Quantitative Prediction of the Location of Carotid Bifurcation and Neurovascular Structures in the Carotid Region: A Cross-Sectional Cadaveric Study.

INTRODUCTION: The carotid region is encountered in vascular and neurological surgery and carries a potential for vascular and cranial nerve trauma. The carotid bifurcation is an especially important landmark and difficult to predict based on currently established landmarks. This study is a detailed analysis of the carotid region and proposes a novel methodology to predict the height of the bifurcation. MATERIALS AND METHODS: Superficial and deep dissections were performed on the anterior triangle of the neck to expose the carotid region in twenty-one formalin-fixed donor cadavers. Musculoskeletal and neurovascular structures were assessed in relation to the carotid bifurcation and the medial border of the clavicle (MBC). RESULTS: The carotid bifurcation occurred, on average, 11.4 mm higher on the left (p < 0.001; 95% CI: 9.28, 13.54). The superior thyroid artery (p < 0.001), facial vein (p < 0.001), and cranial nerve XII (p < 0.001) were all more distal on the left side when measured from the MBC while the angle of the mandible and stylohyoid muscle remained symmetric. Left- and right-sided vascular structures were symmetric when measured from the carotid bifurcation. CONCLUSIONS: Neurovascular structures within the carotid region are likely to be anatomically superior on the left side while vessels are likely to remain symmetric in relation to the carotid bifurcation. When measured from the MBC, the bifurcation height can be predicted by multiplying the distance between the MBC and mastoid process by 0.65 (right side) or 0.74 (left side). This novel methodological estimation may be easily learned and directly implemented in clinical practice.

Biomechanical Aspects of Closing Approaches in Postcarotid Endarterectomy.

The carotid bifurcation tends to develop atherosclerotic stenoses which might interfere with cerebral blood supply. In cases of arterial blockage, the common clinical solution is to remove the plaque via carotid endarterectomy (CEA) surgery. Artery closure after surgery using primary closures along the cutting edge might lead to artery narrowing and restrict blood flow. An alternative approach is patch angioplasty which takes longer time and leads to more during-surgery complications. The present study uses numerical methods with fluid-structure interaction (FSI) to explore and compare the two solutions in terms of hemodynamics and stress and strain fields developed in the artery wall.

Baroreceptor reflex failure: Review of the literature and the potential impact on patients with head and neck cancer.

BACKGROUND: Baroreceptor dysfunction and reflex failure may occur after surgery affecting the carotid artery. The implications for patients undergoing treatment for head and neck cancer are not well described. METHODS: A literature search of PubMed was performed between March 2016 and May 2016. Search terms used individually and in combination included: "baroreflex failure," "carotid sinus sensitivity," "carotid endarterectomy," "carotid body tumor," and "head and neck cancer." Bibliographies of included articles were also reviewed for additional pertinent articles. RESULTS: There is evidence of baroreceptor failure in certain patients after interventions associated with the carotid artery, including carotid endarterectomy and carotid body tumor excision. Few studies have been performed investigating the potential effect of head and neck surgery treatment, including surgery and/or radiation, on baroreflex function. CONCLUSION: Head and neck cancer treatment has the potential to cause baroreflex failure, and this is likely an underrecognized and underdiagnosed condition.

Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats.

