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Sample records for carotid body type

  1. Carotid Body Tumor.

    PubMed

    Bakshi, Satvinder S; Kumar T, Lokesh

    2017-08-14

    A 17 year old girl presented with a progressively increasing swelling in her neck since 9 months. On examination a2*3 cm, firm, pulsatile swelling was felt in the left anterior triangle. The CT scan of the mass was suggestive of a carotid body tumor and urinary cathecholamines were negative. The mass was excised completely.

  2. Multiple effects of nordihydroguaiaretic acid on ionic currents in rat isolated type I carotid body cells

    PubMed Central

    Hatton, C J; Peers, C

    1997-01-01

    The effects of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on the ionic currents of rat carotid body type I cells were investigated by use of whole-cell and outside-out patch clamp techniques. NDGA (5–50 μM) produced a concentration-dependent inhibition of whole-cell K+ currents at all activating test potentials (holding potential −70 mV). The time-course of the inhibition was also concentration-dependent and the effects of NDGA were only reversible following brief periods of exposure (<2 min). Another lipoxygenase inhibitor, phenidone (5 μM), was without effect on whole-cell K+ currents in carotid body type I cells. NDGA (5–50 μM) also inhibited whole-cell Ca2+ channel currents (recorded with Ba2+ as charge carrier) in a concentration-dependent manner. Isolation of voltage-gated K+ channels by use of high [Mg2+] (6 mM), low [Ca2+] (0.1 mM) solutions revealed a direct inhibition of the voltage-sensitive component of the whole-cell K+ current by NDGA (50 μM). In excised, outside-out patches NDGA (20–50 μM) increased large conductance, Ca2+ activated K+ channel activity approximately 10 fold, an effect which could be reversed by either tetraethylammonium (10 mM) or charybdotoxin (30 nM). It is concluded that NDGA activates maxi-K+ channels in carotid body type I cells and over the same concentration range inhibits voltage-sensitive K+ and Ca2+ channels. The inhibition of whole cell K+ currents seen is most likely due to a combination of direct inhibition of the voltage-sensitive K+ current and indirect inhibition of maxi-K+ channel activity through blockade of Ca2+ channels. PMID:9384510

  3. Evidence for two types of nicotinic receptors in the cat carotid body chemoreceptor cells.

    PubMed

    Obeso, A; Gómez-Niño, M A; Almaraz, L; Dinger, B; Fidone, S; González, C

    1997-04-18

    Current concepts on the location and functional significance of nicotinic receptors in the carotid body rest on alpha-bungarotoxin binding and autoradiographic studies. Using an in vitro preparation of the cat carotid body whose catecholamine deposits have been labeled by prior incubation with the tritiated natural precursor [3H]tyrosine, we have found that nicotine induces release of [3H]catecholamines in a dose-dependent manner (IC50 = 9.81 microM). We also found that mecamylamine (50 microM) completely abolished the nicotine-induced release, while alpha-bungarotoxin (100 nM; approximately 20 times its binding Kd) only reduced the release by 56%. These findings indicate that chemoreceptor cells, and perhaps other carotid body structures, contain nicotinic receptors that are not sensitive to alpha-bungarotoxin and force a revision of the current concepts on cholinergic mechanisms in the carotid body chemoreception.

  4. Chemotransduction in the Carotid Body: K+ Current Modulated by Po2 in Type I Chemoreceptor Cells

    NASA Astrophysics Data System (ADS)

    Lopez-Barneo, Jose; Lopez-Lopez, Jose R.; Urena, Juan; Gonzalez, Constancio

    1988-07-01

    The ionic currents of carotid body type I cells and their possible involvement in the detection of oxygen tension (Po2) in arterial blood are unknown. The electrical properties of these cells were studied with the whole-cell patch clamp technique, and the hypothesis that ionic conductances can be altered by changes in Po2 was tested. The results show that type I cells have voltage-dependent sodium, calcium, and potassium channels. Sodium and calcium currents were unaffected by a decrease in Po2 from 150 to 10 millimeters of mercury, whereas, with the same experimental protocol, potassium currents were reversibly reduced by 25 to 50 percent. The effect of hypoxia was independent of internal adenosine triphosphate and calcium. Thus, ionic conductances, and particularly the O2-sensitive potassium current, play a key role in the transduction mechanism of arterial chemoreceptors.

  5. Carotid and Vagal Body Paragangliomas

    PubMed Central

    del Guercio, Luca; Narese, Donatella; Ferrara, Doriana; Butrico, Lucia; Padricelli, Andrea; Porcellini, Massimo

    Between 1972 and 2012, 25 patients presenting 32 paragangliomas of the neck were observed. Tumor locations included the carotid body (CBTs) in 21 patients and the vagus nerve in 4. Four patients had bilateral CBT and one a bilateral vagal tumor; a metachronous bilateral jugulare paraganglioma was diagnosed in one patient with bilateral CBT Shamblin type III. Five patients presented CBTs type II and three type III. Preoperative embolization was performed in 5 CBTs, with no significant difference in blood loss. Twenty-nine paragangliomas were resected (with three internal carotid artery resection): there were no cerebrovascular accident or perioperative death. Nine patients (36%) had cranial nerve palsy prior to surgery and a postoperative nerve dysfunction occurred in four other tumors (16%). Persistent nerve deficits occurred in 3 patients (12%). No evidence of malignancy was shown, intraoperatively or during a postoperative follow-up period (9 months to 18 years; mean: 8 years). PMID:24251239

  6. CaV3.2 T-type Ca²⁺ channels in H₂S-mediated hypoxic response of the carotid body.

    PubMed

    Makarenko, Vladislav V; Peng, Ying-Jie; Yuan, Guoxiang; Fox, Aaron P; Kumar, Ganesh K; Nanduri, Jayasri; Prabhakar, Nanduri R

    2015-01-15

    Arterial blood O2 levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca(2+) channels (VGCCs) are important for carotid body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding the α1H-subunit, and α1H protein is localized to glomus cells, the primary O2-sensing cells in the chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca(2+) concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from CaV3.2 knockout (Cacna1h(-/-)) mice. Since cystathionine-γ-lyase (CSE)-derived H2S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca(2+) concentration and augmented carotid body sensory nerve activity in wild-type mice, and these effects were markedly attenuated in Cacna1h(-/-) mice. In wild-type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia, and these effects were absent in CSE knockout mice. These results demonstrate that CaV3.2 T-type VGCCs contribute to the H2S-mediated carotid body response to hypoxia. Copyright © 2015 the American Physiological Society.

  7. CaV3.2 T-type Ca2+ channels in H2S-mediated hypoxic response of the carotid body

    PubMed Central

    Makarenko, Vladislav V.; Peng, Ying-Jie; Yuan, Guoxiang; Fox, Aaron P.; Kumar, Ganesh K.; Nanduri, Jayasri

    2014-01-01

    Arterial blood O2 levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca2+ channels (VGCCs) are important for carotid body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding the α1H-subunit, and α1H protein is localized to glomus cells, the primary O2-sensing cells in the chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca2+ concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from CaV3.2 knockout (Cacna1h−/−) mice. Since cystathionine-γ-lyase (CSE)-derived H2S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca2+ concentration and augmented carotid body sensory nerve activity in wild-type mice, and these effects were markedly attenuated in Cacna1h−/− mice. In wild-type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia, and these effects were absent in CSE knockout mice. These results demonstrate that CaV3.2 T-type VGCCs contribute to the H2S-mediated carotid body response to hypoxia. PMID:25377087

  8. Myocardial hypertrophy induces carotid body hyperplasia.

    PubMed

    Sivridis, Efthimios; Pavlidis, Pavlos; Fiska, Aliki; Pitsiava, Dimitra; Giatromanolaki, Alexandra

    2011-01-01

    The carotid bodies tend to enlarge after long-standing cardiopulmonary disease. Our objective was to investigate whether cardiac hypertrophy is associated with carotid body hyperplasia. Fifteen autopsy cases with combined left and right ventricular hypertrophy were examined and compared with two control groups (16 cases). The study involved a meticulous dissection of carotid bifurcations, thin serial sections, and morphometric analysis of carotid body volume and cell types (progenitor, dark, light, and sustentacular). There was a significant increase in sustentacular cells in all individuals with cardiac hypertrophy, which was not drug-induced, and accompanied by a similar increase in carotid body volume. Dark or light cell accumulation was detected focally and only in three instances. It appears that the generalized sustentacular cell hyperplasia is the result of long-standing hypoxia, while a superimposed focal prominence of dark or light cells may be proliferative or metaplastic in nature and attributed to short-term hypoxia.

  9. Carotid body disease and the physician--chronic carotid glomitis.

    PubMed Central

    Heath, D.; Khan, Q.; Nash, J.; Smith, P.

    1989-01-01

    There are three types of histological change in the carotid bodies which appear to have physiological and clinical associations. A prominence of the dark variant of chief cells with their contents of met-enkephalin and other peptides appears to be associated with acute exposure to hypoxia. Proliferation of sustentacular cells around the clusters of chief cells appears to be related to ageing and also to systemic hypertension. Recently we have described a new condition of chronic carotid glomitis which is characterized by follicles of lymphocytes and may have a basis in auto-immunity. In the present review we report for the first time plasma cell activity in the carotid bodies of an elderly man, especially around nerve fibrils and unmyelinated axons ensheathed in sustentacular cells. Such appearances are consistent with the view that ageing nerve fibrils may be the antigenic stimulus for the development of chronic carotid glomitis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2692011

  10. Paracrine Signaling in Glial-Like Type II Cells of the Rat Carotid Body.

    PubMed

    Murali, Sindhubarathi; Zhang, Min; Nurse, Colin A

    2015-01-01

    The carotid body (CB) chemosensory complex uses ATP as a key excitatory neurotransmitter that is the main contributor to the sensory discharge during acute hypoxia. The complex includes receptor type I cells, which depolarize and release various neurochemicals including ATP during hypoxia, and contiguous glial-like type II cells which express purinergic P2Y2 receptors (P2Y2R). We previously showed that activation of P2Y2R on rat type II cells led to the opening of pannexin-1 (Panx-1) channels, which acted as conduits for the further release of ATP. More recently, we considered the possibility that other CB neuromodulators may have a similar paracrine role, leading to the activation of type II cells. Here, we examine the evidence that angiotensin II (ANG II), endothelin- (ET-1), and muscarinic agonists (e.g. acetylcholine, ACh) may activate intracellular Ca(2+) signals in type II cells and, in the case of ANG II and ACh, Panx-1 currents as well. Using ratiometric Ca(2+) imaging, we found that a substantial population of type II cells responded to 100 nM ANG II with a robust rise in intracellular Ca(2+) and activation of Panx-1 current. Both effects of ANG II were mediated via AT(1) receptors (AT(1)Rs) and current activation could be inhibited by the Panx-1 channel blocker, carbenoxolone (CBX; 5 μM). Additionally, low concentrations of ET-1 (1 nM) evoked robust intracellular Ca(2+) responses in subpopulations of type II cells. The mAChR agonist muscarine (10 μM) also induced a rise in intracellular Ca(2+) in some type II cells, and preliminary perforated-patch, whole-cell recordings revealed that ACh (10 μM) may activate Panx-1-like currents. These data suggest that paracrine activation of type II cells by endogenous neuromodulators may be a common feature of signal processing in the rat CB.

  11. Radical resection of a Shamblin type III carotid body tumour without cerebro-neurological deficit: Improved technique with preoperative embolization and carotid stenting.

    PubMed

    Ong, H S; Fan, X D; Ji, T

    2014-12-01

    The surgical resection of a large unfavourable Shamblin type III carotid body tumour (CBT) can be very challenging technically, with many potential significant complications. Preoperative embolization aids in shrinking the lesion, reducing intraoperative blood loss, and improving visualization of the surgical field. Preoperative internal carotid artery (ICA) stenting aids in reinforcing the arterial wall, thereby providing a better dissection plane. A woman presented to our institution with a large right-sided CBT. Failure of the preoperative temporary balloon occlusion (TBO) test emphasized the importance of intraoperative preservation of the ipsilateral ICA. A combination of both preoperative embolization and carotid stenting allowed a less hazardous radical resection of the CBT. An almost bloodless surgical field permitted meticulous dissection, hence reducing the risk of intraoperative vascular and nerve injury. Embolization and carotid stenting prior to surgical resection should be considered in cases with bilateral CBT or a skull base orientated high CBT, and for those with intracranial extension and patients who have failed the TBO test. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. Anatomical variations in human carotid bodies.

    PubMed Central

    Khan, Q; Heath, D; Smith, P

    1988-01-01

    The variations in anatomical structure and position of both carotid bodies were noted in 100 consecutive subjects who came to necropsy. Considerable variations in form were found. Although most carotid bodies (83% on the right and 86% on the left) were of the classic ovoid type, an appreciable minority was bilobed (9% on the right and 7% on the left) or double (7% on the right and 6% on the left); 1% were leaf shaped. All these anatomical variants have to be distinguished from the pathologically enlarged carotid body that may have a smooth or finely nodular surface. Anatomical variants (such as the bilobed) may themselves enlarge as a consequence of carotid body hyperplasia. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 PMID:3209707

  13. Can increased visceral adiposity without body weight changes accelerate carotid atherosclerosis in South Korean participants with type 2 diabetes?

    PubMed

    Kim, Chul Sik; Kim, Soo-Kyung; Araneta, Maria Rosario G; Lee, Eun Jig; Barrett-Connor, Elizabeth; Huh, Kab Bum

    2015-01-01

    Type 2 diabetes mellitus (T2DM) and visceral obesity are associated with each other and with cardiovascular diseases. We determined whether increased visceral adiposity without weight gain was associated with sex-specific accelerated carotid atherosclerosis in South Koreans with T2DM. From 2003 to 2012, we recruited 280 participants with T2DM for the Seoul Metabolic Syndrome cohort who had body weight, visceral fat thickness (VFT), and carotid intima-media thickness (CIMT) measured at intervals of 2years. According to VFT change, sex-specific quartiles of clinical characteristics and changes of CIMT were determined. Logistic regression models predicted the odds of the progression of CIMTs in each quartile. During 2years of observation, VFTs fell by 5.2±13.5mm in men (P<0.001) and 3.4±10.5mm in women (P<0.001). Progression of CIMT was only significant for women's maximal CIMT (0.031±0.145mm, P=0.012), while significant improvements in HbA1c were found (0.9%; P<0.001 in both sexes). There were no significant differences in clinical characteristics, or in progression of CIMT in men or women according to 2-year quartiles of VFT change. Our results do not suggest that increased visceral adiposity without body weight changes impacts the CIMT progression in South Korean men or women with T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. CO(2) and pH independently modulate L-type Ca(2+) current in rabbit carotid body glomus cells.

    PubMed

    Summers, Beth A; Overholt, Jeffrey L; Prabhakar, Nanduri R

    2002-08-01

    affect cAMP levels in rabbit carotid bodies. Further, nisoldipine, but not omega-conotoxin MVIIC, prevented augmentation of the Ca(2+) current by CO(2). In addition, when combined, hypercapnia and hypoxia augmented the Ca(2+) current by 26 +/- 4% (n = 7), which is greater than either stimulus alone, suggesting the effects are additive. Taken together, these results indicate that L-type Ca(2+) current is augmented by hypercapnia. The effect of CO(2) is not secondary to changes in pH and seems to be mediated by a protein kinase A-dependent mechanism. Furthermore, hypercapnia and hypoxia act additively in stimulating Ca(2+) current in glomus cells.

  15. Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

    PubMed Central

    Kumar, Prem; Prabhakar, Nanduri R.

    2014-01-01

    The discovery of the sensory nature of the carotid body dates back to the beginning of the 20th century. Following these seminal discoveries, research into carotid body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus-response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the carotid body responds to a wide variety of blood-borne stimuli, including reduced glucose and immune-related cytokines and we therefore also consider the evidence for a polymodal function of the carotid body and its implications. It is clear that the sensory function of the carotid body exhibits considerable plasticity in response to the chronic perturbations in environmental O2 that is associated with many physiological and pathological conditions. The mechanisms and consequences of carotid body plasticity in health and disease are discussed in the final sections of this article. PMID:23728973

  16. RT-PCR and pharmacological analysis of L-and T-type calcium channels in rat carotid body.

    PubMed

    Cáceres, A I; Gonzalez-Obeso, E; Gonzalez, C; Rocher, A

    2009-01-01

    Mechanisms involved in carotid body (CB) chemoreceptor cells O(2)-sensing and responses are not fully understood. So far, it is known that hypoxia depolarizes chemoreceptor cells via O(2)-sensitive K(+)-channel inhibition; calcium influx via voltage-gated channels and neurotransmitter secretion follow. Presence of high voltage activated (HVA) calcium channels in rat CB chemoreceptor cells is well documented, but the presence of low voltage activated (LVH) or T-type calcium channels has not been reported to date. The fact that O(2)-sensitive PC12 cells express T-type channels and that they are inducible by chronic hypoxia (CH) lead us to hypothesize they could be present and play a role in the genesis of the hypoxic response in rat CB chemoreceptor cells. We have analyzed the expression of the three isoforms of T-type calcium channels (alpha1G, alpha1H and alpha1I) and the isoforms alpha1C and alpha1D of L-type calcium channels in rat CB by RT-PCR. We found that rat CB expresses alpha1G and alpha1C subunits. After chronic hypoxic treatment of adult rats (10 degrees O(2), 8 days), expression of alpha1G seems to be down-regulated whereas alpha1C expression is up-regulated. Functionally, it was found that the release of catecholamine induced by hypoxia and high external K({+}) from CB chemoreceptor cells was fully sensitive to L-type channel inhibition (nisoldipine, 2 microM), while specific inhibition of T-channels (mibefradil, 2 microM) inhibited exclusively hypoxia-induced release (50 degrees ). As a whole, present findings demonstrate the presence of T-type as well as L-type calcium channels in rat CB and suggest a selective participation of the T-type channels in the hypoxic activation of chemoreceptor cells.

  17. Type I cell ROS kinetics under hypoxia in the intact mouse carotid body ex vivo: a FRET-based study.

    PubMed

    Bernardini, A; Brockmeier, U; Metzen, E; Berchner-Pfannschmidt, U; Harde, E; Acker-Palmer, A; Papkovsky, D; Acker, H; Fandrey, J

    2015-01-01

    Reactive oxygen species (ROS) mainly originating from NADPH oxidases have been shown to be involved in the carotid body (CB) oxygen-sensing cascade. For measuring ROS kinetics, type I cells of the mouse CB in an ex vivo preparation were transfected with the ROS sensor construct FRET-HSP33. After 2 days of tissue culture, type I cells expressed FRET-HSP33 as shown by immunohistochemistry. In one population of CBs, 5 min of hypoxia induced a significant and reversible decrease of type I cell ROS levels (n = 9 CBs; P < 0.015), which could be inhibited by 4-(2-aminoethyl)benzensulfonylfluorid (AEBSF), a highly specific inhibitor of the NADPH oxidase subunits p47(phox) and p67(phox). In another population of CBs, however, 5 min of hypoxia induced a significant and reversible increase of ROS levels in type I cells (n = 8 CBs; P < 0.05), which was slightly enhanced by administration of 3 mM AEBSF. These different ROS kinetics seemed to coincide with different mice breeding conditions. Type I cells of both populations showed a typical hypoxia-induced membrane potential (MP) depolarization, which could be inhibited by 3 mM AEBSF. ROS and MP closely followed the hypoxic decrease in CB tissue oxygen as measured with an O2-sensitive dye. We conclude that attenuated p47(phox) subunit activity of the NADPH oxidase under hypoxia is the physiological trigger for type I cell MP depolarization probably due to ROS decrease, whereas the observed ROS increase has no influence on type I cell MP kinetics under hypoxia.

  18. Purinergic signalling mediates bidirectional crosstalk between chemoreceptor type I and glial-like type II cells of the rat carotid body.

    PubMed

    Murali, Sindhubarathi; Nurse, Colin A

    2016-01-15

    Carotid body chemoreceptors are organized in clusters containing receptor type I and contiguous glial-like type II cells. While type I cells depolarize and release ATP during chemostimulation, the role of type II cells which express purinergic P2Y2 receptors (P2Y2Rs) and ATP-permeable pannexin-1 (Panx-1) channels, is unclear. Here, we show that in isolated rat chemoreceptor clusters, type I cell depolarization induced by hypoxia, hypercapnia, or high K(+) caused delayed intracellular Ca(2+) elevations (Δ[Ca(2+)]i) in nearby type II cells that were inhibited by the P2Y2R blocker suramin, or by the nucleoside hydrolase apyrase. Likewise, stimulation of P2Y2Rs on type II cells caused a delayed, secondary Δ[Ca(2+)]i in nearby type I cells that was inhibited by blockers of Panx-1 channels, adenosine A2A receptors and 5'-ectonucleotidase. We propose that reciprocal crosstalk between type I and type II cells contributes to sensory processing in the carotid body via purinergic signalling pathways. The mammalian carotid body (CB) is excited by blood-borne stimuli including hypoxia and acid hypercapnia, leading to respiratory and cardiovascular reflex responses. This chemosensory organ consists of innervated clusters of receptor type I cells, ensheathed by processes of adjacent glial-like type II cells. ATP is a major excitatory neurotransmitter released from type I cells and type II cells express purinergic P2Y2 receptors (P2Y2Rs), the activation of which leads to the opening of ATP-permeable, pannexin-1 (Panx-1) channels. While these properties support crosstalk between type I and type II cells during chemotransduction, direct evidence is lacking. To address this, we first exposed isolated rat chemoreceptor clusters to acute hypoxia, isohydric hypercapnia, or the depolarizing stimulus high K(+), and monitored intracellular [Ca(2+)] using Fura-2. As expected, these stimuli induced intracellular [Ca(2+)] elevations (Δ[Ca(2+)]i) in type I cells. Interestingly, however

  19. G proteins in carotid body chemoreception.

    PubMed

    Prabhakar, N R; Kou, Y R; Kumar, G K

    1995-01-01

    G proteins are signal coupling molecules that play major roles in mediating the effects of transmitters as well as certain sensory signals. In the present study we examined whether oxygen chemoreception in the carotid body is coupled to G proteins. Experiments were performed on carotid bodies isolated from anesthetized cats. Presence of G proteins was examined with ADP-ribosylation of the carotid body membranes. Pertussis toxin (PTX), which inactivates G proteins in neuronal tissues, ADP-ribosylated a single band of carotid body protein with a molecular mass of 41 kDa. With cholera toxin (CTX) only a faint band of protein corresponding to approximately 45 kDa was evident. Perfusing the isolated carotid bodies with PTX (2.5 micrograms/min; 60 min) attenuated the sensory response to hypoxia by 52% of the controls. Perfusion with CTX (50 micrograms/min; for 60 min), on the other hand, increased baseline activity and potentiated the hypoxic response by 125% of controls. Heat-inactivated toxins, however, had no influence on the carotid body sensory response to hypoxia. These results suggest that G proteins are present in the chemoreceptor tissue and they seem to be coupled to the transduction and/or to the transmission of the hypoxic stimulus.

  20. A case of carotid body tumor concomitant with carcinoid tumor.

    PubMed

    Mun, Mi Jin; Lee, Jin Choon; Lee, Byung Joo

    2015-02-01

    Neuroendocrine tumors typically fall into two broad categories: those of epithelial origin and those of neural derivation. The former group includes carcinoid tumors and the latter includes paraganglioma. Although paraganglioma and carcinoid tumor have different biologic behaviors, their overlapping histological appearance can pose diagnostic challenges. Carcinoid tumors are rare, slow-growing neuroendocrine tumors arising from the enterochromaffin cells disseminated throughout the gastrointestinal and bronchopulmonary systems. Carotid body tumor is the most common type of extra-adrenal paraganglioma. Paraganglioma tends to grow slowly but can compress adjacent vessel and nerve. A 63-year-old woman showed huge mass extending from carotid body to skull base, encircling internal and external carotid arteries on magnetic resonance image. Surgical removal of carotid body tumor was done after embolization procedure. Postoperative histopathologic examination and immunohistochemical analysis were consistent with paraganglioma concomitant with carcinoid tumor in carotid body. Primary cervical carcinoid tumor is extremely rare, and to the best of our knowledge, this is the first case of concomitant existence of paraganglioma and carcinoid tumor in carotid body.

  1. Relative mitochondrial membrane potential and [Ca2+]i in type I cells isolated from the rabbit carotid body.

    PubMed Central

    Duchen, M R; Biscoe, T J

    1992-01-01

    1. In the accompanying paper (Duchen & Biscoe, 1992) we have described graded changes in autofluorescence derived from mitochondrial NAD(P)H in type I cells of the carotid body in response to changes of PO2 over a physiologically significant range. These observations suggest that mitochondrial function in these cells is unusually sensitive to oxygen and could play a role in oxygen sensing. We have now explored further the relationships between hypoxia, mitochondrial membrane potential (delta psi m) and [Ca2+]i. 2. The fluorescence of Rhodamine 123 (Rh 123) accumulated within mitochondria is quenched by delta psi m. Mitochondrial depolarization thus increases the fluorescence signal. Blockade of electron transport (CN-, anoxia, rotenone) and uncoupling agents (e.g. carbonyl cyanide p-trifluoromethoxy-phenylhydrazone; FCCP) increased fluorescence by up to 80-120%, while fluorescence was reduced by blockade of the F0 proton channel of the mitochondrial ATP synthase complex (oligomycin). 3. delta psi m depolarized rapidly with anoxia, and was usually completely dissipated within 1-2 min. The depolarization of delta psi m with anoxia (or CN-) and repolarization on reoxygenation both followed a time course well characterized as the sum of two exponential processes. Oligomycin (0.2-2 micrograms/ml) hyperpolarized delta psi m and abolished the slower components of both the depolarization with anoxia and of the subsequent repolarization. These data (i) illustrate the role of the F1-F0 ATP synthetase in slowing the rate of dissipation of delta psi m on cessation of electron transport, (ii) confirm blockade of the ATP synthetase by oligomycin at these concentrations, and (iii) indicate significant accumulation of intramitochondrial ADP during 1-2 min of anoxia. 4. Depolarization of delta psi m was graded with graded changes in PO2 below about 60 mmHg. The stimulus-response curves thus constructed strongly resemble those for [Ca2+]i and NAD(P)H with PO2. The change in delta

  2. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia

    PubMed Central

    Makarenko, Vladislav V.; Ahmmed, Gias U.; Peng, Ying-Jie; Khan, Shakil A.; Nanduri, Jayasri; Kumar, Ganesh K.; Fox, Aaron P.

    2015-01-01

    Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca2+]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca2+]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca2+]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca2+ channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca2+]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca2+ currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca2+ influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane. PMID:26561606

  3. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia.

    PubMed

    Makarenko, Vladislav V; Ahmmed, Gias U; Peng, Ying-Jie; Khan, Shakil A; Nanduri, Jayasri; Kumar, Ganesh K; Fox, Aaron P; Prabhakar, Nanduri R

    2016-01-01

    Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca(2+)]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca(2+)]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca(2+)]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca(2+) channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca(2+)]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca(2+) currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca(2+) influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane. Copyright © 2016 the American Physiological Society.

  4. Intracellular pH and its regulation in isolated type I carotid body cells of the neonatal rat.

    PubMed Central

    Buckler, K J; Vaughan-Jones, R D; Peers, C; Nye, P C

    1991-01-01

    1. The dual-emission pH-sensitive fluoroprobe carboxy-SNARF-1 (carboxy-seminaptharhodofluor) was used to measure pHi in type I cells enzymically dispersed from the neonatal rat carotid body. 2. Steady-state pHi in cells bathed in a HEPES-buffered Tyrode solution (pH 7.4) was found to be remarkably alkaline (pHi = 7.77) whereas cells bathed in a CO2-HCO3(-)-buffered Tyrode solution (pH 7.4) had a more 'normal' pHi (pHi = 7.28). These observations were further substantiated by using an independent nullpoint test method to determine pHi. 3. Intracellular intrinsic buffering (beta, determined by acidifying the cell using an NH4Cl pre-pulse) was in the range 7-20 mM per pH unit and appeared to be dependent upon pHi with beta increasing as pHi decreased. 4. In cells bathed in a HEPES-buffered Tyrode solution, pHi recovery from an induced intracellular acid load (10 mM-NH4Cl pre-pulse) was inhibited by the Na(+)-H+ exchange inhibitor ethyl isopropyl amiloride (EIPA; 150 microM) or substitution of Nao+ with N-methyl-D-glucamine (NMG). Both EIPA and Nao+ removal also caused a rapid intracellular acidification, which in the case of Nao+ removal, was readily reversible. The rate of this acidification was similar for both Nao+ removal and EIPA addition. 5. Transferring cells from a HEPES-buffered Tyrode solution to one buffered with 5% CO2-HCO3- resulted in an intracellular acidification which was partially, or wholly, sustained. The rate of acidification upon transfer to CO2-HCO3- was considerably slowed by the membrane permeant carbonic anhydrase inhibitor, acetazolamide, thus indicating the presence of the enzyme in these cells. 6. In CO2-HCO3(-)-buffered Tyrode solution, pHi recovery from an intracellular acidosis (NH4+ pre-pulse) was only partially inhibited by EIPA or amiloride whereas Nao+ removal completely inhibited the recovery. The stilbene DIDS (4,4-diisothiocyanatostilbenedisulphonic acid, 200 microM) also partially inhibited pHi recovery following an induced

  5. Anesthetic approaches in carotid body tumor surgery

    PubMed Central

    Kavakli, Ali Sait; Ozturk, Nilgun Kavrut

    2016-01-01

    OBJECTIVE: Carotid body tumors (CBT) are benign tumors that originate from neural non-chromaffin cells that are typically localized near carotid bifurcation. Surgical removal of the tumor is the most appropriate treatment. General anesthesia is preferred anesthetic technique for CBT surgery. Basic elements of anesthetic management are protection of hemodynamic stability and maintaining cerebral perfusion pressure (CPP). The aim of this study was to evaluate anesthetic management of CBT surgery and present the literature knowledge. METHODS: The study included 10 consecutive patients with diagnosis of CBT who underwent surgery at Antalya Training and Research Hospital, in Antalya, Turkey, between 2013 and 2016. Preoperative demographic details; comorbidities; side of surgical site; duration of operation; length of intensive care unit (ICU) and hospital stay; change of intraoperative blood pressure; use of inotropic drugs, blood products, and analgesics; postoperative visual analogue scale (VAS) pain score; and complications were recorded. RESULTS: According to Shamblin classification, 3 tumors were type I and the remaining 7 were type II. Tumors were located on right side in 6 patients, and on left in 4. Blood loss sufficient to require transfusion was observed in 1 patient. Average intraoperative blood loss was 287±68 mL. Tachycardia and hypertension were observed in 1 patient; bradycardia and hypotension were seen in 4 patients. Infusion for inotropic support was administered to 1 patient. Mean duration of operation was 109±20 minutes. Mean VAS score was 4±1, mean ICU tramadol consumption was 80±25 mg. Duration of stay in ICU and hospital were 2.4±1.1 hours and 3.8±0.7 days, respectively. Mortality and neurological complications were not seen in postoperative period. CONCLUSION: CBT surgery requires close and complex anesthesia management. Protection of hemodynamic stability against sudden hemodynamic changes, monitoring, and maintaining CPP are the most

  6. Neurovascular complications following carotid body paraganglioma resection.

    PubMed

    Lamblin, E; Atallah, I; Reyt, E; Schmerber, S; Magne, J-L; Righini, C A

    2016-11-01

    The present consecutive case series reports our experience in the management of carotid body paraganglioma and aims to assess whether the Shamblin classification or tumor size are predictive of early and late postoperative neurovascular complications. A retrospective study included 54 carotid body tumor resections in 49 patients, between 1980 and 2011. Data comprised early (<1month) and late (18 months) postoperative neurovascular complications. Early postoperative complications occurred in 31 cases, including 30 cases of cranial nerve deficit (56%). Cranial nerve deficit occurred in 83% of Shamblin III carotid body paragangliomas and was associated with significantly larger mean tumor size (4±1.4cm versus 2.9±1.3cm; P<0.01). Shamblin III tumor and tumor size>3.2cm emerged as predictive factors for early postoperative peripheral neurological complications. Eight patients (17%) showed no cranial nerve deficit recovery, even after 18 months' follow-up; no predictive factors could be identified for this. Surgical resection remains the only curative treatment in carotid body paraganglioma, with low vascular morbidity. However, early postoperative nerve deficit remains frequent (56%), although mostly temporary, with 17% definitive sequelae at 18 months. Tumor size and Shamblin classification are predictive of early neurovascular complications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Association between adjunctive metformin therapy in young type 1 diabetes patients with excess body fat and reduction of carotid intima-media thickness.

    PubMed

    Burchardt, Paweł; Zawada, Agnieszka; Kaczmarek, Jolanta; Marcinkaniec, Justyna; Wysocki, Henryk; Wierusz-Wysocka, Bogna; Grzymisławski, Marian; Rzeźniczak, Janusz; Zozulińska-Ziółkiewicz, Dorota; Naskręt, Dariusz

    2016-08-25

    INTRODUCTION    Lipoprotein-associated phospholipase A2 (Lp-PLA2) and cholesteryl ester lipase (CEL) may oxidize low-density lipoproteins (oxLDL). OBJECTIVES    The aim of the study was to determine the influence of metformin on the metabolism of atherogenic lipid fractions in relation to Lp-PLA2 and CEL levels, as well as assess consequent improvement in the intima-media thickness (IMT) of the common carotid artery in young type 1 diabetes patients with excess body fat. PATIENTS AND METHODS    It was an open-label randomized clinical trial that lasted 6 months. It included a total of 84 people with metabolic decompensation (glycated hemoglobin >7.5%, >58.5 mmol/mol) of diabetes. Adjunctive metformin therapy (in addition to insulin) was administered in 42 patients, and the remaining 42 patients received insulin alone. Glycated low-density lipoproteins (LDLs), oxLDL, Lp-PLA2, and CEL were assessed by commercially available enzyme-linked immunosorbent assay kits. Cartoid IMT was measured using the Carotid Analyser for Research tool. Biochemical analyses were performed using routine laboratory techniques. RESULTS    The reduction of mean carotid IMT was observed in young type 1 diabetic adults treated additionally with metformin (0.6 ±0.1 cm vs 0.53 ±0.1 cm; P = 0.002). This effect was probably due to weight reduction (90 ±16 kg vs 87 ±15 kg, P = 0.054) and the decrease in atherogenic glycated LDL levels (1.5 ±0.5 mg/dl vs 1.6 ±1.046 mg/dl, P = 0.006). No such correlations were observed in patients treated with insulin alone. Additionally, in patients receiving metformin, glycated LDL levels were inversely correlated with Lp-PLA2 levels (r = -0.31, P <0.05). CONCLUSIONS    Additional use of metformin in young type 1 diabetic patients with excess body fat leads to a significant reduction of mean IMT in the common carotid artery. Concentrations of CEL and Lp-PLA2 were significantly increased in both study arms despite improved glucose metabolism.

  8. Inhibition of adenylate cyclase attenuates muscarinic Ca²(+) signaling by a PKA-independent mechanism in rat carotid body Type I cells.

    PubMed

    Thompson, Carrie M; Wyatt, Christopher N

    2011-01-31

    Carotid body (CB) Type I cells respond to hypoxia by releasing excitatory and inhibitory neurotransmitters. This mechanism leads to increased firing of the carotid sinus nerve (CSN) which alters breathing to maintain blood gases within the physiological range. Acetylcholine targets both muscarinic and nicotinic receptors in the rat CB, acting postsynaptically on CSN and presynaptically on Type I cells. Muscarinic Ca²(+) signaling is inhibited by the activation of G(i)-coupled receptors including histamine H3 receptors. Here inhibition of adenylate cyclase with SQ22536 mimicked H3 receptor activation. Using Ca²(+) imaging techniques it was observed that inhibition of muscarinic Ca²(+) signaling was independent of protein kinase A (PKA) as PKA inhibitors H89 and KT5720 were without effect on the muscarinic Ca²(+) response. By contrast the Epac (exchange protein activated by cAMP) inhibitor brefeldin A inhibited muscarinic Ca²(+) signaling whereas the Epac activator 8-pCPT-2'-O-Me-cAMP-AM potentiated Ca²(+) signaling. Thus in Type I cells inhibition of adenylate cyclase inhibited muscarinic Ca²(+) signaling via a PKA-independent pathway that may rely upon modulation of Epac.

  9. The human carotid body releases acetylcholine, ATP and cytokines during hypoxia.

    PubMed

    Kåhlin, Jessica; Mkrtchian, Souren; Ebberyd, Anette; Hammarstedt-Nordenvall, Lalle; Nordlander, Britt; Yoshitake, Takashi; Kehr, Jan; Prabhakar, Nanduri; Poellinger, Lorenz; Fagerlund, Malin Jonsson; Eriksson, Lars I

    2014-08-01

    Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)-1β, IL-4, IL-6, IL-8 and IL-10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia-inducible factor-1α and hypoxia-inducible factor-2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information suggesting that the carotid body may play a role in detecting inflammation, providing a link between the immune system and the nervous system.

  10. Carotid body tumours. A 20-year single-institution experience.

    PubMed

    Dalainas, Ilias; Nano, Giovanni; Casana, Renato; Bianchi, Paolo; Stegher, Silvia; Malacrida, Giovanni; Tealdi, Domenico Giuseppe

    2006-01-01

    The aim of this single-institution retrospective study was to review the surgical outcomes of resection of carotid body tumours over the last 20 years in our hospital. From January 1985 to December 2004, 17 patients were admitted to our institution with carotid body tumours. All patients were treated by surgical resection of the tumour. No perioperative deaths occurred. Perioperative comorbidities were more frequent in patients with large carotid body tumours intimately associated with the carotid vessels. Surgical excision of carotid body tumours is safe and effective even in the long term.

  11. Preoperative imaging diagnosis of carotid body tumors.

    PubMed

    Pacheco-Ojeda, Luis A; Martínez-Viteri, Miguel A

    2010-01-01

    Carotid body tumors (CBTs) are relatively frequent lesions encountered at high altitudes, such in as the Andean Mountains. A correct preoperative diagnosis is essential for surgical planning and performance. For this reason, we have reviewed the evolution of our experience in the imaging diagnosis of these tumors. Between 1980 and June 2008, 160 CBTs were diagnosed. A total of 138 tumors were operated on, 4 are waiting for surgery, and 18 were not operated on because of age, medical conditions, or patient refusal. We have reviewed retrospectively the modalities of imaging diagnosis in our patients who underwent operation. Among the 138 tumors operated on, a correct preoperative diagnosis was done in 127 cases (92%). The preoperative diagnosis of the remaining 11 patients was unspecified benign tumor for 6 patients and neck lymph node for 5 patients. The imaging methods performed by different radiologists were conventional ultrasound, color Doppler ultrasound, carotid conventional angiography (CA), axial tomography, magnetic resonance and magnetic resonance angiography, and computed tomographic angiography (CTA). Most patients had more than one image study. Review of radiologist reports revealed a correct diagnosis in all carotid CA, magnetic resonance studies, and CTA. Additionally, CTA appeared to be a valuable method to predict the Shamblin group. Clinical suspicion and current image techniques permit a correct diagnosis in practically all cases of CBT.

  12. Protein phosphorylation signaling mechanisms in carotid body chemoreception.

    PubMed

    Wang, Z Z; He, L; Chen, J; Dinger, B; Stensaas, L; Fidone, S

    1999-01-01

    Chemotransduction in the carotid body occurs in specialized type I cells and likely involves a complex series of regulated events which culminates in the release of neurotransmitter agents and the excitation of afferent nerve fibers. Previous studies have shown that multiple factors, including the levels of calcium and cyclic nucleotide second messengers, are important regulators of the chemoreceptor transduction cascade in type I cells. In addition, increases in electrical excitability induced in type I cells by chronic exposure to hypoxia are mimicked by agents which elevate intracellular cyclic AMP levels [Stea et al., J Neurosci 1995;15:2192-2202]. These and other findings suggest that protein kinases, and the phosphorylation of specific protein targets are important components of the hypoxic transduction machinery. Moreover, protein kinase-mediated cascades may participate in the well-known physiological adjustments which occur in the carotid body during prolonged stimulation. In the current study, our data demonstrate (1) the presence of specific protein kinases and target phosphoproteins in the carotid body, and also in the morphologically similar small intensely fluorescent cells of the superior cervical sympathetic ganglia. (2) Nitric oxide production and efferent inhibition in the chemosensory tissue is reduced in the presence of the specific tyrosine kinase inhibitor, lavendustin A. (3) Hypoxia-induced catecholamine release from type I cells is inhibited by the protein kinase A antagonist, Rp-cAMPs. And finally (4), exposure to chronic hypoxia up-regulates the expression of the tyrosine kinase, fyn, and an important growth regulatory phosphoprotein, growth associated protein-43 (GAP-43). These findings suggest that second messenger-mediated phosphorylation and dephosphorylation of specific protein targets is a mechanism capable of regulating diverse cellular functions in the carotid body during acute and chronic stimulation.

  13. Carbon monoxide: a role in carotid body chemoreception.

    PubMed

    Prabhakar, N R; Dinerman, J L; Agani, F H; Snyder, S H

    1995-03-14

    Carbon monoxide (CO), produced endogenously by heme oxygenase, has been implicated as a neuronal messenger. Carotid bodies are sensory organs that regulate ventilation by responding to alterations of blood oxygen, CO2, and pH. Changes in blood gases are sensed by glomus cells in the carotid body that synapse on afferent terminals of the carotid sinus nerve that projects to respiratory-related neurons in the brainstem. Using immunocytochemistry, we demonstrate that heme oxygenase 2 is localized to glomus cells in the cat and rat carotid bodies. Physiological studies show that zinc protoporphyrin IX, a potent heme oxygenase inhibitor, markedly increases carotid body sensory activity, while copper protoporphyrin IX, which does not inhibit the enzyme, is inactive. Exogenous CO reverses the stimulatory effects of zinc protoporphyrin IX. These results suggest that glomus cells are capable of synthesizing CO and endogenous CO appears to be a physiologic regulator of carotid body sensory activity.

  14. Pathogenic Roles of the Carotid Body Inflammation in Sleep Apnea

    PubMed Central

    2014-01-01

    Breathing difficulties in sleep are a hallmark of sleep-disordered breathing commonly observed in patients with sleep disorders. The pathophysiology of sleep apnea is in part due to an augmented activity of the carotid body chemoreflex. Arterial chemoreceptors in the carotid body are sensitive to inflammatory cytokines and immunogenic molecules in the circulation, because cytokine receptors are expressed in the carotid body in experimental animals and human. Intriguingly, proinflammatory cytokines are also locally produced and released in the carotid body. Also, there are significant increases in the expression of proinflammatory cytokines, cytokine receptors, and inflammatory mediators in the carotid body under hypoxic conditions, suggesting an inflammatory response of the carotid body. These upregulated cytokine signaling pathways could enhance the carotid chemoreceptor activity, leading to an overactivity of the chemoreflex adversely effecting breathing instability and autonomic imbalance. This review aims to summarize findings of the literature relevant to inflammation in the carotid body, with highlights on the pathophysiological impact in sleep apnea. It is concluded that local inflammation in the carotid body plays a pathogenic role in sleep apnea, which could potentially be a therapeutic target for the treatment of the pathophysiological consequence of sleep apnea. PMID:25276055

  15. Current surgical management of carotid body tumors.

    PubMed

    Davila, Victor J; Chang, James M; Stone, William M; Fowl, Richard J; Bower, Thomas C; Hinni, Michael L; Money, Samuel R

    2016-12-01

    Carotid body tumors (CBTs) are rare. Management guidelines may include genetic testing for succinate dehydrogenase (SDH) mutations. We performed an institutional review of the surgical management of CBT. A retrospective analysis (1994-2015) of CBT excisions at our institution was performed. Data obtained included demographics, genetic testing (if performed), intraoperative details, postoperative morbidity, and long-term outcomes. Data from the first CBT excision were included in patients with bilateral tumors. Genetic testing was routinely offered in patients with a family history of CBT or multiple paragangliomas. A total of 183 CBTs (124 female [67.7%]) were excised. A neck mass was present in 106 patients (57.9%), 24 patients (12.1%) presented with tenderness or neck pain, and 3 (1.6%) presented with cranial nerve dysfunction. Computed tomography (57.9%) or magnetic resonance imaging (51.3%) were the most commonly used imaging modalities. Preoperative angiography was performed in 73 patients (39.8%), and 62 of them (84.5%) underwent embolization or internal carotid balloon occlusion testing, or both. Mean tumor diameter was 3.2 cm (range, 0.6-7.2 cm). There were 71 (38.8%), 75 (41%), and 37 (20.2%) Shamblin type 1, 2, and 3 tumors, respectively. Average operating time was 224 minutes (range, 52-696 minutes). Average blood loss was 143.9 mL (range, 10-2000 mL). Arterial reconstruction with an interposition graft was required in 10, and patch angioplasty was performed in four. Cranial nerve injury was permanent in 10 (5.5%), and the rate of stroke was 1% (n = 2). A total of 382 lymph nodes were excised, and all were benign. There were no deaths ≤30 days. Only one patient presented with malignant disease 2 years after CBT excision, and this patient did not undergo genetic testing. Thirty-four (18.6%) had a family history of CBT. SDH testing was performed in 18 patients, and 17 tested positive. Positive genetic testing had a correlation with earlier age

  16. P2Y2 receptor activation opens pannexin-1 channels in rat carotid body type II cells: potential role in amplifying the neurotransmitter ATP.

