Carotid Body Research Articles

Outcomes and Perioperative Complications of Surgical Resection on Canine Carotid Paragangliomas (21 Cases): A Veterinary Society of Surgical Oncology Study.

Carotid body paragangliomas represent an uncommon neoplasm in dogs. The objective of this study was to report outcomes and complications associated with surgical excision of carotid body paragangliomas in 21 dogs. Cases were recruited retrospectively via medical record review from 9 veterinary speciality centres. The perioperative complication rate was 52% (11/21). Complications encountered in this cohort related to removal of carotid body tumour included airway obstruction, aspiration pneumonia, megaesophagus, unilateral laryngeal paralysis, coughing and Horner's syndrome. The overall perioperative mortality rate was 4.7% (1/21 dogs) and median survival time was 554 days for the six patients with known dates of death. One- and two-year survival rates were 61% and 42%, respectively. This is the largest collection of carotid body paraganglioma cases reported in veterinary literature. Based on these results, surgical resection of carotid body paragangliomas was associated with low perioperative mortality and long survival times.

Long-term results of carotid body tumours surgery and predictive analytics on metastatic disease and recurrence.

The determination of clinico-surgical predictors of carotid body tumour (CBT) metastasizing and/or recurrence. Patients with CBT but without a history of its previous treatment who had received inpatient medical aid at a tertiary surgical centre during the period 2011-2021 were retrospectively reviewed to obtain baseline data. Primary endpoints of the study were CBT metastasizing and/or local recurrence after radical surgery (composite endpoint) and overall survival. Secondary endpoint of the study was primary patency of carotid arteries that had been repaired/reconstructed as a result of CBT removal. Suspected predictors of CBT metastasizing/recurrence were young age of CBT onset, positive family history, multifocal paraganglioma, Shamblin type III CBT, carotid bifurcation and/or internal carotid artery (ICA) reconstruction as a result of CBT excision. To detect CBT metastasizing/recurrence, prospective imaging-based whole-body screening was suggested to patients. Fifty-three patients met the eligibility criteria. The overall survival rate was 100% at a median follow-up time of 68 months (interquartile range [IQR] 27‒104.5 months). The primary patency of repaired carotid arteries (n = 9) was 88.9% at a median follow-up time of 99 months (IQR 15.5‒116.5 months). Thirty-nine patients underwent the prospective whole-body screening. Eight (20.5%) patients were diagnosed with metastatic disease (n = 6) or local recurrence (n = 2). Patients with CBT metastasizing/recurrence were younger at age of CBT onset (p = .011), more frequently had Shamblin type III CBT (p = .004) and the necessity for carotid artery repair/reconstruction (p = .041) than patients without metastasizing/recurrence. These two groups were similar in terms of gender (p = .682), the prevalence of multifocal paraganglioma (p = .167) and positive family history (p = .180). Only the belonging of a CBT to Shamblin type III was defined as a statistically significant predictor of CBT metastasizing/recurrence in both univariable and multivariable binary logistic regression analyses (odds ratio 30; 95% confidence interval: 2.649-339.739; p = .006 and odds ratio 75.409; 95% confidence interval: 1.082-5254.557; p = .046, respectively). Multifocal paraganglioma as a predictor exhibited a strong tendency towards statistical significance (p = .09 and p = .072, respectively). Other suspected predictors didn't reach the level of statistical significance either in univariable (p = .151 for positive family history) or in multivariable (p = .211 for age of CBT onset; p = .734 for carotid artery reconstruction/repair) binary logistic regression analyses. Shamblin type III CBT has high potential for metastasizing and recurrence. Patients with Shamblin type III CBT and/or multifocal paraganglioma should be considered for genetic testing as well as preoperative whole-body radiological imaging and long-term postoperative whole-body imaging-based follow-up.