KEY POINTS: Peripheral chemoreflex sensitization is a feature of renovascular hypertension. Carotid sinus nerve denervation (CSD) has recently been shown to relieve hypertension and reduce sympathetic activity in other rat models of hypertension. We show that CSD in renovascular hypertension halts further increases in blood pressure. Possible mechanisms include improvements in baroreceptor reflex sensitivity and renal function, restoration of cardiac calcium signalling towards control levels, and reduced neural inflammation. Our data suggest that the peripheral chemoreflex may be a viable therapeutic target for renovascular hypertension. ABSTRACT: The peripheral chemoreflex is known to be hyper-responsive in both spontaneously hypertensive (SHR) and Goldblatt hypertensive (two kidney one clip; 2K1C) rats. We have previously shown that carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in SHR. In the present study, we show that CSD ameliorates 2K1C hypertension and reveal the potential underlying mechanisms. Adult Wistar rats were instrumented to record ABP via telemetry, and then underwent CSD (n = 9) or sham CSD (n = 9) 5 weeks after renal artery clipping, in comparison with normal Wistar rats (n = 5). After 21 days, renal function was assessed, and tissue was collected to assess sympathetic postganglionic intracellular calcium transients ([Ca2+ ]i ) and immune cell infiltrates. Hypertensive 2K1C rats showed a profound elevation in ABP (Wistar: 98 ± 4 mmHg vs. 2K1C: 147 ± 8 mmHg; P < 0.001), coupled with impairments in renal function and baroreflex sensitivity, increased neuroinflammatory markers and enhanced [Ca2+ ]I in stellate neurons (P < 0.05). CSD reduced ABP in 2K1C+CSD rats and prevented the further progressive increase in ABP seen in 2K1C+sham CSD rats, with a between-group difference of 14 ± 2 mmHg by week 3 (P < 0.01), which was accompanied by improvements in both baroreflex control and spectral indicators of cardiac sympatho-vagal balance. Furthermore, CSD improved protein and albuminuria, decreased [Ca2+ ]i evoked responses from stellate neurons, and also reduced indicators of brainstem inflammation. In summary, CSD in 2K1C rats reduces the hypertensive burden and improves renal function. This may be mediated by improvements in autonomic balance, functional remodelling of post-ganglionic neurons and reduced inflammation. Our results suggest that the peripheral chemoreflex may be considered as a potential therapeutic target for controlling renovascular hypertension.

Carotid baroreceptor stimulation blood pressure response mapped in patients undergoing carotid endarterectomy (C-Map study).

OBJECTIVE: Continuous stimulation of the carotid baroreceptors has been shown to evoke a sustained systolic blood pressure (SBP) reduction in hypertensive subjects. This study conducted a detailed mapping of the SBP and heart rate response to electrical stimulus at different locations in the carotid sinus region in patients undergoing a carotid endarterectomy (CEA). METHODS: The Carotid Sinus Autonomic Response Mapping (C-Map) Study is a multicenter, prospective, non-randomized, acute feasibility study conducted in 10 hypertensive subjects undergoing CEA. Electrode pairs were placed in multiple locations in the region of the carotid sinus for acute stimulation, and the tests were repeated after plaque removal and vessel repair. RESULTS: The configuration that elicited the largest pressure reduction in 8 of 10 patients was with the electrodes arranged longitudinally along the medial (in relation to the bifurcation) wall of the internal carotid artery (ICA) near the bifurcation (11.2±8.1mmHg, p<0.05). There was no difference in average maximum response pre vs. post plaque removal. Spontaneous baroreflex sensitivity increased from 6.0±3.2ms/mmHg pre-CEA to 8.2±5.4ms/mmHg post-CEA (p=0.040). CONCLUSIONS: Endarterectomy surgery did not affect maximal acute stimulation response but improved baroreflex sensitivity acutely. Acute extravascular baroreceptor stimulation (BRS) mapping demonstrated that blood pressure reductions are dependent on electrode location and orientation. In most subjects, the largest SBP reductions were elicited in the region of the medial wall of the ICA. This area can be targeted for future BRS lead design and implant.

Fístula carótido-cavernosa tratada con compresiones carotídeas / Carotid-cavernous fistula successfully treated with carotid compression

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Carotid Sinus/Nerve Stimulation for Treatment of Resistant Hypertension and Heart Failure.