    PubMed

    Zhang, Min; Piskuric, Nikol A; Vollmer, Cathy; Nurse, Colin A

    2012-09-01

    Signal processing in the carotid body (CB) is initiated at receptor glomus (or type I) cells which depolarize and release the excitatory neurotransmitter ATP during chemoexcitation by hypoxia and acid hypercapnia. Glomus cell clusters (GCs) occur in intimate association with glia-like type II cells which express purinergic P2Y2 receptors (P2Y2Rs) but their function is unclear. Here we immunolocalize the gap junction-like protein channel pannexin-1 (Panx-1) in type II cells and show Panx-1 mRNA expression in the rat CB. As expected, type II cell activation within or near isolated GCs by P2Y2R agonists, ATP and UTP (100 μm), induced a rise in intracellular [Ca(2+)]. Moreover in perforated-patch whole cell recordings from type II cells, these agonists caused a prolonged depolarization and a concentration-dependent, delayed opening of non-selective ion channels that was prevented by Panx-1 blockers, carbenoxolone (5 μm) and 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS; 10 μm). Because Panx-1 channels serve as conduits for ATP release, we hypothesized that paracrine, type II cell P2Y2R activation leads to ATP-induced ATP release. In proof-of-principle experiments we used co-cultured chemoafferent petrosal neurones (PNs), which express P2X2/3 purinoceptors, as sensitive biosensors of ATP released from type II cells. In several cases, UTP activation of type II cells within or near GCs led to depolarization or increased firing in nearby PNs, and the effect was reversibly abolished by the selective P2X2/3 receptor blocker, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 μm). We propose that CB type II cells may function as ATP amplifiers during chemotransduction via paracrine activation of P2Y2Rs and Panx-1 channels.

  17. Oxygen and mitochondrial inhibitors modulate both monomeric and heteromeric TASK-1 and TASK-3 channels in mouse carotid body type-1 cells

    PubMed Central

    Turner, Philip J; Buckler, Keith J

    2013-01-01

    In rat arterial chemoreceptors, background potassium channels play an important role in maintaining resting membrane potential and promoting depolarization and excitation in response to hypoxia or acidosis. It has been suggested that these channels are a heterodimer of TASK-1 and TASK-3 based on their similarity to heterologously expressed TASK-1/3 fusion proteins. In this study, we sought to confirm the identity of these channels through germline ablation of Task-1 (Kcnk3) and Task-3 (Kcnk9) in mice. Background K-channels were abundant in carotid body type-1 cells from wild-type mice and comparable to those previously described in rat type-1 cells with a main conductance state of 33 pS. This channel was absent from both Task-1−/− and Task-3−/− cells. In its place we observed a larger (38 pS) K+-channel in Task-1−/− cells and a smaller (18 pS) K+-channel in Task-3−/− cells. None of these channels were observed in Task-1−/−/Task-3−/− double knock-out mice. We therefore conclude that the predominant background K-channel in wild-type mice is a TASK-1/TASK-3 heterodimer, whereas that in Task-1−/− mice is TASK-3 and, conversely, that in Task-3−/− mice is TASK-1. All three forms of TASK channel in type-1 cells were inhibited by hypoxia, cyanide and the uncoupler FCCP, but the greatest sensitivity was seen in TASK-1 and TASK-1/TASK-3 channels. In summary, the background K-channel in type-1 cells is predominantly a TASK-1/TASK-3 heterodimer. Although both TASK-1 and TASK-3 are able to couple to the oxygen and metabolism sensing pathways present in type-1 cells, channels containing TASK-1 appear to be more sensitive. PMID:24042502

  18. The CamKKβ Inhibitor STO609 Causes Artefacts in Calcium Imaging and Selectively Inhibits BKCa in Mouse Carotid Body Type I Cells.

    PubMed

    Jurcsisn, Jennifer G; Pye, Richard L; Ali, Jon; Barr, Barbara L; Wyatt, Christopher N

    2015-01-01

    It has previously been reported that AMP-activated protein kinase (AMPK) may be critical for hypoxic chemotransduction in carotid body type I cells. This study sought to determine the importance of the regulatory upstream kinase of AMPK, CamKKβ, in the acute response to hypoxia in isolated mouse type I cells.Initial data indicated several previously unreported artefacts associated with using the CamKKβ inhibitor STO609 and Ca(2+) imaging techniques. Most importantly Fura-2 and X-Rhod1 imaging revealed that STO609 quenched emission fluorescence even in the absence of intracellular Ca(2+) ([Ca(2+)](I)). Furthermore, STO609 (100 μM) rapidly inhibited outward macroscopic currents and this inhibition was abolished in the presence of the selective BK(Ca) inhibitor paxilline.Taken together these data suggest that ST0609 should be used with caution during Ca(2+) imaging studies as it can directly interact with Ca(2+) binding dyes. The rapid inhibitory effect of STO609 on BK(Ca) was unexpected as the majority of studies using this compound required an incubation of approximately 10 min to inhibit the kinase. Furthermore, as AMPK activation inhibits BK(Ca), inhibiting AMPK's upstream kinases would, if anything, be predicted to have the opposite effect on BK(Ca). Future work will determine if the inhibition of BK(Ca) is via CamKKβ or via an off target action of STO609 on the channel itself.

  19. Evidence that 5-HT stimulates intracellular Ca(2+) signalling and activates pannexin-1 currents in type II cells of the rat carotid body.

    PubMed

    Murali, Sindhubarathi; Zhang, Min; Nurse, Colin A

    2017-07-01

    5-HT is a neuromodulator released from carotid body (CB) chemoreceptor (type I) cells and facilitates the sensory discharge following chronic intermittent hypoxia (CIH). In the present study, we show that, in addition to type I cells, adjacent glial-like type II cells express functional, ketanserin-sensitive 5-HT2 receptors, and their stimulation increases cytoplasmic Ca(2+) derived from intracellular stores. In type II cells, 5-HT activated a ketanserin-sensitive inward current (I5-HT ) that was similar to that (IUTP ) activated by the P2Y2R agonist, UTP. As previously shown for IUTP , I5-HT was inhibited by BAPTA-AM and carbenoxolone (5 μm), a putative blocker of ATP-permeable pannexin (Panx)-1 channels; IUTP was reversibly inhibited by the specific Panx-1 mimetic peptide channel blocker, (10) Panx peptide. Paracrine stimulation of type II cells by 5-HT, leading to ATP release via Panx-1 channels, may contribute to CB excitability, especially in pathophysiological conditions associated with CIH (e.g. obstructive sleep apnoea). Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5-HT and increased autocrine-paracrine 5-HT2 receptor signalling contributes to sensory long-term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial-like type II cells can respond to CB paracrine signals by elevating intracellular calcium (Δ[Ca(2+) ]i ) and activating carbenoxolone-sensitive, ATP-permeable, pannexin (Panx)-1-like channels. In the present study, using dissociated rat CB cultures, we found that 5-HT induced Δ[Ca(2+) ]i responses in a subpopulation of type I cells, as well as in most (∼67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP. The 5-HT-induced Ca(2+) response in type II cells was dose-dependent (EC50 ∼183 nm) and largely inhibited by the 5-HT2A receptor blocker, ketanserin (1 μm), and also arose mainly from intracellular stores. 5-HT also

  20. Selective Expression of Galanin in Neuronal-Like Cells of the Human Carotid Body.

    PubMed

    Di Giulio, Camillo; Marconi, Guya Diletta; Zara, Susi; Di Tano, Andrea; Porzionato, Andrea; Pokorski, Mieczyslaw; Cataldi, Amelia; Mazzatenta, Andrea

    2015-01-01

    The carotid body is a neural-crest-derived organ devoted to respiratory homeostasis through sensing changes in blood oxygen levels. The sensory units are the glomeruli composed of clusters of neuronal-like (type I) cells surrounded by glial-like (type II) cells. During chronic hypoxia, the carotid body shows growth, with increasing neuronal-like cell numbers. We are interested in the signals involved in the mechanisms that underlie such response, because they are not well understood and described. Considering that, in literature, galanin is involved in neurotrophic or neuroprotective role in cell proliferation and is expressed in animal carotid body, we investigated its expression in human. Here, we have shown the expression and localisation of galanin in the human carotid body.

  1. P2Y2 receptor activation opens pannexin-1 channels in rat carotid body type II cells: potential role in amplifying the neurotransmitter ATP

    PubMed Central

    Zhang, Min; Piskuric, Nikol A; Vollmer, Cathy; Nurse, Colin A

    2012-01-01

    Signal processing in the carotid body (CB) is initiated at receptor glomus (or type I) cells which depolarize and release the excitatory neurotransmitter ATP during chemoexcitation by hypoxia and acid hypercapnia. Glomus cell clusters (GCs) occur in intimate association with glia-like type II cells which express purinergic P2Y2 receptors (P2Y2Rs) but their function is unclear. Here we immunolocalize the gap junction-like protein channel pannexin-1 (Panx-1) in type II cells and show Panx-1 mRNA expression in the rat CB. As expected, type II cell activation within or near isolated GCs by P2Y2R agonists, ATP and UTP (100 μm), induced a rise in intracellular [Ca2+]. Moreover in perforated-patch whole cell recordings from type II cells, these agonists caused a prolonged depolarization and a concentration-dependent, delayed opening of non-selective ion channels that was prevented by Panx-1 blockers, carbenoxolone (5 μm) and 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS; 10 μm). Because Panx-1 channels serve as conduits for ATP release, we hypothesized that paracrine, type II cell P2Y2R activation leads to ATP-induced ATP release. In proof-of-principle experiments we used co-cultured chemoafferent petrosal neurones (PNs), which express P2X2/3 purinoceptors, as sensitive biosensors of ATP released from type II cells. In several cases, UTP activation of type II cells within or near GCs led to depolarization or increased firing in nearby PNs, and the effect was reversibly abolished by the selective P2X2/3 receptor blocker, pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 10 μm). We propose that CB type II cells may function as ATP amplifiers during chemotransduction via paracrine activation of P2Y2Rs and Panx-1 channels. PMID:22733659

  2. Effect of acute and chronic cobalt administration on carotid body chemoreceptors responses.

    PubMed

    Morelli, L; Di Giulio, C; Iezzi, M; Data, P G

    1994-06-30

    Chronic cobalt exposure leads to release and production of erythropoietin and consequently to polycythemia. Accordingly, cellular elements sensitive to oxygen in the carotid body, would manifest responses during acute and chronic cobalt administration. The carotid body, detects gas changes (PO2, PCO2/pH) in the arterial blood and regulates ventilation and circulation by the afferent nerve discharge. We hypothesized that cobalt interacts with an oxygen sensitive mechanism in the carotid chemoreception and in erythropoietin producing cells. Twelve cats were anesthetized, paralysed and artificially ventilated; few fiber preparation of carotid sinus nerve were recorded during close intraarterial injection of cobalt. In another protocol, 12 rats received an intraperitoneal dose of CoCl2 (10 mg/kg) daily for 6 weeks. At the end, the carotid body was fixed in situ by superfusion. Ultrastructural and morphometric studies were made. Acute administration (0.08-2.3 mumol) promptly stimulated the chemoreceptor afferents. Type I cells increased significantly along with erythropoiesis in the chronic cobalt treated rats. The stimulatory effects of cobalt on the carotid body chemoreceptor showed that sensitive mechanisms in the kidney and in the carotid body are similar, and cobalt interacts with the physiological responses of oxygen.

  3. Neurotransmission in the carotid body: transmitters and modulators between glomus cells and petrosal ganglion nerve terminals.

    PubMed

    Iturriaga, Rodrigo; Alcayaga, Julio

    2004-12-01

    The carotid body (CB) is the main arterial chemoreceptor. The most accepted model of arterial chemoreception postulates that carotid body glomus (type I) cells are the primary receptors, which are synaptically connected to the nerve terminals of petrosal ganglion (PG) neurons. In response to natural stimuli, glomus cells are expected to release one (or more) transmitter(s) which, acting on the peripheral nerve terminals of processes from chemosensory petrosal neurons, increases the sensory discharge. Among several molecules present in glomus cells, acetylcholine and adenosine nucleotides and dopamine are considered as excitatory transmitter candidates. In this review, we will examine recent evidence supporting the notion that acetylcholine and adenosine 5'-triphosphate are the main excitatory transmitters in the cat and rat carotid bodies. On the other hand, dopamine may act as a modulator of the chemoreception process in the cat, but as an excitatory transmitter in the rabbit carotid body.

  4. Chronic hyperoxic effects on cat carotid body catecholamines and structure.

    PubMed

    Mokashi, A; Di Guilio, C; Morelli, L; Lahiri, S

    1994-06-01

    To account for the loss of O2 chemoreception in the cat carotid body during chronic hyperoxia, we studied the putative neurotransmitter correlates. Also, we studied the structural aspect of the carotid body tissues. We found that catecholamine concentrations increased and that the densecored vesicles in the glomus cells were not depleted, indicating that a lack of transmitters was not the cause for the loss of O2 chemoreception.

  5. Cat carotid body chemoreceptor responses before and after nicotine receptor blockade with alpha-bungarotoxin.

    PubMed

    Mulligan, E; Lahiri, S

    1987-01-01

    The nature of nicotine receptors in the carotid body was studied in anesthetized, paralyzed and artificially ventilated cats. Chemoreceptor discharge in single or few-fiber preparations of the carotid sinus nerve was measured during isocapnic hypoxia, hyperoxic hypercapnia and in response to nicotine injections before and after administration of alpha-bungarotoxin (10 cats) and after alpha-bungarotoxin plus mecamylamine (7 cats) which binds to neuromuscular-type nicotine cholinergic receptors. alpha-Bungarotoxin caused a slight enhancement of the chemoreceptor response to hypoxia without affecting the chemoreceptor stimulation by nicotine. Mecamylamine (1-5 mg, i.v.), a ganglionic-type nicotinic receptor blocker, had no further effect on the response to hypoxia while it completely abolished the chemoreceptor stimulation by nicotine. Thus the nicotinic receptors in the cat carotid body which elicit excitation of chemosensory fibers appear to be of the ganglionic-type. Blockade of neuromuscular and ganglionic types of nicotinic receptors in the carotid body by alpha-bungarotoxin and mecamylamine does not attenuate the chemosensory responses to either hypoxia or hypercapnia. These nicotinic receptors therefore, do not appear to play an essential role in hypoxic or hypercapnic chemoreception in the cat carotid body.

  6. Ultrastructure of the carotid body of the goat.

    PubMed

    Abdel-Magied, E M; Taha, A A

    1995-09-01

    The carotid body of the goat was found to be a small oval or rounded parenchymatous organ. It was characterized by its profound vascularity. Delicate septa divided the parenchyma into small feebly defined lobules. Electron microscopy revealed that the parenchyma comprised type I cells, type II cells, nerve endings, axons and fenestrated dilated capillaries. Type I cells were characterized with electron dense-cored vesicles. They showed variations in size and concentration of the dense-cored vesicles and number of mitochondria. The possibility that these variations are reflections of different stages of activity is discussed. Type II cells were less numerous than type I cells, relatively small and devoid of dense-cored vesicles. They usually surrounded small groups of type I cells and associated nerve endings and axons. Presumptive afferent nerve endings characterized with many clear vesicles, occasional large granular vesicles and varying numbers of slender mitochondria, lay apposed to type I cells. Nerve endings of this kind showed afferent and efferent synaptic junctions with type I cells. Presumptive sympathetic efferent endings were occasionally seen within the lobules but never lay apposed to type I cells or afferent nerve ending.

  7. Carotid body, insulin, and metabolic diseases: unraveling the links

    PubMed Central

    Conde, Sílvia V.; Sacramento, Joana F.; Guarino, Maria P.; Gonzalez, Constancio; Obeso, Ana; Diogo, Lucilia N.; Monteiro, Emilia C.; Ribeiro, Maria J.

    2014-01-01

    The carotid bodies (CB) are peripheral chemoreceptors that sense changes in arterial blood O2, CO2, and pH levels. Hypoxia, hypercapnia, and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN). CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS) activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnea (OSA) is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH) and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future. PMID:25400585

  8. Gasotransmitter Regulation of Ion Channels: A Key Step in O2 Sensing By the Carotid Body

    PubMed Central

    Prabhakar, Nanduri R.

    2014-01-01

    Carotid bodies detect hypoxia in arterial blood, translating this stimulus into physiological responses via the CNS. It is long established that ion channels are critical to this process. More recent evidence indicates that gasotransmitters exert powerful influences on O2 sensing by the carotid body. Here, we review current understanding of hypoxia-dependent production of gasotransmitters, how they regulate ion channels in the carotid body, and how this impacts carotid body function. PMID:24382871

  9. Chemical modification of carotid body chemoreception by sulfhydryls.

    PubMed

    Lahiri, S

    1981-05-29

    Sulfhydryl reagents cause striking augmentation of the chemoreceptor responses of the carotid body to hypoxia. This indicates that a cellular plasma membrane protein with a reactive sulfhydryl group is a constituent part of the chemoreceptor architecture and provides a means of identification, localization, and isolation of the protein.

  10. Carotid body tumors: Surgical experience in 215 cases.

    PubMed

    Pacheco-Ojeda, Luis A

    2017-09-01

    Carotid body tumors (CBT) are very unusual neck lesions. However, at high altitudes, they are less rarely found. This study intended to review our experience in diagnosis and surgical treatment of these lesions. Among 242 clinically diagnosed CBT, 215 tumors, arising in and retrospectively studied. All patients came from the Andean plateaux. Mean age was 52.5 years, 180 were females, and mean size was 4.21 cm. Shamblin type distribution, described in 187 patients, was: Type I 29(15%), type II 118(63%) and type III 40(22%). A correct preoperative diagnosis of CBT was made in 95% of the patients, based on clinical grounds and imaging studies. Complete CBT resection was performed in 209 tumors (97%). Twenty-three (11%) accidental preoperative vessel injuries were successfully repaired. Preoperative blood transfusion was used in only 16 cases. There was no operative mortality. Postoperative complications occurred in 59(27.5%) procedures, mostly minor and related to cranial nerve dysfunction. No stroke occurred in any patient. Seven (3%) cases were malignant. A systematic surgical technique allowed us to perform a complete CBT resection in most patients, unusual operative vascular accidents, low morbidity and no mortality. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  11. [Carotid body paraganglioma in a teenager. Case report].

    PubMed

    López-Vázquez, María Elisa; Llamas-Macías, Francisco Javier; Nuño-Escobar, César; González-Ojeda, Alejandro; Fuentes-Orozco, Clotilde; Macías-Amezcua, Michel Dassaejv

    2014-01-01

    Paragangliomas of the head and neck are neuroendocrine tumors. They have a low incidence (0.6%), are generally benign, have a poorly defined etiology, and multiple factors have been associated with their origin. Humans and other species living at high altitudes (>2000 m above sea level) are subjected to a relatively chronic hypoxia and there is a high prevalence of the development of carotid body hyperplasia and eventually paragangliomas. This disease is usually seen in patients in their 50s and in their 30s if there is a family history. We present the case of a 16 year-old female with acute pharyngitis and growing tumor located on the left side of the neck, without symptoms. A duplex Doppler ultrasound showed a solid nodular lesion on the left carotid bifurcation. A left lateral cervicotomy was performed, finding a highly vascularized tumor of 4 × 3 × 3 cm involving the common carotid from its middle third, the internal carotid up to the cranial base, and the external carotid to its upper third, and intimately related to the trachea, esophagus and cervical spine. The tumor was completely resected and the histopathological analysis corroborated the presence of paragangliomas. The publication of this case is relevant and of clinical interest due to the uncommon age of presentation and the fact that it should be considered as a diagnostic possibility.

  12. Patch clamp study of mouse glomus cells using a whole carotid body.

    PubMed

    Yamaguchi, Shigeki; Lande, Boris; Kitajima, Toshimitsu; Hori, Yuichi; Shirahata, Machiko

    2004-03-04

    Some electrophysiological characteristics of mouse glomus cells (DBA/2J strain) were investigated using an undissociated carotid body. The carotid body with major carotid arteries was placed in a recording chamber, and glomus cells were visualized with a water immersion lens combined with an infrared differential interference video camera. Patch clamp experiments revealed that voltage-gated outward current, but not inward current, was easily observed in glomus cells. Pharmacological experiments and the kinetics of the current suggest that outward current is via delayed rectifier, A type, and large conductance calcium-activated K channels. Furthermore, K current was reversibly attenuated by mild hypoxia. The results suggest electrophysiological similarities of glomus cells among the cat, the rat, and the DBA/2J mouse. The method appears useful for physiological experiments.

  13. Hes1 is required for the development of the superior cervical ganglion of sympathetic trunk and the carotid body.

    PubMed

    Kameda, Yoko; Saitoh, Takayoshi; Nemoto, Noriko; Katoh, Tokio; Iseki, Sachiko

    2012-08-01

    Hes1 gene represses the expression of proneural basic helix-loop-helix (bHLH) factor Mash1, which is essential for the differentiation of the sympathetic ganglia and carotid body glomus cells. The sympathetic ganglia, carotid body, and common carotid artery in Wnt1-Cre/R26R double transgenic mice were intensely labeled by X-gal staining, i.e., the neural crest origin. The deficiency of Hes1 caused severe hypoplasia of the superior cervical ganglion (SCG). At embryonic day (E) 17.5-E18.5, the volume of the SCG in Hes1 null mutants was reduced to 26.4% of the value in wild-type mice. In 4 of 30 cases (13.3%), the common carotid artery derived from the third arch artery was absent in the null mutants, and the carotid body was not formed. When the common carotid artery was retained, the organ grew in the wall of the third arch artery and glomus cell precursors were provided from the SCG in the null mutants as well as in wild-types. However, the volume of carotid body in the null mutants was only 52.5% of the value in wild-types at E17.5-E18.5. These results suggest that Hes1 plays a critical role in regulating the development of neural crest derivatives in the mouse cervical region.

  14. Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia.

    PubMed

    Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C; Bevans-Fonti, Shannon; Yoo, Doo-Young; Han, Woobum; Mesarwi, Omar; Richardson, Ria; Fu, Ya-Yuan; Pasricha, Pankaj J; Schwartz, Alan R; Shirahata, Machiko; Polotsky, Vsevolod Y

    2014-10-01

    Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.-9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity. Copyright © 2014 the American Physiological Society.

  15. The histology of the carotid bodies in highlanders from Ladakh

    NASA Astrophysics Data System (ADS)

    Khan, Q.; Heath, D.; Smith, P.; Norboo, T.

    1988-12-01

    A histological study was made of the carotid bodies in a boy and three adult male highlanders born and residing between altitudes of 3300 m to 4200 m in Ladakh. The carotid bodies were enlarged in two of the men, and in all four subjects showed increased numbers and enlargement of the dark variants of the chief cells of the glomic tissue. In these dark cells the cytoplasm was voluminous, formed streamers and contained many intracytoplasmic vesicles of which some had mused to form larger vesicles that appeared to have discharged from the cell surface. Immunohistochemical studies showed that these cells contained considerable amounts of the peptide met-enkephalin. It is thus considered that prominence of dark cells containing this peptide is characteristic of sustained exposure of the carotid bodies to hypobaric hypoxia. In the middle-aged highlander there was a prominence of sustentacular cells which encroached upon the cores of chief cells and this may be associated with the characteristic loss of hypoxic ventilatory response in the highlander.

  16. General redox environment and carotid body chemoreceptor function.

    PubMed

    Agapito, Maria Teresa; Sanz-Alfayate, Gloria; Gomez-Niño, Angela; Gonzalez, Constancio; Obeso, Ana

    2009-03-01

    Carotid body (CB) chemoreceptor cells detect physiological levels of hypoxia and generate a hyperventilation, homeostatic in nature, aimed to minimize the deleterious effects of hypoxia. Intimate mechanisms involved in oxygen sensing in chemoreceptor cells remain largely unknown, but reactive oxygen species (ROS) had been proposed as mediators of this process. We have determined glutathione levels and calculated glutathione redox potential (E(GSH); indicator of the general redox environment of cells) in rat diaphragms incubated in the presence of oxidizing agents of two types: nonpermeating and permeating through cell membranes; in the latter group, unspecific oxidants and inhibitors of ROS-disposing enzymes were used. Selected concentrations of oxidizing agents were tested for their ability to modify the normoxic and hypoxic activity of chemoreceptor cells measured in vitro as their rate of release of neurotransmitters. Results evidence variable relationships between E(GSH) and the activity of chemoreceptor cells. The independence of chemoreceptor cell activity from the E(GSH) would imply that the ability of the CB to play its homeostatic role is largely preserved in any pathological or toxicological contingency causing oxidative stress. Consistent with this suggestion, it was also found that CB-mediated hypoxic hyperventilation was not altered by treatment of intact animals with agents that markedly decreased the E(GSH) in all tissues assayed.

  17. Amiloride and carotid body chemoreception of hypercapnia and hypoxia.

    PubMed

    Fitzgerald, R S; Shirahata, M; Lahiri, S

    1990-09-01

    The sodium-proton (Na(+)-H+) antiporter has been found in virtually every tissue where its presence has been investigated. Its principal physiological role is to regulate intracellular pH (pHi). Amiloride (10(-3)-10(-4) M) is a known blocker of the antiporter when Na is present in normal physiological concentrations (130-140 x 10(-3) M). In order to determine if the Na(+)-H+ antiporter participated in the chemoreception of hypercapnia or hypoxia anesthetized, paralyzed, artificially ventilated cats were fitted with a loop in the right common carotid artery for the selective perfusion of the carotid body. Neural activity (imp/10 sec) was recorded from single or few fiber preparations during hypercapnia (PaCO2 = 48-64 Torr) while the carotid body was perfused with Krebs-Ringer bicarbonate solution for 2.5 min, then with its own hypercapnic arterial blood (4 min), then with Krebs-Ringer bicarbonate solution containing 0.6-0.8 x 10(-3) M amiloride (2.5 min), then with its own hypercapnic blood (4 min). After 20 min of rest the protocol was repeated during hypoxia (PaO2 = 35-45 Torr). The carotid body response to hypercapnic blood was unaffected by a preceding perfusion of the amiloride-containing solution but the response to hypoxic blood was decreased by 25% by the amiloride-containing solution. The data suggest the possibility of different mechanisms being involved in the chemoreception of hypercapnia and hypoxia.

  18. The Human Carotid Body Gene Expression and Function in Signaling of Hypoxia and Inflammation.

    PubMed

    Kåhlin, Jessica; Mkrtchian, Souren; Ebberyd, Anette; Eriksson, Lars I; Fagerlund, Malin Jonsson

    2015-01-01

    Although animal carotid body oxygen sensing and signaling has been extensively investigated, the human carotid body remains essentially uncharacterized. Therefore, we aimed to study the human carotid body in terms of morphology, global and specific expression of sensing and signaling genes as well as inflammatory genes. The human carotid body response to brief or prolonged hypoxia was studied in carotid body slices from adult surgical patients and ACh, ATP and cytokine release was analyzed. We demonstrate that the human carotid body expresses key oxygen sensing and signaling genes in similarity with animal carotid bodies with a few diverging data. The human carotid body moreover shows enrichment of genes in the inflammatory response and releases pro and anti-inflammatory cytokines in response to prolonged hypoxia. In response to acute hypoxia the human carotid body releases ACh and ATP and we thus translate previous findings in animal models to human tissue. We conclude that by releasing pro- and anti-inflammatory cytokines during hypoxia the human carotid body displays a structural and functional capacity to participate in sensing and mediating systemic inflammation.

  19. Hyperbaric oxygenation alters carotid body ultrastructure and function.

    PubMed

    Torbati, D; Sherpa, A K; Lahiri, S; Mokashi, A; Albertine, K H; DiGiulio, C

    1993-05-01

    We previously demonstrated that chronic normobaric hyperoxia (NH) for 60-67 h attenuated the carotid chemosensory response to hypoxia, probably initiated by the generation of reactive oxygen species (ROS). Since biological systems are affected by oxygen in a dose-dependent manner, we hypothesized that hyperbaric oxygenation (HBO) would affect the cellular mechanisms of oxygen chemoreception in a shorter time. To test the hypothesis, we studied the effects of oxygen at 5 atmospheres absolute (ATA) on cats (n = 7) carotid body ultrastructure and chemosensory responses to hypoxia, hypercapnia, and to bolus injections of cyanide, nicotine and dopamine. Four control cats breathed room air at 1 ATA. At the termination of the experiments, carotid bodies from 4 cats in each group were fixed and prepared for electron microscopy and morphometry. On the average, HBO diminished the chemosensory responsiveness to hypoxia (P < 0.01, unpaired t-test) within about 2 h, supporting the hypothesis. The responses to hypercapnia or bolus injections of cyanide, nicotine and dopamine were normal. HBO did not diminish the distribution of the dense-cored vesicles but significantly increased the mean volume-density of mitochondria and decreased the cristated area per mitochondrion in the glomus cells. The latter suggests a link between oxidative metabolism and chemosensing, and the former excludes availability of neurotransmitters being the cause of the blunted chemosensory response to hypoxia.

  20. Hydrogen sulfide activates the carotid body chemoreceptors in cat, rabbit and rat ex vivo preparations.

    PubMed

    Jiao, Yingfu; Li, Qian; Sun, Biying; Zhang, Guohua; Rong, Weifang

    2015-03-01

    We and others previously reported experimental evidence suggesting an important role for hydrogen sulfide (H2S) in oxygen sensing in murine carotid body chemoreceptors. More recent data implicated abnormal H2S-mediated chemoreceptor signaling in pathological conditions such as chronic heart failure and hypertension. However, the idea of H2S as a mediator of oxygen-sensing in chemoreceptors has been challenged. In particular, it was shown that exogenous H2S inhibited the release of neurotransmitters (ACh and ATP) from the cat carotid body, raising the possibility that there exists significant species difference in H2S-mediated signaling in chemoreceptors. This study was designed specifically to determine the effect of H2S on chemoreceptors in different species. We conducted multiunit extracellular recordings of the sinus nerve in the ex vivo carotid body preparation taken from the rat, the cat and the rabbit. As observed in the mouse carotid body, H2S donors (NaHS or Na2S) evoked qualitatively similar excitatory responses of the afferent sinus nerves of the species studied here. The excitatory effects of the H2S donors were concentration-dependent and reversible. The sinus nerve responses to H2S donors were prevented by blockade of the transmission between type I cells and the afferent terminals, as was the response to hypoxia. These results demonstrate that exogenous H2S exerts qualitatively similar excitatory effects on chemoreceptor afferents of different species. The role of endogenous H2S-mediated signaling in carotid body function in different species awaits further investigation.

  1. Cellular properties and chemosensory responses of the human carotid body

    PubMed Central

    Ortega-Sáenz, Patricia; Pardal, Ricardo; Levitsky, Konstantin; Villadiego, Javier; Muñoz-Manchado, Ana Belén; Durán, Rocío; Bonilla-Henao, Victoria; Arias-Mayenco, Ignacio; Sobrino, Verónica; Ordóñez, Antonio; Oliver, María; Toledo-Aral, Juan José; López-Barneo, José

    2013-01-01

    The carotid body (CB) is the major peripheral arterial chemoreceptor in mammals that mediates the acute hyperventilatory response to hypoxia. The CB grows in response to sustained hypoxia and also participates in acclimatisation to chronic hypoxaemia. Knowledge of CB physiology at the cellular level has increased considerably in recent times thanks to studies performed on lower mammals, and rodents in particular. However, the functional characteristics of human CB cells remain practically unknown. Herein, we use tissue slices or enzymatically dispersed cells to determine the characteristics of human CB cells. The adult human CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). We found that GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. Moreover, glomus cells exhibited voltage-dependent Na+, Ca2+ and K+ currents that were qualitatively similar to those reported in lower mammals. These cells responded to hypoxia with an external Ca2+-dependent increase of cytosolic Ca2+ and quantal catecholamine secretion, as reported for other mammalian species. Interestingly, human glomus cells are also responsive to hypoglycaemia and together these two stimuli can potentiate each other's effects. The chemosensory responses of glomus cells are also preserved at an advanced age. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans. PMID:24167224

  2. Carotid body O2 chemoreception and mitochondrial oxidative phosphorylation.

    PubMed

    Mulligan, E; Lahiri, S; Storey, B T

    1981-08-01

    The effect on carotid chemoreceptor afferents of oligomycin, an inhibitor of mitochondrial oxidative phosphorylation that does not affect energy conservation, was studied in 20 cats that were anesthetized, paralyzed, and artificially ventilated. Responses of single or a few chemoreceptor afferents to changes in arterial O2 tension (PaO2) at constant arterial CO2 tension were recorded. In addition, responses to nicotine, cyanide, and antimycin A or carbonyl cyanide p-tri-fluoromethoxyphenylhydrazone (FCCP) were tested in normoxia. Oligomycin (50-500 microgram) was administered by close intra-arterial injection, and the same tests were repeated at timed intervals. Initially, oligomycin caused vigorous stimulation of carotid chemoreceptor activity. Subsequently, although the afferent fibers were still active and could be vigorously stimulated by nicotine, they no longer responded to changes in PaO2 or to doses of cyanide, antimycin A, or FCCP. These results separate stimulation of chemoreceptor afferents by hypoxia and metabolic inhibitors and uncouplers from that by nicotine and suggest that intact oxidative phosphorylation, required for maintenance of the intracellular high-energy phosphate levels, forms the basis of O2 chemoreception in the carotid body.

  3. [Surgical treatment of tumors of the carotid body with reconstruction of the internal carotid artery].

    PubMed

    Reparaz, L; Magallón, P; Riera, L; Capilla, M T; Merino, M J; Martínez, I; Hernández, A; Sáez, L; Alamo, O; Jiménez Cossío, J A

    1990-01-01

    The experience about treatment in infiltrating tumors of Carotid Corpus, III Degree (Shamblin), is presented. Different methods of carotid reconstruction, and biologic and evolutive characteristics are emphasized, discussing preoperatory study and surgical technics.

  4. The general ultrastructure of the carotid body of the domestic fowl.

    PubMed

    Hodges, R D; King, A S; King, D Z; French, E I

    1975-10-27

    Electron microscopic studies of the carotid body of the domestic fowl (Gallus gallus domesticus) have shown Type I and Type II cells combined with axons into compact groups. The many Type I cells in the depths of the organ had a body, containing the nucleus, and an elongated, flared process. Some of the Type I cells in the superficial regions tended to be spindle-shaped. Type I cells were characterised by membrane-bound, dense-cored vesicles about 120 nm in diameter. Type II cells invested the Type I cells and had axons embedded in them as in Schwann cells. The fine structure of the carotid body in the domestic fowl resembles that of the Lovebird (Uroloncha domestica) and of various amphibia and mammals. The possibility is discussed that the Type I cells may have a chemoreceptor or a general secretory function, or even both of these axons leading to or from Type I cells. The main role of the Type II cells seems to be to provide a pathway for functions together.

  5. Chemoreceptor discharges and cytochrome redox changes of the rat carotid body: Role of heme ligands

    PubMed Central

    Lahiri, Sukhamay; Ehleben, Wilhelm; Acker, Helmut

    1999-01-01

    In superfused in vitro rat carotid body, we recorded chemoreceptor discharges and the redox state of cytochromes simultaneously to identify the primary oxygen-sensing protein controlling transmitter release and electrical activity of the carotid sinus nerve. These parameters were tested under the influence of heme ligands such as oxygen, cyanide, 4-(2-aminoethyl)-benzenesulfonyl fluoride, and CO. During stimulation, there was an initial increase in discharge frequency followed by a decline or suppression of activity. Photometric changes lagged and were maintained as nerve activity decreased. Reducing mitochondrial cytochromes by cyanide or prolonged severe hypoxia, suppressed the chemoreceptor discharge. 4-(2-Aminoethyl)-benzenesulfonyl fluoride, a specific inhibitor of the phagocytic cytochrome b558, also silenced the chemoreceptors after an initial excitation. CO increased the chemoreceptor discharge under normoxia, an effect inhibited by light, when the cytochromes were not reduced. When the discharges were depressed by severe hypoxia, exposure to light excited the chemoreceptors and the cytochromes were reduced. The rapidity of the chemosensory responses to light and lack of effect on dopamine release from type I cells led us to hypothesize that carotid body type I cells and the apposed nerve endings use different mechanisms for oxygen sensing: the nerve endings generate action potentials in association with membrane heme proteins whereas cytosolic heme proteins signal the redox state, releasing modulators or transmitters from type I cells. PMID:10430959

  6. Carotid body chemosensory responses in mice deficient of TASK channels

    PubMed Central

    Ortega-Sáenz, Patricia; Levitsky, Konstantin L.; Marcos-Almaraz, María T.; Bonilla-Henao, Victoria; Pascual, Alberto

    2010-01-01

    Background K+ channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (glomus) cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and hypercapnia in TASK1- and/or TASK3-deficient mice have yielded conflicting results. We have characterized the glomus cell phenotype of TASK-null mice and studied the responses of individual cells to hypoxia and other chemical stimuli. CB morphology and glomus cell size were normal in wild-type as well as in TASK1−/− or double TASK1/3−/− mice. Patch-clamped TASK1/3-null glomus cells had significantly higher membrane resistance and less hyperpolarized resting potential than their wild-type counterpart. These electrical parameters were practically normal in TASK1−/− cells. Sensitivity of background currents to changes of extracellular pH was drastically diminished in TASK1/3-null cells. In contrast with these observations, responsiveness to hypoxia or hypercapnia of either TASK1−/− or double TASK1/3−/− cells, as estimated by the amperometric measurement of catecholamine release, was apparently normal. TASK1/3 knockout cells showed an enhanced secretory rate in basal (normoxic) conditions compatible with their increased excitability. Responsiveness to hypoxia of TASK1/3-null cells was maintained after pharmacological blockade of maxi-K+ channels. These data in the TASK-null mouse model indicate that TASK3 channels contribute to the background K+ current in glomus cells and to their sensitivity to external pH. They also suggest that, although TASK1 channels might be dispensable for O2/CO2 sensing in mouse CB cells, TASK3 channels (or TASK1/3 heteromers) could mediate hypoxic depolarization of normal glomus cells. The ability of TASK1/3−/− glomus cells to maintain a powerful response to hypoxia even after blockade of maxi-K+ channels, suggests the existence of multiple sensor and/or effector mechanisms, which could

  7. CO reveals dual mechanisms of O2 chemoreception in the cat carotid body.

    PubMed

    Lahiri, S; Iturriaga, R; Mokashi, A; Ray, D K; Chugh, D

    1993-11-01

    The hypothesis that CO-binding pigments in the carotid body participate in O2 chemoreception was tested. The chemosensory nerve discharges of cat carotid body perfused and superfused in vitro at 36-37 degrees C with cell-free solution containing CO2-HCO3- (pH approximately equal to 7.39) were recorded to monitor O2 chemoreception. Several levels of PCO (60-550 Torr) at two levels of PO2 (50 Torr-140 Torr) were used. With high PCO of 500-550 Torr at any PO2 the discharge rate peaked promptly but the effect was significantly less than that to hypoxia. At any stage of the CO effect, exposure to light promptly attenuated or eliminated the response, as if the stimulatory effect of hypoxia was absent. Lower PCO of 60-70 Torr attenuated the response to hypoxia which was not suppressed by light. PCO of 140 Torr also attenuated the response to hypoxia and made the activity partially photolabile. During high PCO exposure the excitatory response to cyanide but not to nicotine was attenuated, consistent with the idea that the effects of nicotine are downstream from those of CO. Both inhibitory and excitatory effects of CO were promptly reversible. The results indicate that two types of CO-binding chromophores participate in O2 chemoreception in the carotid body.

  8. Dual effects of nitric oxide on cat carotid body chemoreception.

    PubMed

    Iturriaga, R; Villanueva, S; Mosqueira, M

    2000-09-01

    We studied the effects of nitric oxide (NO) released by NO donors on cat carotid body (CB) chemosensory activity during normoxia and hypoxia. CBs excised from pentobarbital sodium-anaesthetized cats were perfused with Tyrode at 38 degrees C and pH 7.40. The frequency of chemosensory discharges (f(x)) was recorded from the carotid sinus nerve, and changes of NO concentration were measured by a chronoamperometric technique, with NO-selective carbon-fiber microelectrodes inserted in the CB. During steady chemosensory excitation induced by hypoxia, bolus injections of NO (DeltaNO = 0. 5-12 microM), released by S-nitroso-N-acetylpenicillamine (SNAP) and 6-(2-hydroxy-1-methyl-nitrosohydrazino)-N-methyl-1-hexanamine++ + (NOC-9), transiently reduced f(x) in a dose-dependent manner. However, during normoxia, the same concentration of NO (DeltaNO = 0. 5-13 microM) released by the NO donors increased f(x) in a dose-dependent manner. The present results show a dual effect of NO on CB chemoreception that is dependent on the PO(2) levels. During hypoxia, NO is predominantly an inhibitor of chemoreception, whereas, in normoxia, NO increased f(x). The mechanisms by which NO produces chemosensory excitation during normoxia remain to be determined.

  9. Modulatory effects of histamine on cat carotid body chemoreception.

    PubMed

    Del Rio, Rodrigo; Moya, Esteban A; Koenig, Cecilia S; Fujiwara, Kunio; Alcayaga, Julio; Iturriaga, Rodrigo

    2008-12-31

    Histamine has been proposed to be an excitatory transmitter between the carotid body (CB) chemoreceptor (glomus) cells and petrosal ganglion (PG) neurons. The histamine biosynthetic pathway, its storage and release, as well as the presence of histamine H1, H2 and H3 receptors have been found in the CB. However, there is only indirect evidence showing the presence of histamine in glomus cells, or weather its application produces chemosensory excitation. Thus, we studied the histamine immunocytochemical localization in the cat CB, and the effects of histamine, and H1, H2 and H3 receptor blockers on carotid sinus nerve (CSN) discharge, using CB and PG preparations in vitro. We found histamine immunoreactivity in dense-cored vesicles of glomus cells. Histamine induced dose-dependent increases in CSN discharge in the CB, but not in the PG. The H1-antagonist pyrilamine reduced the CB responses induced by histamine, the H2-antagonists cimetidine and ranitidine had no effect, while the H3-antagonist thioperamide enhanced histamine-induced responses. Present data suggests that histamine plays an excitatory modulatory role in the generation of cat CB chemosensory activity.

  10. Effects of angiotensin II on leptin and downstream leptin signaling in the carotid body during acute intermittent hypoxia.

    PubMed

    Moreau, J M; Messenger, S A; Ciriello, J

    2015-12-03

    Angiotensin II (ANG II) is known to promote leptin production and secretion. Although ANG II type 1 receptors (AT1Rs) and leptin are expressed within the carotid body, it is not known whether AT1R and leptin are co-expressed in the same glomus cells nor if these peptides are affected within the carotid body by intermittent hypoxia (IH). This study was done to investigate whether ANG II modulated leptin signaling in the carotid body during IH. Rats were treated with captopril (Capt) or the AT1R blocker losartan (Los) in the drinking water for 3days prior to being exposed to IH (8h) or normoxia (8h). IH induced increases in plasma ANG II and leptin compared to normoxic controls. Capt treatment abolished the plasma leptin changes to IH, whereas Los treatment had no effect on the IH induced increase in plasma leptin. Additionally, carotid body glomus cells containing both leptin and the long form of the leptin receptor (OB-Rb) were found to co-express AT1R protein, and IH increased the expression of only AT1R protein within the carotid body in both Capt- and non-Capt-treated animals. On the other hand, Los treatment did not modify AT1R protein expression to IH. Additionally, Capt and Los treatment eliminated the elevated carotid body leptin protein expression, and the changes in phosphorylated signal transducer and activator of transcription three protein, the short form of the leptin receptor (OB-R100), suppressor of cytokine signaling 3, and phosphorylated extracellular-signal-regulated kinase 1/2 protein expression induced by IH. However, Capt elevated the expression of OB-Rb protein, whereas Los abolished the changes in OB-Rb protein to IH. These findings, taken together with the previous observation that ANG II modifies carotid body chemosensitivity, suggest that the increased circulating levels of ANG II and leptin induced by IH act at the carotid body to alter leptin signaling within the carotid body which in turn may influence chemoreceptor function.