Preoperative Radiological Features in Predicting Complications of Carotid Body Tumor Resection

Preoperative Radiological Features in Predicting Complications of Carotid Body Tumor Resection

Metastatic Malignant Paraganglioma of Rare Sites Failed on Conventional Treatments Demonstrating Beneficial Response to 177Lu-DOTATATE PRRT

AbstractThe incidence of paraganglioma (PGL) is rising due to better imaging modalities employed for evaluating incidentaloma and surveillance of the asymptomatic carriers. Benign and malignant PGLs often cannot be reliably diagnosed on histology alone, and the documentation of metastases is important in the diagnosis of malignancy. Advancement in genomics has improved our understanding of PGL. 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) scan shows a significant superior detection rate compared with other conventional functional and anatomical imaging modalities, can detect rare sites of primary disease in PGL, and also aids in patient selection for peptide receptor radionuclide therapy (PRRT). PRRT is increasingly used in metastatic setting with good symptomatic and biochemical response and disease stabilization in metastatic PGL patients. We present a series of three patients with PGLs located in rare primary sites (sigmoid colon, urinary bladder, and carotid body space), which showed recurrence of disease on conventional treatments and developed metastatic disease in the lymph nodes, liver, skeleton, and lungs. PRRT with 177Lu-DOTATATE achieved symptom control, favorable biochemical and imaging responses, and increased progression-free and overall survival rate in the described patients.

Current Management of Head and Neck Paragangliomas: A Multicenter Series With Long-Term Follow-Up.

To improve our knowledge about head and neck paragangliomas (HN-PGL), the clinical characteristics of all the patients with HN-PGL included in the Spanish Registry were analyzed, as well as the treatment modalities and their outcomes. A total of 202 patients, 67.8% women, aged 53.1 ± 17.4, with 264 HN-PGL, from 16 Spanish hospitals, were included. Tumors were located in the carotid body in 61%, jugular bulb in 20.5%, tympanic area in 10.2%, and along the vagal nerve in 6.4%. Multiple tumors developed in 20.8% and metastatic disease in 4%. A genetic study was done in 64.4% and showed a pathogenic variant in SDHx in 50%. These patients were younger, with no sex predominance, and had more multiple and metastatic tumors. Tumors were treated by surgery in 134 patients, radiotherapy in 33, and other treatments in 20, and were observed without active treatment in 41 patients, who were older, more often asymptomatic, and had smaller tumors. Tumors treated with radiotherapy were larger and more often in locations other than the carotid body. After a median follow-up of 80 months (interquartile range: 41-136), 6.9% had died; among the survivors, 48.4% were disease-free, 42.1% stable, and 9.4% had progressed. The rate of sequelae was similar among patients submitted to surgery, radiotherapy, or observation. We could not identify any prognostic factor for progression. Most HN-PGL are localized slow-growing tumors. Long-term survival is high, even in case of metastasis. Although surgery is the most common treatment, radiotherapy and active surveillance are safe approaches.

7553 Thyroid Paraganglioma: A Complex Tale of the Familiar Thyroid Nodule

Abstract Disclosure: V. Moorthy: None. A. Kondapally: None. L.E. Kimball-Ravari: None. Background: Thyroid paragangliomas are rare and often misdiagnosed on fine-needle aspiration (FNA). Clinical Case & Discussion: A 58-year-old female presented with an asymptomatic “cold” thyroid nodule. Ultrasound demonstrated a 2 cm hypoechoic nodule in the isthmus. FNA yielded a follicular lesion of undetermined significance, and genomic sequencing estimated a 50% risk of malignancy prompting the patient to opt for total thyroidectomy. Histopathology and immunohistochemistry (IHC) confirmed the diagnosis of benign paraganglioma (PGL). SDH-B (succinate dehydrogenase subunit B) was notably absent on IHC. Past medical history is significant for hysterectomy for uterine fibroids and obesity, along with a confirmed family history of Hereditary Leiomyomatosis with Renal Cell Cancer (HLRCC). The patient and several family members tested positive for a pathogenic variant of fumarate hydratase (FH) gene implicated in HLRCC and undergo annual MRIs for cancer surveillance. The loss of SDH-B suggests underlying mutation. Germline SDH mutations occur in 20% of patients with pheochromocytoma and PGLs, predisposing to hereditary syndromes. PGLs are catecholamine-secreting neuroendocrine tumors with carotid body and jugular PGLs accounting for 80% of head and neck PGLs (HNPGLs). Thyroid PGLs originate from the inferior laryngeal paraganglia. They are very rare, often non-secretory, and commonly present as asymptomatic solitary nodules. For these reasons, FNA, while contraindicated, is frequently performed. If FNA is considered, pre-procedural alpha-adrenergic blockade is recommended, although catecholamine secretion triggered by FNA is uncommon. Thyroid PGLs are misdiagnosed on FNA as other thyroid neoplasms. Awareness of the more unique cytopathology of thyroid PGLs and a comprehensive IHC can aid in accurate diagnosis. Interestingly, SDH (complex 2) and FH are closely linked enzymes in the Krebs cycle. Emerging evidence correlates germline FH mutations and hereditary pheochromocytoma-paraganglioma. PGLs are less commonly associated with MEN 2A and 2B, NF type 1, VHL, and Carney-Stratakis syndrome and Carney triad. Therefore, additional testing for SDH, RET, VHL and MAX genes was recommended in this case. Total thyroidectomy or lobectomy with or without elective lymph node dissection remains the treatment of choice. Annual 24-hour urine and plasma metanephrine testing will help screen for potential recurrence. Use of GLP1 agonists for weight loss in this patient warrants further genetic and safety evaluation. Clinical Lesson/Conclusion: Often misdiagnosed on FNA, thyroid paragangliomas are rare, with multiple genetic predispositions. FNA is contraindicated and if considered, must be performed after alpha-blockade. Germline SDH mutations are implicated in PGLs and increasing evidence links FH mutations to hereditary PGLs. Presentation: 6/3/2024