Hypertension and cardiovascular disease are leading causes of morbidity and mortality worldwide. The prevalence of resistant hypertension remains high and is expected to increase. Moreover, there are limitations to therapeutic interventions aimed at treating resistant hypertension and heart failure despite the wide availability of therapeutic agents and dietary and lifestyle modification. Device-based therapy by baroreflex activation via carotid sinus/nerve stimulation is currently undergoing investigation, and promising findings from clinical trials have been published. Baroreflex activation therapy may represent a new approach for treatment of these conditions by reducing sympathetic drive and increasing parasympathetic activity. Here we describe a new technology which is designed to deliver carotid sinus stimulation to electrically activate the carotid baroreceptors and baroreflex, thereby reducing blood pressure and improving cardiac function. The theory, surgical techniques, and clinical trials of carotid sinus stimulation are highlighted.

Initial experience with therapeutic geometric modification of the carotid bulb for true resistant hypertension.

The contribution of carotid baroreceptor feedback in preventing or potentially contributing to the essential hypertensive cascade is poorly understood. It is clear the carotid sinus nerve action potentials are triggered by carotid bulb stretch rather than pressure and are only sustained during pulsatile increases in pressure. In addition, the carotid baroreceptor negative feedback is gradually extinguished in hypertension patients (a phenomenon known as "resetting"). We report a case of significant reduction in blood pressure in a patient with true resistant hypertension after change in the carotid bulb pulsatile strain patterns following the implant of an intravascular prosthesis.

Repeated intravenous doxapram induces phrenic motor facilitation.

Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3 injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (P<0.05 vs. controls), but was 103±8%BL and 112±4%BL in the groups receiving a single dose of 2 or 6mg/kg, respectively. Following bilateral section of the carotid sinus nerves, the acute phrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury.

The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension.

In the spontaneously hypertensive (SH) rat, hyperoxic inactivation of the carotid body (CB) produces a rapid and pronounced fall in both arterial pressure and renal sympathetic nerve activity (RSA). Here we show that CB de-afferentation through carotid sinus nerve denervation (CSD) reduces the overactive sympathetic activity in SH rats, providing an effective antihypertensive treatment. We demonstrate that CSD lowers RSA chronically and that this is accompanied by a depressor response in SH but not normotensive rats. The drop in blood pressure is not dependent on renal nerve integrity but mechanistically accompanied by a resetting of the RSA-baroreflex function curve, sensitization of the cardiac baroreflex, changes in renal excretory function and reduced T-lymphocyte infiltration. We further show that combined with renal denervation, CSD remains effective, producing a summative response indicative of an independent mechanism. Our findings indicate that CB de-afferentation is an effective means for robust and sustained sympathoinhibition, which could translate to patients with neurogenic hypertension.

Novel antihypertensive therapies: renal sympathetic nerve ablation and carotid baroreceptor stimulation.

Therapeutic interventions aimed at reducing high blood pressure still encompass a number of difficulties and limitations. This is the case particularly in resistant hypertension, i.e. a condition characterized by a very high cardiovascular risk. Carotid baroreceptor stimulation and renal sympathetic nerves ablation represent new approaches in the treatment of this condition. This paper will provide a comparison of the effects of the two procedures, highlighting their effects on blood pressure, metabolic profile, target organ damage, safety and tolerability profile.

Timing and efficacy of alternative methods of sympathetic blockade.

Despite the presence of seven different antihypertensive drug classes and over 120 different antihypertensive medications, about 48 % of the 75 million people with hypertension are not reaching their target blood pressure goals. One of the reasons for this lack of control is the failure to adequately inhibit the sympathetic nervous system. Consequently, alternative therapies have been attracting interest. Recent technical advances targeting the sympathetic over-activity of the carotid sinuses (baroreflex activation therapy, BAT) and the renal sympathetic nerves (renal denervation therapy, RDT) have renewed interest in invasive therapies for the treatment of drug-resistant hypertension. Encouraging results from the recent Rheos Pivotal and Symplicity HTN-2 trials on the safety and efficacy of BAT and RDT, respectively, indicate that invasive approaches can safely reduce blood pressure in patients with resistant/refractory hypertension. These approaches, while still experimental in the US, are appropriate for those on more than three fully tolerated doses of antihypertensive medications whose blood pressure is not at goal, i.e. <140/90 mmHg. The present review is focused on the clinical implications of these two technics and when they are appropriate.