  11. Role of Neurotransmitter Gases in the Control of the Carotid Body in Heart Failure

    PubMed Central

    Schultz, Harold D; Del Rio, Rodrigo; Ding, Yanfeng; Marcus, Noah J

    2012-01-01

    The peripheral arterial chemoreflex, arising primarily from the carotid body in most species, plays an important role in the control of breathing and in autonomic control of cardiovascular function. The peripheral chemoreflex is enhanced in heart failure patients and animal models of heart failure and contributes to the sympathetic hyperactivity and breathing instability that exacerbates the progression of the disease. Studies in animal models have shown that carotid body chemoreceptor activity is enhanced under both normoxic and hypoxic conditions in heart failure due to disruption of local mediators that control carotid body function. This brief review highlights evidence that the alterations in the gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide in the carotid body contribute to the exaggerated carotid body function observed in heart failure. PMID:22842006

  12. Evaluating the carotid bodies and renal nerves as therapeutic targets for hypertension.

    PubMed

    McBryde, Fiona D; Hart, Emma C; Ramchandra, Rohit; Paton, Julian F R

    2017-05-01

    Despite the plethora of current treatment options, hypertension remains a difficult condition to adequately control, and there is a pressing need for novel therapeutic strategies. The carotid body has recently become the focus of considerable interest as a potential novel treatment target in essential hypertension. Herein, we appraise the current literature suggesting that the carotid body plays an important causative role to generate sympathetic overactivity and drive increases in arterial pressure, in animal models of hypertension. We also review evidence from human studies showing cardiovascular benefits to the transient inactivation, or surgical removal of carotid bodies, and evaluate the potential benefits of pre-screening to identify patients likely to respond to carotid body-targeted therapy. Finally, given that a high proportion of patients who have undergone renal nerve ablation procedures remain hypertensive, we examine whether the renal nerves are necessary for the drop in blood pressure seen with carotid body removal. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Progression of carotid-artery disease in type 2 diabetic patients: a cohort prospective study

    PubMed Central

    Bosevski, Marijan; Stojanovska, Lily

    2015-01-01

    In order to assess the progression of carotid-artery disease in type 2 diabetic cohort (n=207 patients), the dynamic change in carotid intima-media thickness (CIMT) and the occurrence of plaques were followed for a period of 31.35±10.59 months. The mean CIMT at the beginning of the study was 0.9178±0.1447 mm, with a maximal value of 1.1210±0.2366 mm. The maximal value of CIMT changed by 0.07 mm/year. Progression of CIMT was noted in 86.8% and its regression in 7.8% of patients. The occurrence of carotid plaques was detected in 41.8% of patients. Multiple regression analysis revealed the maximal value of CIMT to be associated with diastolic blood pressure, despite mean CIMT being predicted by body mass index. The presence of peripheral arterial disease and hypo-high-density lipoproteinemia were found to be predictors for the occurrence of carotid plaques. Our data have clinical implications in predicting risk factors for the progression of carotid-artery disease in type 2 diabetic patients for their appropriate management. PMID:26527880

  14. Effects of naloxone on carotid body chemoreception and ventilation in the cat.

    PubMed

    Pokorski, M; Lahiri, S

    1981-12-01

    The effects of intravenous injection of naloxone (0.4 mg.kg-1), an opiate antagonist, on the responses of carotid body chemoreceptor discharge and ventilation to steady-state levels of hypoxia and hypercapnia were investigated in 12 anesthesized cats. After naloxone, carotid chemoreceptor response to hypoxia (PaO2 60--30 Torr) was enhanced, a finding that suggested that the endogenous enkephalin-like peptide present in the carotid body inhibits carotid chemoreceptors. This reasoning is supported by the observation that close intra-arterial injection of met-enkephalin inhibits carotid chemoreceptors and that the effect is blocked by naloxone. After naloxone, ventilation was stimulated even in the absence of a significant stimulation of carotid chemoreceptors during hyperoxia, indicating that ventilation is normally suppressed by endogenous opiates in the central nervous system, an effect disinhibited by naloxone. Also, the ventilatory effect of the peripheral chemoreceptor input was augmented after naloxone.

  15. Cerebral foreign body reaction after carotid aneurysm stenting

    PubMed Central

    Lorentzen, Anastasia Orlova; Nome, Terje; Bakke, Søren Jacob; Scheie, David; Stenset, Vidar

    2016-01-01

    Flow diverter stents are new important tools in the treatment of large, giant, or wide-necked aneurysms. Their delivery and positioning may be difficult due to vessel tortuosity. Common adverse events include intracranial hemorrhage and ischemic stroke, which usually occurs within the same day, or the next few days after the procedure. We present a case where we encountered an unusual intracerebral complication several months after endovascular treatment of a large left internal carotid artery aneurysm, and where brain biopsy revealed foreign body reaction to hydrophilic polymer fragments distally to the stent site. Although previously described, embolization of polymer material from intravascular equipment is rare. We could not identify any other biopsy verified case in the literature, with this particular presentation of intracerebral polymer embolization – a multifocal inflammation spread out through the white matter of one hemisphere without hemorrhage or ischemic changes. PMID:26510943

  16. Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties.

    PubMed

    Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

    2017-01-01

    Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K(+) currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca(2+) levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

  17. Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties

    PubMed Central

    Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

    2017-01-01

    Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied. PMID:28533756

  18. Imaging findings of malignant bilateral carotid body tumors: A case report and review of the literature

    PubMed Central

    LV, HAN; CHEN, XIAOHONG; ZHOU, SHUAI; CUI, SUPING; BAI, YUNLONG; WANG, ZHENCHANG

    2016-01-01

    Carotid body tumors (CBTs) are a rare type of extra-adrenal paraganglioma, which originate from the carotid body. A 29-year-old woman was admitted to the Department of Head and Neck Surgery, Beijing Tongren Hospital (Capital Medical University, Beijing, China) with hoarseness of the throat, which had progressively worsened over seven months. The patient had a family history of CBTs. Computed tomography and ultrasound imaging revealed multiple well-enhanced masses located at the bilateral carotid bifurcation and in the left parapharyngeal space. Surgery and pathological examination confirmed that the patient had developed regional lymph node metastasis. Significantly enhanced multiple pulmonary and hepatic lesions indicated that the patient had also developed distal metastasis. A genetic analysis performed on the family members of the patient revealed that the family carried a mutated succinate dehydrogenase D gene. In the present study, a systemic review of the literature indicated that extra vigilance is required in familial forms of CBT, in order to increase the standard of treatment for CBT patients. PMID:27073498

  19. The von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia.

    PubMed

    Slingo, Mary E; Turner, Philip J; Christian, Helen C; Buckler, Keith J; Robbins, Peter A

    2014-04-01

    The hypoxia-inducible factor (HIF) family of transcription factors coordinates diverse cellular and systemic responses to hypoxia. Chuvash polycythemia (CP) is an autosomal recessive disorder in humans in which there is impaired oxygen-dependent degradation of HIF, resulting in long-term systemic elevation of HIF levels at normal oxygen tensions. CP patients demonstrate the characteristic features of ventilatory acclimatization to hypoxia, namely, an elevated baseline ventilation and enhanced acute hypoxic ventilatory response (AHVR). We investigated the ventilatory and carotid-body phenotype of a mouse model of CP, using whole-body plethysmography, immunohistochemistry, and electron microscopy. In keeping with studies in humans, CP mice had elevated ventilation in euoxia and a significantly exaggerated AHVR when exposed to 10% oxygen, with or without the addition of 3% carbon dioxide. Carotid-body immunohistochemistry demonstrated marked hyperplasia of the oxygen-sensing type I cells, and the cells themselves appeared enlarged with more prominent nuclei. This hypertrophy was confirmed by electron microscopy, which also revealed that the type I cells contained an increased number of mitochondria, enlarged dense-cored vesicles, and markedly expanded rough endoplasmic reticulum. The morphological and ultrastructural changes seen in the CP mouse carotid body are strikingly similar to those observed in animals exposed to chronic hypoxia. Our study demonstrates that the HIF pathway plays a major role, not only in regulating both euoxic ventilatory control and the sensitivity of the response to hypoxia, but also in determining the morphology of the carotid body.

  20. The von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia

    PubMed Central

    Slingo, Mary E.; Turner, Philip J.; Christian, Helen C.; Buckler, Keith J.

    2013-01-01

    The hypoxia-inducible factor (HIF) family of transcription factors coordinates diverse cellular and systemic responses to hypoxia. Chuvash polycythemia (CP) is an autosomal recessive disorder in humans in which there is impaired oxygen-dependent degradation of HIF, resulting in long-term systemic elevation of HIF levels at normal oxygen tensions. CP patients demonstrate the characteristic features of ventilatory acclimatization to hypoxia, namely, an elevated baseline ventilation and enhanced acute hypoxic ventilatory response (AHVR). We investigated the ventilatory and carotid-body phenotype of a mouse model of CP, using whole-body plethysmography, immunohistochemistry, and electron microscopy. In keeping with studies in humans, CP mice had elevated ventilation in euoxia and a significantly exaggerated AHVR when exposed to 10% oxygen, with or without the addition of 3% carbon dioxide. Carotid-body immunohistochemistry demonstrated marked hyperplasia of the oxygen-sensing type I cells, and the cells themselves appeared enlarged with more prominent nuclei. This hypertrophy was confirmed by electron microscopy, which also revealed that the type I cells contained an increased number of mitochondria, enlarged dense-cored vesicles, and markedly expanded rough endoplasmic reticulum. The morphological and ultrastructural changes seen in the CP mouse carotid body are strikingly similar to those observed in animals exposed to chronic hypoxia. Our study demonstrates that the HIF pathway plays a major role, not only in regulating both euoxic ventilatory control and the sensitivity of the response to hypoxia, but also in determining the morphology of the carotid body. PMID:24030664

  1. Carbonic anhydrase and chemoreception in the cat carotid body.

    PubMed

    Iturriaga, R; Lahiri, S; Mokashi, A

    1991-10-01

    To test the hypothesis that CO2 and O2 chemoreception in the carotid body (CB) may depend on its carbonic anhydrase (CA) activity, we used an in vitro cat CB preparation and studied the effects of methazolamide, a permeable CA inhibitor (pK 7.3), on the chemosensory responses to CO2, O2, and nicotine. The isolated CB was perfused and superfused with Tyrode solution, free of CO2-HCO3-, at 36.0 +/- 0.5 degrees C. The frequency of chemosensory discharges was recorded from the whole carotid sinus nerve. The responses to bolus injections (0.3-0.5 ml) of Tyrode solution equilibrated with PCO2 of 38-110 Torr, switching from HEPES to CO2-HCO3- Tyrode (PCO2 = 25-60 Torr) for about 3 min, hypoxic Tyrode (PO2 = 25-30 Torr) for 2-8 min, perfusate flow interruptions for approximately 4 min, and bolus injections of nicotine (4 nmol) were studied before, during, and after perfusion (30-45 min) with methazolamide (42.4 microM). Methazolamide reversibly inhibited, delayed, and reduced the responses to transient CO2 stimulus, diminished the onset of but not the late response to prolonged CO2 stimulus, and delayed but did not decrease the responses to hypoxia and perfusate interruption. The response to nicotine did not change. The results indicated that CA in the glomus cells played a crucial role primarily in the speed and magnitude of the initial response to CO2 stimulus and indirectly influenced O2 chemoreception. These effects were upstream from the nicotine receptor-mediated sensory response.

  2. Impaired ventilatory acclimatization to hypoxia in female mice overexpressing erythropoietin: unexpected deleterious effect of estradiol in carotid bodies.

    PubMed

    Gassmann, Max; Pfistner, Christine; Doan, Van Diep; Vogel, Johannes; Soliz, Jorge

    2010-12-01

    Apart from enhancing the production of red blood cells, erythropoietin (Epo) alters the ventilatory response when oxygen supply is reduced. We recently demonstrated that Epo's beneficial effect on the ventilatory response to acute hypoxia is sex dependent, with female mice being better able to cope with reduced oxygenation. In the present work, we hypothesized that ventilatory acclimatization to chronic hypoxia (VAH) in transgenic female mice (Tg6) harboring high levels of Epo in the brain and blood will also be improved compared with wild-type (WT) animals. Surprisingly, VAH was blunted in Tg6 female mice. To define whether this phenomenon had a central (brain stem respiratory centers) and/or peripheral (carotid bodies) origin, a bilateral transection of carotid sinus nerve (chemodenervation) was performed. This procedure allowed the analysis of the central response in the absence of carotid body information. Interestingly, chemodenervation restored the VAH in Tg6 mice, suggesting that carotid bodies were responsible for the blunted response. Coherently with this observation, the sensitivity to oxygen alteration in arterial blood (Dejour test) after chronic hypoxia was lower in transgenic carotid bodies compared with the WT control. As blunted VAH occurred in female but not male transgenic mice, the involvement of sex female steroids was obvious. Indeed, measurement of sexual female hormones revealed that the estradiol serum level was 4 times higher in transgenic mice Tg6 than in WT animals. While ovariectomy decreased VAH in WT females, this treatment restored VAH in Tg6 female mice. In line with this observation, injections of estradiol in ovariectomized Tg6 females dramatically reduced the VAH. We concluded that during chronic hypoxia, estradiol in carotid bodies suppresses the Epo-mediated elevation of ventilation. Considering the increased application of recombinant Epo for a variety of disorders, our data imply the need to take the patient's hormonal status

  3. Does yawning increase arousal through mechanical stimulation of the carotid body?

    PubMed

    Matikainen, Jorma; Elo, Hannu

    2008-01-01

    Yawning is a stereotyped event that occurs in humans and animals from fish to mammals, but neither its mechanisms nor its functions are entirely known. Its widespread nature suggests that it has important physiological functions. It is associated with stretching of muscles in a large area, but the function of this stretching is understood far from completely. It has been proposed that yawning increases arousal and that it is an arousal defense reflex, whose aim is to reverse brain hypoxia. Whilst yawning has been speculated to have an important role in reversing hypoxia, there is a structure in the neck that is known to be intimately involved in the regulation of oxygen homeostasis, namely the carotid body. It senses acute changes in oxygen levels. In spite of this, a connection has never been proposed either between the carotid body and arousal, or between yawning and the carotid body. We propose that yawning stimulates mechanically the carotid body (and possibly other structures in the neck). We further propose that this stimulation gives rise to increased arousal, alertness and wakefulness and that one important physiological function of yawning is increase of arousal through this stimulation. We also propose that mechanical effects on the shunt system of the carotid body may be involved in this stimulation. Our hypothesis is supported by several facts. For example, yawning causes movements and compressions that may affect the carotid body that is situated strategically at the bifurcation of the common carotid artery. Thus, yawning may stimulate the carotid body. The carotid body is highly vascular and compressions may affect its shunt system and blood flow and for example give rise to release of hormones or other substances. Also several facts related to situations where people yawn or do not yawn support our hypothesis and are discussed. Further support comes from facts related to somnogenic substances, hormones and transmitters, and from facts related to the

  4. KISS1 and KISS1R expression in the human and rat carotid body and superior cervical ganglion.

    PubMed

    Porzionato, A; Fenu, G; Rucinski, M; Macchi, V; Montella, A; Malendowicz, L K; De Caro, R

    2011-05-04

    KISS1 and its receptor, KISS1R, have both been found to be expressed in central nervous system, but few data are present in the literature about their distribution in peripheral nervous structures. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of KISS1 and KISS1R in the rat and human carotid bodies and superior cervical ganglia, also with particular reference to the different cellular populations. Materials consisted of carotid bodies and superior cervical ganglia were obtained at autopsy from 10 adult subjects and sampled from 10 adult Sprague-Dawley rats. Immunohistochemistry revealed diffuse expression of KISS1 and KISS1R in type I cells of both human and rat carotid bodies, whereas type II cells were negative. In both human and rat superior cervical ganglia positive anti-KISS1 and -KISS1R immunostainings were also selectively found in ganglion cells, satellite cells being negative. Endothelial cells also showed moderate immunostaining for both KISS1 and KISS1R. The expression of both kisspeptins and kisspeptin receptors in glomic type I cells and sympathetic ganglion cells supports a modulatory role of KISS1 on peripheral chemoreception and sympathetic function. Moreover, local changes in blood flow have been considered to be involved in carotid body chemoreceptor discharge and kisspeptins and kisspeptin receptors have also been found in the endothelial cells. As a consequence, a possible role of kisspeptins in the regulation of carotid body blood flow and, indirectly, in chemoreceptor discharge may also be hypothesized.

  5. Protein kinase C--a potential modifier of carotid body function.

    PubMed

    Faff, L; Kowalewski, C; Pokorski, M

    1999-04-01

    This article deals with the potential role of protein kinase C (PKC) in signal transduction in the carotid body. The carotid body is a chemosensory organ which, by sensing reductions in arterial blood oxygen tension, is primarily responsible for the hyperventilation of hypoxia. The mechanisms of transduction of the hypoxic stimulus into a neural signal regulating respiration are not clear. Hypoxia increases the phosphoinositide-specific phospholipase C (PLC) activity in the carotid body. The PLC-derived signalling molecules are known to activate PKC. The enzyme might, thus, have the potential to interact with the process of chemoreception. This article demonstrates that PKC is present in the chemoreceptor cells of the cat carotid body and discusses the biology of the enzyme relevant to chemosensory function. This gives rise to the hypothesis that PKC-mediated mechanisms alter chemoreceptor cell function to a sufficient extent to metamorphose the hypoxic signal into an increased discharge frequency in the apposed sinus nerve endings.

  6. Role of TrkB during the postnatal development of the rat carotid body.

    PubMed

    Bavis, Ryan W; Blegen, Halward J; Logan, Sarah; Fallon, Sarah C; McDonough, Amy B

    2015-12-01

    Brain-derived neurotrophic factor (BDNF) supports innervation of the carotid body by neurons projecting from the petrosal ganglion. Although carotid body glomus cells also express TrkB, BDNF's high affinity receptor, the role of BDNF in carotid body growth and O2 sensitivity has not been studied. Neonatal rats were treated with the TrkB antagonist K252a (100 μg kg(-1), i.p., b.i.d.) or vehicle on postnatal days P0-P6 and studied on P7. Carotid body volume was decreased by 35% after chronic K252a (P<0.001); a reduction in carotid body size was also elicited using the more selective TrkB antagonist ANA-12 (500 μg kg(-1), i.p., b.i.d.). In contrast, single-unit chemoafferent responses to 5% O2, measured in vitro, were unaffected by chronic K252a administration. Normoxic and hypoxic ventilation, measured by head-body plethysmography, were also normal after chronic K252a administration, but acute K252a administration produced a slower, deeper breathing pattern during the transition into hypoxia. These data suggest that BDNF regulates postnatal carotid body growth but does not influence the development of glomus cell O2 sensitivity. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Role of TrkB during the postnatal development of the rat carotid body

    PubMed Central

    Bavis, Ryan W.; Blegen, Halward J.; Logan, Sarah; Fallon, Sarah C.; McDonough, Amy B.

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) supports innervation of the carotid body by neurons projecting from the petrosal ganglion. Although carotid body glomus cells also express TrkB, BDNF’s high affinity receptor, the role of BDNF in carotid body growth and O2 sensitivity has not been studied. Neonatal rats were treated with the TrkB antagonist K252a (100 μg kg−1, i.p., b.i.d.) or vehicle on postnatal days P0–P6 and studied on P7. Carotid body volume was decreased by 35% after chronic K252a (P<0.001); a reduction in carotid body size was also elicited using the more selective TrkB antagonist ANA-12 (500 μg kg−1, i.p., b.i.d.). In contrast, single-unit chemoafferent responses to 5% O2, measured in vitro, were unaffected by chronic K252a administration. Normoxic and hypoxic ventilation, measured by head-body plethysmography, were also normal after chronic K252a administration, but acute K252a administration produced a slower, deeper breathing pattern during the transition into hypoxia. These data suggest that BDNF regulates postnatal carotid body growth but does not influence the development of glomus cell O2 sensitivity. PMID:26222433

  8. Mechanisms of carotid body chemoreflex dysfunction during heart failure

    PubMed Central

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

    2015-01-01

    Recent advances have drawn interest in the potential for carotid body (CB) ablation or desensitization as an effective strategy for clinical treatment and management of cardio-respiratory diseases including hypertension, heart failure, diabetes mellitus, metabolic syndrome, and renal failure. These disease states have in common sympathetic overactivity, which plays an important role in the development and progression of the disease and is often associated with breathing dysregulation, which in turn likely mediates or aggravates the autonomic imbalance. Evidence from both chronic heart failure (CHF) patients and animal models indicates that the CB chemoreflex is enhanced in CHF and contributes to the tonic elevation in sympathetic activity and the development of periodic breathing associated with the disease. Although this maladaptive change likely derives from altered function at all levels of the reflex arc, a tonic increase in afferent activity from CB glomus cells is likely to be a main driving force. This report will focus on our understanding of mechanisms that alter CB function in CHF and their potential translational impact on treatment of CHF. PMID:25398713

  9. Anion exchanger and chloride channel in cat carotid body chemotransduction.

    PubMed

    Iturriaga, R; Mokashi, A; Lahiri, S

    1998-05-28

    In order to test the hypothesis that carotid body (CB) chemoreception depends on the functions of anion channels and HCO3-/Cl- exchangers, we studied the effects of the anion channel blocker anthracene-9-carboxylic acid (9-ANC), the carbonic anhydrase inhibitor methazolamide, and the HCO3-/Cl- exchanger blocker 4,4 diisothiocyanatostilbene-2-2'disulfonic acid (DIDS) on the chemosensory discharges of cat CB, perfused-superfused in vitro at 36.5 +/- 0.5 degrees C, with a modified Tyrode solution. The chemosensory responses to hypoxia (PO2 approximately 50 Torr), hypercapnia (PCO2 approximately 60 Torr, pH = 7.10), nicotine (2-4 nmol) and NaCN (20-40 nmol) were recorded. 9-ANC (2 microM) and DIDS (10 microM) decreased the chemosensory baseline activity, and eliminated the initial peak responses to hypercapnia and hypoxia and increased the time to achieve it. Methazolamide (0.13 mM) did not alter the effect of 9-ANC. The steady state responses to hypoxia and hypercapnia were not diminished after 9-ANC but DIDS lowered the responses. Responses to NaCN effects were all diminished but those to nicotine were not affected. The results suggest that the functions of anion channels and HCO3-/Cl- exchangers are important for the resting dischargers and for the fast responses to hypoxia and hypercapnia.

  10. Carotid body oxygen sensing and adaptation to hypoxia.

    PubMed

    López-Barneo, José; Macías, David; Platero-Luengo, Aida; Ortega-Sáenz, Patricia; Pardal, Ricardo

    2016-01-01

    The carotid body (CB) is the principal arterial chemoreceptor that mediates the hyperventilatory response to hypoxia. Our understanding of CB function and its role in disease mechanisms has progressed considerably in the last decades, particularly in recent years. The sensory elements of the CB are the neuron-like glomus cells, which contain numerous transmitters and form synapses with afferent sensory fibers. The activation of glomus cells under hypoxia mainly depends on the modulation of O2-sensitive K(+) channels which leads to cell depolarization and the opening of Ca(2+) channels. This model of sensory transduction operates in all mammalian species studied thus far, including man. However, the molecular mechanisms underlying the modulation of ion channel function by changes in the O2 level are as yet unknown. The CB plays a fundamental role in acclimatization to sustained hypoxia. Mice with CB atrophy or patients who have undergone CB resection due to surgical treatments show a marked intolerance to even mild hypoxia. CB growth under hypoxia is supported by the existence of a resident population of neural crest-derived stem cells of glia-like phenotype. These stem cells are not highly affected by exposure to low O2 tension; however, there are abundant synapse-like contacts between the glomus cells and stem cells (chemoproliferative synapses), which may be needed to trigger progenitor cell proliferation and differentiation under hypoxia. CB hypo- or hyper-activation may also contribute to the pathogenesis of several prevalent human diseases.

  11. Magnetic resonance and computed tomography imaging of a carotid body tumor in a dog

    PubMed Central

    2012-01-01

    A 5-year-old castrated male Labrador Retriever was presented to a referring veterinarian for a swelling in the neck region. Based on the results of histopathology, a carotid body tumor, was diagnosed. The dog was referred to a medical imaging unit for further staging and follow up. This report describes the magnetic resonance (MR) and computed tomographic (CT) appearance of a carotid body tumor. PMID:22507757

  12. Magnetic resonance and computed tomography imaging of a carotid body tumor in a dog.

    PubMed

    Kromhout, Kaatje; Gielen, Ingrid; De Cock, Hilde E V; Van Dyck, Kristof; van Bree, Henri

    2012-04-16

    A 5-year-old castrated male Labrador Retriever was presented to a referring veterinarian for a swelling in the neck region. Based on the results of histopathology, a carotid body tumor, was diagnosed. The dog was referred to a medical imaging unit for further staging and follow up. This report describes the magnetic resonance (MR) and computed tomographic (CT) appearance of a carotid body tumor.

  13. Occurrence of neutral endopeptidase activity in the cat carotid body and its significance in chemoreception.

    PubMed

    Kumar, G K; Runold, M; Ghai, R D; Cherniack, N S; Prabhakar, N R

    1990-05-28

    The carotid body contains both tachykinins and enkephalins. Neutral endopeptidase (NEP, E.C. 3.4.24.11), has been suggested to involve in the metabolism of these neuropeptides in several organs. In the present study we determined neutral endopeptidase activity of the cat carotid body and assessed its significance in chemoreception. The cytosolic and membrane fractions of the carotid body contained NEP-like activity whereas it occurred only in the membrane fractions of the superior cervical and the nodose ganglia. Phosphoramidon, thiorphan and metal ion chelators inhibited NEP-like activity of all the 3 tissues studied; other protease inhibitors, however, were ineffective. Close carotid body administration of phosphoramidon significantly potentiated the carotid body response to low PO2 but not to hypercapnia. The enhanced response to hypoxia following phosphoramidon was further augmented by naloxone, an enkephalin antagonist. These results demonstrate that the glomus tissue contains detectable amounts of NEP-like activity and its inhibition selectively affects the hypoxic response of the carotid body.

  14. A simple technique to achieve bloodless excision of carotid body tumors.

    PubMed

    Spinelli, Francesco; Massara, Mafalda; La Spada, Michele; Stilo, Francesco; Barillà, David; De Caridi, Giovanni

    2014-05-01

    We describe a technique for Shamblin II-III carotid body tumor (CBT) resection to reduce bleeding and neurologic complications during surgery. The technique was based on the fact that CBTs are supplied almost exclusively from the external carotid artery. Therefore, we carefully isolated the origin of the external carotid artery and its distal branches outside the tumor and temporarily clamped all of these vessels after heparin administration. This allowed a safe and bloodless resection as the tumor was dissected from the internal carotid artery in the usual subadventitial plane. The internal carotid artery was never clamped, and respect of peripheral nerves was warranted in the clean and bloodless field. From 2007 to 2010, we treated 11 patients with a CBT: six had a Shamblin II and five had a Shamblin III lesion. Neither perioperative neurologic events nor recurrences occurred after a mean follow-up of 42 months.

  15. Baroreflex activation therapy lowers arterial pressure without apparent stimulation of the carotid bodies.

    PubMed

    Alnima, Teba; Goedhart, Emilie J B M; Seelen, Randy; van der Grinten, Chris P M; de Leeuw, Peter W; Kroon, Abraham A

    2015-06-01

    Carotid baroreflex activation therapy produces a sustained fall in blood pressure in patients with resistant hypertension. Because the activation electrodes are implanted at the level of the carotid sinus, it is conceivable that the nearby located carotid body chemoreceptors are stimulated as well. Physiological stimulation of the carotid chemoreceptors not only stimulates respiration but also increases sympathetic activity, which may counteract the effects of baroreflex activation. The aim of this exploratory study is to investigate whether there is concomitant carotid chemoreflex activation during baroreflex activation therapy. Fifteen participants with the Rheos system were included in this single-center study. At arrival at the clinic, the device was switched off for 2 hours while patients were at rest. Subsequently, the device was switched on at 6 electric settings of high and low frequencies and amplitudes. Respiration and blood pressure measurements were performed during all device activation settings. Multilevel statistical models were adjusted for age, sex, body mass index, antihypertensive therapeutic index, sleep apnea, coronary artery disease, systolic blood pressure, and heart rate. There was no change in end-tidal carbon dioxide, partial pressure of carbon dioxide, breath duration, and breathing frequency during any of the electric settings with the device. Nevertheless, mean arterial pressure showed a highly significant decrease during electric activation (P<0.001). Carotid baroreflex activation therapy using the Rheos system did not stimulate respiration at several electric device activation energies, which suggests that there is no appreciable coactivation of carotid body chemoreceptors during device therapy. © 2015 American Heart Association, Inc.

  16. Neonatal Maternal Separation Augments Carotid Body Response to Hypoxia in Adult Males but Not Female Rats

    PubMed Central

    Soliz, Jorge; Tam, Rose; Kinkead, Richard

    2016-01-01

    Perinatal exposure to adverse experiences disrupts brain development, including the brainstem network that regulates breathing. At adulthood, rats previously subjected to stress (in the form of neonatal maternal separation; NMS) display features reported in patients suffering from sleep disordered breathing, including an increased hypoxic ventilatory response and hypertension. This effect is also sex-specific (males only). Based on these observations, we hypothesized that NMS augments the carotid body's O2-chemosensitivity. Using an isolated and perfused ex vivo carotid body preparation from adult rats we compared carotid sinus nerve (CSN) responses to hypoxia and hypercapnia in carotid bodies harvested from adult rats that either experienced control conditions (no experimental manipulation) or were subjected to NMS (3 h/day from postnatal days 3 to 12). In males, the CSN response to hypoxia measured in preparations from NMS males was 1.5 fold higher than controls. In control rats, the female's response was similar to that of males; however, the increase in CSN activity measured in NMS females was 3.0 times lower than controls. The CSN response to hypercapnia was not influenced by stress or sex. We conclude that NMS is sufficient to have persistent and sex-specific effects on the carotid body's response to hypoxia. Because NMS also has sex-specific effects on the neuroendocrine response to stress, we propose that carotid body function is influenced by stress hormones. This, in turn, leads to a predisposition toward cardio-respiratory disorders. PMID:27729873

  17. Preoperative embolization in carotid body tumor surgery: is it required?

    PubMed

    Zeitler, Daniel M; Glick, Joelle; Har-El, Gady

    2010-05-01

    We compared estimated blood loss (EBL) in patients who underwent surgical excision of carotid body tumors (CBTs) after preoperative superselective angiography with embolization (PSE) with that in patients who underwent excision of CBTs without PSE. We performed a retrospective chart review of a consecutive case series in a single surgeon's practice within an academic tertiary care medical center. Twenty-five patients underwent surgical resection of a CBT from 1989 to 2009. From 1989 to 1996, 10 consecutive patients had PSE of the CBT, whereas the subsequent 15 patients (1996 to 2009) had no PSE. Demographic data including age, sex, and tumor size were collected. The EBL was obtained from intraoperative records and operative notes dictated at the time of surgery. Tumor size was based on preoperative radiographic measurements by a senior radiologist and the surgeon. In the 10 patients with PSE, the mean age was 41 years (range, 22 to 72 years) and the mean tumor size was 4.8 cm (range, 2.9 to 8.3 cm). The mean EBL was 305 mL (range, 50 to 1,000 mL); 2 patients had an EBL of more than 400 mL. In the 15 patients without PSE, the mean age was 43.7 years (range, 20 to 75 years) and the mean tumor size was 4.4 cm (range, 2.8 to 7.9 cm). The mean EBL was 265.6 mL (range, 40 to 900 mL); 2 patients had an EBL of more than 400 mL. There were no significant differences between the 2 groups with regard to age, tumor size, or EBL. Preoperative superselective angiography with embolization of a CBT does not lead to a significant reduction in intraoperative EBL.

  18. Carotid body potentiation during chronic intermittent hypoxia: implication for hypertension

    PubMed Central

    Del Rio, Rodrigo; Moya, Esteban A.; Iturriaga, Rodrigo

    2014-01-01

    Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH). It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB) chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14, and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS, and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function. PMID:25429271

  19. Revisiting cAMP signaling in the carotid body

    PubMed Central

    Nunes, Ana R.; Holmes, Andrew P.; Conde, Sílvia V.; Gauda, Estelle B.; Monteiro, Emília C.

    2014-01-01

    Chronic carotid body (CB) activation is now recognized as being essential in the development of hypertension and promoting insulin resistance; thus, it is imperative to characterize the chemotransduction mechanisms of this organ in order to modulate its activity and improve patient outcomes. For several years, and although controversial, cyclic adenosine monophosphate (cAMP) was considered an important player in initiating the activation of the CB. However, its relevance was partially displaced in the 90s by the emerging role of the mitochondria and molecules such as AMP-activated protein kinase and O2-sensitive K+ channels. Neurotransmitters/neuromodulators binding to metabotropic receptors are essential to chemotransmission in the CB, and cAMP is central to this process. cAMP also contributes to raise intracellular Ca2+ levels, and is intimately related to the cellular energetic status (AMP/ATP ratio). Furthermore, cAMP signaling is a target of multiple current pharmacological agents used in clinical practice. This review (1) provides an outline on the classical view of the cAMP-signaling pathway in the CB that originally supported its role in the O2/CO2 sensing mechanism, (2) presents recent evidence on CB cAMP neuromodulation and (3) discusses how CB activity is affected by current clinical therapies that modify cAMP-signaling, namely dopaminergic drugs, caffeine (modulation of A2A/A2B receptors) and roflumilast (PDE4 inhibitors). cAMP is key to any process that involves metabotropic receptors and the intracellular pathways involved in CB disease states are likely to involve this classical second messenger. Research examining the potential modification of cAMP levels and/or interactions with molecules associated with CB hyperactivity is currently in its beginning and this review will open doors for future explorations. PMID:25389406

  20. Carotid artery remodelling in relation to body fat distribution, inflammation and sustained weight loss in obesity.

    PubMed

    Kardassis, D; Schönander, M; Sjöström, L; Karason, K

    2014-05-01

    Obesity is known to be associated with carotid artery remodelling, but less is known about how body fat distribution, inflammation and weight loss may affect this relation. Ultrasonography, dual-energy X-ray absorptiometry and computed tomography were performed to evaluate carotid artery intima-media thickness (IMT), body composition and fat distribution, respectively. Participants were divided into three matched study groups (n = 44 per group): obese patients with sustained weight loss 10 years after bariatric surgery [surgery group, body mass index (BMI) 31.5 kg m(-2)]; obese patients who maintained stable weight during the same time period (obese group, BMI 42.5 kg m(-2)); and normal weight subjects (lean group, BMI 24.4 kg m(-2)). Patients in the surgery group, compared with those in the obese group, had slightly lower common carotid artery (CCA) IMT (0.75 ± 0.18 vs. 0.78 ± 0.17 mm) and common carotid bulb (CCB) IMT (0.92 ± 0.32 vs. 0.97 ± 0.32 mm); however, these differences were not statistically significant. Lean individuals, compared with those in the surgery group, had significantly lower CCA and CCB IMT values (P < 0.001). In forward stepwise multiple regression analyses including all subjects (n = 132), CCA IMT was predicted mainly by visceral adipose tissue, but was also related to blood pressure and levels of triglycerides and high-sensitivity C-reactive protein. Carotid lumen diameter was primarily influenced by lean body mass. Visceral adiposity was the main determinant of premature carotid artery atherosclerosis, possibly through elevated blood pressure, dyslipidaemia and inflammation. Lean body mass predicted carotid artery lumen diameter. Obese patients with long-term sustained weight loss did not have thinner carotid artery walls compared with their weight-stable obese counterparts. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  1. Optical measurements of the dependence of chemoreception on oxygen pressure in the cat carotid body.

    PubMed

    Rumsey, W L; Iturriaga, R; Spergel, D; Lahiri, S; Wilson, D F

    1991-10-01

    The relationship between oxygen pressure (PO2) in the carotid body and carotid sinus nerve discharge was evaluated in the isolated perfused/superfused cat carotid body using the oxygen-dependent quenching of phosphorescence. Images of phosphorescence intensity arising from Pd-coproporphyrin within the microcirculation of the carotid body provided measurements of intravascular PO2. These measurements were substantiated by determining phosphorescence life-time. The carotid body was perfused in the isolated state via the common carotid artery with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered Tyrode solution, pH 7.4, at a constant pressure of 80 mmHg. Superfusion was maintained with similar media equilibrated with 100% argon. PO2 in the exchange vessels was markedly less than that in the perfusate entering the carotid artery, 23 +/- 3 and 45 +/- 3 Torr for normoxic (111 +/- 15 Torr) and hyperoxic (345 +/- 72 Torr) perfusates, respectively. Chemosensory discharge rose slowly in response to a brief interruption of perfusate flow as PO2 steadily declined from either of these capillary PO2 values to approximately 10 Torr. Between approximately 10 and 3 Torr, chemosensory discharge increased strikingly, concomitant with an enhanced rate of oxygen disappearance, from -36 +/- 4 to -69 +/- 13 (92% change) and -28 +/- 3 to -48 +/- 3 (71% change) Torr/s for normoxic and hyperoxic perfusates, respectively. As PO2 fell below approximately 3 Torr, oxygen disappearance slowed and neural activity decayed. Thus the relationships between microvascular PO2 and chemosensory discharge and between oxygen disappearance and neural discharge suggest that oxygen metabolism in the carotid body determines the expression of oxygen chemoreception.

  2. Effects of hypoxia on catecholamine synthesis in rabbit carotid body in vitro

    PubMed Central

    Fidone, S.; Gonzalez, C.; Yoshizaki, K.

    1982-01-01

    1. Unanaesthetized, unrestrained rabbits were exposed for 3 hr in a chamber to either air, hypoxic gas mixtures (10% or 14% O2 in N2) or a hyperoxic gas mixture (50% O2 in N2). The carotid bodies were then removed and incubated for 3 hr in modified Tyrode media equilibrated with 100% O2 and containing either [3H]tyrosine or [3H]DOPA. The contents of [3H]DA and [3H]NA in the tissue were determined as described in the preceding paper. 2. When [3H]DOPA was used as precursor, neither labelled dopamine (DA) or noradrenaline (NA) synthesis was increased in carotid bodies from rabbits exposed to 10% O2 in N2. Following exposure to 10% O2 in N2 and incubation with [3H]tyrosine, however, [3H]DA synthesis was increased by 72% above control (air) values while [3H]NA synthesis was unchanged. Less severe hypoxia, 14% O2 in N2, resulted in a smaller increase in [3H]DA synthesis, i.e. 53% above control value. Again, [3H]NA synthesis was unchanged. Similar experiments with the superior cervical ganglion involving exposure of the animals to either 10% or 14% O2 in N2 did not produce any change in the amounts of [3H]DA or [3H]NA synthesized from [3H]tyrosine when compared to control animals breathing air. 3. Sympathectomy of the carotid body or transection of the carotid sinus nerve 12-15 days prior to hypoxic exposure (10% O2 in N2) did not alter the increase in [3H]DA synthesis compared to normally innervated carotid bodies. 4. Carotid bodies incubated with [3H]tyrosine for 2 hr in an alternating O2/N2 sequence (5 min in media equilibrated with 100% O2 followed by 3 min in media equilibrated with 100% N2) synthesized 37% more [3H]DA than control carotid bodies similarly exposed to an alternating O2/O2 sequence. [3H]NA synthesis was unchanged. However, tissue levels of non-metabolized [3H]tyrosine were reduced by 19% in the carotid bodies exposed to the O2/N2 sequence. 5. Exposure of rabbits for 3 hr to 50% O2 in N2, followed by incubation of their carotid bodies in [3H

  3. AMP-ACTIVATED PROTEIN KINASE MEDIATES CAROTID BODY EXCITATION BY HYPOXIA*

    PubMed Central

    Wyatt, Christopher N.; Mustard, Kirsty J.W.; Pearson, Selina A.; Dallas, Mark L; Atkinson, Lucy; Kumar, Prem; Peers, Chris; Hardie, D. Grahame; Evans, A. Mark

    2007-01-01

    Early detection of an O2 deficit in the bloodstream is essential to initiate corrective changes in the breathing pattern of mammals. Carotid bodies serve an essential role in this respect;their type I cells depolarize when O2 levels fall, causing voltage-gated Ca2+ entry. Subsequent neurosecretion elicits increased afferent chemosensory fibre discharge to induce appropriate changes in respiratory function (1). Whilst depolarization of type I cells by hypoxia is known to arise from K+ channel inhibition, the identity of the signalling pathway has been contested and the coupling mechanism is unknown (2). We tested the hypothesis that AMP-activated protein kinase (AMPK)1 is the effector of hypoxic chemotransduction. AMPK is co-localized at the plasma membrane of type I cells with O2-sensitive K+ channels. In isolated type I cells, activation of AMPK using AICAR inhibited O2-sensitive K+ currents (carried by large conductance Ca2+-activated (BKCa) channels and TASK-like channels), leading to plasma membrane depolarization, Ca2+ influx and increased chemosensory fibre discharge. Conversely, the AMPK antagonist compound C reversed the effects of hypoxia and AICAR on type I cell and carotid body activation. These results suggest that AMPK activation is both sufficient and necessary for the effects of hypoxia. Furthermore, AMPK activation inhibited currents carried by recombinant BKCa channels while purified AMPK phosphorylated the α subunit of the channel in immunoprecipitates, an effect that was stimulated by AMP and inhibited by compound C. Our findings demonstrate a central role for AMPK in stimulus-response coupling by hypoxia, and identify for the first time a link between metabolic stress and ion channel regulation in an O2-sensing system. PMID:17179156

  4. [Arterial chemoreceptors: cellular and molecular mechanisms in the adaptative and homeostatic function of the carotid body].

    PubMed

    González, C; Rocher, A; Zapata, P

    The carotid body is a sensory chemoreceptor organ located in the vicinity of the carotid bifurcation. Structurally it is composed of cell clusters formed by chemoreceptor and supporting cells. The sensory nerve endings of the carotid sinus nerve penetrate the clusters to synapse with chemoreceptor cells. The carotid body plays an important role in the control of ventilation during hypoxia, hypercapnia and acidosis. Hypoxia and other natural stimuli are detected by chemoreceptor cells which upon stimulation increase their rate of release of neurotransmitters. Neurotransmitters in turn increase the action potential frequency in the carotid sinus nerve which via its central projections to the brainstem activates ventilation. This review is devoted to the cellular aspects of the function of this chemoreceptor organ. From a brief description of the complex structure of the carotid body, we go to present a summary of the main prevailing theories concerning the transduction mechanisms for hypoxic and acidic/hypercapnic stimuli, with special emphasis on the electrical properties of cultured chemoreceptors cells. A special attention is provided to the possible significance of reactive oxygen species as mediators of the hypoxic transduction cascade. The neurotransmission between chemoreceptor cells and the sensory nerve endings is also covered in certain detail. After a brief historical presentation of the theories of communication between these two structures, we examine, following the classical criteria of neurotransmission, the functional significance of acetylcholine, dopamine, substance P and other neurotransmitters known to be present in chemoreceptor cells.

  5. Effects of low oxygen on the release of dopamine from the rabbit carotid body in vitro

    PubMed Central

    Fidone, S.; Gonzalez, C.; Yoshizaki, K.