7068 Paraganglioma in Cyanotic Congenital Heart Disease

Abstract Disclosure: R. Lis: None. V. Hamidi: None. Paragangliomas arise from the non-chromaffin cells of the parasympathetic nervous system, which are composed of glomus cells. These function as chemoreceptors in response to hypoxia. Carotid body paragangliomas have been linked to conditions with chronic hypoxia. This was first seen in residents of high altitude locations in a case report presented by Saldana et. al and regression of a paraganglioma with resolution of hypoxia was reported by Gruber et. al. There have been few additional case reports of Paraganglioma in other hypoxic states. We present a rare case of a functional Paraganglioma in a patient with Cyanotic Congenital Heart Disease (CCHD).This is a 19 year old female with a history of CCHD due to double inlet left ventricle and transposition of the great arteries. Soon after birth, she had a fontan procedure. She subsequently developed fontan associated liver disease as well as chronic kidney disease, hypertension, sinus node dysfunction, and complete heart block. Her baseline oxygen saturation was 78-85%. Her heart rate was 40-49 beats per minute with upcoming plans for pacemaker placement. Her blood pressure ranged 90/50 to 150/80 mmHg on Amlodipine 5 mg and Lisinopril 2.5 mg. She routinely received abdominal imaging to monitor her liver disease. A liver MRI incidentally revealed a retroperitoneal mass concerning for a paraganglioma. Serum Normetanephrines were found to be 26.60 nmol/L (reference range less than 0.89). 24 hr Urine Norepinephrine was 1,187 ug/d (reference range 14-20). Further imaging was negative for additional sites of disease. Given her complete heart block, she was started on alpha blockade only prior to pacemaker placement. After the pacemaker was placed, she was started on beta blockade and underwent surgical resection of her paraganglioma. The pathology confirmed paraganglioma and mutation testing was negative for germline mutations including SDH, VHL, RET, NF1 mutations. Paragangliomas in patients with CCHD have been scarcely described in the literature given the rarity of both of these conditions. However, there is a relatively increased incidence of paragangliomas in the CCHD population due to chronic hypoxia triggering the hypoxia pathway. EPAS1 mutated HIF2alpha is often found to be the culprit in these patients. In addition, case reports have often described these patients to either be asymptomatic or have potential symptoms masked by their cardiac disease. Therefore, CCHD patients are at increased risk for paragangliomas and warrant additional awareness and regular screening. Screening has been proposed to start after 10 years of hypoxia in a case review by Agarwal et. al. as paraganglioma incidence in CCHD populations has not been seen before age 11. Incidence of recurrence is not yet widely studied, but significant concern for recurrence is warranted if the etiology of hypoxia is not reversed. Presentation: 6/3/2024

The carotid body chemoreceptors: hard to silence the know-it-alls.

The carotid body chemoreceptors: hard to silence the know-it-alls.

Distribution and morphology of serotonin transporter-immunoreactive type I cells in the rat carotid body.