Carotid baroreceptor activation for the treatment of resistant hypertension and heart failure.

Carotid baroreceptors play an important role in blood pressure regulation through modification of sympathetic nervous activity. Conditions associated with increased sympathetic activity, such as resistant hypertension and heart failure, represent potential targets for carotid baroreceptor activation. Recent technological advances made available a small device, like a pacemaker, that constantly activates carotid baroreceptors. Primary experimental and clinical data obtained from use of this device point toward significant blood pressure reduction in patients with resistant hypertension, as well as beneficial effects on cardiac structure and function. A large feasibility trial revealed promising results; however, the first randomized study in patients with resistant hypertension raised several concerns regarding the efficacy and safety of baroreceptor activation with the device. This review critically evaluates available data obtained with carotid baroreceptor activation, emphasizing data acquired during the past year, and discusses the advantages and disadvantages as well as the future prospects of this intervention.

Baroreceptor and chemoreceptor contributions to the hypertensive response to bilateral carotid occlusion in conscious mice.

This study aimed to characterize the role played by baroreceptors and chemoreceptors in the hypertensive response to bilateral carotid occlusion (BCO) in conscious C57BL mice. On the day before the experiments the animals were implanted with pneumatic cuffs around their common carotid arteries and a femoral catheter for measurement of arterial pressure. Under the same surgical approach, groups of mice were submitted to aortic or carotid sinus denervation or sham surgery. BCO was performed for 30 or 60 s, promoting prompt and sustained increase in mean arterial pressure and fall in heart rate. Compared with intact mice, the hypertensive response to 30 s of BCO was enhanced in aortic-denervated mice (52 ± 4 vs. 41 ± 4 mmHg; P < 0.05) but attenuated in carotid sinus-denervated mice (15 ± 3 vs. 41 ± 4 mmHg; P < 0.05). Suppression of peripheral chemoreceptor activity by hyperoxia [arterial partial pressure of oxygen (Pa(O(2))) > 500 mmHg] attenuated the hypertensive response to BCO in intact mice (30 ± 6 vs. 51 ± 5 mmHg in normoxia; P < 0.05) and abolished the bradycardia. It did not affect the hypertensive response in carotid sinus-denervated mice (20 ± 4 vs. 18 ± 3 mmHg in normoxia; P < 0.05). The attenuation of the hypertensive response to BCO by carotid sinus denervation or hyperoxia indicates that the hypertensive response in conscious mice is mediated by both baro- and chemoreceptors. In addition, aortic denervation potentiates the hypertensive response elicited by BCO in conscious mice.

Rostral ventrolateral medullary but not medullary lateral tegmental field neurons mediate sympatho-sympathetic reflexes in cats.

This study was designed to build on past work from this laboratory by testing the hypothesis that medullary lateral tegmental field (LTF) neurons play a critical role in mediating sympathoexcitatory responses to activation of sympathetic afferent fibers. We studied the effects of microinjection of N-methyl-d-aspartate (NMDA) or non-NMDA receptor antagonists or muscimol bilaterally into the LTF on the area under the curve of the computer-averaged sympathoexcitatory potential in the right inferior cardiac nerve elicited by short trains of stimuli applied to afferent fibers in the left inferior cardiac or left splanchnic nerve (CN, SN) of baroreceptor-denervated and vagotomized cats anesthetized with a mixture of diallylbarbiturate and urethane. In contrast to our hypothesis, sympathoexcitatory responses to stimulation of CN (n = 5-7) or SN (n = 4-7) afferent fibers were not significantly affected by these procedures. We then determined whether the rostral and caudal ventrolateral medulla (RVLM, CVLM) and nucleus tractus solitarius (NTS) were involved in mediating these reflexes. Blockade of non-NMDA, but not NMDA, receptors in the RVLM significantly reduced the area under the curve of the sympathoexcitatory responses to electrical stimulation of either CN (P = 0.0110; n = 6) or SN (P = 0.0131; n = 5) afferent fibers. Neither blockade of excitatory amino acid receptors nor chemical inactivation of CVLM or NTS significantly affected the responses. These data show that activation of non-NMDA receptors in the RVLM is a critical step in mediating the sympatho-sympathetic reflex.