    1982-01-01

    1. Rabbit carotid bodies were pre-loaded with [3H]dopamine (DA) synthesized from [3H]tyrosine and then mounted in a vertical drop-type superfusion chamber which permitted simultaneous collection of released [3H]DA and recording of chemoreceptor discharge from the carotid sinus nerve. 2. The time course of the spontaneous release of [3H]DA (superfusion with media equilibrated with 100% O2) in the presence of monoamine oxidase inhibitors exhibited two linear components, an initial steep phase followed after 3-4 hr by a later slower phase of release. 3. When a 5 min low O2 stimulus was delivered during the initial steep linear component of resting [3H]DA release, there was an abrupt increase in release, the magnitude of which was stimulus-dependent. 4. The efflux of total radioactivity from the preparation declined exponentially with time; under resting conditions it was principally non-metabolized [3H]tyrosine. During stimulation, however the efflux increased, and 60-80% of the radioactivity could be attributed to [3H]DA. 5. For a given low O2 stimulus, the ratio of [3H]DA release during the stimulus period over that in the preceding control period remained approximately the same throughout a single experiment. Ratios for different low O2 stimuli (50, 40, 30, 20, 10 and 0% O2 in N2) yielded a parabolic relationship when plotted against stimulus intensity. 6. Transection of the carotid sinus nerve or removal of the superior cervical ganglion 12-15 days prior to the experiment did not affect the release of [3H]DA at moderate stimulus intensities (superfusion with media equilibrated with 30% or 10% O2 in N2) but both procedures significantly depressed release at the highest stimulus intensity (100% N2). 7. Chemoreceptor discharge and [3H]DA release were simultaneously monitored in experiments using superfusion media free of monoamine oxidase inhibitors. In these experiments, the efflux of [3H]dihydroxyphenyl acetic acid (DOPAC) was also measured. The increase in peak

  6. New predictors of complications in carotid body tumor resection.

    PubMed

    Kim, Gloria Y; Lawrence, Peter F; Moridzadeh, Rameen S; Zimmerman, Kate; Munoz, Alberto; Luna-Ortiz, Kuauhyama; Oderich, Gustavo S; de Francisco, Juan; Ospina, Jorge; Huertas, Santiago; de Souza, Leonardo R; Bower, Thomas C; Farley, Steven; Gelabert, Hugh A; Kret, Marcus R; Harris, E John; De Caridi, Giovanni; Spinelli, Francesco; Smeds, Matthew R; Liapis, Christos D; Kakisis, John; Papapetrou, Anastasios P; Debus, Eike S; Behrendt, Christian-A; Kleinspehn, Edgar; Horton, Joshua D; Mussa, Firas F; Cheng, Stephen W K; Morasch, Mark D; Rasheed, Khurram; Bennett, Matthew E; Bismuth, Jean; Lumsden, Alan B; Abularrage, Christopher J; Farber, Alik

    2017-06-01

    This study examined the relationship between two new variables, tumor distance to base of skull (DTBOS) and tumor volume, with complications of carotid body tumor (CBT) resection, including bleeding and cranial nerve injury. Patients who underwent CBT resection between 2004 and 2014 were studied using a standardized, multi-institutional database. Demographic, perioperative, and outcomes data were collected. CBT measurements were determined from computed tomography, magnetic resonance imaging, and ultrasound examination. There were 356 CBTs resected in 332 patients (mean age, 51 years; 72% female); 32% were classified as Shamblin I, 43% as Shamblin II, and 23% as Shamblin III. The mean DTBOS was 3.3 cm (standard deviation [SD], 2.1; range, 0-10), and the mean tumor volume was 209.7 cm(3) (SD, 266.7; range, 1.1-1642.0 cm(3)). The mean estimated blood loss (EBL) was 257 mL (SD, 426; range, 0-3500 mL). Twenty-four percent of patients had cranial nerve injuries. The most common cranial nerves injured were the hypoglossal (10%), vagus (11%), and superior laryngeal (5%) nerves. Both Shamblin grade and DTBOS were statistically significantly correlated with EBL of surgery and cranial nerve injuries, whereas tumor volume was statistically significantly correlated with EBL. The logistic model for predicting blood loss and cranial nerve injury with all three variables-Shamblin, DTBOS, and volume (R(2) = 0.171, 0.221, respectively)-was superior to a model with Shamblin alone (R(2) = 0.043, 0.091, respectively). After adjusting for Shamblin grade and volume, every 1-cm decrease in DTBOS was associated with 1.8 times increase in risk of >250 mL of blood loss (95% confidence interval, 1.25-2.55) and 1.5 times increased risk of cranial nerve injury (95% confidence interval, 1.19-1.92). This large study of CBTs demonstrates the value of preoperatively determining tumor dimensions and how far the tumor is located from the base of the skull. DTBOS and tumor volume, when used

  7. Chronic hyperoxia alters the expression of neurotrophic factors in the carotid body of neonatal rats.

    PubMed

    Dmitrieff, Elizabeth F; Wilson, Julia T; Dunmire, Kyle B; Bavis, Ryan W

    2011-02-15

    Chronic exposure to hyperoxia alters the postnatal development and innervation of the rat carotid body. We hypothesized that this plasticity is related to changes in the expression of neurotrophic factors or related proteins. Rats were reared in 60% O(2) from 24 to 36h prior to birth until studied at 3d of age (P3). Protein levels for brain-derived neurotrophic factor (BDNF) were significantly reduced (-70%) in the P3 carotid body, while protein levels for its receptor, tyrosine kinase B, and for glial cell line-derived neurotrophic factor (GDNF) were unchanged. Transcript levels in the carotid body were downregulated for the GDNF receptor Ret (-34%) and the neuropeptide Vgf (-67%), upregulated for Cbln1 (+205%), and unchanged for Fgf2; protein levels were not quantified for these genes. Immunohistochemical analysis revealed that Vgf and Cbln1 proteins are expressed within the carotid body glomus cells. These data suggest that BDNF, and perhaps other neurotrophic factors, contribute to abnormal carotid body function following perinatal hyperoxia.

  8. Evidence for a carotid body homolog in the lizard Tupinambis merianae.

    PubMed

    Reichert, Michelle N; Brink, Deidre L; Milsom, William K

    2015-01-15

    The homolog to the mammalian carotid body has not yet been identified in lizards. Observational studies and evolutionary history provide indirect evidence for the existence of a chemoreceptor population at the first major bifurcation of the common carotid artery in lizards, but a chemoreceptive role for this area has not yet been definitively demonstrated. We explored this possibility by measuring changes in cardiorespiratory variables in response to focal arterial injections of the hypoxia mimic sodium cyanide (NaCN) into the carotid artery of 12 unanesthetized specimens of Tupinambis merianae. These injections elicited increases in heart rate (f(H); 101±35% increase) and respiratory rate (f(R); 620±119% increase), but not mean arterial blood pressure (MAP). These responses were eliminated by vagal denervation. Similar responses were elicited by injections of the neurotransmitters acetylcholine (ACh) and serotonin (5-HT) but not norepinephrine. Heart rate and respiratory rate increases in response to NaCN could be blocked or reduced by antagonists to ACh (atropine) and/or 5-HT (methysergide). Finally, using immunohistochemistry, we demonstrate the presence of putative chemoreceptive cells immunopositive for the cholinergic cell marker vesicular ACh transporter (VAChT) and 5-HT on internal lattice-like structures at the carotid bifurcation. These results provide evidence in lizards for the existence of dispersed chemoreceptor cells at the first carotid bifurcation in the central cardiovascular area that have similar properties to known carotid body homologs, adding to the picture of chemoreceptor evolution in vertebrates.

  9. Carotid baroreceptor influence on forearm vascular resistance during low level lower body negative pressure

    NASA Technical Reports Server (NTRS)

    Thompson, Cynthia A.; Ludwig, David A.; Convertino, Victor A.

    1991-01-01

    The degree of forearm vasoconstriction induced by low levels of lower body negative pressure (LBNP) provides a measure of the responsiveness of the cardiopulmonary baroreflex. The validity of this measurement is based on the assumption that this vasoconstriction response is not influenced by unloading of carotid baroreceptors. To test the hypothesis that arterial baroreceptor unloading does not alter the degree of forearm vascular resistance during low levels of LBNP, 12 subjects were exposed to -15 and -20 mm Hg LBNP with and without additional artificial (+ 10 mm Hg neck pressure) unloading of the carotid baroreceptors. There was no measurable influence of carotid unloading on forearm vascular resistance at either level of LBNP. It is concluded that forearm vascular resistance measured during cardiopulmonary baroreceptor unloading is unaffected by carotid baroreceptor unloading within the magnitude encountered during low levels of LBNP.

  10. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension.

    PubMed

    Moraes, Davi J A; Machado, Benedito H; Paton, Julian F R

    2015-07-15

    Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension.

  11. Efferent inhibition of carotid body chemoreception in chronically hypoxic cats.

    PubMed

    Lahiri, S; Smatresk, N; Pokorski, M; Barnard, P; Mokashi, A

    1983-11-01

    The effects of chronic hypoxia on carotid chemoreceptor afferent activity before and after sectioning the carotid sinus nerves (CSN) were studied in cats exposed to 10% O2 for 21-49 days in a chamber at sea level. For comparison, chronically normoxic cats at sea level were also studied. The cats were anesthetized, paucifiber preparation for the measurement of carotid chemosensory activity from a small slip of CSN was made, and their steady-state responses to 4-5 levels of arterial pressure of O2 (PaO2) at a constant PaCO2 and to 3-4 levels of PaCO2 in hyperoxia were measured before and after sectioning the CSN. The chemosensory response to hypoxia in the cats with intact CSN after chronic exposure to hypoxia was not reduced relative to the cats that breathed room air at sea level. Sectioning the CSN significantly augmented the chemosensory responses to hypoxia in all the chronically hypoxic but not significantly in the normoxic cats. The responses to moderate hypercapnia during hyperoxia were not significantly changed by cutting the CSN in either group. We conclude that there is a significant CSN efferent inhibition of chemosensory activity due to chronic hypoxia in the cat. This implies that without the efferent inhibition the hypoxic chemosensitivity is increased by chronic hypoxia.

  12. Long-term regulation of carotid body function: acclimatization and adaptation--invited article.

    PubMed

    Prabhakar, N R; Peng, Y-J; Kumar, G K; Nanduri, J; Di Giulio, C; Lahiri, Sukhamay

    2009-01-01

    Physiological responses to hypoxia either continuous (CH) or intermittent (IH) depend on the O(2)-sensing ability of the peripheral arterial chemoreceptors, especially the carotid bodies, and the ensuing reflexes play important roles in maintaining homeostasis. The purpose of this article is to summarize the effects of CH and IH on carotid body function and the underlying mechanisms. CH increases baseline carotid body activity and sensitizes the response to acute hypoxia. These effects are associated with hyperplasia of glomus cells and neovascularization. Enhanced hypoxic sensitivity is due to alterations in ion current densities as well as changes in neurotransmitter dynamics and recruitment of additional neuromodulators (endothelin-1, ET-1) in glomus cells. Morphological alterations are in part due to up-regulation of growth factors (e.g. VEGF). Hypoxia-inducible factor-1 (HIF-1), a transcriptional activator might underlie the remodeling of carotid body structure and function by CH. Chronic IH, on the other hand, is associated with recurrent apneas in adults and premature infants. Two major effects of chronic IH on the adult carotid body are sensitization of the hypoxic sensory response and long-lasting increase in baseline activity i.e., sensory long-term facilitation (LTF) which involve reactive oxygen species (ROS) and HIF-1. In neonates, chronic IH leads to sensitization of the hypoxic response but does not induce sensory LTF. Chronic IH-induced sensitization of the carotid body response to hypoxia increases the likelihood of unstable breathing perpetuating in more number of apneas, whereas sensory LTF may contribute to increased sympathetic tone and systemic hypertension associated with recurrent apneas.

  13. Long-Term Regulation of Carotid Body Function: Acclimatization and Adaptation – Invited Article

    PubMed Central

    Prabhakar, N.R.; Peng, Y.-J.; Kumar, G.K.; Di Giulio, C.; Lahiri, Sukhamay

    2014-01-01

    Physiological responses to hypoxia either continuous (CH) or intermittent (IH) depend on the O2-sensing ability of the peripheral arterial chemoreceptors, especially the carotid bodies, and the ensuing reflexes play important roles in maintaining homeostasis. The purpose of this article is to summarize the effects of CH and IH on carotid body function and the underlying mechanisms. CH increases baseline carotid body activity and sensitizes the response to acute hypoxia. These effects are associated with hyperplasia of glomus cells and neovascularization. Enhanced hypoxic sensitivity is due to alterations in ion current densities as well as changes in neurotransmitter dynamics and recruitment of additional neuromodulators (endothelin-1, ET-1) in glomus cells. Morphological alterations are in part due to up-regulation of growth factors (e.g. VEGF). Hypoxia-inducible factor-1 (HIF-1), a transcriptional activator might underlie the remodeling of carotid body structure and function by CH. Chronic IH, on the other hand, is associated with recurrent apneas in adults and premature infants. Two major effects of chronic IH on the adult carotid body are sensitization of the hypoxic sensory response and long-lasting increase in baseline activity i.e., sensory long-term facilitation (LTF) which involve reactive oxygen species (ROS) and HIF-1. In neonates, chronic IH leads to sensitization of the hypoxic response but does not induce sensory LTF. Chronic IH-induced sensitization of the carotid body response to hypoxia increases the likelihood of unstable breathing perpetuating in more number of apneas, whereas sensory LTF may contribute to increased sympathetic tone and systemic hypertension associated with recurrent apneas. PMID:19536494

  14. Iatrogenic central retinal artery occlusion after carotid body tumor embolization and excision.

    PubMed

    Rangel, Carlos M; Jaramillo, Sergio; Varón, Clara L; Prada, Angélica M

    2017-01-01

    Objective: To report a case of iatrogenic central retinal artery occlusion after embolization and surgical resection of carotid body paraganglioma. Methods: Case report Results: One adult female patient presented with persistent unilateral visual loss after embolization with Embosphere(®) and Contour(®) microparticles of carotid body tumor. Fluorescein angiography revealed intraluminal microspheres in the central retinal artery ramifications. OCT revealed intraretinal spherical, hyporeflective particles with posterior shadowing. Conclusions: Central retinal artery occlusion should be assessed as a possible complication after surgical repair of head and neck paragangliomas.

  15. Iatrogenic central retinal artery occlusion after carotid body tumor embolization and excision

    PubMed Central

    Rangel, Carlos M.; Jaramillo, Sergio; Varón, Clara L.; Prada, Angélica M.

    2017-01-01

    Objective: To report a case of iatrogenic central retinal artery occlusion after embolization and surgical resection of carotid body paraganglioma. Methods: Case report Results: One adult female patient presented with persistent unilateral visual loss after embolization with Embosphere® and Contour® microparticles of carotid body tumor. Fluorescein angiography revealed intraluminal microspheres in the central retinal artery ramifications. OCT revealed intraretinal spherical, hyporeflective particles with posterior shadowing. Conclusions: Central retinal artery occlusion should be assessed as a possible complication after surgical repair of head and neck paragangliomas. PMID:28401029

  16. Effect of CO on VO2 of carotid body and chemoreception with and without Ca2+.

    PubMed

    Lahiri, S; Buerk, D G; Osanai, S; Mokashi, A; Chugh, D K

    1997-09-10

    This study was done using high PCO (> 500 Torr at PO2 of 120 Torr) in the carotid body perfusate in vitro, and recording simultaneously the activity of the whole carotid sinus nerve (CSN) and VO2 of the carotid body. In the cascade of excitation of CSN by high PCO in the dark [light eliminated the excitation; S. Lahiri, News Physiol. Sci. 9 (1992) 161-165], Ca2+ effects occur at the level of neurosecretion after the level of oxygen consumption, according to the following scheme: CO-hypoxia-->VO2 decrease-->K+ conductance decrease-->cell depolarization-->cytosolic Ca2+ rise-->neurosecretion-->neural discharge. Thus, a part of the hypothesis was that [Ca2+] decrease, being a downstream event, may not affect VO2 of the carotid body. Also, to determine to what extent the intracellular calcium stores contribute to cystolic [Ca2+] and chemosensory discharge with high PCO, we tested the effect of interruption of perfusate flow with medium nominally free of [Ca2+] on CSN excitation and VO2 of the carotid body with and without high PCO. High PCO in the dark decreased carotid body VO2, independent of [Ca2+]o. CSN excitation was always enhanced by high PCO, and its sensitivity to perfusate flow interruption. Also, nominally Ca(2+)-free solution increased the latency and decreased the rate of rise and peak activity of CSN during interruption of perfusate flow, but CO augmented the responses. This reversal effect by CO suggests that Ca2+ is released from intracellular stores, because CO has no other way to excite the chemoreceptors than by acting on the intracellular stores.

  17. Aortic and carotid body chemoreception in prolonged hyperoxia in the cat.

    PubMed

    Mokashi, A; Lahiri, S

    1991-11-01

    Carotid body chemosensory response to hypoxia is attenuated as a result of prolonged normobaric hyperoxia (NH) in the cat. The effect of NH is likely to be due to high cellular PO2 and O2-related free radicals. Accordingly, the effect would be less if O2 delivery to the chemoreceptor tissue could be compromised. The aortic bodies, which appear to have less of a circulatory O2 delivery, as suggested by their vigorous responses to a slight compromise of O2 flow compared with those of the carotid body, could provide a suitable testing material for the hypothesis. We tested the hypothesis by studying both aortic and carotid body chemoreceptors in the same cats (n = 6) which were exposed to nearly 100% O2 for about 60 h. These chemoreceptor organs were also studied in 6 control cats which were maintained in room air at sea-level. The cats were anesthetized and their carotid and aortic chemosensory fibers were identified by the usual procedure, and their responses to hypoxia and hypercapnia and to bolus injections (i.v.) of cyanide and nicotine were measured. In the NH cats, the carotid but not aortic chemosensory responses to hypoxia and cyanide were attenuated and to hypercapnia (both onset and steady state) augmented. The aortic chemoreceptors were stimulated by hypoxia, hypercapnia, cyanide and nicotine both in the NH and the control cats similarly. The results support the hypothesis that it is presumably a higher tissue blood flow and hence a higher concentration of O2-related free radicals which ultimately led to the specific attenuation of O2 chemoreception in the carotid body.

  18. Role of. alpha. sub 2 -adrenergic receptors in the carotid body response to hypoxia

    SciTech Connect

    Kou, Y.R.; Ernsberger, P.; Cherniack, N.S.; Prabhakar, N.R. )

    1990-02-26

    Clonidine, which acts in part as an {alpha}{sub 2}-adrenergic receptor agonist, depresses ventilation. The authors examined the role of {alpha}{sub 2}-receptors in carotid chemoreceptor activity. The density of {alpha}{sub 2}-receptors was determined in membrane fractions of 18 cat carotid bodies using {sup 125}I-iodoclonidine with 0.1 mM epinephrine or 10 {mu}M SKF-86466 defining nonspecific binding. {alpha}{sub 2}-Adrenergic receptor density averaged 0.6{plus minus}0.1 fmol/carotid body (mean {plus minus} SEM) and was comparable to other sympathetic target tissues. The authors then studied the effects of an agonist (guanabenz) and an antagonist (SKF-86466; 6-Cl-N-methyl-2,3,4,5-tetrahydro-1-H3-benzazepine) specific for {alpha}{sub 2}-receptors on baseline and hypoxia-stimulated carotid body discharge, in 10 anesthetized, paralyzed and artificially ventilated cats. Intracarotid infusion of guanabenz for 5 minutes caused a dose-dependent depression of the baseline activity and reduced the chemoreceptor response to hypoxia by 88.0{plus minus}5.8% of the vehicle-injected controls. Intravenous administration of SKF-86466 reversed the effects of guanabenz on the carotid body activity. in contrast, chemoreceptor depression caused by dopamine was unaffected by SKF-86466. SKF-86466 alone increased baseline discharge and potentiated the chemoreceptor response to hypoxia by 34.0 {plus minus} 9.6% of the controls. These results demonstrate that {alpha}{sub 2}-adrenergic receptors are present in the cat carotid body and they exert an inhibitory influence on the chemoreceptor response to hypoxia.

  19. Sleep-mediated heart rate variability after bilateral carotid body tumor resection.

    PubMed

    Niemeijer, Nicolasine D; Corssmit, Eleonora P M; Reijntjes, Robert H A M; Lammers, Gert Jan; van Dijk, J Gert; Thijs, Roland D

    2015-04-01

    The carotid bodies are thought to play an important role in sleep-dependent autonomic changes. Patients who underwent resection of bilateral carotid body tumors have chronically attenuated baroreflex sensitivity. These subjects provide a unique opportunity to investigate the role of the baroreflex during sleep. One-night ambulatory polysomnography (PSG) recording. Participants' homes. Nine patients with bilateral carotid body tumor resection (bCBR) (four women, mean age 50.4 ± 7.2 years) and nine controls matched for age, gender, and body mass index. N/A. Sleep parameters were obtained from PSG. Heart rate (HR) and its variability were calculated using 30-s epochs. In bCBR patients, HR was slightly but not significantly increased during wake and all sleep stages. The effect of sleep on HR was similar for patients and controls. Low frequency (LF) power of the heart rate variability spectrum was significantly lower in bCBR patients in active wakefulness, sleep stage 1 and REM sleep. No differences were found between patients and controls for high frequency (HF) power and the LF/HF ratio. Bilateral carotid body tumor resection (bCBR) is associated with decreased low frequency power during sleep, suggesting impaired baroreflex function. Despite this, sleep-related heart rate changes were similar between bCBR patients and controls. These findings suggest that the effects of sleep on heart rate are predominantly generated through central, non-baroreflex mediated pathways. © 2015 Associated Professional Sleep Societies, LLC.

  20. Effects of osmotic changes on the chemoreceptor cell of rat carotid body.

    PubMed

    Molnár, Zoltán; Petheo, Gábor L; Fülöp, Csaba; Spät, András

    2003-01-15

    The carotid body plays a crucial role in cardiorespiratory regulation. In the present study we investigated the effect of osmotic changes on cytoplasmic calcium concentration ([Ca(2+)](c)) and pH (pH(i)) of isolated chemoreceptor cells of the rat carotid body. In CO(2)/HCO(3)(-)-buffered medium, reduction of osmolality from the control level of 300 mosmol kg(-1) to 250-285 mosmol kg(-1) resulted in a rise in [Ca(2+)](c), as measured with Indo-1, whereas elevation of osmolality to 350 mosmol kg(-1) had no effect. The Ca(2+) response required extracellular Ca(2+) and was reduced by application of the L-type Ca(2+) channel antagonist nifedipine (10 microM). The hyposmosis-induced Ca(2+) response could be prevented by application of niflumic acid (300 microM), an inhibitor of the swelling-activated Cl(-) channel. In whole-cell patch-clamp experiments niflumic acid abolished the swelling-activated Cl(-) current but only slightly depressed the Ca(2+) current. The inhibition of Ca(2+) current by niflumic acid does not account for its action in preventing of hyposmosis-induced Ca(2+) response, which seems to be initiated by Cl(-)-mediated depolarisation. Withdrawal of CO(2)/HCO(3)(-) also prevented the Ca(2+) response. Reduction of the osmotic concentration by 50 mosmol kg(-1) induced a small but sustained decrease in pH(i), while elevation by 50 mosmol kg(-1) had an inverse effect, as measured fluorimetrically with carboxy SNARF-1. Our conclusion is that in the rat chemoreceptor cell the activation of Cl(-) channels, e.g. by hyposmotic challenge, induces depolarisation, which, in turn, activates voltage-gated Ca(2+) channels.

  1. Towards the Sensory Nature of the Carotid Body: Hering, De Castro and Heymans†

    PubMed Central

    de Castro, Fernando

    2009-01-01

    The carotid body or glomus caroticum is a chemosensory organ bilaterally located between the external and internal carotid arteries. Although known by anatomists since the report included by Von Haller and Taube in the mid XVIII century, its detailed study started the first quarter of the XX. The Austro-German physiologist Heinrich E. Hering studied the cardio-respiratory reflexes searched for the anatomical basis of this reflex in the carotid sinus, while the Ghent School leaded by the physio-pharmacologists Jean-François Heymans and his son Corneille focussed in the cardio-aortic reflexogenic region. In 1925, Fernando De Castro, one of the youngest and more brilliant disciples of Santiago Ramón y Cajal at the Laboratorio de Investigaciones Biológicas (Madrid, Spain), profited from some original novelties in histological procedures to study the fine structure and innervation of the carotid body. De Castro unravelled them in a series of scientific papers published between 1926 and 1929, which became the basis to consider the carotid body as a sensory receptor (or chemoreceptor) to detect the chemical changes in the composition of the blood. Indeed, this was the first description of arterial chemoreceptors. Impressed by the novelty and implications of the work of De Castro, Corneille Heymans invited the Spanish neurologist to visit Ghent on two occasions (1929 and 1932), where both performed experiences together. Shortly after, Heymans visited De Castro at the Instituto Cajal (Madrid). From 1932 to 1933, Corneille Heymans focused all his attention on the carotid body his physiological demonstration of De Castro's hypothesis regarding chemoreceptors was awarded with the Nobel Prize in Physiology or Medicine in 1938, just when Spain was immersed in its catastrophic Civil War. PMID:20057927

  2. Towards the sensory nature of the carotid body: hering, de castro and heymansdagger.

    PubMed

    de Castro, Fernando

    2009-01-01

    The carotid body or glomus caroticum is a chemosensory organ bilaterally located between the external and internal carotid arteries. Although known by anatomists since the report included by Von Haller and Taube in the mid XVIII century, its detailed study started the first quarter of the XX. The Austro-German physiologist Heinrich E. Hering studied the cardio-respiratory reflexes searched for the anatomical basis of this reflex in the carotid sinus, while the Ghent School leaded by the physio-pharmacologists Jean-François Heymans and his son Corneille focussed in the cardio-aortic reflexogenic region. In 1925, Fernando De Castro, one of the youngest and more brilliant disciples of Santiago Ramón y Cajal at the Laboratorio de Investigaciones Biológicas (Madrid, Spain), profited from some original novelties in histological procedures to study the fine structure and innervation of the carotid body. De Castro unravelled them in a series of scientific papers published between 1926 and 1929, which became the basis to consider the carotid body as a sensory receptor (or chemoreceptor) to detect the chemical changes in the composition of the blood. Indeed, this was the first description of arterial chemoreceptors. Impressed by the novelty and implications of the work of De Castro, Corneille Heymans invited the Spanish neurologist to visit Ghent on two occasions (1929 and 1932), where both performed experiences together. Shortly after, Heymans visited De Castro at the Instituto Cajal (Madrid). From 1932 to 1933, Corneille Heymans focused all his attention on the carotid body his physiological demonstration of De Castro's hypothesis regarding chemoreceptors was awarded with the Nobel Prize in Physiology or Medicine in 1938, just when Spain was immersed in its catastrophic Civil War.

  3. Subclinical Carotid Atherosclerosis in Asymptomatic Subjects With Type 2 Diabetes Mellitus.

    PubMed

    Rubinat, Esther; Marsal, Josep Ramon; Vidal, Teresa; Cebrian, Cristina; Falguera, Mireia; Vilanova, Ma Belen; Betriu, Àngels; Fernández, Elvira; Franch, Josep; Mauricio, Dídac

    2016-01-01

    Subjects with type 2 diabetes mellitus are considered to be at high risk for cardiovascular disease. The identification of carotid atherosclerosis is a validated surrogate marker of cardiovascular disease. Nurses are key professionals in the improvement and intensification of cardiovascular preventive strategies. The aim is to study the presence of carotid atherosclerosis in a group of asymptomatic subjects with type 2 diabetes mellitus and no previous clinical cardiovascular disease. A total of 187 patients with type 2 diabetes mellitus and 187 age- and sex-matched subjects without type 2 diabetes mellitus were studied in this cross-sectional, observational, cohort study. Standard operational procedures were applied by the nursing team regarding physical examination and carotid ultrasound assessment. Common, bulb, and internal carotid arteries were explored by measuring intima-media thickness and identifying atherosclerotic plaques. Carotid intima-media thickness (c-IMT) and carotid plaque prevalence were significantly greater in diabetic subjects than in the control group. Carotid plaques and c-IMT were more frequent in men than in women and increased with increasing age. In the multivariate analysis, age, gender, waist circumference, systolic blood pressure, and hypercholesterolemia were positively associated with c-IMT, whereas age, gender, and weight were positively associated with carotid plaque. The current nurse-led study shows that subjects with type 2 diabetes mellitus have a high prevalence of subclinical atherosclerosis that is associated with cardiovascular risk factors.

  4. Sleep-Mediated Heart Rate Variability after Bilateral Carotid Body Tumor Resection

    PubMed Central

    Niemeijer, Nicolasine D.; Corssmit, Eleonora P.M.; Reijntjes, Robert H.A.M.; Lammers, Gert Jan; van Dijk, J. Gert; Thijs, Roland D.

    2015-01-01

    Study Objectives: The carotid bodies are thought to play an important role in sleep-dependent autonomic changes. Patients who underwent resection of bilateral carotid body tumors have chronically attenuated baroreflex sensitivity. These subjects provide a unique opportunity to investigate the role of the baroreflex during sleep. Design: One-night ambulatory polysomnography (PSG) recording. Setting: Participants' homes. Participants: Nine patients with bilateral carotid body tumor resection (bCBR) (four women, mean age 50.4 ± 7.2 years) and nine controls matched for age, gender, and body mass index. Interventions: N/A. Measurements: Sleep parameters were obtained from PSG. Heart rate (HR) and its variability were calculated using 30-s epochs. Results: In bCBR patients, HR was slightly but not significantly increased during wake and all sleep stages. The effect of sleep on HR was similar for patients and controls. Low frequency (LF) power of the heart rate variability spectrum was significantly lower in bCBR patients in active wakefulness, sleep stage 1 and REM sleep. No differences were found between patients and controls for high frequency (HF) power and the LF/HF ratio. Conclusions: Bilateral carotid body tumor resection (bCBR) is associated with decreased low frequency power during sleep, suggesting impaired baroreflex function. Despite this, sleep-related heart rate changes were similar between bCBR patients and controls. These findings suggest that the effects of sleep on heart rate are predominantly generated through central, non-baroreflex mediated pathways. Citation: Niemeijer ND, Corssmit EP, Reijntjes RH, Lammers GJ, van Dijk JG, Thijs RD. Sleep-mediated heart rate variability after bilateral carotid body tumor resection. SLEEP 2015;38(4):633–639. PMID:25325476

  5. Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells

    PubMed Central

    Ortega-Sáenz, Patricia; Pardal, Ricardo; García-Fernández, María; López-Barneo, José

    2003-01-01

    Carotid body glomus cells release transmitters in response to hypoxia due to the increase of excitability resulting from inhibition of O2 -regulated K+ channels. However, the mechanisms involved in the detection of changes of O2 tension are unknown. We have studied the interaction between glomus cell O2 sensitivity and inhibition of the mitochondrial electron transport chain (ETC) in a carotid body thin slice preparation in which catecholamine release from intact single glomus cells can be monitored by amperometry. Inhibition of the mitochondrial ETC at proximal and distal complexes induces external Ca2+-dependent catecholamine secretion. At saturating concentration of the ETC inhibitors, the cellular response to hypoxia is maintained. However, rotenone, a complex I blocker, selectively occludes the responsiveness to hypoxia of glomus cells in a dose-dependent manner. The effect of rotenone is mimicked by 1-methyl-4-phenylpyridinium ion (MPP+), an agent that binds to the same site as rotenone, but not by complex I inhibitors acting on different sites. In addition, the effect of rotenone is not prevented by incubation of the cells with succinate, a substrate of complex II. These data strongly suggest that sensitivity to hypoxia of carotid body glomus cells is not linked in a simple way to mitochondrial electron flow and that a rotenone (and MPP+)-sensitive molecule critically participates in acute oxygen sensing in the carotid body. PMID:12626666

  6. Coexpression of Galanin and Nestin in the Chemoreceptor Cells of the Human Carotid Body.

    PubMed

    Mazzatenta, Andrea; Marconi, Guya D; Macchi, Veronica; Porzionato, Andrea; Cataldi, Amelia; Di Giulio, Camillo; Pokorski, Mieczyslaw

    2016-01-01

    The carotid body is a highly specialized chemoreceptive organ of neural crest origin whose role is to detect changes in arterial oxygen content. The sensory units are the chemoreceptor cells, which are neuronal-like cells, surrounded by sustentacular or glial-like cells. It is suggested that the carotid body contains self-renewing multipotent stem cells, which are putatively represented by glial-like sustentacular cells. The mechanisms of renewal of neuronal-like cells are unclear. Recently, we have demonstrated the expression of galanin, a peptide promoting neurogenesis, in chemoreceptor cells in the human CB. Thus, in the present study we seek to determine whether galanin expression in chemoreceptor cells could be matched with that of nestin, a peptide that is a marker of multipotent neural stem cells, or rather with the glial fibrillary acidic protein (GFAP), a marker for glial cells. The latter would underscore the pluasibly essential role of sustentacular cells in the self-renewal capability of chemorecetors. We found that galanin expression is matched with nestin in chemoreceptor cells of the human carotid body, but not with that of GFAP. Thus, galanin expression in chemoreceptor cells could provide a signal for neurogenesis and chemoreceptor cell differentiation in the carotid body.

  7. Interaction of dopamine and haloperidol with O2 and CO2 chemoreception in carotid body.

    PubMed

    Lahiri, S; Nishino, T; Mokashi, A; Mulligan, E

    1980-07-01

    Effects of dopamine and of a dopaminergic blocker, haloperidol, on the responses of carotid body chemoreceptors to hypoxia and hypercapnia were investigated in 16 anesthetized cats. Intravenous infusion of dopamine (10-20 micrograms.min-1) decreased carotid body chemoreceptor responses to hypoxia and hypercapnia. The effect was greater at higher levels of arterial oxygen and carbon dioxide tension (PaO2 and PaCO2) stimulus. Thus, the magnitude of the dopamine effect depended on the degree of both PO2- and PCO2-mediated excitation of the receptors. Haloperidol potentiated responses to both hypoxia and hypercapnia but apparently did not stimulate the receptors in the absence of these stimuli. Potentiation by haloperidol and inhibition by dopamine of excitatory effects due to PaO2 decrease and PaCO2 increase are complementary. The data suggest that chemoreception of dopamine, O2, and CO2 converge at some site in the carotid body. Persistence of hypoxic and hypercapnic responses, following dopamine-blocking doses of haloperidol, does not support the theory that regulation of dopamine release is responsible for O2 and CO2 chemoreception in carotid body of the cat.

  8. Two cytochrome oxygen consumption model and mechanism for carotid body chemoreception.

    PubMed

    Nair, P K; Buerk, D G; Whalen, W J; Schubert, R W

    1986-01-01

    We have measured sinus nerve discharge, tissue PO2 and oxygen consumption (VO2) in cat carotid bodies under different experimental conditions using our recessed oxygen microelectrode. Our results indicate that the change in chemoreceptor activity with oxygen disappearance following blood flow occlusion can be related to a two cytochrome model for oxygen consumption as previously proposed by Mills and Jöbsis (1972).

  9. Carotid labyrinth of amphibians.

    PubMed

    Kusakabe, Tatsumi

    2002-11-01

    The amphibian carotid labyrinth is a characteristic maze-like vascular expansion at the bifurcation of the common carotid artery into the internal and external carotid arteries. The carotid labyrinths of anurans are spherical and those of urodeles are oblong. In the intervascular stroma of both anuran and urodelan carotid labyrinths, the glomus cells (type I cells, chief cells) are distributed singly or in clusters between connective tissue cells and smooth muscle cells. In fluorescence histochemistry, the glomus cells emit intense fluorescence for biogenic monoamines. In fine structure, the glomus cells are characterized by a number of dense-cored vesicles in their cytoplasm. The glomus cells have long, thin cytoplasmic processes, some of which are closely associated with smooth muscle cells, endothelial cells, and pericytes. Afferent, efferent, and reciprocal synapses are found on the glomus cells. The morphogenesis of the carotid labyrinth starts in the larvae at the point where the carotid arch descends to the internal gills. Through the early stages of larval development, the slightly expanded region of the external carotid artery becomes closely connected with the carotid arch. By the end of the foot stage, the expanded region becomes globular, and at the final stage of metamorphosis the carotid labyrinth is close to its adult form. In fine structure, the glomus cells appear as early as the initial stage of larval development. At the middle stages of development, the number of dense-cored vesicles increases remarkably. Distinct afferent synapses are found in juveniles, although efferent synapses can be seen during metamorphosis. The carotid labyrinth is innervated by nerve fibers containing several kinds of regulatory neuropeptides. Double-immunolabeling in combination with a multiple dye filter system demonstrates the coexistence of two different neuropeptides. The amphibian carotid labyrinth has been electrophysiologically confirmed to have arterial chemo

  10. Effects of nitric oxide gas on cat carotid body chemosensory response to hypoxia.

    PubMed

    Iturriaga, R; Mosqueira, M; Villanueva, S

    2000-02-14

    It has been proposed that nitric oxide (NO) is an inhibitory modulator of carotid body (CB) chemoreception to hypoxia. However, the effects of NO gas on carotid chemoreception have not been tested yet. The role played by NO has been revealed by the use of pharmacological tools (i.e., NO donors and NO synthase inhibitors). Here, we studied the effects of NO gas (25 ppm in N(2)) on the chemosensory response to hypoxia (PO(2) approximately 30 Torr) in the cat CB perfused in vitro. During steady hypoxic chemoreceptor excitation, bolus injections or perfusion of Tyrode equilibrated with NO reduced the increased frequency of carotid chemosensory discharges (f(x)). Perfusion for 2 min of Tyrode equilibrated with NO also reduced the rate of the rise of the chemosensory response, as well as the maximal amplitude, as compared with the normal chemosensory response to hypoxia. Present results provide direct evidence that NO gas is an inhibitory modulator of CB hypoxic chemoreception.

  11. Carotid Intima Media Thickness as a Reflection of Generalized Atherosclerosis is Related to Body Mass Index in Ischemic Stroke Patients.

    PubMed

    Singh, Amit Shankar; Atam, Virendra; Patel, Munna Lal; Chaudhary, Shyam Chand; Sawlani, Kamal Kumar; Das, Liza

    2013-03-01

    Carotid artery intima media thickness reflects the ongoing process of atherosclerosis in the body. The pathologic process occurring in the obese patients in the vascular system is atherosclerosis which is an important cause of ischemic stroke. Body mass index is an indirect measure of obesity in general population. The study was to assess the role of carotid artery intima media thickness as a marker of atherosclerosis and its relation with body mass index in ischemic stroke patients. Body mass index of the all stroke patients was calculated by using formula body mass in kilograms divided by the square of height in meters. The patients were classified in four groups of body mass index according to Indian standards. Carotid sonography was done to assess the common carotid artery intima media thickness in millimeters by using high resolution 7.5 MHz sonography technique. The average Carotid intima media thickness in this study was 9.23mm. There was a significant association found between increasing carotid artery intima media thickness and groups of body mass index (P- <0.05) in ischemic stroke patients. Body mass index as an indicator of obesity and carotid intima media thickness both are very important risk factors for ischemic stroke and are associated with each other.

  12. Carotid body chemoreception in the absence and presence of CO2-HCO3-.

    PubMed

    Iturriaga, R; Lahiri, S

    1991-12-24

    Carotid body (CB) chemosensory responses to natural and pharmacological stimuli were studied in vitro in the presence and nominal absence of CO2-HCO3- in the perfusion-superfusion media. The CBs obtained from cats (n = 10), anesthetized with sodium pentobarbitone, were simultaneously perfused and superfused with a modified Tyrode solution at 36.5 +/- 0.5 degrees C, equilibrated respectively with PO2 of 120 and less than 20 Torr. The Tyrode, nominally free of CO2-HCO3- (HEPES-NaOH, pH 7.38, 310 mOsm), was used first. Subsequently the Tyrode containing HEPES-HCO3-, equilibrated with PCO2 of 36.8 Torr (pH 7.38) was used. Chemosensory discharges were recorded from the carotid sinus nerve. Both hypoxia (PO2 = 20-25 Torr) and ischemic hypoxia stimulated the discharge in the absence and presence of CO2-HCO3-. However, the presence of CO2-HCO3- significantly raised the baseline activity, augmented the speed, sensitivity and the maximal responses to both types of hypoxia. Hypercapnic perfusate (PCO2 = 65 Torr at pH 7.17) produced a peak response equally promptly in the absence and presence of CO2-HCO3- in the ongoing perfusate but generated a larger and more sustained response. Presence of CO2-HCO3- strongly potentiated the responses to cyanide (10(-10)-10(-7) mol) but less strikingly the responses to nicotine (10(-11)-10(-8) mol). Thus, the extracellular CO2-HCO3- significantly improved the response to hypoxia but was not essential for O2 chemoreception. The underlying mechanisms of the effect of CO2-HCO3- is likely to be mediated by the Cl(-)-HCO3- anion exchanger in the pH regulation of glomus cells.

  13. Release of dopamine and chemoreceptor discharge induced by low pH and high PCO2 stimulation of the cat carotid body.

    PubMed Central

    Rigual, R; López-López, J R; Gonzalez, C

    1991-01-01

    1. Cat carotid bodies were incubated with the precursor [3H]tyrosine to label the catecholamine deposits and then mounted in a superfusion chamber which allowed simultaneous collection of the released [3H]dopamine (DA) and recording of action potentials from the carotid sinus nerve. 2. Low pH (7.2-6.6) superfusion of the carotid bodies for periods of 10 min produced a parallel increase in the release of [3H]DA and chemoreceptor discharge. 3. Carotid sinus nerve denervation of the carotid body 12-15 days prior to the experiments did not modify the release of [3H]DA elicited by low pH. 4. Superfusion of the carotid bodies with Ca(2+)-free, high-Mg2+ (1.6 mM) media reduced basal release of [3H]DA and chemoreceptor discharge by about 30%. Release evoked by low pH was reduced by 82%. Peak and average chemoreceptor discharge recorded in response to low pH were reduced by 28%. 5. Solutions containing weak acids (sodium acetate, 10 mM), adjusted at pH 7.4, elicited release of [3H]DA and increased chemoreceptor discharge. 6. With HCO3-CO2-buffered superfusion media, a reduction of bicarbonate to 5.6 mM (pH 6.8), an increase in CO2 to 20% (pH 6.8), or a simultaneous increase in CO2 to 20% and bicarbonate to 90 mM (pH 7.4), resulted in all cases in a corresponding increase in [3H]DA release and chemoreceptor discharge. The most effective stimulus was 20% CO2-pH 6.8 and the least effective 5% CO2-5.6 mM-HCO3-pH 6.8. 7. Inhibition of carbonic anhydrase with acetazolamide while perfusing the carotid bodies with a 20% CO2-equilibrated (pH 7.4) solution resulted in comparable reductions in the release of [3H]DA and chemoreceptor discharge. 8. It is concluded that the effective acidic stimulus at the carotid body chemoreceptors is an increase in hydrogen ion concentration in type I cells. It is also concluded that DA plays a critical role in the genesis of carotid sinus nerve discharges. PMID:1841956

  14. Carotid Ultrasound Imaging

    MedlinePlus

    ... Index A-Z Ultrasound - Carotid Carotid ultrasound uses sound waves to produce pictures of the carotid arteries ... pictures of the inside of the body using sound waves. Ultrasound imaging, also called ultrasound scanning or ...

  15. Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body.

    PubMed

    Thompson, Emma L; Ray, Clare J; Holmes, Andrew P; Pye, Richard L; Wyatt, Christopher N; Coney, Andrew M; Kumar, Prem

    2016-08-01

    .4 ± 0.4 to 5.1 ± 0.8 ml min(-1)  mmHg(-1) ). These effects were attenuated by either resection of the carotid sinus nerve or propranolol. Physiological concentrations of adrenaline increased the CO2 sensitivity of freshly dissociated carotid body type I cells in vitro. These findings suggest that adrenaline release can account for the ventilatory hyperpnoea observed during hypoglycaemia by an augmented carotid body and whole body ventilatory CO2 sensitivity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  16. The discovery of sensory nature of the carotid bodies--invited article.

    PubMed

    De Castro, F

    2009-01-01

    Although the carotid body (or glomus caroticum) was a structure familiar to anatomists in the XVIIIth century, it was not until the beginning of the XXth century that its role was revealed. It was then that the German physiologist Heinrich Hering described the respiratory reflex and he began to study the anatomical basis of this reflex focusing on the carotid region, and the carotid sinus in particular. At this time, the physiologists and pharmacologists associated with Jean-François Heymans and his son (Corneille) in Ghent (Belgium) adopted a different approach to resolve this issue, and they centred their efforts on the cardio-aortic reflexogenic region. However, at the Laboratorio de Investigaciones Biológicas (Madrid, Spain), one of the youngest and more brilliant disciples of Santiago Ramón y Cajal, Fernando De Castro, took advantage of certain technical advances to study the fine structure of the carotid body (De Castro, 1925). In successive papers (1926, 1928, 1929), De Castro unravelled most of the histological secrets of this small structure and described the exact localisation of the "chemoreceptors" within the glomus. Indeed, his was the first description of cells specifically devoted to detect changes in the chemical composition of blood. Heymans was deeply interested in the work of De Castro, and he extended two invitations to the Spanish neurologist to visit (1929 and 1932) so that they could share their experiences. From 1932-1933, Corneille Heymans focused his attention on the carotid body and his physiological demonstration of De Castro's hypothesis regarding chemoreceptors led to him obtaining the Nobel Prize in Physiology or Medicine in 1938, while Spain was immersed in its catastrophic Civil War.

  17. Evidence for histamine as a new modulator of carotid body chemoreception.

    PubMed

    Rio, R Del; Moya, E A; Alcayaga, J; Iturriaga, R

    2009-01-01

    It has been proposed that histamine is an excitatory transmitter between the glomus cells of the carotid body (CB) and the nerve endings of the petrosal ganglion (PG) neurons. The histamine biosynthetic pathway and the presence of histamine H1, H2 and H3 receptors have been reported in the CB. Thus, histamine meets some of the criteria to be regarded as a transmitter. However, there is no evidence that glomus cells contain histamine, or whether its application produces chemosensory excitation. Therefore, we studied its immunocytochemical localization on cat CB and its effects on chemosensory activity. Using perfused and superfused in vitro CB and PG preparations, we assessed the effects of histamine hydrochloride on chemosensory discharges and of histamine H1, H2 and H3 receptor blockers. We found the presence of histamine immunoreactivity in dense-core vesicles in glomus cells. In an in vitro CB preparation we performed pharmacological experiments to characterize histamine effects. The application of histamine hydrochloride (0.5-1,000 microg) to the CB produces a dose-dependent increase in the carotid sinus nerve activity. The H1 receptor blockade with pyrilamine 500 nM produces partial decrease of the histamine-induced response, whereas the H2 receptor blockade (ranitidine 100microM) fail to abolish the histamine excitatory effects. Antagonism of the H3 receptor results in an increase in carotid body chemosensory activity. On the other hand, application of histamine to the isolated PG had no effect on the carotid nerve discharge. Our results suggest that histamine is a modulator of the carotid body chemoreception through H1 and H3 receptor activation.

