ClinicalTrials.gov NCT01939912.

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg(-1) min(-1)) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function.

While the ventilatory response to hypoxia is known to be mediated by the carotid bodies, the origin of the haemodynamic alterations evoked by hypoxia is less certain. Bilateral carotid body removal (CBR) performed to treat congestive heart failure may serve as a model to improve our understanding of haemodynamic responses to hypoxia in humans. We studied six congestive heart failure patients before and 1 month after CBR [median (interquartile range): age, 58.5 (56-61) years old; and ejection fraction, 32 (25-34)%]. Peripheral chemosensitivity (hypoxic ventilatory response) was equated to the slope relating lowest oxygen saturation to highest minute ventilation following exposures to hypoxia. Likewise, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) slopes were calculated as slopes relating the lowest oxygen saturations to the highest SBP, DBP and HR responses. We found that CBR reduces the hypoxic ventilatory response (91%, P 0.05), SBP (71%, P 0.05) and DBP slopes (59%, P = 0.07). In contrast, the HR slope remained unchanged. The dissociation between the blood pressure and HR responses after CBR shows involvement of a different chemoreceptive site(s) maintaining the response to acute hypoxia. We conclude that carotid bodies are responsible for ventilatory and blood pressure responses, while the HR response might be mediated by the aortic bodies. The significant reduction of the blood pressure response to hypoxia after CBR suggests a decrease in sympathetic tone, which is of particular clinical relevance in congestive heart failure.

Background Augmented reflex response from peripheral chemoreceptors characterises chronic heart failure (CHF), contributes to autonomic imbalance and exercise intolerance and predicts poor outcome. Methods and results We present a case of a 56-year-old male patient with ischaemic CHF, who underwent surgical, unilateral carotid body resection to reduce peripheral chemosensitivity. At 2-month and 6-month follow-ups, we document a persistent decrease in peripheral chemosensitivity accompanied by an improvement in exercise capacity, sleep disordered breathing and quality of life. Autonomic balance was favourably affected as evidenced by improved heart rate variability and augmented cardiac baroreflex sensitivity. There were no procedure-related adverse events. Conclusions Denervation of a carotid body may offer a clinical strategy to restore autonomic balance and improve morbidity in heart failure (NCT01653821).