The present study reexamined the immunolocalization of membranous serotonin transporter (SERT) in the rat carotid body, and demonstrated SERT-immunoreactive cells of unreported morphology. SERT was immunohistochemically localized in a very small population of cell clusters or single type I cells (2.8%) immunoreactive for synaptophysin, the marker of these cells. Intense SERT immunoreactivity outlined the perinuclear cytoplasm and multiple cytoplasmic processes of type I cells. Of SERT-immunoreactive type I cells, 14.6% and 32.6% were immunoreactive for tyrosine hydroxylase (TH) and dopamine beta-hydroxylase, respectively, while 75.9% were immunoreactive for serotonin (5-HT). 5-HT-immunoreactive products were localized in cell bodies rather than cytoplasmic processes. SERT-immunoreactive type I cells were composed of an oval cell body with multiple threads and spherical or elongated cytoplasmic processes. Clusters or single SERT-immunoreactive type I cells were localized between or attached to other TH-immunoreactive type I cells by cell bodies or variform cytoplasmic processes. SERT-immunoreactive type I cells mainly contained bassoon-immunoreactive products in their cell bodies rather than their variform cytoplasmic processes. These results demonstrated the characteristic morphology of SERT-immunoreactive type I cells, which extend multiple cytoplasmic processes with variform terminal parts. Their morphology might be suitable for uptake of 5-HT to control the serotonergic modulation in the carotid body.

Epigenetic upregulation of carotid body angiotensin signaling increases blood pressure.

Epigenetic changes can be shaped by a wide array of environmental cues as well as maternal health and behaviors. One of the most detrimental behaviors to the developing fetus is nicotine exposure. Perinatal nicotine exposure remains a significant risk factor for cardiovascular health and in particular, hypertension. Increased basal carotid body activity and excitation are significant contributors to hypertension. This study investigated the epigenetic changes to carotid body activity induced by perinatal nicotine exposure resulting in carotid body-mediated hypertension. Using a rodent model of perinatal nicotine exposure, we show that angiotensin II type 1 receptor is upregulated in the carotid bodies of nicotine-exposed offspring. These changes were attributed to an upregulation of genetic promotion as DNA methylation of angiotensin II type 1 receptor occurred within intron regions, exemplifying an upregulation of genetic transcription for these genes. Nicotine increased angiotensin signaling in vitro . Carotid body reactivity to angiotensin was increased in perinatal nicotine-exposed offspring compared to control offspring. Further, carotid body denervation reduced arterial pressure as a result of suppressed efferent sympathetic activity in perinatal nicotine-exposed offspring. Our data demonstrate that perinatal nicotine exposure adversely affects carotid body afferent sensing, which augments efferent sympathetic activity to increase vasoconstrictor signaling and induce hypertension. Targeting angiotensin signaling in the carotid bodies may provide a way to alleviate hypertension acquired by adverse maternal uterine environments in general and perinatal nicotine exposure in particular.

Low-intensity focused ultrasound combined with microbubbles for non-invasive downregulation of rabbit carotid body activity in the treatment of hypertension.

Targeting the carotid body (CB) is a new approach in treating hypertension. This study investigates the efficacy and safety of ultrasound combined with microbubbles in targeting CB to treat hypertension. Twenty-seven hypertensive rabbits were randomly assigned to three groups: microbubbles only (sham group, n = 11), ultrasound plus microbubbles (LIFU group, n = 11), and bilateral carotid sinus nerve denervation (CSND group, n = 5). Four weeks post-intervention, blood pressure, hypoxic ventilatory response (HVR), blood pressure variability (BPV), heart rate variability (HRV), biochemical indicators, neurohormones, and histopathology were assessed in all groups. The results indicated significant reductions in systolic and diastolic blood pressure in the LIFU and CSND groups post-intervention, along with decreases in BPV, HRV, and catecholamines. HVR results showed a 35.10% reduction in CB activity in the LIFU group compared to the sham group, which was significantly lower than the reduction in the CSND group compared to the sham group (73.85%). Histopathology and transmission electron microscopy confirmed CB damage and cell apoptosis, with immunofluorescence showing a reduction in type I and II cells. In conclusion, LIFU combined with microbubbles can reduce blood pressure by lowering CB and sympathetic nerve activity.

Reductive stress in mitochondria isolated from the carotid body of type 1 diabetic male Wistar rats.