  18. Neural responses of the cat carotid and aortic bodies to hypercapnia and hypoxia.

    PubMed

    Fitzgerald, R S; Dehghani, G A

    1982-03-01

    The response (imp . s-1) of single- or few-fiber preparations from the carotid body (10 experiments) and the aortic body (5 experiments) to various levels of hypercapnia on different backgrounds of hypoxia were analyzed by two statistical techniques--analysis of variance and the Duncan's new multiple-range test. These analyses showed an initial statistically significant increase in the slope of the response to increasing arterial pressure of CO2 (PaCO2) as PaO2 fell. But the slope of the response to carbon dioxide later showed a clear tendency to become less; i.e., no significant increase in imp . s-1 when a PaCO2 rose (substantially) with normoxic (carotid body) and hypoxic (carotid and aortic bodies) backgrounds. The response of the aortic body to hypercapnia showed no statistically significant increase if the background was hyperoxia or normoxia. The characteristic of the chemoreceptor to become saturated in its response to carbon dioxide while still retaining its ability to respond to hypoxia suggests the possibility that at least some of the mechanisms involved in the chemoreception of hypoxia differ from those involved in the chemoreception of hypercapnia.

  19. Percutaneous Injection of Lidocaine Within the Carotid Body Area in Carotid Artery Stenting: An 'Old-New' Technique

    SciTech Connect

    Mourikis, Dimitrios; Chatoupis, Konstantinos; Katsenis, Konstantinos; Vlahos, Lampros; Chatziioannou, Achilles

    2008-07-15

    Severe bradycardia is a common untoward effect during balloon angioplasty when performing carotid artery stenting. Therefore atropine injection even before dilatation and the presence of an anesthesiologist are advocated in all patients. In the surgical literature, injection of a local anesthetic agent into the carotid sinus before carotid endarterectomy was performed in an attempt to ameliorate perioperative hemodynamic instability. This study was undertaken to test the hypothesis that percutaneous infiltration of the carotid sinus with local anesthetic immediately before balloon dilatation reduces bradycardia and ameliorates the need for atropine injection or the presence of an anesthesiologist. Infiltration of the carotid sinus with 5 ml of 1% lidocaine, 3 min before dilatation, was performed in 30 consecutive patients. No one exhibited any significant rhythm change that required atropine injection. The anesthesiologist did not face any hemodynamic instability during the carotid artery stenting procedure.

  20. Correlation between adenosine triphosphate levels, dopamine release and electrical activity in the carotid body: support for the metabolic hypothesis of chemoreception.

    PubMed

    Obeso, A; Almaraz, L; Gonzalez, C

    1985-11-25

    An unsolved issue for the arterial chemoreceptors is the mechanism by which hypoxia and other natural stimuli lead to an increase of activity in the carotid sinus nerve. According to the 'metabolic hypothesis', the hypoxic activation of the carotid body (CB) is mediated by a decrease of the ATP levels in the type I cells, which then release a neurotransmitter capable of exciting the sensory nerve endings. Using an in vitro preparation of cat CB, we report that ATP levels in the CB do in fact decrease when the organs are exposed to moderate, short lasting hypoxia (5 min 20% O2). Additionally, we found that decreases in ATP levels induced by 2-deoxyglucose (2 mM) or sodium cyanide (0.1 mM) are closely correlated with dopamine release from type I cells and electrical activity in the carotid sinus nerve elicited by these agents. The possible cause-effect relationship of these events is discussed.

  1. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body.

    PubMed

    Annese, Valentina; Navarro-Guerrero, Elena; Rodríguez-Prieto, Ismael; Pardal, Ricardo

    2017-04-18

    Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Nuclear magnetic resonance-determined lipoprotein subclasses and carotid intima-media thickness in type 1 diabetes.

    PubMed

    Basu, Arpita; Jenkins, Alicia J; Zhang, Ying; Stoner, Julie A; Klein, Richard L; Lopes-Virella, Maria F; Garvey, W Timothy; Lyons, Timothy J

    2016-01-01

    Dyslipidemia has been linked to vascular complications of Type 1 diabetes (T1DM). We investigated the prospective associations of nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP) and conventional lipid profiles with carotid intima-media thickness (IMT) in T1DM. NMR-LSP and conventional lipids were measured in a subset of Diabetes Control and Complications Trial (DCCT) participants (n = 455) at study entry ('baseline', 1983-89), and were related to carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC Year 12 (2004-2006). Associations were defined using multiple linear regression stratified by gender, and following adjustment for HbA1c, diabetes duration, body mass index, albuminuria, DCCT randomization group, smoking status, statin use, and ultrasound devices. In men, significant positive associations were observed between some baseline NMR-subclasses of LDL (total IDL/LDL and large LDL) and common and/or internal carotid IMT, and between conventional total- and LDL-cholesterol and non-HDL-cholesterol and common carotid IMT, at EDIC Year 12; these persisted in adjusted analyses (p < 0.05). Large LDL particles and conventional triglycerides were positively associated with common carotid IMT changes over 12 years (p < 0.05). Inverse associations of mean HDL diameter and large HDL concentrations, and positive associations of small LDL with common and/or internal carotid IMT (all p < 0.05) were found, but did not persist in adjusted analyses. No significant associations were observed in women. NMR-LSP-derived LDL particles, in addition to conventional lipid profiles, may help in identifying men with T1DM at highest risk for vascular disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Nuclear magnetic resonance-determined lipoprotein subclasses and carotid intima-media thickness in type 1 diabetes

    PubMed Central

    Basu, Arpita; Jenkins, Alicia J.; Zhang, Ying; Stoner, Julie A.; Klein, Richard L.; Lopes-Virella, Maria F.; Garvey, W. Timothy; Lyons, Timothy J.

    2015-01-01

    Background Dyslipidemia has been linked to vascular complications of Type 1 diabetes (T1DM). We investigated the prospective associations of nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP) and conventional lipid profiles with carotid intima-media thickness (IMT) in T1DM. Methods NMR-LSP and conventional lipids were measured in a subset of Diabetes Control and Complications Trial (DCCT) participants (n=455) at study entry (‘baseline’, 1983–89), and were related to carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC Year 12 (2004–2006). Associations were defined using multiple linear regression stratified by gender, and following adjustment for HbA1c, diabetes duration, body mass index, albuminuria, DCCT randomization group, smoking status, statin use, and ultrasound devices. Results In men, significant positive associations were observed between some baseline NMR-subclasses of LDL (total IDL/LDL and large LDL) and common and/or internal carotid IMT, and between conventional total- and LDL-cholesterol and non-HDL-cholesterol and common carotid IMT, at EDIC Year 12; these persisted in adjusted analyses (p<0.05). Large LDL particles and conventional triglycerides were positively associated with common carotid IMT changes over 12 years (p<0.05). Inverse associations of mean HDL diameter and large HDL concentrations, and positive associations of small LDL with common and/or internal carotid IMT (all p<0.05) were found, but did not persist in adjusted analyses. No significant associations were observed in women. Conclusion NMR-LSP-derived LDL particles, in addition to conventional lipid profiles, may help in identifying men with T1DM at highest risk for vascular disease. PMID:26600440

  4. CT AND MRI FEATURES OF CAROTID BODY PARAGANGLIOMAS IN 16 DOGS.

    PubMed

    Mai, Wilfried; Seiler, Gabriela S; Lindl-Bylicki, Britany J; Zwingenberger, Allison L

    2015-01-01

    Carotid body tumors (paragangliomas) arise from chemoreceptors located at the carotid bifurcation. In imaging studies, this neoplasm may be confused with other neck neoplasms such as thyroid carcinoma. The purpose of this retrospective, cross-sectional study was to describe computed tomographic (CT) and magnetic resonance imaging (MRI) characteristics of confirmed carotid body tumors in a multi-institutional sample of dogs. A total of 16 dogs met inclusion criteria (14 examined using CT and two with MRI). The most common reason for imaging was a palpable cervical mass or respiratory signs (i.e., dyspnea or increased respiratory noises). The most commonly affected breed was Boston terrier (n = 5). Dogs were predominantly male castrated (n = 10) and the median age was 9 years [range 3-14.5]. Most tumors appeared as a large mass centered at the carotid bifurcation, with poor margination in six dogs and discrete margins in ten dogs. Masses were iso- to hypoattenuating to adjacent muscles in CT images and hyperintense to muscles in T1- and T2-weighted MRI. For both CT and MRI, masses typically showed strong and heterogeneous contrast enhancement. There was invasion into the adjacent structures in 9/16 dogs. In six of these nine dogs, the basilar portion of the skull was affected. The external carotid artery was entrapped in seven dogs. There was invasion into the internal jugular vein in three dogs, and into the external jugular, maxillary, and linguo-facial veins in one dog. Imaging characteristics helped explain some clinical presentations such as breathing difficulties, Horner's syndrome, head tilt, or facial nerve paralysis. © 2015 American College of Veterinary Radiology.

  5. Body composition and common carotid artery remodeling in a healthy population.

    PubMed

    Kozakova, Michaela; Palombo, Carlo; Paterni, Marco; Anderwald, Christian-Heinz; Konrad, Thomas; Colgan, Mary-Paula; Flyvbjerg, Allan; Dekker, Jacqueline

    2008-09-01

    An independent association between obesity and preclinical carotid atherosclerosis has been demonstrated, however, the pathophysiological links were not clearly established. Body composition (BC) influences systemic hemodynamics and may participate in the remodeling of common carotid artery (CCA), independently of risk factors. This study evaluated the association between CCA structure and BC in a large population of healthy subjects. This was a cross-sectional study. The study was conducted at 19 European centers. The study included 627 healthy subjects (252 men, age 30-60 yr, body mass index 17-40 kg/m2). CCA luminal diameter and intima-media thickness were measured on digitized ultrasound images. Acoustic properties of CCA wall were evaluated by digital densitometric analysis and described in terms of mean gray level. BC was assessed by electrical bioimpedance. Insulin sensitivity (euglycemic hyperinsulinemic clamp) and plasma adiponectin levels were measured. Associations between CCA structure, age, BC, and metabolic and atherosclerotic risk factors were analyzed by multivariate regression models. Independent factors affecting CCA diameter were fat-free mass and waist girth (standardized r = 0.44 and 0.12; P < 0.01 and < 0.0001; R2 = 0.35); independent correlates of intima-media thickness were age, CCA diameter, systolic blood pressure, and low-density lipoprotein-cholesterol (standardized r = 0.39, 0.25, 0.10, and 0.14; P < 0.005-0.0001; R2 = 0.40). The mean gray level of carotid wall was independently associated with age and waist girth (standardized r = 0.23 and 0.12; P < 0.0001 and = 0.001; R2 = 0.30). Findings of this cross-sectional study suggest that BC modulates CCA diameter, and may induce adaptive changes in carotid wall thickness, independently of metabolic and atherosclerotic factors. Central adiposity modifies the acoustic properties of carotid wall.

  6. Color Doppler Ultrasound in Diagnosis and Assessment of Carotid Body Tumors: Comparison with Computed Tomography Angiography.

    PubMed

    Jin, Zhan-Qiang; He, Wen; Wu, Dong-Fang; Lin, Mei-Ying; Jiang, Hua-Tang

    2016-09-01

    A carotid body tumor (CBT) is a rare, non-chromaffin paraganglioma, and its diagnosis mainly depends on imaging modalities. The aim of this study was to investigate the ability of color Doppler ultrasound (CDU) in the diagnosis and assessment of CBT based on computed tomography (CT). We retrospectively reviewed the CDU and CT features of 49 consecutive CBTs and 23 schwannomas from 67 patients and compared these findings with surgical resection specimens. The mean size of CBT lesions on ultrasound scans and CT angiography (CTA) was 3.24 cm ± 0.82 cm (range, 1.6-5.2 cm) and 3.84 cm ± 1.08 cm (range, 1.8-6.8 cm), respectively, which had statistically significant difference (t = 9.815, p = 0.000). The vascularity of CBT lesions was richer than that of schwannoma lesions (p < 0.05). Intra-lesional vascularities feeding CBT mostly arose from the external carotid artery and had spectrum characteristics including low velocity and resistance. Peak systolic velocity (PSV) and resistance index (RI) of the vasa vasorum were 39.8 cm/s ± 19.8 cm/s and 0.54 ± 0.06, respectively. There was the correlation between CTA and CDU in identifying Shamblin type I CBT lesions, while CTA technique was superior for CDU, identifying Shamblin type II and III CBT lesions. Accuracy, specificity and sensitivity of CDU in diagnosing CBTs were 87.5% (63 of 72), 82.6% (19 of 23) and 89.8% (44 of 49), respectively. Both accuracy and sensitivity of CTA in diagnosing CBTs were 100%. CDU can be useful for assessment of Shamblin's type and intra-lesional blood flow of CBTs before its metastases, while CT imaging can reveal the relationship between lesions and adjacent arteries, as well as the involvement of the skull base. CDU combined with CT imaging can be used as an optimal detection modality for the assessment and management of CBT.

  7. Morphological differences of the carotid body among C57/BL6 (B6), A/J, and CSS B6A1 mouse strains.

    PubMed

    Chai, Sam; Gillombardo, Carl B; Donovan, Lucas; Strohl, Kingman P

    2011-08-15

    The C57/BL6 (B6) mouse strain exhibits post-hypoxic frequency decline and periodic breathing, as well as greater amount of irregular breathing during rest in comparison to the A/J and to the B6a1, a chromosomal substitution strain whereby the A/J chromosome 1 is bred onto the B6 background (Han et al., 2002; Yamauchi et al., 2008a,b). The hypothesis was that morphological differences in the carotid body would associate with such trait variations. After confirming strain differences in post-hypoxic ventilatory behavior, histological examination (n=8 in each group) using hematoxylin and eosin (H&E) staining revealed equivalent, well-defined tissue structure at the bifurcation of the carotid arteries, an active secretory parenchyma (type I cells) from the supportive stromal tissue, and clustering of type I cells in all three strains. Tyrosine hydroxylase (TH) immunohistochemical staining revealed a typical organization of type I cells and neurovascular components into glomeruli in all three strains. Image analysis from 5 μm sections from each strain generated a series of cytological metrics. The percent carotid body composition of TH+ type I cells in the A/J, B6 and B6a1 was 20±4%, 39±3%, and 44±3%, respectively (p=0.00004). However, cellular organization in terms of density and ultrastructure in the B6a1 is more similar to the B6 than to the A/J. These findings indicate that genetic mechanisms that produce strain differences in ventilatory function do not associate with carotid body structure or tyrosine hydroxylase morphology, and that A/J chromosome 1 does not contribute much to B6 carotid body morphology.

  8. Selective inhibition of the carotid body sensory response to hypoxia by the substance P receptor antagonist CP-96,345.

    PubMed

    Prabhakar, N R; Cao, H; Lowe, J A; Snider, R M

    1993-11-01

    Carotid bodies are sensory organs for monitoring arterial oxygen and CO2. Previous studies have shown that chemoreceptor tissue contains substance P (SP) and exogenously administered SP augments chemosensory discharge. In the present study, we examined the physiological importance of SP in carotid body chemoreception by using a selective nonpeptide SP [neurokinin (NK) 1] receptor antagonist CP-96,345. In experiments performed on anesthetized cats, sensory discharge was recorded from the carotid body in situ. To control for alterations in blood flow, additional studies were conducted on the carotid body in vitro. In in vivo studies, close carotid body (intraarterial) administration of CP-96,345 attenuated the sensory response to hypoxia in a dose-dependent manner with 73% of the response abolished at doses of 0.3-0.6 mg/kg. Comparable doses of the (2R,3R)-enantiomer had no effect on hypoxia-induced excitation, indicating that the effect of CP-96,345 was not due to nonspecific action. In contrast, the carotid body response to high CO2 was not affected by CP-96,345, implying that only the hypoxic response is mediated by NK-1 receptor and confirming that the effect of the SP antagonist was not due to nonspecific actions. Marked attenuation of the sensory response to hypoxia was also obtained in the carotid body in vitro, suggesting that the effects of the NK-1 antagonist were not secondary to cardiovascular changes. These results demonstrate that CP-96,345 attenuates or abolishes the chemosensory response to hypoxia but not to CO2 and suggest that SP mediates the hypoxia-induced sensory excitation in the cat carotid body via NK-1 receptor activation.

  9. Research Report: Intermittent hypobaric hypoxia and hyperbaric oxygen on GAP-43 in the rat carotid body.

    PubMed

    Peng, Zhengwu; Fan, Juan; Liu, Ling; Kuang, Fang; Xue, Fen; Wang, Bairen

    2015-01-01

    Adaptive changes in the carotid body (CB) including the expression of the growth-associated protein-43 (GAP-43) have been studied in response to low, but not high, oxygen exposure. Expression of GAP-43 in the CB of rats under different atmospheric pressures and oxygen partial pressure (PO2) conditions was investigated. Mature male Sprague-Dawley rats were exposed to intermittent hypobaric hypoxia (IHH, 0, 1, 2 and 3 weeks), intermittent hyperbaric oxygen (IHBO2, 0, 1, 5 and 10 days, sacrificed six hours or 24 hours after the last HBO2 exposure), and intermittent hyperbaric normoxia (IHN, same treatment pattern as IHBO2). GAP-43 was highly expressed (mainly in type I cells) in the CB of normal rats. IHH u-regulated GAP-43 expression in the CB with significant differences (immunohistochemical staining [IHC]: F(3,15)=40.64, P < 0.01; western blot [WB]: F(3,16) = 53.52, P < 0.01) across the subgroups. GAP-43 expression in the CB was inhibited by IHBO2 (controls vs. IHBO2 groups, IHC: F(6,30) = 15.85, P < 0.01; WB: F(6,29) = 15.95, P < 0.01). No detectable changes in GAP-43 expression were found for IHN. These findings indicated that different PO2 conditions, but not air pressures, played an important role in the plasticity of the CB, and that GAP-43 might be a viable factor for the plasticity of the CB.

  10. Contribution of endothelin-1 to the enhanced carotid body chemosensory responses induced by chronic intermittent hypoxia.

    PubMed

    Rey, Sergio; Del Rio, Rodrigo; Iturriaga, Rodrigo

    2006-05-01

    Chronic intermittent hypoxia (CIH) enhances carotid body (CB) chemosensory responses to acute hypoxia. We tested the hypothesis that endothelin-1 (ET-1), an excitatory modulator of CB chemoreception may contribute to the enhanced CB chemosensory responses in cats exposed to cyclic hypoxic episodes repeated during 8 h for 4 days. Accordingly, we measured the ET-1 immunoreactivity (ET-ir) in the CB and plasma. Using a perfused CB preparation, we studied the effects of exogenous ET-1 and bosentan, a non-selective endothelin receptor type A and B antagonist, on the frequency of chemosensory discharges (f(x)) during normoxia, mild and severe hypoxia. We found that CIH increased ET-ir in the CB by approximately 10-fold leaving ET-1 plasma levels unchanged. Application of ET-1 to control and CIH-treated CBs produced long-lasting dose-dependent increases in f(x), although the dose-response curve showed a rightward-shift in the CIH-treated CBs. CIH increased baseline f(x) and hypoxic chemosensory responses, which were reduced by 50 microM bosentan in CBs from CIH-treated cats. Present results suggest that a local increase of ET-1 in the CB may contribute to the enhanced chemosensory responses induced by CIH predominantly through a vasomotor mechanism.

  11. Hypoxia transduction by carotid body chemoreceptors in mice lacking dopamine D(2) receptors.

    PubMed

    Prieto-Lloret, J; Donnelly, D F; Rico, A J; Moratalla, R; González, C; Rigual, R J

    2007-10-01

    Hypoxia-induced dopamine (DA) release from carotid body (CB) glomus cells and activation of postsynaptic D(2) receptors have been proposed to play an important role in the neurotransmission process between the glomus cells and afferent nerve endings. To better resolve the role of D(2) receptors, we examined afferent nerve activity, catecholamine content and release, and ventilation of genetically engineered mice lacking D(2) receptors (D(2)(-/-) mice). Single-unit afferent nerve activities of D(2)(-/-) mice in vitro were significantly reduced by 45% and 25% compared with wild-type (WT) mice during superfusion with saline equilibrated with mild hypoxia (Po(2) approximately 50 Torr) or severe hypoxia (Po(2) approximately 20 Torr), respectively. Catecholamine release in D(2)(-/-) mice was enhanced by 125% in mild hypoxia and 75% in severe hypoxia compared with WT mice, and the rate of rise was increased in D(2)(-/-) mice. We conclude that CB transduction of hypoxia is still present in D(2)(-/-) mice, but the response magnitude is reduced. However, the ventilatory response to acute hypoxia is maintained, perhaps because of an enhanced processing of chemoreceptor input by brain stem respiratory nuclei.

  12. Endovascular management of symptomatic cerebral malperfusion due to carotid dissection after type A aortic dissection repair.

    PubMed

    Casana, R; Tolva, V; Majnardi, A Robecchi; Bianchi, P G; Addobati, L; Bertoni, G B; Cireni, L V; Silani, V

    2011-10-01

    Type A acute aortic dissection is a surgical emergency, and supra-aortic trunk involvement may be complicated by stroke in 6% to 20% of cases. A 66-year-old Caucasian female patient underwent a composite repair of the ascending aorta for type A aortic dissection. Postoperative period was complicated by episodes of "drop attack." Doppler ultrasound of supra-aortic trunks revealed an intimal flap occluding right internal carotid artery. Multiple stenting was performed from carotid bifurcation to internal carotid artery in order to exclude the dissection intimal flap. After endovascular procedure physiatrist considered that motor functional improvement was better than expected, and we support that endovascular resolution of carotid malperfusion led to a better outcome. According to other experience, endovascular procedure resulted as a safe and effective way. Moreover, ultrasound monitoring of supra-aortic trunks in postoperative period is recommended.

  13. Carotid baroreceptor stimulation alters cutaneous vascular conductance during whole-body heating in humans

    PubMed Central

    Keller, David M; Davis, Scott L; Low, David A; Shibasaki, Manabu; Raven, Peter B; Crandall, Craig G

    2006-01-01

    Prior studies investigating carotid baroreflex control of the cutaneous vasculature have yielded mixed findings. However, previously used methodological and analytical techniques may limit the ability to detect carotid baroreflex-mediated changes in cutaneous vascular conductance (CVC). The aim of this study was to test the hypothesis that dynamic carotid baroreceptor stimulation (i.e. 5 s trials) using neck pressure (NP, simulated carotid hypotension) and neck suction (NS, simulated carotid hypertension) will decrease and increase CVC, respectively, during normothermic and whole-body heating conditions in resting humans. Data were obtained from nine subjects (age, 31 ± 2 year). The ratio of forearm skin blood flux (laser-Doppler flowmetry) and arterial blood pressure (Finapres) was used as an index of CVC. Multiple 5 s trials of NP (+40Torr) and NS (−60Torr), as well as breath-hold/airflow control trials, were applied during end-expiratory breath-holds while subjects were normotheric and heat stressed (change in core temperature ∼0.75°C). CVC responses to each NP and NS trial were averaged into 1 s intervals during the following periods: 3 s prestimulus, 5 s during stimulus, and 5 s poststimulus. Peak CVC responses (3 s average) to NP and NS were compared to prestimulus values using paired t test. During normothermia, NP decreased CVC by 0.032 ± 0.007 arbitrary units (a.u.) mmHg−1; (P < 0.05); however, breath-hold/airflow control trials resulted in similar decreases in CVC. NS did not change CVC (Δ = 0.002 ± 0.005 a.u. mmHg−1; P = 0.63). During whole-body heating, NP decreased CVC (by 0.16 ± 0.04 a.u. mmHg−1; (P < 0.05), whereas NS increased CVC by 0.07 ± 0.03 a.u. mmHg−1; (P < 0.05). Furthermore, these changes were greater than, or directionally different from, the breath-hold/airflow control trials. These findings indicate that carotid baroreceptor stimulation elicits dynamic changes in CVC and that these changes are more apparent during whole-body

  14. Tasting arterial blood: what do the carotid chemoreceptors sense?

    PubMed

    Prabhakhar, Nanduri R; Joyner, Michael J

    2014-01-01

    The carotid bodies are sensory organs that detect the chemical composition of the arterial blood. The carotid body sensory activity increases in response to arterial hypoxemia and the ensuing chemoreflex regulates vital homeostatic functions. Recent studies suggest that the carotid bodies might also sense arterial blood glucose and circulating insulin levels. This review focuses on how the carotid bodies sense O2, glucose, and insulin and some potential implications of these sensory functions on physiological regulation and in pathophysiological conditions. Emerging evidence suggests that carbon monoxide (CO)-regulated hydrogen sulfide (H2S), stemming from hypoxia, depolarizes type I cells by inhibiting certain K(+) channels, facilitates voltage-gated Ca(2+) influx leading to sensory excitation of the carotid body. Elevated CO and decreased H2S renders the carotid bodies insensitive to hypoxia resulting in attenuated ventilatory adaptations to high altitude hypoxia, whereas reduced CO and high H2S result in hypersensitivity of the carotid bodies to hypoxia and hypertension. Acute hypoglycemia augments the carotid body responses to hypoxia but that a prolonged lack of glucose in the carotid bodies can lead to a failure to sense hypoxia. Emerging evidence also indicates that carotid bodies might sense insulin directly independent of its effect on glucose, linking the carotid bodies to the pathophysiological consequences of the metabolic syndrome. How glucose and insulin interact with the CO-H2S signaling is an area of ongoing study.

  15. Tasting arterial blood: what do the carotid chemoreceptors sense?

    PubMed Central

    Prabhakhar, Nanduri R.; Joyner, Michael J.

    2015-01-01

    The carotid bodies are sensory organs that detect the chemical composition of the arterial blood. The carotid body sensory activity increases in response to arterial hypoxemia and the ensuing chemoreflex regulates vital homeostatic functions. Recent studies suggest that the carotid bodies might also sense arterial blood glucose and circulating insulin levels. This review focuses on how the carotid bodies sense O2, glucose, and insulin and some potential implications of these sensory functions on physiological regulation and in pathophysiological conditions. Emerging evidence suggests that carbon monoxide (CO)-regulated hydrogen sulfide (H2S), stemming from hypoxia, depolarizes type I cells by inhibiting certain K+ channels, facilitates voltage-gated Ca2+ influx leading to sensory excitation of the carotid body. Elevated CO and decreased H2S renders the carotid bodies insensitive to hypoxia resulting in attenuated ventilatory adaptations to high altitude hypoxia, whereas reduced CO and high H2S result in hypersensitivity of the carotid bodies to hypoxia and hypertension. Acute hypoglycemia augments the carotid body responses to hypoxia but that a prolonged lack of glucose in the carotid bodies can lead to a failure to sense hypoxia. Emerging evidence also indicates that carotid bodies might sense insulin directly independent of its effect on glucose, linking the carotid bodies to the pathophysiological consequences of the metabolic syndrome. How glucose and insulin interact with the CO-H2S signaling is an area of ongoing study. PMID:25642193

  16. Characterization of ectonucleotidase expression in the rat carotid body: regulation by chronic hypoxia.

    PubMed

    Salman, Shaima; Vollmer, Cathy; McClelland, Grant B; Nurse, Colin A

    2017-09-01

    The carotid body (CB) chemoreflex maintains blood Po2 and Pco2/H(+) homeostasis and displays sensory plasticity during exposure to chronic hypoxia. Purinergic signaling via P1 and P2 receptors plays a pivotal role in shaping the afferent discharge at the sensory synapse containing catecholaminergic chemoreceptor (type I) cells, glial-like type II cells, and sensory (petrosal) nerve endings. However, little is known about the family of ectonucleotidases that control synaptic nucleotide levels. Using quantitative PCR (qPCR), we first compared expression levels of ectonucleoside triphosphate diphosphohydrolases (NTPDases1,2,3,5,6) and ecto-5'-nucleotidase (E5'Nt/CD73) mRNAs in juvenile rat CB vs. brain, petrosal ganglia, sympathetic (superior cervical) ganglia, and a sympathoadrenal chromaffin (MAH) cell line. In whole CB extracts, qPCR revealed a high relative expression of surface-located members NTPDase1,2 and E5'Nt/CD73, compared with low NTPDase3 expression. Immunofluorescence staining of CB sections or dissociated CB cultures localized NTPDase2,3 and E5'Nt/CD73 protein to the periphery of type I clusters, and in association with sensory nerve fibers and/or isolated type II cells. Interestingly, in CBs obtained from rats reared under chronic hypobaric hypoxia (~60 kPa, equivalent to 4,300 m) for 5-7 days, in addition to the expected upregulation of tyrosine hydroxylase and VEGF mRNAs, there was a significant upregulation of NTPDase3 and E5'Nt/CD73 mRNA, but a downregulation of NTPDase1 and NTPDase2 relative to normoxic controls. We conclude that NTPDase1,2,3 and E5'Nt/CD73 are the predominant surface-located ectonucleotidases in the rat CB and suggest that their differential regulation during chronic hypoxia may contribute to CB plasticity via control of synaptic ATP, ADP, and adenosine pools. Copyright © 2017 the American Physiological Society.

  17. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation

    PubMed Central

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-01-01

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge. PMID:25063821

  18. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    PubMed

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge.

  19. Endothelins in the cat petrosal ganglion and carotid body: effects and immunolocalization.

    PubMed

    Rey, Sergio; Del Rio, Rodrigo; Alcayaga, Julio; Iturriaga, Rodrigo

    2006-01-19

    In response to hypoxia, chemoreceptor cells of the carotid body (CB) release transmitters, which acting on the petrosal ganglion (PG) neuron terminals, increase the chemoafferent discharge. Additionally, vasoactive molecules produced within the CB may modulate hypoxic chemoreception by controlling blood flow and tissue PO2. Endothelin-1 (ET-1) increases basal CB chemosensory discharges in situ, probably due to its vasoconstrictor action. However, the actions of ET-1 on PG neurons or its expression in the PG are not known. Using immunohistochemistry, we found that endothelin-like peptides are expressed in the cat PG and CB under normoxic conditions. Exogenous applications of ET-1 increased the chemosensory activity in the vascularly perfused CB but were ineffective on either the CB or PG superfused preparations, both of which are devoid of vascular control. Thus, our data indicate that the excitatory effect of ET-1 in the carotid chemoreceptor system appears to be mainly due to a vasoconstrictor effect in the CB blood vessels.

  20. Respiratory modulation of carotid and aortic body reflex left ventricular inotropic responses in the cat.

    PubMed

    Daly, M D; Jones, J F

    1998-06-15

    1. The reflex changes in the inotropic state of the left ventricle, measured as the dP/dt max (maximum rate of change of pressure), occurring in response to selective stimulation of the carotid and aortic body chemoreceptors by sodium cyanide, were studied in the cat anaesthetized with a mixture of chloralose and urethane. 2. The animals were artificially ventilated with an open pneumothorax. The heart rate and mean arterial blood pressure were maintained constant. 3. With on-going central respiratory activity, stimulation of the carotid bodies caused an increase in respiratory movements. Variable changes in left ventricular dP/dt max occurred, the predominant response being an increase. The mean change was 8.3 +/- 2.9 % from a control value of 6850 +/- 450 mmHg s-1. Stimulation of the aortic bodies resulted in a smaller increase in respiration or no effect, but a significant increase occurred in left ventricular dP/dt max of 19.6 +/- 2.9 % from a control value of 6136 +/- 228 mmHg s-1. No significant changes in left ventricular end-diastolic pressure occurred in response to stimulation of either group of chemoreceptors. 4. Tests of chemoreceptor stimulations were repeated during temporary suppression of the secondary respiratory mechanisms: the central respiratory drive was suppressed reflexly by electrical stimulation of the central cut ends of both superior laryngeal nerves and lung stretch afferent activity was minimized by stopping artificial respiration. Carotid body stimulation again evoked variable responses, the predominant now being a reduction in left ventricular dP/dt max of 3.1 % from a control value of 5720 +/- 320 mmHg s-1, which was significantly different to that occurring during on-going spontaneous respiration. Aortic body stimulation caused an increase in left ventricular dP/dt max similar to the response during on-going spontaneous respiration. 5. The positive inotropic responses were mediated via the sympathetic nervous system, as indicated by

  1. Calcium Phosphate Product Is Associated with Subclinical Carotid Atherosclerosis in Type 2 Diabetes

    PubMed Central

    Ramírez-Morros, Anna; Granado-Casas, Minerva; Martinez-Alonso, Montserrat; Real, Jordi; Castelblanco, Esmeralda; Esquerda, Aureli; Cao, Gonzalo; Alonso, Núria

    2017-01-01

    Aims To assess whether circulating 25-hydroxyvitamin D3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease. Methods We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained. Results We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg2/dL2) product was positively associated with the presence of carotid plaques (ORadj = 1.078; 95% CI: 1.017–1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness (cIMT; mm) (βadj ± SE = −0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM. PMID:28840128

  2. Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia

    PubMed Central

    Iturriaga, Rodrigo; Andrade, David C.; Del Rio, Rodrigo

    2014-01-01

    The carotid body (CB) plays a main role in the maintenance of the oxygen homeostasis. The hypoxic stimulation of the CB increases the chemosensory discharge, which in turn elicits reflex sympathetic, cardiovascular, and ventilatory adjustments. An exacerbate carotid chemosensory activity has been associated with human sympathetic-mediated diseases such as hypertension, insulin resistance, heart failure, and obstructive sleep apnea (OSA). Indeed, the CB chemosensory discharge becomes tonically hypereactive in experimental models of OSA and heart failure. Chronic intermittent hypoxia (CIH), a main feature of OSA, enhances CB chemosensory baseline discharges in normoxia and in response to hypoxia, inducing sympathetic overactivity and hypertension. Oxidative stress, increased levels of ET-1, Angiotensin II and pro-inflammatory cytokines, along with a reduced production of NO in the CB, have been associated with the enhanced carotid chemosensory activity. In this review, we will discuss new evidence supporting a main role for the CB chemoreceptor in the autonomic and cardiorespiratory alterations induced by intermittent hypoxia, as well as the molecular mechanisms involved in the CB chemosensory potentiation. PMID:25520668

  3. Clinical characteristics and remedies in 45 Iranians with carotid body tumors.

    PubMed

    Nazari, Iraj; Aarabi Moghaddam, Fatemeh; Zamani, Mohammad Mahdi; Salimi, Javad

    2012-01-01

    Carotid body tumors (CBTs) are rare, slow-growing tumors that should be considered in evaluating every lateral neck mass. This single center study was performed to define demographic features, clinical characteristics and remedies of Iranian patients with CBT. A retrospective review of prospectively collected data was done on 45 patients with 50 CBTs who have been referred to Sina Hospital, Tehran, Iran, during a 10-year period, were investigated in this study. The demographic characteristics, clinical and pathologic features, imagings, preoperative treatments, surgical approach and complications were analyzed. The study group predominantly consisted of females (82%). Age of diagnosis was 18 to 75 years old. Five patients had bilateral CBT. Family history of CBT was positive in seven patients. Most of CBTs were ≤ 3cm in size. All of the patients presented with a neck mass, mostly without pain (84%). Other symptoms included vertigo 4%, dysphasia 4% and tinnitus 2%. There was no patient with cranial nerve involvement at presentation. The most common imaging helping the diagnosis was color Doppler sonography. Three patients had preoperative embolization. All patients underwent surgery and seven patients had post-operative cranial nerve injury. Nine cases underwent external carotid artery ligation and four ones had external carotid repair. Post operative mortality rate was one patient. This study provides epidemiological data on patients with CBT in Iran, which could be useful for health care workers in prompt diagnosis and appropriate work ups for patient's families in bilateral CBTs.

  4. Ipsilateral foetal-type posterior cerebral artery is associated with cognitive decline after carotid revascularisation

    PubMed Central

    2014-01-01

    Background Stenosis of the internal carotid artery has been associated with cognitive impairment and decline. However, studies testing the effect of carotid revascularisation on cognition have had conflicting results. This may in part be explained by variation in the flow territory of the carotid artery. In 12 to 36% of the patients, the posterior cerebral artery is mainly or exclusively supplied by the internal carotid artery via a foetal-type posterior cerebral artery. In these patients, ipsilateral carotid artery stenosis is likely to result in a larger area with hypoperfusion than in case of a normal posterior cerebral artery. Patients with a foetal-type posterior cerebral artery could therefore benefit more from revascularisation. We compared the effects of carotid revascularisation on cognition between patients with a foetal-type and those with a normal posterior cerebral artery. Methods Patients with symptomatic internal carotid artery stenosis ≥ 50%, enrolled in the International Carotid Stenting Study (ICSS) at a single centre, underwent detailed neuropsychological examinations before and 6 months after revascularisation. Cognitive test results were standardized into z-scores, from which a cognitive sumscore was calculated. The primary outcome was the change in cognitive sumscore between baseline and follow-up. Changes in cognitive sumscore were compared between patients with an ipsilateral foetal-type and those with a normal posterior cerebral artery, as assessed with CT or MR angiography. Results Of 145 patients enrolled in ICSS at the centre during the study period, 98 had both angiography at baseline and neuropsychological examination at baseline and at 6-months follow-up. The cognitive sum score decreased by 0.28 (95% confidence interval, 0.10 to 0.45) in 13 patients with an ipsilateral foetal-type posterior cerebral artery and by 0.07 (95% CI, 0.002 to 0.15) in 85 patients with a normal posterior cerebral artery (mean difference, -0.20; 95% CI

  5. Fractal analysis of the structural complexity of the connective tissue in human carotid bodies

    PubMed Central

    Guidolin, Diego; Porzionato, Andrea; Tortorella, Cinzia; Macchi, Veronica; De Caro, Raffaele

    2014-01-01

    The carotid body (CB) may undergo different structural changes during perinatal development, aging, or in response to environmental stimuli. In the previous literature, morphometric approaches to evaluate these changes have considered quantitative first order parameters, such as volumes or densities, while changes in spatial disposition and/or complexity of structural components have not yet been considered. In the present study, different strategies for addressing morphological complexity of CB, apart from the overall amount of each tissue component, were evaluated and compared. In particular, we considered the spatial distribution of connective tissue in the carotid bodies of young control subjects, young opiate-related deaths and aged subjects, through analysis of dispersion (Morisita's index), gray level co-occurrence matrix (entropy, angular second moment, variance, correlation), and fractal analysis (fractal dimension, lacunarity). Opiate-related deaths and aged subjects showed a comparable increase in connective tissue with respect to young controls. However, the Morisita's index (p < 0.05), angular second moment (p < 0.05), fractal dimension (p < 0.01), and lacunarity (p < 0.01) permitted to identify significant differences in the disposition of the connective tissue between these two series. A receiver operating characteristic (ROC) curve was also calculated to evaluate the efficiency of each parameter. The fractal dimension and lacunarity, with areas under the ROC curve of 0.9651 (excellent accuracy) and 0.8835 (good accuracy), respectively, showed the highest discriminatory power. They evidenced higher level of structural complexity in the carotid bodies of opiate-related deaths than old controls, due to more complex branching of intralobular connective tissue. Further analyses will have to consider the suitability of these approaches to address other morphological features of the CB, such as different cell populations, vascularization, and innervation

  6. Fractal analysis of the structural complexity of the connective tissue in human carotid bodies.

    PubMed

    Guidolin, Diego; Porzionato, Andrea; Tortorella, Cinzia; Macchi, Veronica; De Caro, Raffaele

    2014-01-01

    The carotid body (CB) may undergo different structural changes during perinatal development, aging, or in response to environmental stimuli. In the previous literature, morphometric approaches to evaluate these changes have considered quantitative first order parameters, such as volumes or densities, while changes in spatial disposition and/or complexity of structural components have not yet been considered. In the present study, different strategies for addressing morphological complexity of CB, apart from the overall amount of each tissue component, were evaluated and compared. In particular, we considered the spatial distribution of connective tissue in the carotid bodies of young control subjects, young opiate-related deaths and aged subjects, through analysis of dispersion (Morisita's index), gray level co-occurrence matrix (entropy, angular second moment, variance, correlation), and fractal analysis (fractal dimension, lacunarity). Opiate-related deaths and aged subjects showed a comparable increase in connective tissue with respect to young controls. However, the Morisita's index (p < 0.05), angular second moment (p < 0.05), fractal dimension (p < 0.01), and lacunarity (p < 0.01) permitted to identify significant differences in the disposition of the connective tissue between these two series. A receiver operating characteristic (ROC) curve was also calculated to evaluate the efficiency of each parameter. The fractal dimension and lacunarity, with areas under the ROC curve of 0.9651 (excellent accuracy) and 0.8835 (good accuracy), respectively, showed the highest discriminatory power. They evidenced higher level of structural complexity in the carotid bodies of opiate-related deaths than old controls, due to more complex branching of intralobular connective tissue. Further analyses will have to consider the suitability of these approaches to address other morphological features of the CB, such as different cell populations, vascularization, and innervation.

  7. Modulation of the hypoxic sensory response of the carotid body by 5-hydroxytryptamine: role of the 5-HT2 receptor.

    PubMed

    Jacono, F J; Peng, Y-J; Kumar, G K; Prabhakar, N R

    2005-02-15

    Previous studies have shown that glomus cells of the carotid body express 5-hydroxytryptamine (5-HT). The aim of this study was to elucidate the role of 5-HT on the hypoxic sensory response (HSR) of the carotid body. Sensory activity was recorded from multi-fiber (n=16) and single-fiber (n=8) preparations of ex vivo carotid bodies harvested from anesthetized, adult rats. 5-HT (3 microM) had no significant effect on the magnitude or on the onset of the HSR. However, 5-HT consistently prolonged the time necessary for the sensory activity to return to baseline following the termination of the hypoxic challenge. Ketanserin (40 microM), a 5-HT2 receptor antagonist completely prevented 5-HT-induced prolongation of the HSR, whereas had no effect on the control HSR (onset, magnitude, and time for decay without 5-HT). Carotid bodies expressed 5-HT, but hypoxia did not facilitate 5-HT release. These observations suggest that 5-HT is not critical for the HSR of the rat carotid body, but it modulates the dynamics of the HSR via its action on 5-HT2 receptors.

  8. A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes

    PubMed Central

    Pollex, Rebecca L; Spence, J David; House, Andrew A; Fenster, Aaron; Hanley, Anthony JG; Zinman, Bernard; Harris, Stewart B; Hegele, Robert A

    2005-01-01

    Background Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. Methods The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21–69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol:high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. Results At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels >0.70 when comparing intima-media thickness measurements for diabetics versus non

  9. Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha.