Neonatal stress and attenuation of the hypercapnic ventilatory response in adult male rats: the role of carotid chemoreceptors and baroreceptors.

Neonatal maternal separation (NMS) is a form of stress that disrupts respiratory control development. Awake adult male rats previously subjected to NMS show a ventilatory response to hypercapnia (HCVR; Fi(CO(2)) = 0.05) 47% lower than controls; however, the underlying mechanisms are unknown. To address this issue, we first tested the hypothesis that carotid bodies contribute to NMS-related attenuation of the HCVR by using carotid sinus nerve section or Fi(O(2)) manipulation to maintain Pa(O(2)) constant (iso-oxic) during hypercapnic hyperpnea. We then determined whether NMS-related augmentation of baroreflex sensitivity contributes to the reduced HCVR in NMS rats. Nitroprusside and phenylephrine injections were used to manipulate arterial blood pressure in both groups of rats. Pups subjected to NMS were separated from their mother 3 h/day from postnatal days 3 to 12. Control rats were undisturbed. At adulthood, rats were anesthetized [urethane (1g/kg) + isoflurane (0.5%)], and diaphragmatic electromyogram (dEMG) was measured under baseline and hypercapnic conditions (Pa(CO(2)): 10 Torr above baseline). The relative minute activity response to hypercapnia of anesthetized NMS rats was 34% lower than controls. Maintaining Pa(O(2)) constant during hypercapnia reversed this phenotype; the HCVR of NMS rats was 45% greater than controls. Although the decrease in breathing frequency during baroreflex activation was greater in NMS rats, the change observed within the range of pressure change observed during hypercapnia was minimal. We conclude that NMS-related changes in carotid body sensitivity to chemical stimuli and/or its central integration is a key mechanism in the attenuation of HCVR by NMS.

Clinical results of carotid denervation by adventitial stripping in carotid sinus syndrome.

AIMS: Older patients with spells of syncope may suffer from a carotid sinus syndrome (CSS). Patients with invalidating CSS routinely receive pacemaker treatment. This study evaluated the safety and early outcome of a surgical technique termed carotid denervation by adventitial stripping for CSS treatment. METHODS: Carotid sinus massage (CSM) during cardiovascular monitoring confirmed CSS in patients with a history of repeated syncope and dizziness. The internal carotid artery was surgically denervated by adventitial stripping over a minimum distance of 3 cm via a standard open approach. Patient characteristics, perioperative complications and 30-day success rate were analyzed. RESULTS: A total of 39 carotid denervation procedures was performed in 27 individuals (23 males, mean age 70+/-3 years) between 1980 and 2007 in a single institution. Eleven patients had a bilateral hypersensitive carotid sinus. Procedure related complications included wound hematoma (n=4), neuropraxia of the marginal mandibular branch of the facial nerve (n=2) and dysrhythmia responding to conservative treatment (n=3). Significant alterations in systolic and diastolic blood pressure and heart rate were not observed. One patient developed a cerebral ischaemic vascular accident on the 24th postoperative day. One patient with residual disease had a successful redenervation within 1 month after the initial operation. Two patients with persistent symptoms received a pacemaker but also to no avail. At 30-day follow up 25 of 27 patients (93%) were free of syncope, and 24 free of a pacemaker (89%). CONCLUSION: Carotid denervation by adventitial stripping of the proximal carotid internal artery is effective and safe and may offer a valid alternative for pacemaker treatment in patients with carotid sinus syndrome.