The carotid body (CB) senses changes in arterial O2 partial pressure (pO2) and glucose levels; therefore, it is key for the detection of hypoxia and hypoglycemia. The CB has been suggested to detect pO2 through an increase in reactive oxygen species (ROS) in the mitochondria. However, the mechanism protecting the chemoreceptor cells and their mitochondria from ROS and hyperglycemia is poorly understood. Here we measured glutathione levels in CB mitochondria of control and in streptozotocin (STZ)-induced type 1 diabetic male Wistar rats. We found a dramatic reduction in total glutathione from 11.45 ± 1.30 μmol/mg protein in control rats to 1.45 ± 0.31 μmol/mg protein in diabetic rats. However, the ratio of reduced to oxidized glutathione, a measure of the redox index, was increased in diabetic rats compared to controls. We conclude that the mitochondria of CB chemoreceptor cells in type 1 diabetic male Wistar rats were likely under glutathione-reducing stress.

Endothelial cells and fibroblasts mediate the microenvironmental regulatory network of carotid body paraganglioma

Objective:To explore the gene expression characteristics of endothelial cells and fibroblasts in the microenvironment of SDHD-mutated carotid body tumors（SDHD-CBT）, to fine the functional enrichment of each subcluster, and to further explore the network of cell-cell interactions in the microenvironment of SDHD-CBT. Methods:The bioinformatics analysis was used to download and reanalyze the single-nuclear RNA sequencing data of SDHD-CBT, SDHB mutated thoracic and abdominal paraganglioma（SDHB-ATPGL）, SDHB-CBT, and normal adrenal medulla（NAM）, to clarify the information of cell populations of the samples. We focused on exploring the gene expression profiles of endothelial cells and fibroblasts subclusters, and performed functional enrichment analysis based on Gene Ontology（GO） resources. CellChat was used to compare the cell-cell interactions networks of different clinical samples and predict significant signaling pathways in SDHD-CBT. Results:A total of 7 cell populations were profiled. The main subtypes of endothelial cells in SDHD-CBT are arterial and venous endothelial cells, and the main subtypes of fibroblasts are myofibroblasts and pericytes. Compared to NAM, SDHB-CBT and SDHB-ATPGL, cell communication involving endothelial cells and fibroblasts in SDHD-CBT is more abundant, with significant enrichment in pathways such as FGF, PTN, WNT, PROS, PERIOSTIN, and TGFb. Conclusion:Endothelial cells and fibroblasts in SDHD-CBT are heterogeneous and involved in important cellular interactionprocesses, in which the discovery of FGF，PTN，WNT，PROS，PERIOSTIN and TGFb signals may play an important role in the regulation of microenvironment of SDHD-CBT.

To introduce a new method of resection of carotid body tumor with preservation of the internal carotid artery ----microscopic coagulation method

Objective:To introduce the surgical experience of carotid body tumor（CBT） resection with preservation of internal carotid artery. Methods:The clinical data of 109 patients with CBT were retrospectively analyzed. The key points of surgical techniques were summarized, the imaging and pathological results were comprehensively analyzed, and the postoperative complications were observed. Results:Of the 109 patients, 28 were Shamblin Ⅰ, 46 were Shamblin Ⅱ, and 35 were Shamblin Ⅲ. Synaptophysin（SYN） and soluble protein-100（S-100） were positive in all cases. There was a positive correlation between the average expression area percentage of S-100 and SYN in pathological tissue of 17 patients（r=0.48）, and the difference was statistically significant（P<0.05）. The average operation time was（148.4±46.2） minutes, the average intraoperative blood loss was（64.7±22.8） mL, and the average hospital stay was（15.2±2.6） days. Three patients underwent tumor resection combined with external carotid artery ligation, 1 patient underwent tumor resection combined with internal carotid artery ligation, and the remaining patients underwent tumor resection alone. The overall rate of intraoperative vascular ligation was 3.7% and the rate of nerve injury was 6.4%. According to preoperative CTA, intraoperative situation and postoperative pathological results, a new classification of CBT was proposed, which could intuitively reflect the gap between the tumor and the carotid artery and the nature of the tumor. Conclusion:Surgical resection of CBT is recommended after diagnosis. The potential gap between the tumor and the blood vessels was found under the microscope. Low energy bipolar electrocoagulation was used to coagulate and cut off the fibrous connective tissue between the tumor and gradually separated along the adventitia of the artery. The carotid artery could be preserved in most cases while the tumor was completely removed, and the amount of intraoperative bleeding and the incidence of complications were reduced. It is particularly important to identify the difficult cases before operation.