    PubMed

    Fernández, Ricardo; González, Sergio; Rey, Sergio; Cortés, Paula P; Maisey, Kevin R; Reyes, Edison-Pablo; Larraín, Carolina; Zapata, Patricio

    2008-07-01

    In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N(2) for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O(2) tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS i.v.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-alpha receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-alpha, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-alpha injections

  10. Association between serum 25-hydroxyvitamin D and carotid atherosclerotic plaque in Chinese type 2 diabetic patients

    PubMed Central

    Ding, Ya-Hui; Wei, Tie-Ming; Qian, Lin-Yan; Ma, Yuan; Lao, Di-Bo; Yao, Bin; Pang, Jie

    2017-01-01

    Abstract In this study, we investigated the distribution of vitamin D and its association with carotid atherosclerotic plaque (CP) in Chinese type 2 diabetic (T2D) patients. We performed a cross-sectional study in 210 T2D and 94 age- and gender-matched nondiabetic patients during winter months, by determining serum 25-hydroxyvitamin D (25(OH)D) levels in both diabetic and nondiabetic controls. We carried out measurements of B-mode ultrasonography of carotid arteries in each T2D patient. The 25(OH)D concentration was 26.25 nmol/L among the T2D patients. About 93.3% T2D patients suffered from hypovitaminosis D. First, we found a clear inverse correlation between the 25(OH)D concentration and CP (P <0.001). Second, an association between 25(OH)D and macrovascular disease was significant (P = 0.005). In multivariate logistic regression analysis, decreasing 25(OH)D concentration was markedly associated with CP in T2D patients. Third, after adjusting for the confounding factors, we also observed a positive correlation between low levels of 25(OH)D in T2D patients with CP, when the following parameters were measured: old age (odds ratio [OR] = 2.533, P = 0.013); smoking (OR = 3.872, P = 0.001); and high level of low-density lipoprotein (LDL) cholesterol (OR = 2.776, P = 0.009). Thus, we concluded that high prevalence of hypovitaminosis D exists in Chinese T2D patients. Further, we found a significant association between low concentration of serum 25(OH)D and the existence of high body mass index, and high circulating LDL to be substantially positive predictors of patients with CP in T2D. PMID:28353575

  11. The risk factors associated with ultrasonic tissue characterization of carotid plaque in type 2 diabetic patients.

    PubMed

    Irie, Yoko; Katakami, Naoto; Kaneto, Hideaki; Takahara, Mitsuyoshi; Sakamoto, Ken'ya; Kosugi, Keisuke; Shimomura, Iichiro

    2014-01-01

    Little is known about the related factors of plaque echogenicity in diabetic subjects. This was a single-center, retrospective, study investigating a subgroup of patients of a previously published trial. We enrolled 179 middle-aged and older Japanese type 2 diabetic patients with carotid plaque, and examined the parameters related with echogenicity of carotid plaque evaluated by gray-scale median (GSM). Proportion of males and body mass index (BMI) were significantly higher and HDL-cholesterol was significantly lower in the patients with low GSM (< 48) plaques (n = 89) as compared to those without it (n = 90). A multiple logistic regression analysis with gender, BMI, and HDL-cholesterol as independent variables and the presence of low GSM plaques as an objective variable showed that male (odds ratio (OR) 2.36, 95%CI 1.05-5.31, p = 0.037) and BMI (OR 1.12 [1.01-1.24], p = 0.029) were independently associated with low GSM plaques. Another multiple logistic regression analysis with gender, BMI, and low-HDL-cholesterolemia (HDL-C < 40 mg/dl) as independent variables showed that low-HDL-cholesterolemia (OR 2.30 [1.03-5.13], p = 0.042) and BMI (OR 1.11 [1.00-1.22], p = 0.046) were independently associated with low GSM plaques. Our study suggests that gender, BMI and low-HDL-cholesterol are important determinants of the content of the vascular wall in diabetic subjects. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Tetrodotoxin as a Tool to Elucidate Sensory Transduction Mechanisms: The Case for the Arterial Chemoreceptors of the Carotid Body

    PubMed Central

    Rocher, Asuncion; Caceres, Ana Isabel; Obeso, Ana; Gonzalez, Constancio

    2011-01-01

    Carotid bodies (CBs) are secondary sensory receptors in which the sensing elements, chemoreceptor cells, are activated by decreases in arterial PO2 (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and glomus cells) increase their rate of release of neurotransmitters that drive the sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem where reflex responses are coordinated. When challenged with hypoxic hypoxia, the physiopathologically most relevant stimulus to the CBs, they are activated and initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute volume ventilation promotes CO2 removal from alveoli and a decrease in alveolar PCO2 ensues. Reduced alveolar PCO2 makes possible alveolar and arterial PO2 to increase minimizing the intensity of hypoxia. The ventilatory effect, in conjunction the cardiocirculatory components of the CB chemoreflex, tend to maintain an adequate supply of oxygen to the tissues. The CB has been the focus of attention since the discovery of its nature as a sensory organ by de Castro (1928) and the discovery of its function as the origin of ventilatory reflexes by Heymans group (1930). A great deal of effort has been focused on the study of the mechanisms involved in O2 detection. This review is devoted to this topic, mechanisms of oxygen sensing. Starting from a summary of the main theories evolving through the years, we will emphasize the nature and significance of the findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of current models of O2-sensing. PMID:22363245

  13. Contribution of in vivo microvascular PO2 in the cat carotid body chemotransduction.

    PubMed

    Lahiri, S; Rumsey, W L; Wilson, D F; Iturriaga, R

    1993-09-01

    To understand the interplay between microcirculatory control and carotid body (CB) function, we simultaneously measured carotid body microvascular PO2 (CBM PO2) and chemosensory activity in the cat in vivo under several experimental conditions. Cats were anesthetized with pentobarbital sodium, paralyzed, and artificially ventilated. CBs were exposed, and steady-state CBM PO2 was measured by the O2-dependent quenching of the phosphorescence of Pd-meso-tetra-(4-carboxyphenyl)porphine, which was administered intravenously. A few fibers of the carotid sinus nerve were used to record chemosensory discharges. At arterial PO2 (PaO2) of 103.4 +/- 4.1 Torr, CBM PO2 was 52.5 +/- 3.6 Torr (n = 9). Graded lowering of PaO2 from 160 to 50 Torr resulted in nearly proportional decreases in CBM PO2, but at lower PaO2 the decrease in CBM PO2 became more substantial. As PaO2 decreased, chemosensory discharge increased in parallel with CBM PO2. Hypercapnia and hypocapnia did not significantly change the relationship between PaO2 and CBM PO2, although the chemosensory discharge responded significantly. CBM PO2 and chemosensory discharge were not affected by hemorrhagic hypotension until arterial blood pressure fell below approximately 50 Torr and then CBM PO2 decreased and chemosensory discharge increased. The lack of a significant effect of hemorrhagic hypotension indicated that O2 delivery to CB was almost independent of the systemic blood pressure. Taken together, the observations suggest that CB microcirculation and PO2 are subject to control by intrinsic mechanisms and that CBM PO2 is compatible with oxidative metabolism playing a role in O2 chemoreception during hypoxia.

  14. Comparison of retrocarotid and caudocranial dissection techniques for the surgical treatment of carotid body tumors.

    PubMed

    Hinojosa, Carlos A; Ortiz-Lopez, Laura J; Anaya-Ayala, Javier E; Orozco-Sevilla, Vicente; Nunez-Salgado, Ana E

    2015-10-01

    Carotid body tumors (CBTs) are rare neoplasms. Complete surgical resection is the curative therapy and is considered the therapeutic gold standard. This study compared the retrocarotid dissection (RCD) technique with the standard caudocranial dissection (SCCD) technique in operative time, blood loss, vascular or nerve injuries, and hospital stay. A retrospective review was conducted of patients with CBTs who underwent surgical treatment with the RCD technique at the National Institute of Medical Sciences and Nutrition "Salvador Zubirán" in Mexico City from July 2007 to January 2013. This cohort was compared with an historical cohort treated with standard SCCD from 1995 to 2007 at the same institution. A total of 68 procedures (41 SCCD, 27 RCD) were performed in 68 patients (91% women) with a mean age of 54 years (standard deviation [SD], 15 years). According to the Shamblin classification, 6 CBTs were type I (9%), 35 were type II (51%), and 27 were type III (40%). Comparative analysis identified mean blood loss of 480 mL (SD, 380 mL) in the RCD group and 690 mL (SD, 680 mL) for the SCCD cohort (P < .31). The mean procedural time was 172 minutes (SD, 60 minutes) for the RCD group and 260 minutes (SD, 100 minutes) for the SCCD group (P < .001). Hospital stay was significantly shorter for the RCD group with an average of 5 days (SD, 2 days) compared with 9 days (SD, 6 days) for the SCCD cohort (P < .0001). Cranial nerve deficit occurred in 17 patients, consisting of six transient nerve palsies in the RCD cohort and 11 in the SCCD group. Postoperative cerebrovascular accidents occurred in three patients in the SCCD cohort, with none observed in the RCD group. This translates into a rate of 22% of postoperative neurologic complications for the RCD cohort and 34% in the SCCD group (P < .08). Significant differences in intraoperative vascular injuries were not observed. The RCD technique is a safe and viable option for the surgical resection of CBTs. In our experience

  15. Effect of hypoxia and hypercapnia on catecholamine content in cat carotid body.

    PubMed

    Fitzgerald, R S; Garger, P; Hauer, M C; Raff, H; Fechter, L

    1983-05-01

    The purpose of this study was to determine the content of catecholamines (CA) in the cat carotid body before and after 0.5 h exposures to normoxic normocapnia [arterial O2 partial pressure (Pao2) 126 +/- 28 Torr, arterial CO2 partial pressure (Paco2) 36.4 +/- 1.5 Torr], hypoxic normocapnia (Pao2 25 +/- 3 Torr, Paco2 36.7 +/- 3.3 Torr), and normoxic hypercapnia (Pao2 132 +/- 13 Torr, Paco2 = 98.2 +/- 7.6 Torr). CA synthesis was blocked using alpha-methylparatyrosine methyl ester (AMPT) prior to alterations in the inspired air. There was a significant decrease in carotid body content of dopamine (DA), norepinephrine (NE), and epinephrine (E) 1 h after AMPT administration. Analysis of variance and Duncan new multiple range procedures revealed that during the subsequent 0.5-h exposures to normoxia, hypoxia, or hypercapnia, only the decrease in DA during hypoxia was significantly greater than that during normoxia; the loss during hypercapnia was not. The decreases in NE during the three exposures were indistinguishable among themselves as were the decreases in E. The decrease in CA content is probably attributable to increased release. The data reveal that the release of CAs during the chemoreception of hypoxia is different from that during the chemoreception of hypercapnia and support the concept of different mechanisms for the chemoreception of hypoxia and hypercapnia.

  16. Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats.

    PubMed

    Joseph, Vincent; Soliz, Jorge; Soria, Ruddy; Pequignot, Jacqueline; Favier, Roland; Spielvogel, Hilde; Pequignot, Jean Marc

    2002-03-01

    We tested the hypothesis that ovarian steroids stimulate breathing through a dopaminergic mechanism in the carotid bodies. In ovariectomized female rats raised at sea level, domperidone, a peripheral D2-receptor antagonist, increased ventilation in normoxia (minute ventilation = +55%) and acute hypoxia (+32%). This effect disappeared after 10 daily injections of ovarian steroids (progesterone + estradiol). At high altitude (3,600 m, Bolivian Institute for High-Altitude Biology-IBBA, La Paz, Bolivia), neutered females had higher carotid body tyrosine hydroxylase activity (the rate-limiting enzyme for catecholamine synthesis: +129%) and dopamine utilization (+150%), lower minute ventilation (-30%) and hypoxic ventilatory response (-57%), and higher hematocrit (+18%) and Hb concentration (+21%) than intact female rats. Consistent signs of arterial pulmonary hypertension (right ventricular hypertrophy) also appeared in ovariectomized females. None of these parameters was affected by gonadectomy in males. Our results show that ovarian steroids stimulate breathing by lowering a peripheral dopaminergic inhibitory drive. This process may partially explain the deacclimatization of postmenopausal women at high altitude.

  17. Single and combined effects of body composition phenotypes on carotid intima-media thickness.

    PubMed

    Melo, X; Santa-Clara, H; Santos, D A; Pimenta, N M; Pinto, R; Minderico, C S; Fernhall, B; Sardinha, L B

    2016-08-01

    Central fatness might be a more sensitive predictor of atherosclerotic changes in children than are total body fat measures. However, it is unclear whether a total body fat measure coupled with an estimate of a more central pattern of fat accumulation predicts increased carotid intima-media-thickness (cIMT) better than either measure alone. The objective of the study is to identify the ability of a combination of simple anthropometric screening tools or a combination of objective measures of body composition to predict cIMT. cIMT was assessed on the common carotid artery in 349 children aged 11-12 years old (183 girls). Body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) were dichotomized according to established criteria and indices of total body (TBFI) and abdominal (ABFMI) fat were assessed by dual-energy X-ray absorptiometry and categorized (increased risk ≥85%). Single and combined associations among anthropometric and laboratorial measures with the risk of having increased cIMT (≥85%) and discriminatory performance were tested with logistic regression analysis and Receiver Operator Curve analysis. Children with higher total fatness (BMI and TBFI) or higher central pattern of fat accumulation (WC, WHtR and BFMI) were in higher risk for increased cIMT [odds ratio (OR): 2.08-3.24). The risk for increased cIMT was not higher among children who coupled high total and high central fatness (OR: 2.27-3.10). Combination of total and central measures of fat does not improve the prediction of increased cIMT in children. Simple surrogate measures of fatness can be used to predict increased cIMT urging special attention to those children who exhibit increased abdominal fat. © 2015 World Obesity.

  18. Plasma Homocysteine and Carotid Intima-Media Thickness in Type 1 Diabetes: A Prospective Study

    PubMed Central

    Stoner, Julie A.; Thorpe, Suzanne R.; Klein, Richard L.; Lopes-Virella, Maria F.; Garvey, W. Timothy; Lyons, Timothy J.

    2014-01-01

    OBJECTIVE Plasma homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes. RESEARCH DESIGN AND METHODS tHcy levels were measured once, in plasma obtained in 1997-1999 from patients (n=599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC “Year 6” (1998-2000) and “Year 12” (2004-2006), using B-mode ultra-sonography. RESULTS After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p<0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p<0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors. CONCLUSIONS In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997-1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes. PMID:25063949

  19. Giant Extracranial Aneurysm of the Internal Carotid Artery in Neurofibromatosis Type 1

    PubMed Central

    Moratti, C.; Andersson, T.

    2012-01-01

    Summary Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder characterized by cutaneous pigmentations, neurofibromas, Lisch nodules and neuroectodermal tumors. Supra-aortic vessel aneurysms may affect patients with NF-1 and can be associated with rupture, ischemic complications and compression symptoms. We describe a 48-year-old woman with NF-1 and an extracranial 3×5 cm right internal carotid artery aneurysm. After balloon test occlusion the patient was treated with parent artery sacrifice which led to significant shrinkage on follow-up MR and reduction of compression symptoms. The literature concerning internal carotid artery aneurysms associated with NF-1 is reviewed evaluating the possible therapeutic options. PMID:22958775

  20. Peptide receptor radionuclide therapy with (177)Lu DOTATATE in a case of recurrent carotid body paraganglioma with spinal metastases.

    PubMed

    Gupta, Santosh Kumar; Singla, Suhas; Karunanithi, Sellam; Damle, Nishikant; Bal, Chandrasekhar

    2014-05-01

    Paragangliomas are rare benign neuroendocrine tumors, and 80% of all paragangliomas are either carotid body tumors or glomus jugulare tumors. We present a case of recurrent unresectable carotid body paraganglioma with nodal and T7 vertebral metastases in a 30-year-old man 6 years postsurgery detected with Ga DOTANOC PET/CT and was administered with peptide receptor radionuclide therapy using Lu DOTATATE. After 5 cycles of Lu DOTATATE (total cumulative activity of 750 mCi [27 GBq]), significant response at the primary site on Ga DOTANOC PET/CT and complete disappearance of nodal and T7 vertebral metastases were noted.

  1. The relationship between distribution of body fat mass and carotid artery intima-media thickness in Korean older adults.

    PubMed

    Park, Jin-Kee; Park, Hyuntae; Kim, Kwi-Baek

    2015-10-01

    [Purpose] The aim of this study was to examine the relationships between the amount and distribution of body fat and the carotid intima-media thickness to explore whether coronary artery disease risk may be mediated through effects on the amount of fat mass in older adults. [Subjects and Methods] A total of 200 elderly females was participated. The percentage of body fat mass was measured by the bioelectrical impedance analysis method, and the carotid intima-media thickness was measured by B-mode ultrasound. Analysis of covariance was performed to assess independent associations between the four categories of percentage of body fat mass and the carotid intima-media thickness after multivariate adjustment. Logistic regression analyses were utilized to calculate odds ratios and 95% confidence intervals for examining independent associations between percentage of body fat mass and the estimated risk of coronary artery disease. [Results] Analysis of covariance showed that the carotid intima-media thickness was significantly thick in both obesity and overweight groups. When multivariate-adjusted OR for the estimated risk of coronary artery disease, the odds ratios for the obesity and overweight groups were 3.0 (95% confidence interval, 1.1 to 8.7) and 2.5 (95% confidence interval, 1.0 to 6.1), respectively. [Conclusion] This study demonstrates that elderly females with a high body fat mass are more likely to have the estimated risk of CAD than who fit body fat mass in elderly female.

  2. The relationship between distribution of body fat mass and carotid artery intima-media thickness in Korean older adults

    PubMed Central

    Park, Jin-Kee; Park, Hyuntae; Kim, Kwi-Baek

    2015-01-01

    [Purpose] The aim of this study was to examine the relationships between the amount and distribution of body fat and the carotid intima-media thickness to explore whether coronary artery disease risk may be mediated through effects on the amount of fat mass in older adults. [Subjects and Methods] A total of 200 elderly females was participated. The percentage of body fat mass was measured by the bioelectrical impedance analysis method, and the carotid intima-media thickness was measured by B-mode ultrasound. Analysis of covariance was performed to assess independent associations between the four categories of percentage of body fat mass and the carotid intima-media thickness after multivariate adjustment. Logistic regression analyses were utilized to calculate odds ratios and 95% confidence intervals for examining independent associations between percentage of body fat mass and the estimated risk of coronary artery disease. [Results] Analysis of covariance showed that the carotid intima-media thickness was significantly thick in both obesity and overweight groups. When multivariate-adjusted OR for the estimated risk of coronary artery disease, the odds ratios for the obesity and overweight groups were 3.0 (95% confidence interval, 1.1 to 8.7) and 2.5 (95% confidence interval, 1.0 to 6.1), respectively. [Conclusion] This study demonstrates that elderly females with a high body fat mass are more likely to have the estimated risk of CAD than who fit body fat mass in elderly female. PMID:26633917

  3. Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms.

    PubMed

    Valdés, Viviana; Mosqueira, Matías; Rey, Sergio; Del Rio, Rodrigo; Iturriaga, Rodrigo

    2003-01-01

    We tested the hypothesis that nitric oxide (NO) produced within the carotid body is a tonic inhibitor of chemoreception and determined the contribution of neuronal and endothelial nitric oxide synthase (eNOS) isoforms to the inhibitory NO effect. Accordingly, we studied the effect of NO generated from S-nitroso-N-acetylpenicillamide (SNAP) and compared the effects of the nonselective inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) and the selective nNOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on chemosensory dose-response curves induced by nicotine and NaCN and responses to hypoxia (Po(2) approximately 30 Torr). CBs excised from pentobarbitone-anesthetized cats were perfused in vitro with Tyrode at 38 degrees C and pH 7.40, and chemosensory discharges were recorded from the carotid sinus nerve. SNAP (100 microM) reduced the responses to nicotine and NaCN. l-NAME (1 mM) enhanced the responses to nicotine and NaCN by increasing their duration, but TRIM (100 microM) only enhanced the responses to high doses of NaCN. The amplitude of the response to hypoxia was enhanced by l-NAME but not by TRIM. Our results suggest that both isoforms contribute to the NO action, but eNOS being the main source for NO in the cat CB and exerting a tonic effect upon chemoreceptor activity.

  4. Carotid body chemosensory excitation induced by nitric oxide: involvement of oxidative metabolism.

    PubMed

    Mosqueira, Matias; Iturriaga, Rodrigo

    2002-08-01

    Nitric oxide (NO) produces a dual effect on carotid body (CB) oxygen chemoreception. At low concentration, NO inhibits chemosensory response to hypoxia, while in normoxia, medium and high [NO] increases the frequency of carotid chemosensory discharges (f(x)). Since NO and peroxynitrite inhibit mitochondrial respiration, it is plausible that the NO-induced excitation may depend on the mitochondrial oxidative metabolism. To test this hypothesis, we studied the effects of oligomycin, FCCP and antimycin A that produce selective blockade of hypoxic and NaCN-induced chemosensory responses, leaving nicotinic response less affected. CBs excised from pentobarbitone-anaesthetised cats were perfused in vitro with Tyrode (P(O(2)) approximately 125 Torr, pH 7.40 at 38 degrees C). Hypoxia (P(O(2)) approximately equal 30 Torr), NaCN and nicotine (1-100 microg) and S-nitroso-N-acetylpenicillamide (SNAP, 300-600 microg) increased f(x). Oligomycin (12.5-25 microg), antimycin A (10 microg) and FCCP (5 microM) transiently increased f(x). Subsequently, chemosensory responses to hypoxia, NaCN and SNAP were reduced or abolished, while the response to nicotine was less affected. The electron donor system tetramethyl-p-phenylene diamide and ascorbate that bypasses the electron chain blockade produced by antimycin A, restores the excitatory responses to NaCN and SNAP. Present results suggest that the chemoexcitatory effect of NO depends on the integrity of mitochondrial metabolism.

  5. Acute oxygen sensing by the carotid body: from mitochondria to plasma membrane.

    PubMed

    Chang, Andy J

    2017-08-17

    Maintaining oxygen homeostasis is crucial to the survival of animals. Mammals respond acutely to changes in blood oxygen levels by modulating cardiopulmonary function. The major sensor of blood oxygen that regulates breathing is the carotid body (CB), a small chemosensory organ located at the carotid bifurcation. When arterial blood oxygen levels drop in hypoxia, neuroendocrine cells in the CB called glomus cells are activated to signal to afferent nerves that project to the brainstem. The mechanism by which hypoxia stimulates CB sensory activity has been the subject of many studies over the last 90 years. Two discrete models emerged that argue for the seat of oxygen sensing to lie either in the plasma membrane or mitochondria of CB cells. Recent studies are bridging the gap between these models by identifying hypoxic signals generated by changes in mitochondrial function in the CB that can be sensed by plasma membrane proteins on glomus cells. The CB is important for physiological adaptation to hypoxia, and its dysfunction contributes to sympathetic hyperactivity in common conditions such as sleep-disordering breathing, chronic heart failure, and insulin resistance. Understanding the basic mechanism of oxygen sensing in the CB could allow us to develop strategies to target this organ for therapy. In this short review, I will describe two historical models of CB oxygen sensing and new findings that are integrating these models. Copyright © 2017, Journal of Applied Physiology.

  6. Prevalence by sex of preclinical carotid atherosclerosis in newly diagnosed type 2 diabetes.

    PubMed

    Catalan, M; Herreras, Z; Pinyol, M; Sala-Vila, A; Amor, A J; de Groot, E; Gilabert, R; Ros, E; Ortega, E

    2015-08-01

    There is clinical trial evidence that only early, intensive risk factor control can reduce cardiovascular disease (CVD) morbidity and mortality in type 2 diabetes (T2DM). However, there is little information regarding preclinical atherosclerosis at diabetes diagnosis. We assessed carotid atherosclerosis in new-onset T2DM and control individuals without prior CVD. In a cross-sectional case-control study, we determined intima-media thickness (IMT) and plaque (IMT ≥1.5 mm) by ultrasound at all carotid sites in new-onset T2DM patients and controls. We assessed 106 T2DM patients, median age 62 years, 46% women, 19% smokers, 54% with hypertension, and 41% with dyslipidemia and 99 non-diabetic subjects matched by age, sex, and cardiovascular risk factors. Compared to controls, T2DM patients had higher common carotid artery (CCA)-IMT (median 0.725 vs. 0.801 mm, p = 0.01), bulb-IMT (0.976 vs. 1.028 mm, p = 0.12), and internal carotid artery (ICA)-IMT (0.727 vs. 0.802 mm, p = 0.04). The prevalence of total plaque (60% vs. 72%, p = 0.06), ICA plaque (20% vs. 42%, p < 0.01), and harboring ≥3 plaques (16% vs. 35% p < 0.01) was also higher in T2DM. Plaque score (sum of maximum plaque heights) was also higher (p < 0.01) in T2DM. Diabetic women showed more advanced carotid atherosclerosis than diabetic men when they were compared with their respective non-diabetic counterparts. There is a high prevalence of preclinical atherosclerosis (carotid plaque presence and burden) in new-onset T2DM subjects, especially in women. Early, still reversible, preclinical atherosclerosis may explain in part why early intervention is effective to prevent CVD in this patient population. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Hypoxic pulmonary vasoconstriction, carotid body function and erythropoietin production in adult rats perinatally exposed to hyperoxia.

    PubMed

    Prieto-Lloret, Jesus; Ramirez, Maria; Olea, Elena; Moral-Sanz, Javier; Cogolludo, Angel; Castañeda, Javier; Yubero, Sara; Agapito, Teresa; Gomez-Niño, Angela; Rocher, Asuncion; Rigual, Ricardo; Obeso, Ana; Perez-Vizcaino, Francisco; González, Constancio

    2015-06-01

    Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is maintained. Loss of pulmonary hypoxic vasoconstriction is not linked to alterations in oxygen-sensitive K(+) currents in pulmonary artery smooth muscle cells. Loss of hypoxic vasoconstriction is associated with early postnatal oxidative damage and corrected by an antioxidant diet. Perinatal hyperoxia damages carotid body chemoreceptor cell function and the antioxidant diet does not reverse it. The hypoxia-elicited increase in erythropoietin plasma levels is not affected by perinatal hyperoxia. The potential clinical significance of the findings in clinical situations such as pneumonia, chronic obstructive pulmonary disease or general anaesthesia is considered. Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55-60% O2 for the last 5-6 days of pregnancy and 4 weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2 -sensitivity of K(+) currents in the PASMC of hyperoxic animals is normal, indicating that

  8. Hypoxic pulmonary vasoconstriction, carotid body function and erythropoietin production in adult rats perinatally exposed to hyperoxia

    PubMed Central

    Prieto-Lloret, Jesus; Ramirez, Maria; Olea, Elena; Moral-Sanz, Javier; Cogolludo, Angel; Castañeda, Javier; Yubero, Sara; Agapito, Teresa; Gomez-Niño, Angela; Rocher, Asuncion; Rigual, Ricardo; Obeso, Ana; Perez-Vizcaino, Francisco; González, Constancio

    2015-01-01

    Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55–60% O2 for the last 5–6 days of pregnancy and 4 weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2-sensitivity of K+ currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal hyperoxia also abrogated responses elicited by hypoxia on catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal hyperoxia, comparable to oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional pneumonias, atelectases or general anaesthesia in adult life. Key points Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is

  9. Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2: role of carotid body CO2

    PubMed Central

    Smith, Curtis A; Blain, Grégory M; Henderson, Kathleen S; Dempsey, Jerome A

    2015-01-01

    Abstract We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO2. The effect of CB normoxic hypocapnia, normocapnia and hypercapnia (carotid body  ≈ 22, 41 and 68 mmHg, respectively) on the ventilatory CO2 sensitivity of central chemoreceptors was studied in seven awake dogs with vascularly-isolated and extracorporeally-perfused CBs. Chemosensitivity with one CB was similar to that in intact dogs. In four CB-denervated dogs, absence of hyper-/hypoventilatory responses to CB perfusion with of 19–75 mmHg confirmed separation of the perfused CB circulation from the brain. The group mean central CO2 response slopes were increased 303% for minute ventilation ()(P ≤ 0.01) and 251% for mean inspiratory flow rate (VT/TI) (P ≤ 0.05) when the CB was hypercapnic vs. hypocapnic; central CO2 response slopes for tidal volume (VT), breathing frequency (fb) and rate of rise of the diaphragm EMG increased in 6 of 7 animals but the group mean changes did not reach statistical significance. Group mean central CO2 response slopes were also increased 237% for (P ≤ 0.01) and 249% for VT/TI(P ≤ 0.05) when the CB was normocapnic vs. hypocapnic, but no significant differences in any of the central ventilatory response indices were found between CB normocapnia and hypercapnia. These hyperadditive effects of CB hyper-/hypocapnia agree with previous findings using CB hyper-/hypoxia.We propose that hyperaddition is the dominant form of chemoreceptor interaction in quiet wakefulness when the chemosensory control system is intact, response gains physiological, and carotid body chemoreceptors are driven by a wide range of O2 and/or CO2. Key points The influence of specific carotid body (CB) normoxic hypocapnia, hypercapnia and normocapnia on the ventilatory sensitivity of central chemoreceptors to systemic hypercapnia was assessed in seven awake dogs with extracorporeal perfusion of the

  10. Blood pressure, heart rate and arterial blood gas reactions to acute hypoxia in carotid body denervated spontaneously hypertensive rats.

    PubMed

    Huckstorf, C; Behm, R; Habeck, J O; Rückborn, K; Franz, U

    1987-01-01

    The role of the peripheral arterial chemoreceptors in the reflex control of respiration and the cardiovascular systems was studied in spontaneously hypertensive rats (SHR). In carotid body denervated and in sham-operated control rats mean arterial blood pressure, heart rate, respiratory rate and arterial blood gases were measured under normoxic conditions and in acute normobaric hypoxia. Under normoxia the carotid body denervated SHR differ from the sham-operated ones only in significantly lowered arterial pO2 and pH and in significantly increased pCO2 values. The carotid body denervated SHR react to acute hypoxia with a significantly smaller increase in respiratory rate, a more pronounced fall in the arterial pO2 and a greater decrease in mean arterial blood pressure than the sham-operated control rats. Our results suggest that carotid body chemoreceptors in SHR are of great importance in regulating respiration but of secondary consequence regarding the reflex control of the cardiovascular system.

  11. Volatile Anaesthetic Depression of the Carotid Body Chemoreflex-Mediated Ventilatory Response to Hypoxia: Directions for Future Research

    PubMed Central

    Pandit, J. J.

    2014-01-01

    In assessing whether volatile anaesthetics directly depress the carotid body response to hypoxia it is necessary to combine in meta-analysis studies of when it is “functionally isolated” (e.g., recordings are made from its afferent nerve). Key articles were retrieved (full papers in English) and subjected to quantitative analysis to yield an aggregate estimate of effect. Results from articles that did not use such methodology were assessed separately from this quantitative approach, to see what could be learned also from a nonquantitative overview. Just 7 articles met the inclusion criteria for hypoxia and just 6 articles for hypercapnia. Within these articles, the anaesthetic (mean dose 0.75, standard deviation (SD) 0.40 minimum alveolar concentration, MAC) statistically significantly depressed carotid body hypoxic response by 24% (P = 0.041), but a similar dose (mean 0.81 (0.42) MAC) did not affect the hypercapnic response. The articles not included in the quantitative analysis (31 articles), assessed qualitatively, also indicated that anaesthetics depress carotid body function. This conclusion helps direct future research on the anaesthetic effects on putative cellular/molecular processes that underlie the transduction of hypoxia in the carotid body. PMID:24808974

  12. Trigeminal and carotid body inputs controlling vascular resistance in muscle during post-contraction hyperaemia in cats

    PubMed Central

    de Burgh Daly, M; Cook, M N

    1999-01-01

    In anaesthetized cats, the effects of stimulation of the receptors in the nasal mucosa and carotid body chemoreceptors on vascular resistance in hindlimb skeletal muscle were studied to see whether the responses were the same in active as in resting muscle. The measurements of vascular resistance were taken, first, in resting muscle, and second, in the immediate post-contraction hyperaemic phase that followed a 30 s period of isometric contractions.Stimulation of the receptors in the nasal mucosa caused reflex apnoea and vasoconstriction in muscle. The latter response was attenuated when the test was repeated during post-contraction hyperaemia.Stimulations of the carotid bodies were made during a period of apnoea evoked reflexly by electrical stimulation of both superior laryngeal nerves. This apnoea prevented any effects of changes in respiration on the carotid body reflex vascular responses. Stimulation of the carotid bodies evoked hindlimb muscle vasoconstriction. In the post-contraction hyperaemic period, the response was reduced or abolished. A similar attenuation of the reflex vasoconstrictor responses occurred in decentralized muscles stimulated through their motor roots in the cauda equina.Evidence is presented that the attenuation of the vasoconstrictor responses evoked by the two reflexes is a phenomenon localized to the contracting muscles themselves resulting from an interaction between sympathetic neuronal activity and the local production of metabolites.The results are discussed in relation to the metabolic needs of tissues in relation to asphyxial defence mechanisms such as occur in the diving response. PMID:10050020

  13. Role of the Carotid Body in the Pathophysiology of Heart Failure

    PubMed Central

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

    2013-01-01

    Important recent advances implicate a role of the carotid body (CB) chemoreflex in sympathetic and breathing dysregulation in several cardio-respiratory diseases, drawing renewed interest in its potential implications for clinical treatment. Evidence from both chronic heart failure (CHF) patients and animal models indicates that the CB chemoreflex is enhanced in CHF, and contributes to the tonic elevation in sympathetic nerve activity (SNA) and periodic breathing associated with the disease. Although this maladaptive change likely derives from altered function at all levels of the reflex arc, a change in afferent function of the CB is likely to be a main driving force. This review will focus on recent advances in our understanding of the pathophysiological mechanisms that alter CB function in CHF and their potential translational impact on treatment of chronic heart failure (CHF). PMID:23824499

  14. Does Shamblin's classification predict postoperative morbidity in carotid body tumors? A proposal to modify Shamblin's classification.

    PubMed

    Luna-Ortiz, Kuauhyama; Rascon-Ortiz, Mario; Villavicencio-Valencia, Veronica; Herrera-Gomez, Angel

    2006-02-01

    The objective of this study was to analyze the possible correlation between Shamblin's classification and post-surgical morbidity in the treatment of carotid body tumors (CBTs). Seventy-two patients with carotid body tumors were seen over a 22-year period. Twenty-three patients were excluded as they did not comply with the criteria of the objectives. All patients were grouped according to Shamblin's classification. We propose a modification to this classification and make a comparison by analyzing the surgical time and bleeding, as well as the neurological and vascular damage. We resected 50 CBTs in 49 patients, ranging in age from 18 to 73 years. Three groups were formed: group I with 8 (16%) patients, group II with 17 (34%) and group III with 24 (49%). Post-surgical neurological damage was observed in one patient (12.5%) from group I, in six (35%) from group II and in nine patients (37.5%) from group III. Vascular sacrifice had to be performed in 21% of class II tumors and in 8.7% of class III. None of the class I tumors required vascular sacrifice. No statistically significant difference existed for vascular or neurological risk in relation to Shamblin's classification. However, when analyzed according to the classification proposed herein, there was a correlation between Shamblin's classification and vascular sacrifice (P =0.001). There was a statistically significant correlation between the original Shamblin and the modified Shamblin regarding surgical time and bleeding. Shamblin's classification predicts only vascular morbidity. Neurological morbidity is not reflected in it and only reflects the surgeon's experience with CBT resections. Surgical time and bleeding are directly related to the Shamblin as it reflects the size of tumors in relation to the blood vessels. Shamblin's classification must be modified to be more objective so that the international reports can accurately reflect the morbidity related to it.

  15. Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation

    PubMed Central

    Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Hodges, Matthew R.

    2013-01-01

    A current and major unanswered question is why the highly sensitive central CO2/H+ chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔV̇E/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P < 0.05), and glutamine and dopamine were significantly below pre-CBD levels (P < 0.05). Serotonin, substance P, and epinephrine were variable but not significantly (P > 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase–expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex. PMID:23869058

  16. Stimulus interaction between CO and CO2 in the cat carotid body chemoreception.

    PubMed

    Osanai, S; Chugh, D K; Mokashi, A; Lahiri, S

    1996-03-04

    Since high PCO in the dark works like hypoxia in the carotid body chemoreceptors and since hypoxia shows a stimulus interaction with CO2, it is hypothesized that high PCO will show a similar interaction with PCO2 in the chemosensory excitation in the dark. We tested the hypothesis using cat carotid body perfused and superfused in vitro with Po2 of about 100 Torr. In one series, the chemosensory discharges were tested at three levels of PCO2 at high PCO of 500 Torr in the absence and presence of light. In the dark, normocapnia (PCO2 approximately 30 Torr) with high PCO promptly stimulated the sensory discharges to a peak, subsiding to a lower level. In hypocapnia (PCO2 approximately 18 Torr) with high PCO, all phases of activities were significantly lower than those of normocapnia, showing stimulus interaction. Hypercapnia saturated the activity with high PCO and seems to preclude a clear demonstration of stimulus interaction. In another series, an intermediate level of PCO (approximately 150 Torr), which showed a half-maximal activity in normoxia, showed a clear interaction with hypercapnia in the dark. With high PCO, bright light promptly reduced the activity to baseline at all PCO2 levels. This then increased somewhat to a steady-state. Withdrawal of the light was followed by a sharp rise in the activity to a peak which then fell to a somewhat lower level of steady-state. The peak discharge rate in the presence of light did not differ significantly from those of PCO2 alone.

  17. The Effects of Preoperative Embolization on Carotid Body Paraganglioma Surgery: A Systematic Review and Meta-analysis.

    PubMed

    Jackson, Ryan S; Myhill, Jeffrey A; Padhya, Tapan A; McCaffrey, Judith C; McCaffrey, Thomas V; Mhaskar, Rahul S

    2015-12-01

    There is no definitive consensus on the impact of preoperative embolization on carotid body paraganglioma management. The purpose of this study was to assess the effects of preoperative embolization on carotid body paraganglioma excision. A systematic search was conducted without limits, and it included studies published on or before July 2013 from PubMed, CINAHL, Web of Knowledge, and the Cochrane Library. Relevant synonyms for the search terms "paraganglioma,"carotid body tumor," and "embolization" were applied. Studies evaluating patients undergoing surgical intervention with embolization for carotid body tumors were included. Two reviewers independently assessed the titles and abstracts for inclusion and extracted the data. The guidelines set forth by the Cochrane Collaboration were followed in the process of data extraction. Data were pooled with a fixed effects model, and standardized mean difference (SMD) and 95% confidence intervals (95% CIs) are reported. A total of 22 studies (15 nonrandomized studies with a comparator, 7 single-arm studies) were included, enrolling 578 patients with 607 tumors. Patients undergoing preoperative embolization had significantly less estimated blood loss compared with those of surgical excision only (12 studies; 295 tumors; SMD: -0.52; 95% CI: -0.77, -0.28). Patients undergoing preoperative embolization had less operative time compared with that of surgical excision only (6 studies; 174 tumors; SMD: -0.46; 95% CI: -0.77, -0.14). Surgical excision with preoperative embolization appears to decrease estimated blood loss and operative time when compared with that without preoperative embolization for carotid body paragangliomas. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  18. Carotid Intima-Media Thickness, Ankle-Arm Index, and Inflammation Profile in Mexican Patients with Early and Late Onset Type 2 Diabetes.

    PubMed

    Contreras-Rodríguez, Alicia; Gómez-Díaz, Rita A; Tanus-Hajj, Janet; Talavera, Juan O; Mondragón-González, Rafael; Wacher, Niels H

    2015-01-01

    Type 2 diabetes is strongly linked to an increased incidence of cardiovascular outcomes. Carotid artery intima-media thickness and ankle-arm index are non-invasive complementary measures as subclinical markers of atherosclerosis. To evaluate the association of carotid intima-media thickness, ankle-arm index, and inflammation profile in Mexican patients with early- and late-onset type 2 diabetes mellitus. We included 145 subjects at an academic medical center: 77 patients with early-onset (< 40 years of age) and 33 patients with late-onset (≥ 40 years) type 2 diabetes mellitus, and 35 healthy volunteers. Clinical history, anthropometrics, blood chemistry, lipids profile, glycosylated hemoglobin A1c, cytokines, and high-sensitivity C-reactive protein were determined; carotid and lower limb ultrasound were taken. Groups were compared with ANOVA or Kruskal-Wallis, Student's t or Mann-Whitney U. Spearman or Pearson correlation and logistic regression analysis were used. There were anthropometric and biochemical differences between the three groups. Concentrations of interleukin-1β, -4 and -6 were significantly higher in patients with late versus early onset diabetes. There were differences in carotid intima-media thickness and ankle-arm index between early and late onset. Age, body mass index, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, waist circumference, and glycosylated hemoglobin A1c showed direct correlation with carotid intima-media thickness, while ankle-arm index showed inverse correlation with blood pressure, glycosylated hemoglobin A1c, time with disease, age at onset, triglycerides, and fibrinogen. Multivariate analysis showed an association between carotid intima-media thickness and disease duration; ankle-arm index with disease duration and high-sensitivity C-reactive protein; while only body mass index associated with end diastolic flow velocity. Our findings suggest that carotid intima-media thickness and ankle-arm index

  19. Overt and subclinical baroreflex dysfunction following bilateral carotid body tumor resection: pathophysiology, diagnosis, and implications for management.

    PubMed

    Ghali, Michael G Z; Srinivasan, Visish M; Hanna, Ehab; DeMonte, Franco

    2017-02-25

    Carotid body paragangliomas are rare, usually benign, tumors arising from glomus cells of the carotid body. Bilateral involvement is present in ∼5% of sporadic cases and up to one-third of familial cases. In the majority of patients undergoing bilateral resection of carotid body tumors (CBTs), a condition known as baroreflex failure syndrome (BFS) develops following resection of the second tumor characterized by headache, anxiety, emotional lability, orthostatic lightheadedness, hypertension, and tachycardia. This is believed to result from damage to the carotid baroreceptor apparatus. Patients without overt cardiovascular abnormalities may have subclinical baroreceptor dysfunction evident only on specific testing, measuring HR and sympathetic nerve responses to baro-loading (eg., phenylephrine) and baro-unloading (e.g., Valsalva maneuver). Given the high incidence of BFS in patients undergoing bilateral resection of CBTs, it is suggested that operation be limited to unilateral resection of the dominant/symptomatic lesion and non-surgical intervention (i.e., embolization, radiotherapy) on the contralateral side. Alternatively, refinement of surgical technique to prevent injury to elements of the baroreceptor apparatus may prevent this unfortunate complication of bilateral tumor resection. We present a case of a 16 year old girl with bilateral jugular vagale and carotid body tumors who developed hypertension following surgical resection of her left jugular vagale tumor and worsening of hypertension concurrent with progression, eventually requiring intensity-modulated radiation therapy and a resection for significant progression of her left jugular vagale tumor. Our case illustrates the generalizability of BFS to patients with tumors involving the vagal baro-afferent fibers.

  20. Intracellular pH and oxygen chemoreception in the cat carotid body in vitro.

    PubMed

    Iturriaga, R; Rumsey, W L; Lahiri, S; Spergel, D; Wilson, D F

    1992-06-01

    To test the hypothesis that O2 chemoreception in the carotid body (CB) is mediated by cellular acidosis, we simultaneously measured responses of the chemosensory and intracellular pH (pHi) to agents that are known to change pHi and studied the effects of hypoxia and ischemia on these variables in the cat CB. The CB was perfused and superfused in vitro with a modified Tyrode's solution at 36.0 +/- 0.5 degrees C with or without CO2-HCO3- (pH 7.40) and equilibrated at a given PO2. Chemosensory discharges were recorded from the whole carotid sinus nerve. To measure pHi changes, the CB was loaded with the pH-sensitive indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, and the fluorescence (excitation 420-490 nm, emission greater than 515 nm) was detected by an intensified charged coupled device camera with an epifluorescence macroscope. Boluses of Tyrode's solution (0.5 ml, free of CO2-HCO3-) containing sodium acetate or NH4Cl prolonged perfusion of acid Tyrode's solution (pH 7.20-6.50), and boluses of Tyrode's solution with CO2-HCO3- were used. A decrease of fluorescence indicated pHi turning acid, and an increase of fluorescence indicated a change in alkaline pHi. Chemosensory activity varied inversely with the fluorescence change after application of these agents. Interruption of perfusate flow or application of hypoxic perfusate resulted in large increases in chemosensory discharge without any change in the fluorescence. The results indicated that chemosensory responses to brief ischemia and hypoxia were not mediated by a fall of pHi of CB cells, whereas those to CO2 and extracellular acidity were associated with decreases in pHi.

  1. Influence of age, body mass index, and blood pressure on the carotid intima-media thickness in normotensive and hypertensive patients.

    PubMed

    Honzikova, Natasa; Labrova, Ruzena; Fiser, Bohumil; Maderova, Eva; Novakova, Zuzana; Zavodna, Eva; Semrad, Borivoj

    2006-10-01

    We investigated whether body mass index and blood pressure have an additive influence on the carotid intima-media thickness (IMT). In 27 patients treated for hypertension (47.2+/-8.7 years) and 23 normotensive subjects (44.1+/-8.1 years), 24-h recording of blood pressure was performed. The carotid IMT was determined by ultrasonography and baroreflex sensitivity by a spectral method from 5-min recordings of blood pressure. Significant differences between hypertensive and normotensive subjects were observed for carotid IMT (0.60+/-0.08 vs. 0.51+/-0.07 mm; p<0.001) and baroreflex sensitivity (3.5+/-1.8 vs. 5.6+/-2.1 ms/mm Hg; p<0.001). Hierarchical multiple regression analysis (p<0.01) showed that carotid IMT was positively correlated with age (p<0.001) and body mass index (p<0.05) in normotensive subjects. The increased carotid IMT in hypertensive patients was not additively influenced by either age or body mass index. Baroreflex sensitivity decreased with age (p<0.01) and with carotid IMT (p<0.05) in normotensive subjects only. Multiregression analysis showed that an additive influence of age and body mass index on the development of carotid IMT is essential only in normotensive subjects. In hypertensive subjects the influence of blood pressure predominates, as documented by a comparison of the carotid IMT between hypertensive and normotensive subjects.

  2. Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

    PubMed Central

    Marcus, Noah J; Rio, Rodrigo; Schultz, Evan P; Xia, Xiao-Hong; Schultz, Harold D

    2014-01-01

    In congestive heart failure (CHF), carotid body (CB) chemoreceptor activity is enhanced and is associated with oscillatory (Cheyne–Stokes) breathing patterns, increased sympathetic nerve activity (SNA) and increased arrhythmia incidence. We hypothesized that denervation of the CB (CBD) chemoreceptors would reduce SNA, reduce apnoea and arrhythmia incidence and improve ventricular function in pacing-induced CHF rabbits. Resting breathing, renal SNA (RSNA) and arrhythmia incidence were measured in three groups of animals: (1) sham CHF/sham–CBD (sham–sham); (2) CHF/sham–CBD (CHF–sham); and (3) CHF/CBD (CHF–CBD). Chemoreflex sensitivity was measured as the RSNA and minute ventilatory () responses to hypoxia and hypercapnia. Respiratory pattern was measured by plethysmography and quantified by an apnoea–hypopnoea index, respiratory rate variability index and the coefficient of variation of tidal volume. Sympatho-respiratory coupling (SRC) was assessed using power spectral analysis and the magnitude of the peak coherence function between tidal volume and RSNA frequency spectra. Arrhythmia incidence and low frequency/high frequency ratio of heart rate variability were assessed using ECG and blood pressure waveforms, respectively. RSNA and responses to hypoxia were augmented in CHF–sham and abolished in CHF–CBD animals. Resting RSNA was greater in CHF–sham compared to sham–sham animals (43 ± 5% max vs. 23 ± 2% max, P < 0.05), and this increase was not found in CHF–CBD animals (25 ± 1% max, P < 0.05 vs. CHF–sham). Low frequency/high frequency heart rate variability ratio was similarly increased in CHF and reduced by CBD (P < 0.05). Respiratory rate variability index, coefficient of variation of tidal volume and apnoea–hypopnoea index were increased in CHF–sham animals and reduced in CHF–CBD animals (P < 0.05). SRC (peak coherence) was increased in CHF–sham animals (sham–sham 0.49 ± 0.05; CHF–sham 0.79

  3. Blood donation, body iron status and carotid intima-media thickness.

    PubMed

    Engberink, Mariëlle F; Geleijnse, Johanna M; Durga, Jane; Swinkels, Dorine W; de Kort, Wim L A M; Schouten, Evert G; Verhoef, Petra

    2008-02-01

    Iron could promote free radical formation, which may lead to injury of the arterial wall and atherosclerosis. Blood donation may reduce cardiovascular risk by lowering body iron status. We collected data on blood donation history and intima-media thickness of the common carotid artery (CIMT) in 819 subjects (50-70 years), who were recruited from municipal and blood bank registries in The Netherlands. Serum iron parameters were assessed, including non-transferrin bound iron (NTBI) that has recently been found in conditions of iron overload. Serum ferritin was lower in current donors (n=443; 44 microg/L) than in ex-donors (n=120; 114 microg/L) and never-donors (n=256; 124 microg/L, P for trend <0.001). For NTBI, values were 2.33, 2.54, and 2.51 micromol/L, respectively (P<0.05). CIMT was slightly reduced in frequent donors (i.e., > or =49 times during life or > or =2 times per year), although not statistically significant. CIMT was not significantly related to NTBI. Frequent blood donation, resulting in lowered body iron, might give some protection against accelerated atherosclerosis.

  4. Imaging carotid body chemodectomas with 68Ga-DOTA-NOC PET-CT

    PubMed Central

    Naswa, N; Kumar, A; Sharma, P; Bal, C; Malhotra, A; Kumar, R

    2012-01-01

    Objective The purpose of the present study was to evaluate the role of 68-gallium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-1-Nal3-octreotide (68Ga-DOTA-NOC) positron emission tomography CT (PET-CT) in carotid body chemodectomas (CBCs). Methods : 5 patients with known CBCs (conventional imaging and angiography) were evaluated retrospectively (3 males, 2 females; mean age 36.6 years). All underwent PET-CT after injection of 148 MBq (4 mCi) of 68Ga-DOTA-NOC. Results : At baseline there were four bilateral CBCs and one unilateral CBC with an additional glomus tympanicum and bilateral glomus jugulare tumour in these five patients. All these lesions showed intense uptake on 68Ga-DOTA-NOC PET-CT. Apart from these known lesions, additional tumours were detected in three patients; glomus jugulare in one, aortic body tumour and multiple abdominal paragangliomas in another and unsuspected vertebral metastasis in the last. Overall it led to a change in management in 3 of the 5 patients (60%). Conclusion : 68Ga-DOTA-NOC PET-CT is a promising non-invasive imaging modality in the detection and characterisation of CBCs. PMID:22096221

  5. Oxygen sensing by the carotid body: mechanisms and role in adaptation to hypoxia.

    PubMed

    López-Barneo, José; González-Rodríguez, Patricia; Gao, Lin; Fernández-Agüera, M Carmen; Pardal, Ricardo; Ortega-Sáenz, Patricia

    2016-04-15

    Oxygen (O2) is fundamental for cell and whole-body homeostasis. Our understanding of the adaptive processes that take place in response to a lack of O2(hypoxia) has progressed significantly in recent years. The carotid body (CB) is the main arterial chemoreceptor that mediates the acute cardiorespiratory reflexes (hyperventilation and sympathetic activation) triggered by hypoxia. The CB is composed of clusters of cells (glomeruli) in close contact with blood vessels and nerve fibers. Glomus cells, the O2-sensitive elements in the CB, are neuron-like cells that contain O2-sensitive K(+)channels, which are inhibited by hypoxia. This leads to cell depolarization, Ca(2+)entry, and the release of transmitters to activate sensory fibers terminating at the respiratory center. The mechanism whereby O2modulates K(+)channels has remained elusive, although several appealing hypotheses have been postulated. Recent data suggest that mitochondria complex I signaling to membrane K(+)channels plays a fundamental role in acute O2sensing. CB activation during exposure to low Po2is also necessary for acclimatization to chronic hypoxia. CB growth during sustained hypoxia depends on the activation of a resident population of stem cells, which are also activated by transmitters released from the O2-sensitive glomus cells. These advances should foster further studies on the role of CB dysfunction in the pathogenesis of highly prevalent human diseases. Copyright © 2016 the American Physiological Society.

  6. Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion.

    PubMed

    Ortega-Sáenz, Patricia; Macías, David; Levitsky, Konstantin L; Rodríguez-Gómez, José A; González-Rodríguez, Patricia; Bonilla-Henao, Victoria; Arias-Mayenco, Ignacio; López-Barneo, José

    2016-12-15

    Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB). In biotin-deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis. Remarkably, glomus cells from these animals have normal electrical and neurochemical properties. However, they show a marked decrease in the size of quantal dopaminergic secretory events. Inhibitors of the vesicular monoamine transporter 2 (VMAT2) mimic the effect of biotin deficiency. In biotin-deficient animals, VMAT2 protein expression decreases in parallel with biotin depletion in CB cells. These data suggest that dopamine transport and/or storage in small secretory granules in glomus cells depend on biotin. Biotin is a water-soluble vitamin required for the function of carboxylases as well as for the regulation of gene expression. Here, we report that biotin accumulates in unusually large amounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). We show in a biotin-deficient rat model that the vitamin rapidly disappears from the blood and other tissues (including the AM), while remaining at relatively high levels in the CB. We have also observed that, in comparison with other peripheral neural tissues, CB cells contain high levels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Biotin-deficient rats show a syndrome characterized by marked weight loss, metabolic lactic acidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably, CB cells from biotin-deficient animals have normal electrophysiological and neurochemical (ATP levels and catecholamine synthesis) properties; however

  7. Carotid intima media thickness in type 2 diabetes mellitus with ischemic stroke

    PubMed Central

    Kota, Sunil Kumar; Mahapatra, Girija Ballav; Kota, Siva Krishna; Naveed, Syed; Tripathy, Prabhas Rranjan; Jammula, Sruti; Modi, Kirtikumar D.

    2013-01-01

    Background: Diabetes mellitus is associated with high cardiovascular risk. Carotid intima media thickness (CIMT) is used commonly as a noninvasive test for the assessment of degree of atherosclerosis. The objective of this study was to find out the cut-off point for CIMT for ischemic stroke in patients with type 2 diabetes mellitus (T2DM) and to correlate CIMT with various parameters like smoking, hypertension, lipid profile and duration of T2DM. Materials and Methods: A total of 80 subjects in the age group of 30–75 years (M:F = 57:23) were selected and divided into three groups, i.e. diabetes with ischemic stroke, diabetes and healthy subjects. All the participants were subjected to B-mode ultrasonography of both common carotid arteries to determine CIMT, along with history taking, physical examination and routine laboratory investigations including included fasting and 2-hour postprandial blood sugar, blood urea, serum creatinine, lipid profile, glycated hemoglobin, and microalbuminuria. Results: Patients with T2DM with or without ischemic stroke were found to have significantly higher prevalence of increased CIMT and a value greater than 0.8 mm was found to be associated with the occurrence of stroke. The mean carotid IMT of the group as a whole was 0.840 ± 0.2 mm. The mean carotid IMT was not significantly different between T2DM patients with or without ischemic stroke (1.06 ± 0.2 vs. 0.97 ± 0.26 mm, P = 0.08). However, the mean CIMT was significantly higher in diabetic subjects compared to healthy subjects (1.01 ± 0.28 mm vs. 0.73 ± 0.08, P = 0.006). Other parameters like higher age, smoking, hypertension, hyperlipidemia, low HDL cholesterol, the glycemic parameters and the duration of diabetes were independently and significantly related to CIMT. Conclusion: A high CIMT is a surrogate and reliable marker of higher risk of ischemic stroke amongst type 2 diabetic patients. Our study demonstrates the utility of carotid IMT as a simple non

  8. Carotid intima media thickness in type 2 diabetes mellitus with ischemic stroke.

    PubMed

    Kota, Sunil Kumar; Mahapatra, Girija Ballav; Kota, Siva Krishna; Naveed, Syed; Tripathy, Prabhas Rranjan; Jammula, Sruti; Modi, Kirtikumar D

    2013-07-01

    Diabetes mellitus is associated with high cardiovascular risk. Carotid intima media thickness (CIMT) is used commonly as a noninvasive test for the assessment of degree of atherosclerosis. The objective of this study was to find out the cut-off point for CIMT for ischemic stroke in patients with type 2 diabetes mellitus (T2DM) and to correlate CIMT with various parameters like smoking, hypertension, lipid profile and duration of T2DM. A total of 80 subjects in the age group of 30-75 years (M:F = 57:23) were selected and divided into three groups, i.e. diabetes with ischemic stroke, diabetes and healthy subjects. All the participants were subjected to B-mode ultrasonography of both common carotid arteries to determine CIMT, along with history taking, physical examination and routine laboratory investigations including included fasting and 2-hour postprandial blood sugar, blood urea, serum creatinine, lipid profile, glycated hemoglobin, and microalbuminuria. Patients with T2DM with or without ischemic stroke were found to have significantly higher prevalence of increased CIMT and a value greater than 0.8 mm was found to be associated with the occurrence of stroke. The mean carotid IMT of the group as a whole was 0.840 ± 0.2 mm. The mean carotid IMT was not significantly different between T2DM patients with or without ischemic stroke (1.06 ± 0.2 vs. 0.97 ± 0.26 mm, P = 0.08). However, the mean CIMT was significantly higher in diabetic subjects compared to healthy subjects (1.01 ± 0.28 mm vs. 0.73 ± 0.08, P = 0.006). Other parameters like higher age, smoking, hypertension, hyperlipidemia, low HDL cholesterol, the glycemic parameters and the duration of diabetes were independently and significantly related to CIMT. A high CIMT is a surrogate and reliable marker of higher risk of ischemic stroke amongst type 2 diabetic patients. Our study demonstrates the utility of carotid IMT as a simple non-invasive screening test for the assessment of atherosclerosis risk

  9. Postsynaptic action of GABA in modulating sensory transmission in co-cultures of rat carotid body via GABAA receptors

    PubMed Central

    Zhang, Min; Clarke, Katherine; Zhong, Huijun; Vollmer, Cathy; Nurse, Colin A

    2009-01-01

    GABA is expressed in carotid body (CB) chemoreceptor type I cells and has previously been reported to modulate sensory transmission via presynaptic GABAB receptors. Because low doses of clinically important GABAA receptor (GABAAR) agonists, e.g. benzodiazepines, have been reported to depress afferent CB responses to hypoxia, we investigated the potential contribution of GABAAR in co-cultures of rat type I cells and sensory petrosal neurones (PNs). During gramicidin perforated-patch recordings (to preserve intracellular Cl−), GABA and/or the GABAA agonist muscimol (50 μm) induced a bicuculline-sensitive membrane depolarization in isolated PNs. GABA-induced whole-cell currents reversed at ∼−38 mV and had an EC50 of ∼10 μm (Hill coefficient =∼1) at −60 mV. During simultaneous PN and type I cell recordings at functional chemosensory units in co-culture, bicuculline reversibly potentiated the PN, but not type I cell, depolarizing response to hypoxia. Application of the CB excitatory neurotransmitter ATP (1 μm) over the soma of functional PN induced a spike discharge that was markedly suppressed during co-application with GABA (2 μm), even though GABA alone was excitatory. RT-PCR analysis detected expression of GABAergic markers including mRNA for α1, α2, β2, γ2S, γ2L and γ3 GABAAR subunits in petrosal ganglia extracts. Also, CB extracts contained mRNAs for GABA biosynthetic markers, i.e. glutamate decarboxylase (GAD) isoforms GAD 67A,E, and GABA transporter isoforms GAT 2,3 and BGT-1. In CB sections, sensory nerve endings apposed to type I cells were immunopositive for the GABAAR β subunit. These data suggest that GABA, released from the CB during hypoxia, inhibits sensory discharge postsynaptically via a shunting mechanism involving GABAA receptors. PMID:19029183

  10. Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii

    PubMed Central

    Chavez-Valdez, Raul; Mason, Ariel; Nunes, Ana R.; Northington, Frances J.; Tankersley, Clarke; Ahlawat, Rajni; Johnson, Sheree M.

    2012-01-01

    Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% (P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% (P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% (P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs. PMID:22422797

  11. The carotid body in the duck and the consequences of its denervation upon the cardiac responses to immersion

    PubMed Central

    Jones, D. R.; Purves, M. J.

    1970-01-01

    1. The anatomy of the carotid body and its afferent nerve supply was studied in the duck and a method of denervating the carotid body which ensures a satisfactory post-operative course is described. 2. The effect of denervating the carotid body upon the cardiac response to immersion of the head in water was studied in ten ducks which at the time of the test were unanaesthetized. 3. When the nerves were intact, immersion of the head caused a fall in heart rate after a latent period of between 1 and 9 sec to an average of 24% of the resting rate after 30 sec. Simultaneous measurement of arterial oxygen tension (Pa, O2) in the brachiocephalic artery showed a rapid initial fall during the initial 10 sec from control levels, 93-103 mm Hg, to between 42 and 47 mm Hg, followed by a gradual fall of 3-5 mm Hg for each subsequent 30 sec period of submergence. 4. Following carotid body denervation, the latent period before heart rate started to fall was no different from control but the average fall in heart rate was now to 90% of the resting rate and brachiocephalic Pa. O2 continued to fall steadily during submergence reaching levels of between 10 and 21 mm Hg by the end of the second minute. 5. Stimulation of the central end of branches of the IXth (glossopharyngeal) nerve supplying the glottis caused apnoea and bradycardia. 6. It is concluded that apnoea and bradycardia during submergence in the duck is initiated reflexly from receptors in the nares, pharynx and glottis but that the profound degree of bradycardia and mechanisms which maintain a relatively high Pa, O2 are regulated by peripheral chemoreceptor activity. ImagesPlate 1 PMID:5501002

  12. Central role of carotid body chemoreceptors in disordered breathing and cardiorenal dysfunction in chronic heart failure

    PubMed Central

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

    2014-01-01

    Oscillatory breathing (OB) patterns are observed in pre-term infants, patients with cardio-renal impairment, and in otherwise healthy humans exposed to high altitude. Enhanced carotid body (CB) chemoreflex sensitivity is common to all of these populations and is thought to contribute to these abnormal patterns by destabilizing the respiratory control system. OB patterns in chronic heart failure (CHF) patients are associated with greater levels of tonic and chemoreflex-evoked sympathetic nerve activity (SNA), which is associated with greater morbidity and poor prognosis. Enhanced chemoreflex drive may contribute to tonic elevations in SNA by strengthening the relationship between respiratory and sympathetic neural outflow. Elimination of CB afferents in experimental models of CHF has been shown to reduce OB, respiratory-sympathetic coupling, and renal SNA, and to improve autonomic balance in the heart. The CB chemoreceptors may play an important role in progression of CHF by contributing to respiratory instability and OB, which in turn further exacerbates tonic and chemoreflex-evoked increases in SNA to the heart and kidney. PMID:25505417

  13. Effects of almitrine on the release of catecholamines from the rabbit carotid body in vitro.

    PubMed

    Almaraz, L; Rigual, R; Obeso, A; Evrard, Y; Gonzalez, C

    1992-07-01

    1. Almitrine increases ventilation by stimulating the carotid body (CB) arterial chemoreceptors but neither its intraglomic target nor its mechanism of action have been elucidated. 2. We have tested the hypothesis that chemoreceptor cells are targets for almitrine by studying its effects on the release of 3H-catecholamines in an in vitro rabbit CB preparation. 3. It was found that almitrine (0.3 and 1.5 x 10(-6) M; i.e. 0.2 and 1 mg ml-1) increases the resting release of 3H-catecholamines from CBs (previously loaded with [3H]-tyrosine) incubated in a balanced 95% O2/5% CO2-equilibrated solution. 4. Almitrine at a concentration of 3 x 10(-6) M (2 mg l-1) also augmented the release of 3H-catecholamines elicited by incubating the CBs in a hypoxic solution (equilibrated with 7% O2/5% CO2 in N2), by high external K+ (35 mM) and by veratridine (2 x 10(-5) M), but did not modify release induced by dinitrophenol (7.5 x 10(-5) M). 5. At the same concentration (3 x 10(-6) M), almitrine increased the rate of dopamine synthesis and was ineffective in modifying the cyclic AMP levels in either normoxic or hypoxic CBs. 6. It is concluded that chemoreceptor cells are the intraglomic targets for almitrine. The mechanisms of action of almitrine on chemoreceptor cells are discussed.

  14. Carotid body: a new target for rescuing neural control of cardiorespiratory balance in disease.

    PubMed

    Fitzgerald, Robert S

    2014-01-01

    Significant insight into the mechanisms involved in chronic heart failure (CHF) have been provided by Schultz and his associates at the University of Nebraska Medical Center with the use of pacing-induced heart failure rabbits. Critical among the CHF mechanisms was the role of the carotid body (CB). The stimulated CB produces a wide array of systemic reflex responses; certainly those in the cardiopulmonary (CP) system are the most important in CHF. This generates a question as to whether the CB could serve as a target for some kind of treatment to reestablish control of cardiorespiratory balance in CHF. Any treatment would have to be based on a solid understanding of the mechanisms of chemosensing by the CB as well as the transducing of that sensing into neural activity sent to the medullary centers and regions of autonomic outflow to the periphery. Two avenues of treatment could be to (1) silence or attenuate the CB's neural output pharmacologically and (2) excise the CBS. There is a long history of CB removal mostly as a remedy for chronic obstructive lung disease. Results have been inconclusive as to the effectiveness of this procedure. But if carefully planned, the procedure might be a helpful treatment.

  15. Cat carotid body oxygen metabolism and chemoreception described by a two-cytochrome model.

    PubMed

    Nair, P K; Buerk, D G; Whalen, W J

    1986-02-01

    We have analyzed O2 disappearance curves (DCs) in cat carotid bodies (CBs) measured with our O2 microelectrode, after stopping flow of either blood (108 DCs in 12 cats) or a hemoglobin-free (Locke) perfusion solution (35 DCs in 6 cats). Prior to occlusion, the mean tissue PO2 levels were 74.5 +/- 2.8 (SE) Torr in blood-perfused CBs and 103.4 +/- 2.6 in Locke-perfused CBs. The O2 consumption rates (VO2) determined from the initial 3 s of the DCs were 1.46 +/- 0.08 and 1.50 +/- 0.10 (SE) ml O2 . 100 g-1 . min-1, respectively, for the blood-perfused and Locke-perfused CBs. The change in total sinus nerve activity from the CB was also measured following stopped flow. The nerve activity began to increase immediately, providing further evidence that classic hypoxia is not the mechanism of chemoreceptor discharge. However, about two-thirds of the increased activity in blood-perfused CBs occurred after tissue PO2 levels fell below 20 Torr. As the CB tissue PO2 decreased, the O2 disappearance rate (-dPO2/dt) also decreased for both experimental conditions, indicating that the CB VO2 varies with O2 concentration. The increase in nerve discharge and O2 disappearance rate can be interpreted by a two-cytochrome model for O2 metabolism, with both high and low affinities.

  16. Non-additive interactions between mitochondrial complex IV blockers and hypoxia in rat carotid body responses

    PubMed Central

    Donnelly, David F; Kim, Insook; Mulligan, Eileen M; Carroll, John L

    2013-01-01

    The metabolic hypothesis of carotid body chemoreceptor hypoxia transduction proposes an impairment of ATP production as the signal for activation. We hypothesized that mitochondrial complex IV blockers and hypoxia would act synergistically in exciting afferent nerve activity. Following a pretreatment with low dosage sodium cyanide (10-20μM), the hypoxia-induced nerve response was significantly reduced along with hypoxia-induced catecholamine release. However, in isolated glomus cells, the intracellular calcium response was enhanced as initially predicted. This suggests a cyanide-mediated impairment in the step between the glomus cell intracellular calcium rise and neurotransmitter release from secretory vesicles. Administration of a PKC blocker largely reversed the inhibitory actions of cyanide on the neural response. We conclude that the expected synergism between cyanide and hypoxia occurs at the level of glomus cell intracellular calcium but not at downstream steps due to a PKC-dependent inhibition of secretion. This suggests that at least one regulatory step beyond the glomus cell calcium response may modulate the magnitude of chemoreceptor responsiveness. PMID:24096081

  17. Potential role of H2O2 in chemoreception in the cat carotid body.

    PubMed

    Osanai, S; Mokashi, A; Rozanov, C; Buerk, D G; Lahiri, S

    1997-03-19

    The hypothesis that H2O2 plays a critical role in hypoxic chemoreception in the cat carotid body (CB) was tested using a perfused-superfused preparation in vitro, measuring chemosensory discharge and CB tissue PO2 (PtiO2). According to the hypothesis NADPH mediated, PO2 dependent increase in H2O2 production would hyperpolarize the glomus cell, decreasing the chemosensory discharge. Thus, lactate and aminotriazole which would increase H2O2 concentration, would decrease the chemosensory discharge during hypoxia. However, 2.5-5.0 mM lactate and 25 mM aminotriazole did not diminish the hypoxic response. But, 2.5 mM lactate decreased the chemosensory discharge during normoxia which can be explained by an increase of CB PtiO2. Diethyldithiocarbamic acid (5 mM), which blocks the conversion of superoxide to H2O2, also diminished the chemosensory discharge, presumably due to an increased CB PtiO2. Menadione (increasing H2O2) and t-butyl hydroperoxide irreversibly decreased the chemosensory discharge, and the data are not useful. H2O2 increased the PO2 of the perfusate, and therefore could not be tested against PO2. Thus, perturbation of endogenous or exogenous H2O2 did not provide any evidence for its critical role in O2 chemoreception.

  18. THE IMPACT OF HYDROGEN SULFIDE (H2S) ON NEUROTRANSMITTER RELEASE FROM THE CAT CAROTID BODY

    PubMed Central

    Fitzgerald, Robert S.; Shirahata, Machiko; Chang, Irene; Kostuk, Eric; Kiihl, Samara

    2011-01-01

    Do cat carotid bodies (CBs) increase their release of acetylcholine and ATP in response to H2S? Two CBs, incubated in a Krebs Ringer bicarbonate solution at 37° C, exhibited a normal response to hypoxia -- increased release of acetylcholine (ACh) and ATP. They were challenged with several concentrations of Na2S, an H2S donor. H2S, a new gasotransmitter, is reported to open KATP channels. Under normoxic conditions the CBs reduced their release of ACh and ATP below control values. They responded identically to pinacidil, a well-known KATP channel opener. CB glomus cells exhibited a positive immunohistochemical signal for cystathione-β-synthetase, a H2S synthesizing enzyme, and for a subunit of the KATP channel. The data suggest that Na2S may have opened the glomus cells’ KATP channels, hyperpolarizing the cells, thus reducing their tonic release of ACh and ATP. Since during hypoxia H2S levels rise, the glomus cells responding very actively to hypoxia may be protected from over-exertion by the H2S opening of the KATP channels. PMID:21292043

  19. Effects of almitrine on the release of catecholamines from the rabbit carotid body in vitro.

    PubMed Central

    Almaraz, L.; Rigual, R.; Obeso, A.; Evrard, Y.; Gonzalez, C.

    1992-01-01

    1. Almitrine increases ventilation by stimulating the carotid body (CB) arterial chemoreceptors but neither its intraglomic target nor its mechanism of action have been elucidated. 2. We have tested the hypothesis that chemoreceptor cells are targets for almitrine by studying its effects on the release of 3H-catecholamines in an in vitro rabbit CB preparation. 3. It was found that almitrine (0.3 and 1.5 x 10(-6) M; i.e. 0.2 and 1 mg ml-1) increases the resting release of 3H-catecholamines from CBs (previously loaded with [3H]-tyrosine) incubated in a balanced 95% O2/5% CO2-equilibrated solution. 4. Almitrine at a concentration of 3 x 10(-6) M (2 mg l-1) also augmented the release of 3H-catecholamines elicited by incubating the CBs in a hypoxic solution (equilibrated with 7% O2/5% CO2 in N2), by high external K+ (35 mM) and by veratridine (2 x 10(-5) M), but did not modify release induced by dinitrophenol (7.5 x 10(-5) M). 5. At the same concentration (3 x 10(-6) M), almitrine increased the rate of dopamine synthesis and was ineffective in modifying the cyclic AMP levels in either normoxic or hypoxic CBs. 6. It is concluded that chemoreceptor cells are the intraglomic targets for almitrine. The mechanisms of action of almitrine on chemoreceptor cells are discussed. PMID:1504753

  20. Effects of mitochondrial poisons on glutathione redox potential and carotid body chemoreceptor activity.

    PubMed

    Gomez-Niño, A; Agapito, M T; Obeso, A; Gonzalez, C

    2009-01-01

    Low oxygen sensing in chemoreceptor cells involves the inhibition of specific plasma membrane K(+) channels, suggesting that mitochondria-derived reactive oxygen species (ROS) link hypoxia to K(+) channel inhibition, subsequent cell depolarization and activation of neurotransmitter release. We have used several mitochondrial poisons, alone and in combination with the antioxidant N-acetylcysteine (NAC), and quantify their capacity to alter GSH/GSSG levels and glutathione redox potential (E(GSH)) in rat diaphragm. Selected concentrations of mitochondrial poisons with or without NAC were tested for their capacity to activate neurotransmitter release in chemoreceptor cells and to alter ATP levels in intact rat carotid body (CB). We found that rotenone (1 microM), antimycin A (0.2 microg/ml) and sodium azide (5mM) decreased E(GSH); NAC restored E(GSH) to control values. At those concentrations mitochondrial poisons activated neurotransmitter release from CB chemoreceptor cells and decreased CB ATP levels, NAC being ineffective to modify these responses. Additional experiments with 3-nitroprionate (5mM), lower concentrations of rotenone and dinitrophenol revealed variable relationships between E(GSH) and chemoreceptor cell neurotransmitter release responses and ATP levels. These findings indicate a lack of correlation between mitochondrial-generated modifications of E(GSH) and chemoreceptor cells activity. This lack of correlation renders unlikely that alteration of mitochondrial production of ROS is the physiological pathway chemoreceptor cells use to signal hypoxia.

  1. Plasticity in the brain: influence of bilateral carotid body resection (bCBR) on central CO2 sensitivity.

    PubMed

    Dahan, Albert; Sarton, Elise; Teppema, Luc

    2008-01-01

    We investigated the effect of bilateral carotid body resection (bCBR) in a patient with bilateral carotid body tumors on central CO2 sensitivity. We applied multiple square-wave changes in end-tidal CO2 and measured ventilation before the first surgery and at regular intervals for 3 years after surgery. The data were analyzed using a two-compartment model of the ventilatory control system. bCBR resulted in the loss of the fast response to CO2, and a sharp reduction in the magnitude of central CO2 sensitivity (a reduction of about 80% within 3 months after bCBR). Central CO2 sensitivity gradually increased to pre-operative values within 2 years after surgery. These observations are a strong indication for (1) the existence of a tonic influence from the peripheral chemoreceptors of the carotid bodies on central CO2 drive; (2) absence of any recovery of the peripheral drive after bCBR; and (3) neural plasticity causing the regeneration of central drive after bCBR.

  2. Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients

    PubMed Central

    2014-01-01

    Background HIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT. Methods Cross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher’s exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models. Results L-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p = 0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95% CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95% CI: 0.732-0.817) in those with lipodystrophy (p = 0.671). Conclusions

  3. Carotid body chemoreception: the importance of CO2-HCO3- and carbonic anhydrase. (review).

    PubMed

    Iturriaga, R

    1993-01-01

    The current hypotheses of carotid body (CB) chemoreception regard the glomus cells as the initial site of stimulus transduction. The consensus is that the transduction of chemical stimulus is coupled with the release of transmitter(s) from the glomus cells, which in turn generates action potentials in the afferent nerve terminals. Carbonic anhydrase (CA) is present in the glomus cells of the CB. Inhibition of CA activity in the CB in situ reduces the carotid chemosensory responses to CO2 and to O2, suggesting a common mechanism of chemosensing for both stimuli. However, CA inhibitors also block the red blood cell enzyme. Thus, the CO2 hydration reaction does not come to completion within the transit time of the blood from the lung to the CB. A steady-state reaction is not reached until later and so the PCO2 and pH levels in arterial blood samples are not the same as those sensed by the CB. Experiments in vitro using cat CB perfused and superfused with cell-free solutions, which had been pre-equilibrated with respiratory gases, strongly support the proposition that the CA activity in CB cells is essential for the speed and amplitude of the initial response to CO2 and for its subsequent adaptation. The immediate response to hypoxia also is delayed, but the late steady-state was less dependent on CA activity. In the nominal absence of CO2-HCO3- from the perfusate, hypoxic chemoreception persisted and its magnitude is not affected by CA inhibition, except for a delay which may be due to the initial alkaline pH of the glomus cells. Recent experiments performed in isolated glomus cells and in the whole CB show that hypoxia does not modify significantly the intracellular pH. By its simple catalytic function, CA can speed up the approach of the CO2 hydration reaction to equilibrium. However, CA may also contribute in the steady-state to the regulation of pHi by providing a continuous supply of H+ and HCO3-. Furthermore, CA performs a facilitatory role in the physiological

  4. Interleukin-1β promotes the neurogenesis of carotid bodies by stimulating the activation of ERK1/2.

    PubMed

    Xue, Fen; Liu, Ling; Fan, Juan; He, ShanShan; Li, Rui; Peng, Zheng-Wu; Wang, Bai-Ren

    2015-12-01

    The carotid body (CB) is a complex sensory organ that functions to sense homeostatic O2 in the blood. Previous studies have shown that CBs express interleukin (IL)-1 receptor type I and that the chemosensitivity of CBs is increased following stimulation with pro-inflammatory cytokines. However, the effects of pro-inflammatory cytokines, such as IL-1β, on the neurogenesis of CB are unclear. Thus, in this study, we aimed to assess the effects of IL-1β and intermittent hypobaric hypoxia (IHH) plus IL-1β on the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, tyrosine hydroxylase (TH) and the expression of nestin, a well-established stem cell marker in the nervous system. The results showed that TH, nestin expression and ERK1/2 phosphorylation were increased in the rat CB following intraperitoneal injection of IL-1β. Moreover, IL-1β had additive effects on IHH. These results suggested that the plasticity of CB was increased following treatment with IL-1β and that ERK1/2 may be involved in neurogenic signaling in CBs. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes.

    PubMed

    Kawamoto, Ryuichi; Ninomiya, Daisuke; Hasegawa, Yoichi; Kasai, Yoshihisa; Kusunoki, Tomo; Ohtsuka, Nobuyuki; Kumagi, Teru; Abe, Masanori

    2016-01-01

    Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 ± 8 (mean ± SD) years and 205 women aged 81 ± 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (β = -0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13-0.58 mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT ≥1.0 mm including plaque and carotid plaque was 0.46 (0.23-0.93) and 0.32 (0.17-0.60) in the Tertile-3 group (0.87-1.93 mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.

  6. Carotid intima-media thickness in pediatric type 1 diabetic patients.

    PubMed

    Rabago Rodriguez, Rocio; Gómez-Díaz, Rita A; Tanus Haj, Janet; Avelar Garnica, Francisco Jose; Ramirez Soriano, Eleazar; Nishimura Meguro, Elisa; Aguilar-Salinas, Carlos A; Wacher, Niels H

    2007-10-01

    To compare the carotid artery intima-media thickness in Hispanic pediatric type 1 diabetic patients against that in healthy control subjects matched for age, sex, height, and BMI. The evaluation consisted of anthropometric measurements, biochemical parameters, and a carotid Doppler and real-time ultrasound, in which carotid artery intima-media thickness (cIMT), peak systolic velocity, and end diastolic velocity were measured using standardized procedures. A total of 52 diabetic patients and 47 control subjects were included. No significant differences existed in the characteristics between case and control subjects (mean age 11.8 +/- 3.1 vs. 11.8 +/- 2.8 years, weight 42.2 +/- 15.3 vs. 44.2 +/- 14.4 kg, height 1.45 +/- 0.15 vs. 1.47 +/- 0.15 m, BMI 19.3 +/- 3.2 vs. 19.9 +/- 4.4 kg/m2, systolic blood pressure 99.1 +/- 9.9 vs. 99.6 +/- 9 mmHg, and diastolic blood pressure 63 +/- 6.4 vs. 62.0 +/- 5.7 mmHg, respectively). The mean duration of diabetes was 4.8 +/- 3.2 years (range 6-144 months), and the mean A1C was 8.6 +/- 1.6%. A significantly higher cIMT was found in the patients with type 1 diabetes (0.463 +/- 0.04 vs. 0.441 +/- 0.04 mm; P = 0.001). In contrast, both peak systolic velocity (107.1 +/- 22.8 vs. 119.3 +/- 19.2, P < 0.005) and end diastolic velocity (28.4 +/- 6.0 vs. 33.0 +/- 7.0, P < 0.001) were higher in the control subjects. Type 1 diabetes is associated with higher cIMT and decreased flow velocities in a Hispanic pediatric population.

  7. Expression of nitric oxide-containing structures in the rat carotid body.

    PubMed

    Atanasova, Dimitrinka Y; Dimitrov, Nikolay D; Lazarov, Nikolai E

    2016-10-01

    The carotid body (CB) is a major peripheral arterial chemoreceptor organ that evokes compensatory reflex responses so as to maintain gas homeostasis. It is dually innervated by sensory fibers from petrosal ganglion (PG) neurons, and autonomic fibers from postganglionic sympathetic neurons of the superior cervical ganglion (SCG) and parasympathetic vasomotor fibers of intrinsic ganglion cells in the CB. The presence of nitric oxide (NO), a putative gaseous neurotransmitter substance in a number of neuronal and non-neuronal structures, was examined in the CB, PG and SCG of the rat using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS) immunohistochemistry and retrograde tracing. One week after injecting the retrograde tracer Fast Blue (FB) in the CB, we found that a subset of perikarya in the caudal portions of the PG and SCG were FB-labeled. Histochemistry and immunohistochemistry revealed that the majority of large- and medium-sized PG and SCG cells were NADPH-d positive and displayed a strong NOS immunostaining. We also observed that many varicose nerve fibers penetrating the CB and enveloping the glomus cells and blood vessels were NADPH-d reactive and expressed the constitutive isoforms of NOS, nNOS and eNOS. In addition, some autonomic microganglion cells embedded within, or located at the periphery of the CB, and not glomus or sustentacular cells were nNOS-immunopositive while CB microvasculature expressed eNOS. The present results suggest that NO is a transmitter in the autonomic nerve endings supplying the CB and is involved in efferent chemoreceptor inhibition by a dual mechanism.

  8. Ionic mechanisms for the transduction of acidic stimuli in rabbit carotid body glomus cells.

    PubMed Central

    Rocher, A; Obeso, A; Gonzalez, C; Herreros, B

    1991-01-01

    1. The release of [3H]dopamine (DA) in response to inhibition of the Na+ pump or to intracellular acid load was studied in rabbit carotid bodies (CB) previously incubated with the precursor [3H]tyrosine. The ionic requirements of the release response and the involvement of specific ion transport systems were investigated. 2. Inhibition of the Na+ pump, by incubating the CB with ouabain or in K(+)-free medium, evokes a DA release response which requires the presence of Na+ and Ca2+ in the medium and is insensitive to nisoldipine. This suggests that the response is triggered by entry of external Ca2+ through Na(+)-Ca2+ exchange, a consequence of the increase in intracellular Na+ resulting from inhibition of the pump. 3. Incubation of the CB in medium equilibrated with 20% CO2 at pH 6.6, or in medium containing the protonophore dinitrophenol (DNP) or the weak acid propionate, elicits a DA release response which requires also the presence of Na+ and Ca2+ in the medium and is insensitive to dihydropyridines. 4. Ethylisopropylamiloride (EIPA), an inhibitor of the Na(+)-H+ exchanger, markedly decreases the release response elicited by DNP or propionate in bicarbonate-free medium, but has not any effect in bicarbonate-buffered medium. In the latter condition, the EIPA-insensitive release of DA is inhibited by reducing the HCO3- concentration in the medium to 2 mM or by removal of Cl-, suggesting that in bicarbonate-buffered medium a Na(+)-dependent HCO3(-)-Cl- exchanger is involved in the release response. 5. It is concluded that the release of DA by the chemoreceptor cells in response to acidic stimulation is triggered by entry of external Ca2+ through Na(+)-Ca2+ exchange. This exchange is promoted by the increase of intracellular Na+ that results from the operation of Na(+)-coupled H(+)-extruding mechanisms activated by the acid load. PMID:1668755

  9. Some reflections on intermittent hypoxia. Does it constitute the translational niche for carotid body chemoreceptor researchers?

    PubMed

    Gonzalez, Constancio; Yubero, Sara; Gomez-Niño, M Angela; Agapito, Teresa; Rocher, Asuncion; Rigual, Ricardo; Obeso, Ana; Montserrat, Jose M

    2012-01-01

    The views presented in this article are the fruit of reflections and discussion with my colleagues at Valladolid and with the members of the Sleep Apnea Hypopnea Syndrome Group of the CIBERES (Spain). We have assembled the article in three sections. In the first one we provide a mechanistic description of obstructive sleep apnea (OSA) and all of its components, including the repetitive episodes of upper airways (UA) obstruction and accompanying hypoxic hypoxia, the respiratory efforts to fight and overcome the obstruction, and the sleep fragmentation due to the hypoxia-triggered arousal reactions, all events occurring during sleep hours with frequencies that might reach up >40-50 episodes/sleep hour. When OSA is accompanied by some of the elements of a big cohort of associated pathologies (vascular, metabolic, and neuropsychiatric) it conforms the obstructive sleep apnea syndrome (OSAS). The high frequency of OSAS in adults (>35 years old) and the costs in every regard of the treatment makes the syndrome a primary importance socio-sanitary problem. In the second section, we describe the experimental models of OSAS, basically the episodic repetitive hypoxic model described by Fletcher and coworkers in 1992, today named in short intermittent hypoxia (IH). From these lines, we want to call for some kind of consensus among researchers to lessen the dispersion of IH protocols. Finally, in the last section we intend to share our optimism with all ISAC members. The optimism is based on the recognition that carotid body (CB) chemoreceptors are critical elements of one of the main pathophysiologic loops in the genesis of OSAS. Therefore, we believe that all of us, as ISAC members, are well qualified to contribute in multidisciplinary research teams with well defined translational interests.

  10. Glucose sensing by carotid body glomus cells: potential implications in disease

    PubMed Central

    Gao, Lin; Ortega-Sáenz, Patricia; García-Fernández, María; González-Rodríguez, Patricia; Caballero-Eraso, Candela; López-Barneo, José

    2014-01-01

    The carotid body (CB) is a key chemoreceptor organ in which glomus cells sense changes in blood O2, CO2, and pH levels. CB glomus cells have also been found to detect hypoglycemia in both non-primate mammals and humans. O2 and low-glucose responses share a common final pathway involving membrane depolarization, extracellular calcium influx, increase in cytosolic calcium concentration, and neurotransmitter secretion, which stimulates afferent sensory fibers to evoke sympathoadrenal activation. On the other hand, hypoxia and low glucose induce separate signal transduction pathways. Unlike O2 sensing, the response of the CB to low glucose is not altered by rotenone, with the low glucose-activated background cationic current unaffected by hypoxia. Responses of the CB to hypoglycemia and hypoxia can be potentiated by each other. The counter-regulatory response to hypoglycemia by the CB is essential for the brain, an organ that is particularly sensitive to low glucose. CB glucose sensing could be altered in diabetic patients, particularly those under insulin treatment, as well as in other medical conditions such as sleep apnea or obstructive pulmonary diseases, where chronic hypoxemia presents with plastic modifications in CB structure and function. The current review will focus on the following main aspects: (1) the CB as a low glucose sensor in both in vitro and in vivo models; (2) molecular and ionic mechanisms of low glucose sensing by glomus cells, (3) the interplay between low glucose and O2 sensing in CB, and (4) the role of CB low glucose sensing in the pathophysiology of cardiorespiratory and metabolic diseases, and how this may serve as a potential therapeutic target. PMID:25360117

  11. Purinergic stimulation of carotid body efferent glossopharyngeal neurones increases intracellular Ca2+ and nitric oxide production.

    PubMed

    Lowe, Michael; Park, Sung Jin; Nurse, Colin A; Campanucci, Verónica A

    2013-07-01

    The mammalian carotid body (CB) is a peripheral chemosensory organ that controls ventilation and is innervated by both afferent and efferent nerve fibres. The afferent pathway is stimulated by chemoexcitants, such as hypoxia, hypercapnia and acidosis. The efferent pathway causes inhibition of the sensory discharge via release of NO that originates mainly from neuronal nitric oxide synthase (nNOS)-positive autonomic neurones within the glossopharyngeal nerve (GPN). Recent studies in the rat indicate that these inhibitory GPN neurones and their processes express purinergic P2X receptors and can be activated by ATP, a key excitatory CB neurotransmitter. Here we tested the hypothesis that purinergic agonists stimulate a rise in [Ca(2+)]i, leading to nNOS activation and NO production in isolated GPN neurones, using the fluorescent probes fura-2 and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA), respectively. ATP caused a dose-dependent increase in [Ca(2+)]i in GPN neurones (EC50 ≈ 1.92 μm) that was markedly inhibited by a combination of 100 μm suramin (a non-specific P2X blocker) and 100 nm Brilliant Blue G (a selective P2X7 blocker). ATP also stimulated NO production in GPN neurones, as revealed by an increase in DAF fluorescence; this NO signal was inhibited by purinergic blockers, chelators of extracellular Ca(2+), the nNOS inhibitor l-NAME and the NO scavenger carboxy-PTIO. The P2X2/3 and P2X7 agonists α,β,-methylene ATP and benzoyl ATP mimicked the effects of ATP. Taken together, these data indicate that ATP may contribute to negative feedback inhibition of CB sensory discharge via purinergic stimulation of NO production in efferent fibres.

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

    PubMed

    Del Rio, Rodrigo; Andrade, David C; Lucero, Claudia; Arias, Paulina; Iturriaga, Rodrigo

    2016-08-01

    Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. © 2016 American Heart Association, Inc.

  13. Testing the metabolic hypothesis of O2 chemoreception in the cat carotid body in vitro.

    PubMed

    Buerk, D G; Iturriaga, R; Lahiri, S

    1994-03-01

    It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the high-energy state without net production of ATP. The metabolic hypothesis for O2 chemoreception in the carotid body (CB) predicts that 1) oligomycin should diminish O2 consumption and attenuate O2 chemoreception and 2) uncouplers should reverse the effect of oligomycin by increasing O2 consumption without restoring O2 chemoreception. These predictions were tested by simultaneously measuring CB chemosensory discharge from the sinus nerve and the rate of tissue O2 disappearance (dPO2/dt) during interruption of perfusate flow in perfused-superfused cat CB preparations (n = 9). O2 consumption was calculated from dPO2/dt. Flow-interruption responses were measured before and after oligomycin (1-microgram bolus) and subsequently after dinitrophenol (50 microM). Chemosensory responses to bolus injections of hypercapnic Tyrode solution, cyanide, or nicotine were also tested periodically. Oligomycin diminished dPO2/dt from -2.67 +/- 0.30 to -2.02 +/- 0.19 (SE) Torr/s (P < 0.004, paired t test) and reduced the maximal sensory response from 196 +/- 43 to 124 +/- 12 impulses/s (P < 0.002, paired t test) while augmenting the initial response to CO2. Dinitrophenol reversed the metabolic depressant effect of oligomycin but further suppressed the chemosensory response. These results confirm the above predictions and strengthen the metabolic hypothesis for O2 chemoreception in the CB.

  14. Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

    PubMed Central

    Moya, Esteban A.; Arias, Paulina; Varela, Carlos; Oyarce, María P.; Del Rio, Rodrigo; Iturriaga, Rodrigo

    2016-01-01

    Oxidative stress is involved in the development of carotid body (CB) chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO−), a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO− scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir) in the CB, the CB chemosensory discharge, and arterial blood pressure (BP) in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day) for 7 days. Ebselen (10 mg/kg/day) was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 ± 14.9 versus 22.9 ± 4.2 a.u.), reduced CB chemosensory response to 5% O2 (266.5 ± 13.4 versus 168.6 ± 16.8 Hz), and decreased mean BP (116.9 ± 13.2 versus 82.1 ± 5.1 mmHg). Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO− formation. PMID:26798430

  15. PO2 in the carotid body perfused and/or superfused with cell-free media.

    PubMed

    Whalen, W J; Nair, P

    1976-08-01

    We measured with a micro-O2 electrode the tissue PO2 (PtO2) in the cat carotid body (CB) to see whether it was adequately oxygenated when perfused or superfused with artificial, cell-free (c-f) solutions (pH = 7.4; temp = 35-38 degrees C). To obtain a relative measure of O2 consumption (VO2), we also measured the rate of disappearance of O2 following stoppage of the blood flow, and compared these disappearance curves with those during stoppage of the c-f perfusion solutions. In 14 cats normal (blood perfusion) PtO2 values ranged from 10 to 104 mmHG; chi = 72 +/- 4 (SE--as used throughout). During 3 h of c-f perfusion with air-equilibrated Locke's solution, PtO2 ranged from 62 to about 160 mmHg; chi = 133 +/- 4. When perfused with Fay's equilibrated with 98% O2-2% CO2 no PtO2 values in the CB were below 300 mmHg (4 cats). In eight additional cats the CB was cleared of blood then superfused with saline equilibrated with 50% O2 underneath and air-equilibrated saline over. Less than 5% of the PtO2 values found were below 5 mmHg. We conclude that most studies on the artificially perfused or superfused CB cannot be invalidated on the basis that the preparations were hypoxic. O2 disappearance curves taken during blood perfusion were significantly faster than during c-f perfusion indicating a marked reduction in VO2 with c-f perfusion.