Recovery of ventilatory and metabolic responses to hypoxia in neonatal rats after chronic hypoxia

Chronic hypoxia (CH) during postnatal development attenuates the hypoxic ventilatory response (HVR) in mammals, but there are conflicting reports on whether this plasticity is permanent or reversible. This study tested the hypothesis that CH-induced respiratory plasticity is reversible in neonatal rats and investigated whether the initial plasticity or recovery differs between sexes. Rat pups were exposed to 3 d of normobaric CH (12 % O2) beginning shortly after birth. Ventilation and metabolic CO2 production were then measured in normoxia and during an acute hypoxic challenge (12 % O2) immediately following CH and after 1, 4–5, and 7 d in room air. CH pups hyperventilated when returned to normoxia immediately following CH, but normoxic ventilation was similar to age-matched control rats within 7 d after return to room air. The early phase of the HVR (minute 1) was only blunted immediately following the CH exposure, while the late phase of the HVR (minute 15) remained blunted after 1 and 4–5 d in room air; recovery appeared complete by 7 d. However, when normalized to CO2 production, the late phase of the hypoxic response recovered within only 1 d. The initial blunting of the HVR and subsequent recovery were similar in female and male rats. Carotid body responses to hypoxia (in vitro) were also normal in CH pups after approximately one week in room air. Collectively, these data indicate that ventilatory and metabolic responses to hypoxia recover rapidly in both female and male neonatal rats once normoxia is restored following CH.

Management of bilateral head and neck paragangliomas at a single-institution across four decades.

Bilateral head and neck paragangliomas (HNPGLs) require nuanced management to balance tumor control with functional preservation. All patients seen at a single-institution for bilateral paraganglioma between 1983 and 2023 were retrospectively reviewed. Demographics, genetic testing results, and tumor characteristics were analyzed and compared to treatment modality and cranial nerve outcomes. There were 49 patients with 116 tumors (90 carotid body tumors [CBTs], 15 vagal paragangliomas [VPs], and 11 jugular paragangliomas [JPs]). Twenty-six patients had SDH pathologic variants (PV). Surgical management was more commonly utilized in younger patients (OR: 0.97, 95% CI: 0.950-0.992) and for JPs (OR: 9, 95% CI: 1.386-58.443). In surgical cases, CBTs had a lower risk of postoperative cranial nerve deficits compared to JPs and VPs (OR: 0.095, 95% CI: 0.013-0.692). Younger patients with bilateral HNPGLs, especially those with JP and CBT, are more often treated with surgery. CBTs have lowest risk of cranial nerve deficits after surgery.

A rare association of pheochromocytoma, paraganglioma, and pituitary adenoma (3PA): A case report and literature review.

3P association (3PA) is a rare condition with co-occurrence of pituitary adenoma and pheochromocytoma/paraganglioma. There have been less than a hundred documented cases of 3PA, which can be sporadic or related to genetic mutations. The present case report describes the first Iranian patient with 3PA and a 90th case of 3PA in the available literature. A 36-year-old Caucasian male was admitted with headache and sudden increase in blood pressure. An abdominal CT scan revealed a retroperitoneal mass posterior to the inferior vena cava, later removed and diagnosed as a pheochromocytoma. Four years later, he noticed occasional mild headaches and a painless mass on the right side of his neck. The ultrasonography evaluations suggested a carotid body tumor, which was surgically removed. About a month after his second surgery, the severity of the patient's headaches worsened, and he developed right homonymous hemianopia. A brain MRI showed a mass in favor of macroadenoma, craniopharyngioma, or meningioma, and elevated prolactin level led to the diagnosis of macroprolactinoma. Based on the provided history, this patient was diagnosed with 3PA, and a genetic study identified a positive succinate-dehydrogenase-complex subunit b mutation, possibly linked to his family history of carotid body tumor. He has remained symptom-free during his visits every 3 months. The number of cases diagnosed with 3PA worldwide is increasing. Using clinical and genetic assessments, we can timely diagnose and adequately monitor individuals with or at risk of 3PA.

Hypertension and Device-Based Therapies for Resistant Hypertension: An Up-to-Date Review.

Hypertension is the most prevalent modifiable risk factor associated with cardiovascular mortality. The World Health Organization (WHO) estimates that hypertension directly or indirectly causes the death of at least nine million people globally every year. The number of people living with hypertension (blood pressure (BP) of ≥140 mmHg systolic or ≥90 mmHg diastolic or on medication) doubled between 1990 and 2019, from 650 million to 1.3 billion. Despite a plethora of antihypertensivedrugs widely available, a sizable part of the antihypertensive population stays uncontrolled. The unmet need of controlling BP in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. Several device-based approaches have been introduced to lower BP, and most of these strategies aim to modulate autonomic nervous system activity. Importantly, when considering a device-based treatment, each patient's underlying pathophysiology is considered, and the procedural risks are weighed against the cardiovascular risk attributed to the elevated BP.In November 2023, the FDA approved two renal denervation (RDN) devices. This manuscript discusses current interventional devices and procedures recently approved (RDN) and others in the clinical testing stage for arterial hypertension intervention or management.As we list below, all others have shown promising results and are being evaluated on a larger clinical trial.The new device-based classes are as follows: catheter-based RDN, baroreflex amplification, arteriovenous (AV) malformation, carotid body (CB) ablation, pacemaker-based cardiac neuromodulation, electro-acupuncture, and deep brain stimulation. Baroreflex amplification uses peripheral neuromodulation, while AV malformation leverages AV anastomosis. CB ablation modulates chemoreceptors, and pacemaker-based neuromodulation adjusts atrioventricular intervals. Electro-acupuncture proves potential, and deep brain stimulation offers central nervous system intervention.

Hif-2α programs oxygen chemosensitivity in chromaffin cells.

The study of transcription factors that determine specialized neuronal functions has provided invaluable insights into the physiology of the nervous system. Peripheral chemoreceptors are neurone-like electrophysiologically excitable cells that link the oxygen concentration of arterial blood to the neuronal control of breathing. In the adult, this oxygen chemosensitivity is exemplified by type I cells of the carotid body, and recent work has revealed one isoform of the hypoxia-inducible transcription factor (HIF), HIF-2α, as having a nonredundant role in the development and function of that organ. Here, we show that activation of HIF-2α, including isolated overexpression of HIF-2α but not HIF-1α, is sufficient to induce oxygen chemosensitivity in adult adrenal medulla. This phenotypic change in the adrenal medulla was associated with retention of extra-adrenal paraganglioma-like tissues resembling the fetal organ of Zuckerkandl, which also manifests oxygen chemosensitivity. Acquisition of chemosensitivity was associated with changes in the adrenal medullary expression of gene classes that are ordinarily characteristic of the carotid body, including G protein regulators and atypical subunits of mitochondrial cytochrome oxidase. Overall, the findings suggest that, at least in certain tissues, HIF-2α acts as a phenotypic driver for cells that display oxygen chemosensitivity, thus linking 2 major oxygen-sensing systems.

Carotid body tumor: characteristics and surgical outcome

BackgroundCarotid body tumors are uncommon neuroendocrine growths near the carotid bifurcation. While some advocate preoperative embolization to minimize bleeding, others avoid it due to complications. This study shares the experience of a single center in managing patients with carotid body tumors without practicing preoperative embolization.MethodsThis was a cross-sectional study of patients with carotid body tumors managed between 2020 and 2024. Data were collected from the hospital’s registry. When necessary, routine blood tests, neck ultrasonography, and computed tomography scans were conducted. The tumors were categorized according to Shamblin’s classification. The average duration of follow-up was 20 months.ResultsThe study involved 25 patients, 22 (88%) females and 3 (12%) males. Their ages ranged from 27 to 85 years old. Twenty (80%) cases presented with neck swelling, and six (24%) had a positive medical history. Tumors were mainly on the right side (52%), with 20 (80%) showing ill-defined neck masses. Tumor sizes ranged from 1.5 to 7 cm, with Shamblin type II tumors being discovered in the majority of cases (72%). Types of tumors were significantly associated with the tumor size (p-value < 0.05). Blood transfusion was required in five cases (20%), three from type III and two from type II, with none from type I (p-value = 0.001). Temporary neurological deficits occurred in 3 cases (12%). No functional impairment or mortality was recorded.ConclusionsCarotid body tumors are rare tumors with an unknown etiology. Operation without practicing preoperative embolization may be feasible with an acceptable outcome.