  16. Uric acid, carotid intima-media thickness and body composition in prepubertal children.

    PubMed

    Bassols, J; Martínez-Calcerrada, J M; Prats-Puig, A; Carreras-Badosa, G; Díaz-Roldán, F; Osiniri, I; Riera-Pérez, E; de Zegher, F; Ibáñez, L; López-Bermejo, A

    2016-10-01

    Increased uric acid is an independent biomarker for cardiovascular disease in obese adolescents and adults. We investigated whether uric acid relates to carotid intima-media thickness (cIMT) in prepubertal children, and whether body mass index (BMI) and preperitoneal fat modulate this association. 359 asymptomatic prepubertal Caucasian children were stratified according to BMI categories (171 with BMI-SDS < 0; 188 with BMI-SDS ≥ 0) and according to preperitoneal fat levels (180 with preperitoneal fat <50th centile; 179 with preperitoneal fat >50th centile). Uric acid levels, insulin resistance (homeostasis model assessment insulin resistance; HOMA-IR), C-reactive protein (CRP), triacylglycerol (TG), systolic blood pressure (SBP), abdominal fat and cIMT (both by ultrasound) were assessed. Uric acid was associated with several cardiovascular risk factors, namely higher HOMA-IR, CRP, TG, BMI, waist, SBP, preperitoneal fat and cIMT (all P < 0.001 to P < 0.0001). Significant BMI and preperitoneal fat interactions were documented in the relationship between uric acid and cIMT (both P < 0.05), as uric acid was preferentially related to cIMT in heavier children (β = 0.247, P < 0.001, r(2)  = 9.1%) and in children with more preperitoneal fat (β = 0.263, P < 0.0001, r(2)  = 11.9%). Serum uric acid is associated with cIMT in asymptomatic prepubertal children. Both higher BMI and preperitoneal fat aggravate the potential risk of atherosclerotic disease imposed by higher concentrations of uric acid. © 2015 World Obesity.

  17. Glucose sensing by carotid body glomus cells: potential implications in disease.

    PubMed

    Gao, Lin; Ortega-Sáenz, Patricia; García-Fernández, María; González-Rodríguez, Patricia; Caballero-Eraso, Candela; López-Barneo, José

    2014-01-01

    The carotid body (CB) is a key chemoreceptor organ in which glomus cells sense changes in blood O2, CO2, and pH levels. CB glomus cells have also been found to detect hypoglycemia in both non-primate mammals and humans. O2 and low-glucose responses share a common final pathway involving membrane depolarization, extracellular calcium influx, increase in cytosolic calcium concentration, and neurotransmitter secretion, which stimulates afferent sensory fibers to evoke sympathoadrenal activation. On the other hand, hypoxia and low glucose induce separate signal transduction pathways. Unlike O2 sensing, the response of the CB to low glucose is not altered by rotenone, with the low glucose-activated background cationic current unaffected by hypoxia. Responses of the CB to hypoglycemia and hypoxia can be potentiated by each other. The counter-regulatory response to hypoglycemia by the CB is essential for the brain, an organ that is particularly sensitive to low glucose. CB glucose sensing could be altered in diabetic patients, particularly those under insulin treatment, as well as in other medical conditions such as sleep apnea or obstructive pulmonary diseases, where chronic hypoxemia presents with plastic modifications in CB structure and function. The current review will focus on the following main aspects: (1) the CB as a low glucose sensor in both in vitro and in vivo models; (2) molecular and ionic mechanisms of low glucose sensing by glomus cells, (3) the interplay between low glucose and O2 sensing in CB, and (4) the role of CB low glucose sensing in the pathophysiology of cardiorespiratory and metabolic diseases, and how this may serve as a potential therapeutic target.

  18. Study of the effects of age and body mass index on the carotid wall vibration: extraction methodology and analysis.

    PubMed

    Yousefi Rizi, Fereshteh; Setarehdan, Seyed Kamaledin; Behnam, Hamid; Alizadeh Sani, Zahra

    2014-07-01

    This study aims to non-invasively extract the vibrations of the carotid wall and evaluate the changes in the carotid artery wall caused by age and obesity. Such evaluation can increase the possibility of detecting wall stiffness and atherosclerosis in its early stage. In this study, a novel method that uses a phase-tracking method based on the continuous wavelet transform calculates the carotid wall motion from the ultrasound radio frequency signals. To extract the high-frequency components of the wall motion, wall vibration, the empirical mode decomposition was then used. The posterior wall (intima-media) motion and vibration were extracted for 54 healthy volunteers (mean age: 33.87 ± 14.73 years), including 13 overweight subjects (body mass index > 25) and 14 female participants using their radio frequency signals. The results showed that the dominant frequency of the wall vibration correlates with age (r = -0.5887, p < 0.001) and body mass index (r = -0.4838, p < 0.001). The quantitative analysis further demonstrated that the dominant frequency of the vibration in the radial direction of the carotid wall decreases by age and is lower in overweight subjects. Besides, the peak-to-peak amplitude of the wall vibration showed significant correlations with age (r = -0.5456, p < 0.001) and body mass index (r = -0.5821, p < 0.001). The peak-to-peak amplitude also decreases by age and is lower in overweight subjects. However, there were no significant correlations between these features of the wall vibrations and systolic/diastolic blood pressure and sex. Our proposed measures were certified using the calculated arterial stiffness indices. The average power spectrum of the elderly subjects'wall motion in the frequency range of the wall vibration (>100 Hz) is decreased more in comparison with the young subjects. Our results revealed that the proposed method may be useful for detecting the stiffness and distortion in the carotid wall that occur prior to wall thickening

  19. Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients.

    PubMed

    Cardellini, Marina; Marini, Maria Adelaide; Frontoni, Simona; Hribal, Marta Letizia; Andreozzi, Francesco; Perticone, Francesco; Federici, Massimo; Lauro, Davide; Sesti, Giorgio

    2007-01-01

    The aim of this study was to investigate whether insulin resistance is independently associated with early manifestations of atherosclerosis. To this end, 176 normotensive offspring of type 2 diabetic patients were subjected to euglycemic hyperinsulinemic clamp to assess insulin sensitivity. Early atherosclerosis was studied by ultrasonography of the common carotid artery. Of the total 176 subjects, 145 were glucose tolerant, 18 had impaired fasting glucose, and 13 had impaired glucose tolerance. Univariate correlations showed that age, body mass index, waist, blood pressure, 2-h postchallenge glucose, fasting insulin, triglycerides, interleukin-6, fibrinogen, and white blood cell count were significantly correlated with carotid intima-media thickness (IMT), whereas HDL cholesterol and glucose disposal showed a negative correlation. A stepwise multivariate regression analysis including sex, age, waist circumference, smoking status, systolic blood pressure, diastolic blood pressure, triglyceride, HDL cholesterol, 2-h postchallenge glucose, plasma IL-6, fibrinogen, white blood cell count, insulin-stimulated glucose disposal, and fasting insulin showed that the four variables that remained significantly associated with carotid IMT were waist circumference, insulin-stimulated glucose disposal, white blood cell count, and diastolic blood pressure, accounting for 33.7% of its variation. These findings support the concept that insulin sensitivity, rather than plasma insulin levels, is associated with early atherosclerosis in nondiabetic normotensive offspring of type 2 diabetic patients.

  20. Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome.

    PubMed

    Kim, Jeong Gyun; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Jeong Eun

    2014-02-01

    Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure.

  1. Spontaneous Carotid-Cavernous Fistula in the Type IV Ehlers-Danlos Syndrome

    PubMed Central

    Kim, Jeong Gyun; Cho, Won-Sang; Kim, Jeong Eun

    2014-01-01

    Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure. PMID:24653803

  2. Reduced to oxidized glutathione ratios and oxygen sensing in calf and rabbit carotid body chemoreceptor cells

    PubMed Central

    Sanz-Alfayate, G; Obeso, A; Agapito, M T; González, C

    2001-01-01

    The aim of this work was to test the redox hypotheses of O2 chemoreception in the carotid body (CB). They postulate that hypoxia alters the levels of reactive oxygen species (ROS) and the ratio of reduced to oxidized glutathione (GSH/GSSG), causing modifications to the sulfhydryl groups/disulfide bonds of K+ channel proteins, which leads to the activation of chemoreceptor cells. We found that the GSH/GSSG ratio in normoxic calf CB (30.14 ± 4.67; n = 12) and hypoxic organs (33.03 ± 6.88; n = 10), and the absolute levels of total glutathione (0.71 ± 0.07 nmol (mg tissue)−1, normoxia vs. 0.76 ± 0.07 nmol (mg tissue)−1, hypoxia) were not statistically different. N-Acetylcysteine (2 mm; NAC), a precursor of glutathione and ROS scavenger, increased normoxic glutathione levels to 1.03 ± 0.06 nmol (mg tissue)−1 (P < 0.02) and GSH/GSSG ratios to 59.05 ± 5.05 (P < 0.001). NAC (20 μm–10 mm) did not activate or inhibit chemoreceptor cells as it did not alter the normoxic or the hypoxic release of 3H-catecholamines (3H-CAs) from rabbit and calf CBs whose CA deposits had been labelled by prior incubation with the natural CA precursor 3H-tyrosine. NAC (2 mm) was equally ineffective in altering the release of 3H-CAs induced by stimuli (high external K+ and ionomycin) that bypass the initial steps of the hypoxic cascade of activation of chemoreceptor cells, thereby excluding the possibility that the lack of effect of NAC on normoxic and hypoxic release of 3H-CAs results from a concomitant alteration of Ca2+ channels or of the exocytotic machinery. The present findings do not support the contention that O2 chemoreception in the CB is linked to variations in the GSH/GSSG quotient as the redox models propose. PMID:11711574

  3. Properties of a transient K+ current in chemoreceptor cells of rabbit carotid body.

    PubMed Central

    López-López, J R; De Luis, D A; Gonzalez, C

    1993-01-01

    1. Adult rabbit carotid body chemoreceptor cells, enzymatically dispersed and short-term cultured, exhibit an inactivating outward K+ current that is reversibly inhibited by low PO2. In the present work we have characterized the biophysical and pharmacological properties of this current using the whole-cell voltage clamp recording technique. 2. Inactivating current was recorded after blockage of Ca2+ currents with extracellular Co2+, Cd2+, or after complete washing out of Ca2+ channels. 3. The threshold of activation of this inactivating current was about -40 mV. Current activated very quickly (mean rise time 4.8 +/- 0.42 ms at +60 mV) but inactivated more slowly. Inactivation was well fitted by two exponentials with time constants of 79.7 +/- 6.6 and 824 +/- 42.8 ms (at +40 mV). The inactivation process showed a little voltage dependence. 4. The steady-state inactivation was well fitted by a Boltzman function. Inactivation was fully removed at potentials negative to -80 mV and was complete at voltages near -10 mV; 50% inactivation occurred at -41 mV. 5. Recovery from inactivation had several components and was voltage dependent. Initial recovery was fast, but full recovery, even at -100 mV, required more than 30 s. 6. Inactivating current was selectively blocked by 4-aminopyridine (4-AP), in a dose-dependent manner (IC50, 0.2 mM). The duration of chemoreceptor cells action potentials was augmented by 1 mM 4-AP from 2.3 +/- 0.36 to 7.0 +/- 0.25 ms at 0 mV. Tetraethylamonium (TEA), at concentrations above 5 mM, blocked inactivating and non-inactivating components of the whole K+ current. 7. Inactivating current was modulated by cyclic AMP (cAMP). Bath application of 2 mM dibutyryl cAMP reduced peak amplitude by 18.7 +/- 2.9% (at +30 mV) and slowed down the rise time of the current. The effect was not voltage dependent. Forskolin (10-20 microM) also affected inactivating current, by accelerating the inactivation process. In the same preparations neither dibutyryl c

  4. The role of nitric oxide in carotid chemoreception.

    PubMed

    Wang, Z Z; Dinger, B G; Stensaas, L J; Fidone, S J

    1995-01-01

    Immunocytochemical and histochemical studies of cat and rat carotid bodies have revealed a plexus of nitric oxide synthase (NOS)-positive nerve fibers associated with lobules of chemosensory type I cells as well as with the carotid body vasculature. NOS-positive fibers originate from (1) autonomic neurons located in the carotid body and distributed along the carotid sinus nerve (CNS) and IXth cranial nerve which terminate in the adventitial layer of carotid body blood vessels, and (2) from unipolar sensory neurons of the petrosal (IXth nerve) ganglion. Carotid bodies incubated with the NO precursor, 3H-arginine, yield 3H-citrulline, the detectable coproduct of NO synthesis. Furthermore, electrical stimulation of the CNS or exposure of carotid bodies to hypoxic incubation media elevates 3H-citrulline formation. Millimolar concentrations of L-arginine inhibit chemoreceptor activity evoked by hypoxia, an effect which is reversed by the specific NOS antagonist, L-NG-nitroarginine methylester (L-NAME, 0.1 mM). Electrical stimulation of CNS C fibers elevates cyclic GMP in the carotid body vasculature and lobules of type I cells. Cyclic GMP production is reduced during stimulation in the presence of L-NAME, a finding consistent with the known ability of NO to activate a soluble form of guanylate cyclase. Further studies showed that brief (< 1 min) stimulation of CNS C fibers inhibits basal chemoreceptor discharge in a perfused/superfused in vitro carotid body preparation, whereas prolonged (> 5 min) stimulation is required to inhibit the response to hypoxia. The inhibitory effect is reversed by L-NAME. Our combined anatomical, neuropharmacological and electrophysiological data suggest that NO plays a dual role in mediating CNS inhibition, one via its actions on the organ's vasculature and the other through direct effects on the chemosensory type I cells. The former pathway involves cholinergic/NOS presumptive parasympathetic autonomic neurons, while the latter may be

  5. Endovascular Treatment of a Carotid Dissecting Pseudoaneurysm in a Patient with Ehlers-Danlos Syndrome Type IV with Fatal Outcome

    SciTech Connect

    Lim, Siok Ping Duddy, Martin J.

    2008-01-15

    We present a patient with Ehlers-Danlos syndrome type IV (EDS IV) with a carotid dissecting pseudoaneurysm causing severe carotid stenosis. This lesion was treated endovascularly. Unfortunately, the patient died of remote vascular catastrophes (intracranial hemorrhage and abdominal aortic rupture). This unique case illustrates the perils of endovascular treatment of EDS IV patients and the need for preoperative screening for concomitant lesions. It also shows that a dissecting pseudoaneurysm can feasibly be treated with a covered stent and that closure is effective using Angioseal in patients with EDS IV.

  6. K+ channels in O2 sensing and postnatal development of carotid body glomus cell response to hypoxia

    PubMed Central

    Kim, Donghee

    2016-01-01

    The sensitivity of carotid body chemoreceptors to hypoxia is low just after birth and increases over the first few weeks of the postnatal period. At present, it is believed that the hypoxia-induced excitation of carotid body glomus cells begins with the inhibition of the outward K+ current via one or more O2 sensors. Although the nature of the O2 sensors and their signals that inhibit the K+ current are not well defined, studies suggest that the postnatal maturation of the glomus cell response to hypoxia is largely due to the increased sensitivity of K+ channels to hypoxia. As KV, BK and TASK channels that are O2-sensitive contribute to the K+ current, it is important to identify the O2 sensor and the signaling molecule for each of these K+ channels. Various O2 sensors (mitochondrial hemeprotein, hemeoxygenase-2, NADPH oxidase) and associated signals have been proposed to mediate the inhibition of K+ channels by hypoxia. Studies suggest that a mitochondrial hemeprotein is likely to serve as an O2 sensor for K+ channels, particularly for TASK, and that multiple signals may be involved. Thus, changes in the sensitivity of the mitochondrial O2 sensor to hypoxia, the sensitivity of K+ channels to signals generated by mitochondria, and/or the expression levels of K+ channels are likely to account for the postnatal maturation of O2 sensing by glomus cells. PMID:22801091

  7. Lower body positive pressure application with an antigravity suit in acute carotid occlusion.

    PubMed

    Berthet, Karine; Lukaszewicz, Anne Claire; Bousser, Marie-Germaine; Payen, Didier

    2010-04-01

    The challenge in acute stroke is still to reperfuse as early as possible the ischemic territory. Since fibrinolytic therapies have a limited window with potential risk of bleeding, having a nonpharmacologic mean to recruit vessels in area surrounding necrosis might be useful. We propose here to use antigravity suit inflated at "venous" pressure levels to shift blood towards thoracic and brain territories. We report two cases of spectacular clinical recovery after acute carotid occlusion.

  8. The effect of discrete stimulation of carotid body chemoreceptors on atrial natriuretic peptide in anaesthetized dogs.

    PubMed Central

    al-Obaidi, M; Whitaker, E M; Karim, F

    1991-01-01

    1. In seven chloralose-anaesthetized and artificially ventilated beagles, the carotid sinus regions were vascularly isolated and perfused with either arterial or mixed (arterial and venous) blood (PO2 46.4 +/- 1.5 mmHg, mean +/- S.E.M.) to stimulate the chemoreceptors at constant flow and pressure. Cervical vagosympathetic trunks were ligated in all dogs, and gallamine triethiodide (2.0 mg kg-1 h-1, I.V.) was given in five dogs. Right atrial pressure was measured in all dogs, and left atrial pressure in four dogs. Mean aortic pressure was held constant (91.0 +/- 3.0 mmHg) by means of a reservoir connected to the animal via the common carotid and femoral arteries. Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay and urinary sodium by flame photometry. 2. In seven dogs with mean carotid sinus pressure maintained at 96.0 +/- 4.3 mmHg, stimulation of the carotid chemoreceptors for 25 min produced significant increases in left atrial pressure of 41.2 +/- 3.3% (n = 4; P less than 0.005) from 5.4 +/- 0.6 cmH2O and of 30.9 +/- 4.5% (n = 7; P less than 0.002) in ANP from 31.6 +/- 2.1 pg ml-1. However, chemoreceptor stimulation produced significant decreases in urine flow rate of 26.1 +/- 1.9% (n = 9; P less than 0.001) from 0.29 +/- 0.03 ml min-1 (100 g kidney weight)-1 and sodium excretion of 29.0 +/- 2.3% (P less than 0.001) from 8.5 +/- 1.7 mumol min-1 (100 g kidney weight)-1 but right atrial pressure and heart rate did not change significantly. In three of the dogs, beta-adrenoceptor blockade by atenolol (2 mg kg-1, I.V.) greatly reduced the effects of chemoreceptor stimulation on plasma levels of ANP. 3. The results show, for the first time, that discrete stimulation of the carotid chemoreceptors caused an increase in plasma ANP levels, probably due to the reflex increase in atrial pressure that results from an inhibition of the cardiac sympathetic nerves, and an increase in venous return from a reduction of peripheral vascular capacitance. PMID

  9. Association of V249I and T280M variants of fractalkine receptor CX3CR1 with carotid intima-media thickness in a mexican population with type 2 diabetes.

    PubMed

    Gómez-Díaz, Rita A; Gutiérrez, Jorge; Contreras-Rodriguez, Alicia; Valladares-Salgado, Adán; Tanus-Hajj, Janet; Mondragón-González, Rafael; Talavera, Juan O; Mejía-Benitez, María Aurora; García-Mena, Jaime; Cruz, Miguel; Wacher, Niels H

    2017-01-01

    To evaluate the association of the V249I and T280M variants of CX3CR1 fractalkine gene with carotid intima-media thickness in Mexican subjects with and without type 2 diabetes. We analyzed the V249I and T280M variants of the CX3CR1 receptor by TaqMan assays in 111 subjects with type 2 diabetes and 109 healthy controls. Hemoglobin A1c, glucose, and lipid profile were determined. A significant increase in carotid intima-media thickness was observed in type 2 diabetes patients (0.979 ± 0.361 mm) compared to healthy controls (0.588 ± 0.175 mm). In subjects carrying the MM variant of the T280M polymorphism, hemoglobin A1c was higher (p = 0.008). Classic risk factors for atherosclerosis showed no differences between carriers of the T280M and V249I variants. Controls with the II249 genotype associated with carotid intima-media thickness (0.747 ± 0.192 mm; p = 0.041), and this difference remained significant even after adjusting factors such as age, gender, and body mass index (OR: 7.7; 95% CI: 1.269-47.31; p = 0.027). V249I genotype of the fractalkine receptor showed a protector role in patients with type 2 diabetes. The T280M genotype is associated with increased carotid intima-media thickness in Mexican individuals with or without type 2 diabetes.

  10. Increased age, high body mass index and low HDL-C levels are related to an echolucent carotid intima-media: the METEOR study.

    PubMed

    Peters, S A E; Lind, L; Palmer, M K; Grobbee, D E; Crouse, J R; O'Leary, D H; Evans, G W; Raichlen, J; Bots, M L; den Ruijter, H M

    2012-09-01

    Echolucent plaques are related to a higher cardiovascular risk. Studies to investigate the relationship between echolucency and cardiovascular risk in the early stages of atherosclerosis are limited. We studied the relationship between cardiovascular risk factors and echolucency of the carotid intima-media in low-risk individuals. Data were analysed from the Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin (METEOR) study, a randomized placebo-controlled trial including 984 individuals which showed that rosuvastatin attenuated the rate of change of carotid intima-media thickness (CIMT). In this post hoc analysis, duplicate baseline ultrasound images from the far wall of the left and right common carotid arteries were used for the evaluation of the echolucency of the carotid intima-media, measured by grey-scale median (GSM) on a scale of 0-256. Low GSM values reflect echolucent, whereas high values reflect echogenic structures. The relationship between baseline GSM and cardiovascular risk factors was evaluated using linear regression models. Mean baseline GSM (± SD) was 84 ± 29. Lower GSM of the carotid intima-media was associated with older age, high body mass index (BMI) and low levels of high-density lipoprotein cholesterol (HDL-C) [beta -4.49, 95% confidence interval (CI) -6.50 to -2.49; beta -4.51, 95% CI -6.43 to -2.60; beta 2.45, 95% CI 0.47 to 4.42, respectively]. Common CIMT was inversely related to GSM of the carotid intima-media (beta -3.94, 95% CI -1.98 to -5.89). Older age, high BMI and low levels of HDL-C are related to echolucency of the carotid intima-media. Hence, echolucency of the carotid intima-media may be used as a marker of cardiovascular risk profile to provide more information than thickness alone. © 2012 The Association for the Publication of the Journal of Internal Medicine.

  11. Original report of bilateral carotid body tumors with 2 rare concomitant anatomic findings, an ectopic parathyroid gland and cervical thymus, with literature review.

    PubMed

    Westbrook, Benjamin J; Harsha, Wayne J; Strenge, Karen

    2013-03-01

    Carotid body tumors are uncommon neoplasms with unique epidemiology and management demands. Cervical embryology is complex. Developmental abnormalities can result in ectopic displacement of native tissues. We present the case of a 21-year-old female with bilateral carotid body paragangliomas who presented to our clinic seeking excision of the symptomatic right-sided tumor. The patient was successfully treated with surgical excision. Two rare anatomic variants were identified in her surgical specimen: a carotid sheath parathyroid gland and ectopic thymus tissue. This patient represents an unreported combination of pathologic and anatomic phenomena. The paraganglioma resulted from a familial genetic mutation that is well studied in this patient's ethnic population (Dutch), and the literature on this topic is reviewed herein. The 2 anatomic variants likely represent a single, embryologic glitch that will carry no physiologic sequelae. The clinical application of this ectopic anatomy and the common embryologic origins are discussed. Copyright © 2011 Wiley Periodicals, Inc.

  12. A Short-Term Fasting in Neonates Induces Breathing Instability and Epigenetic Modification in the Carotid Body.

    PubMed

    Shirahata, Machiko; Tang, Wan-Yee; Kostuk, Eric W

    2015-01-01

    The respiratory control system is not fully developed in newborn, and data suggest that adequate nutrition is important for the development of the respiratory control system. Infants need to be fed every 2-4 h to maintain appropriate energy levels, but a skip of feeding can occur due to social economical reasons or mild sickness of infants. Here, we asked questions if a short-term fasting (1) alters carotid body (CB) chemoreceptor activity and integrated function of the respiratory control system; (2) causes epigenetic modification within the respiratory control system. Mouse pups (carotid sinus nerve activity appeared to be depressed after fasting. Moreover, fasting increased global 5mC and 5-hmC content in DNA isolated from the CB but not DNA in the superior cervical ganglion (SCG). Methylation specific PCR (MSPCR) revealed that fasting increased methylation of leptin and socs3 genes. The results suggest fasting inhibits CB activity leading to hypoventilation, and low glucose does not compensate the low CB activity. Epigenetic effect on CB function/activity may be related to the prolonged effect of fasting on ventilation.

  13. Separation of carotid body chemoreceptor responses to O2 and CO2 by oligomycin and by antimycin A.

    PubMed

    Mulligan, E; Lahiri, S

    1982-03-01

    The cat carotid chemoreceptor O2 and CO2 responses can be separated by oligomycin and by antimycin A. Both of these agents greatly diminish or abolish the chemoreceptor O2 response but not the nicotine or CO2 responses. After either oligomycin or antimycin, the responses to increases and decreases in arterial CO2 partial pressure (PaCO2) consisted of increases and decreases in activity characterized respectively by exaggerated overshoots and undershoots. These were eliminated by the carbonic anhydrase inhibitor, acetazolamide, suggesting that they resulted from changes in carotid body tissue pH. The steady-state PaCO2 response remaining after oligomycin was no longer dependent on arterial O2 partial pressure (PaO2). All effects of antimycin were readily reversible in about 20 min. The separation of the responses to O2 and CO2 indicates that there may be at least partially separate pathways of chemoreception for these two stimuli. The similarity of the oligomycin and antimycin results supports the metabolic hypothesis of chemoreception.

  14. Dopamine increases in cat carotid body during excitation by carbon monoxide: implications for a chromophore theory of chemoreception.

    PubMed

    Buerk, D G; Chugh, D K; Osanai, S; Mokashi, A; Lahiri, S

    1997-12-11

    Studies of dopamine (DA) release were conducted with 10 perfused/superfused cat carotid bodies using shallow recessed Nafion polymer-coated microsensors (tips approximately 5 microns). Simultaneous measurements of tissue DA and neuronal discharge (ND) from the sinus nerve were made after switching from normoxic, normocapnic control perfusate (20% O2, 5% CO2, balance N2) to a normoxic, normocapnic perfusate equilibrated with a high tension (> 550 Torr) of carbon monoxide (CO). When high PCO perfusate was delivered in the dark, ND increased from a baseline of 89 +/- 24 (SE) impulses/s, to a peak excitation of 374 +/- 44 impulses/s within 15-30 s. Excitation then diminished to a plateau of 281 +/- 36 impulses/s within 1-2 min. Both peak and plateau ND were significantly above baseline (P < 0.05). Average tissue DA values increased above basal levels by +7.2 +/- 1.0 and +5.6 +/- 0.6 microns, respectively, during the peak and plateau ND phases (P < 0.05). Bright light restored the chemosensory activity to baseline, but had no effect on DA. Both chemosensory excitation and tissue DA responses to high CO in the dark were diminished in 3 carotid bodies perfused with Ca(2+)-free solutions. Responses were reduced even further with Ca2+ chelator (EGTA) in the perfusate. The results suggest that the effect of high PCO on DA release and chemosensory excitation are dependent on Ca2+ in the media, but the two events are not coupled.

  15. The respiratory response to carbon dioxide in humans with unilateral and bilateral resections of the carotid bodies

    PubMed Central

    Fatemian, Marzieh; Nieuwenhuijs, Diederik J F; Teppema, Luc J; Meinesz, Sietske; van der Mey, Andel G L; Dahan, Albert; Robbins, Peter A

    2003-01-01

    The acute hypercapnic ventilatory response (AHCVR) arises from both peripheral and central chemoreflexes. In humans, one technique for identifying the separate contributions of these chemoreflexes to AHCVR has been to associate the rapid component of AHCVR with the peripheral chemoreflex and the slow component with the central chemoreflex. Our first aim was to validate this technique further by determining whether a single slow component was sufficient to describe AHCVR in patients with bilateral carotid body resections (BR) for glomus cell tumours. Our second aim was to determine whether the slow component of AHCVR was diminished following carotid body resection as has been suggested by studies in experimental animals. Seven BR subjects were studied together with seven subjects with unilateral resections (UR) and seven healthy controls. A multifrequency binary sequence in end-tidal PCO2 was employed to stimulate ventilation dynamically under conditions of both euoxia and mild hypoxia. Both two- and one-compartment models of AHCVR were fitted to the data. For BR subjects, the two-compartment model fitted significantly better on 1 out of 13 occasions compared with 22 out of 28 occasions for the other subjects. Average values for the chemoreflex sensitivity of the slow component of AHCVR differed significantly (P < 0.05) between the groups and were 0.95, 1.38 and 1.50 l min−1 Torr−1 for BR, UR and control subjects, respectively. We conclude that, without the peripheral chemoreflex, AHCVR is adequately described by a single slow component and that BR subjects have sensitivities for the slow component that are lower than those of control subjects. PMID:12717011

  16. Carotid Ultrasound

    MedlinePlus

    ... this page from the NHLBI on Twitter. Carotid Ultrasound Also known as carotid duplex. Carotid ultrasound is a painless imaging test that uses high- ... of your carotid arteries. This test uses an ultrasound machine, which includes a computer, a screen, and ...

  17. In the carotid body, galanin is a signal for neurogenesis in young, and for neurodegeneration in the old and in drug-addicted subjects.

    PubMed

    Mazzatenta, Andrea; Marconi, Guya D; Zara, Susi; Cataldi, Amelia; Porzionato, Andrea; Di Giulio, Camillo

    2014-01-01

    The carotid body is a highly specialized chemoreceptive structure for the detection of and reaction to hypoxia, through induction of an increase in hypoxia inducible factor. As tissue hypoxia increases with aging and can have dramatic effects in respiratory depression induced by drug addiction, we investigated the carotid body in young and old healthy subjects in comparison with drug-addicted subjects, including the expression of the neurotransmitter galanin. Galanin expression was recently reported for neuronal-like cells of the human carotid body, and it is implicated in several functions in neurons. In particular, this includes the regulation of differentiation of neural stem cells, and participation in the development and plasticity of the nervous system. Using immunohistochemistry detection, we demonstrate that galanin expression in the human carotid body in healthy older subjects and drug-addicted subjects is significantly reduced in comparison with healthy young subjects. This demonstrates not only the effects of normal aging and senescence, but also in the drug-addicted subjects, this appears to be due to a disorganization of the chemo-sensory region. With both aging and drug addiction, this results in a physiological reduction in neuronal-like cells, coupled with interlobular and intralobular increases in connective tissue fibers. Consequently, in both aging and drug addiction, this reduction of neuronal-like cells and the regeneration suggest that the carotid body is losing its sensory capabilities, with the transmission of chemoreceptive signals dramatically and vitally reduced. The level of galanin expression would thus provide a signal for neurogenesis in young subjects, and for neurodegeneration in older and drug-addicted subjects.

  18. Assessment of Increase in Aortic and Carotid Intimal Medial Thickness in Type 1 Diabetic Patients

    PubMed Central

    Dayem, Soha M. Abd El; Battah, Ahmed A.; El Bohy, Abo El Magd

    2016-01-01

    AIM: To assess aortic and carotid intima-media thickness (aIMT and cIMT) in diabetic patients. PATIENTS AND METHODS: The study included 75 type 1 diabetic patients and 30 age and sex matched healthy volunteer. A blood sample was taken for analysis of HbA1 and lipid profile and the urine sample was taken for analysis of albumin/creatinine ratio. aIMT and cIMT via ultrasound were also done. RESULTS: cIMT & aIMT were significantly higher in diabetics. aIMT was found to be significantly higher than cIMT in diabetic patients (0.72 ± 0.11 vs. 0.52 ± 0.06, P = 0.0001). Ten of our patients (14%) with normal cIMT revealed significantly increased aIMT. aIMT had a significant positive correlation with age of patients, waist/hip ratio & cIMT. CONCLUSION: Diabetic patients had increased aIMT and cIMT with a relatively greater increase in the aIMT than in the cIMT. Because atherosclerosis begins first in the intima of the aorta, these data suggest that the aIMT might provide the best currently available noninvasive marker of preclinical atherosclerosis in children. We recommend frequent follow up of diabetic patients for early detection of diabetic complication. PMID:28028403

  19. Fatal Peritoneal Bleeding Following Embolization of a Carotid-Cavernous Fistula in Ehlers-Danlos Syndrome Type IV

    SciTech Connect

    Usinskiene, Jurgita; Mazighi, Mikael; Bisdorff, Annouk; Houdart, Emmanuel

    2006-12-15

    We report the case of a 25-year-old woman treated for a spontaneous carotid-cavernous fistula in a context of Ehlers-Danlos syndrome type IV. Embolization with a transvenous approach was achieved without complications; however, the patient died 72 hr later of massive intraperitoneal bleeding. At autopsy, no lesion of the digestive arteries was identified. Possible causes of this bleeding are discussed.

  20. The differential anti-inflammatory effects of exercise modalities and their association with early carotid atherosclerosis progression in patients with type 2 diabetes.

    PubMed

    Kadoglou, N P E; Fotiadis, G; Kapelouzou, A; Kostakis, A; Liapis, C D; Vrabas, I S

    2013-02-01

    Adipokines, visfatin, apelin, vaspin and ghrelin have emerged as novel cardiovascular risk factors. We aimed to evaluate the effects of different exercise modalities on the aforementioned novel adipokines and carotid intima-media thickness in patients with Type 2 diabetes mellitus. One hundred patients with Type 2 diabetes were equivalently (n = 25) randomized into four groups: (1) a control group with patients encouraged to perform self-controlled exercise; (2) a supervised aerobic exercise group (exercise four times/week, 60 min/session, 60-75% of maximum heart rate); (3) a resistance training group (60-80% baseline maximum load achieved in one repetition); and (4) a combined aerobic exercise plus resistance training group, as in groups 2 and 3. All participants had HbA(1c) levels ≥ 48 mmol/mol (≥ 6.5%), without overt diabetic vascular complications. Blood samples, clinical characteristics, peak oxygen uptake and carotid intima-media thickness measurements were obtained at baseline and at the end of the study, after 6 months. At baseline, there were non-significant differences between groups. All active groups significantly ameliorated glycaemic profile, insulin sensitivity and triglycerides levels compared with the control group (P < 0.05). Aerobic training further improved lipids, systolic blood pressure and exercise capacity compared with the resistance training and the control groups (P < 0.05). Moreover, high-sensitivity C-reactive protein and visfatin decreased, while vaspin and apelin circulating levels increased within the aerobic exercise group and the aerobic exercise plus resistance training group, and compared with the other groups (P < 0.05). Within- and between-group comparisons showed negligible alterations in ghrelin serum levels and body weight after all exercise modalities. Finally, aerobic training attenuated the carotid intima-media thickness progression (0.017 ± 0.006 mm) compared with the control subjects (0.129

  1. Chronic caffeine intake in adult rat inhibits carotid body sensitization produced by chronic sustained hypoxia but maintains intact chemoreflex output.

    PubMed

    Conde, Silvia V; Ribeiro, Maria J; Obeso, Ana; Rigual, Ricardo; Monteiro, Emilia C; Gonzalez, Constancio

    2012-12-01

    Sustained hypoxia produces a carotid body (CB) sensitization, known as acclimatization, which leads to an increase in carotid sinus nerve (CSN) activity and ensuing hyperventilation greater than expected from the prevailing partial pressure of oxygen. Whether sustained hypoxia is physiological (high altitude) or pathological (lung disease), acclimatization has a homeostatic implication because it tends to minimize hypoxia. Caffeine, the most commonly ingested psychoactive drug and a nonselective adenosine receptor antagonist, alters CB function and ventilatory responses when administered acutely. Our aim was to investigate the effect of chronic caffeine intake on CB function and acclimatization using four groups of rats: normoxic, caffeine-treated normoxic, chronically hypoxic (12% O₂, 15 days), and caffeine-treated chronically hypoxic rats. Caffeine was administered in drinking water (1 mg/ml). Caffeine ameliorated ventilatory responses to acute hypoxia in normoxic animals without altering the output of the CB (CSN neural activity). Caffeine-treated chronically hypoxic rats exhibited a decrease in the CSN response to acute hypoxia tests but maintained ventilation compared with chronically hypoxic animals. The findings related to CSN neural activity combined with the ventilatory responses indicate that caffeine alters central integration of the CB input to increase the gain of the chemoreflex and that caffeine abolishes CB acclimatization. The putative mechanisms involved in sensitization and its loss were investigated: expression of adenosine receptors in CB (A(2B)) was down-regulated and that in petrosal ganglion (A(2A)) was up-regulated in caffeine-treated chronically hypoxic rats; both adenosine and dopamine release from CB chemoreceptor cells was increased in chronic hypoxia and in caffeine-treated chronic hypoxia groups.

  2. Nonalcoholic Fatty Liver Disease is Associated with Increased Carotid Intima-Media Thickness in Type 1 Diabetic Patients

    PubMed Central

    Zhang, Lei; Guo, Kaifeng; Lu, Junxi; Zhao, Fangya; Yu, Haoyong; Han, Junfeng; Bao, Yuqian; Chen, Haibing; Jia, Weiping

    2016-01-01

    A growing body of evidence suggests that NAFLD is associated with an increased risk of incident CVD events both in patients without diabetes and in those with type 2 diabetes (T2DM). However, no published data are available regarding the association between NAFLD and C-IMT in T1DM. A total of 722 patients (371 men) with T1DM were included in this cross-sectional study. The main outcome measures were detection of NAFLD, C-IMT and classical risk factors. The mean age of the subjects was 46.2 years, and 51.1% were male. The prevalence of NAFLD was 15.9%. NAFLD patients had a markedly greater C-IMT (0.81 ± 0.25 vs. 0.69 ± 0.18 mm; p < 0.001) and frequency of carotid plaque (28.9% vs. 16.9%; p < 0.05) than those without fatty liver. Moreover, the differences in C-IMT remained after adjusting for potential confounders. A stepwise linear regression analysis revealed that age (standardized β, 0.326; p < 0.001), NAFLD (standardized β, 0.151, p < 0.001), and hsCRP (standardized β, 0.115, p = 0.008) were independently associated with C-IMT in all subjects. Our data show NAFLD is associated with elevated C-IMT in T1DM independent of conventional cardiovascular disease risk factors. PMID:27226159

  3. Increased carotid intima-media thickness in Brazilian adolescents with type 1 diabetes mellitus.

    PubMed

    Fusaro, Maria Fernanda Gontijo Sepulveda; Zanini, Jovita Lane Soares Santos; Silva, Ivani Novato

    2016-01-01

    Increased carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is an independent predictor of future cardiovascular events, and has been reported in children with various chronic diseases, including type 1 diabetes mellitus (DM1). Evaluate CIMT and its association with cardiovascular risk factors in Brazilian adolescents with DM1. Cross-sectional study of 118 adolescents, 57 with DM1 and no chronic complications related to the disease, and 61 healthy individuals. Clinical, biochemical, and high-resolution B-mode ultrasonographic evaluations according to the Consensus Statement of the American Society of Echocardiography CIMT Task Force were performed. Adolescents with diabetes (66.6% female) were 14.5 ± 2.9 years old and had 9.0 ± 4.0 years of disease duration. The healthy adolescents (62.3% female) were 14.3 ± 2.6 years old. All the adolescents had blood pressure within their reference ranges. In 66% of DM1 adolescents the systolic blood pressure was >50th percentile. Increased CIMT was observed in adolescents with diabetes compared with those in the control group: 0.53 vs 0.51 mm (p < 0.004) on the right side, and 0.55 vs 0.51 mm (p < 0.001) on the left side. CIMT presented independent and positive associations with diabetes duration, total cholesterol level, low-density lipoprotein cholesterol level, and systolic blood pressure percentile in DM1 adolescents. Increased CIMT was observed in young Brazilian adolescents with DM1, and was associated with cardiovascular risk factors. CIMT assessment may be useful for the early identification and monitoring of cardiovascular risk in this age group.

  4. Effects of changes in chemoreceptor activity on extracellular K+ and Ca2+ activities in the cat carotid body.

    PubMed

    O'Regan, R G; Acker, H

    1988-04-05

    In anaesthetized, paralysed and artificially ventilated cats triple-barrelled ion-selective microelectrodes (ISMs) were inserted into the right carotid body in order to measure extracellular activities of K+ ([K+]o) and Ca2+ ([Ca2+]o) simultaneously. In 3 experiments a method involving iron deposition located the tips of the ISMs in the cellular islands of the organ. A thin cannula inserted into the right carotid artery (i.c.) via the lingual artery was used to infuse Ringer-Locke solutions (0.1-0.5 ml/min) containing either sodium cyanide (NaCN), acetylcholine (ACh) or dopamine (DA). Analysis of the effects of administration of NaCN (20-100 micrograms/min i.c.) showed that during this procedure [K+]o increased and [Ca2+]o decreased by mean values (+/- S.D.) of 0.99 +/- 0.82 and 0.22 +/- 0.06 mM respectively. During administration of ACh (20-50 micrograms/min i.c.) [K+]o increased and [Ca2+]o decreased respectively by mean values (+/- S.D.) of 3.18 +/- 3.0 and 0.31 +/- 0.14 mM. Decreases in [K+]o and [Ca2+]o by mean values (+/- S.D.) of 1.53 +/- 1.64 and 0.34 +/- 0.33 mM respectively were associated with administration of DA (20-50 micrograms/min i.c.). The predominant influences exerted by NaCN and ACh on chemoreceptor activity were excitatory whereas administration of DA caused either inhibition, excitation or a combination of these two effects. Stimulation of the sympathetic supply to the carotid body was associated with either increases, decreases or no reaction of chemosensory activity, [K+]o and [Ca2+]o. The changes in [K+]o associated with the various procedures may reflect the state of polarization within the chemoreceptor complex. Decreases in [Ca2+]o usually accompanied the performance of all procedures and may have resulted from an increased influx of this ion from the interstitial fluids into the cells for the purpose of provoking neurotransmitter release. However, the time course of the changes in [K+]o and [Ca2+]o were considerably slower in onset and

  5. Carotid artery surgery

    MedlinePlus

    Carotid endarterectomy; CAS surgery; Carotid artery stenosis - surgery; Endarterectomy - carotid artery ... through the catheter around the blocked area during surgery. Your carotid artery is opened. The surgeon removes ...

  6. Relationship between frequency of hypoglycemic episodes and changes in carotid atherosclerosis in insulin-treated patients with type 2 diabetes mellitus

    PubMed Central

    Mita, Tomoya; Katakami, Naoto; Shiraiwa, Toshihiko; Yoshii, Hidenori; Kuribayashi, Nobuichi; Osonoi, Takeshi; Kaneto, Hideaki; Kosugi, Keisuke; Umayahara, Yutaka; Gosho, Masahiko; Shimomura, Iichiro; Watada, Hirotaka

    2017-01-01

    The effect of hypoglycemia on the progression of atherosclerosis in patients with type 2 diabetes mellitus (T2DM) remains largely unknown. This is a post hoc analysis of a randomized trial to investigate the relationship between hypoglycemic episodes and changes in carotid intima-media thickness (IMT). Among 274 study subjects, 104 patients experienced hypoglycemic episodes. Increases in the mean IMT and left maximum IMT of the common carotid arteries (CCA) were significantly greater in patients with hypoglycemia compared to those without hypoglycemia. Classification of the patients into three groups according to the frequency of hypoglycemic episodes showed that high frequency of hypoglycemic events was associated with increases in mean IMT-CCA, and left max-IMT-CCA and right max-IMT-CCA. In addition, repetitive episodes of hypoglycemia were associated with a reduction in the beneficial effects of sitagliptin on carotid IMT. Our data suggest that frequency of hypoglycemic episodes was associated with changes in carotid atherosclerosis. PMID:28067320

  7. Human carotid body neuroglobin, vascular endothelial growth factor and inducible nitric oxide synthase expression in heroin addiction.

    PubMed

    Zara, S; Porzionato, A; De Colli, M; Macchi, V; Cataldi, A; De Caro, R; Di Giulio, C

    2013-07-01

    The carotid body (CB) represents the prime site for detecting and responding to hypoxia. Since the role of heroin in respiratory depression with consequent hypoxia is known, the authors were able to investigate morphological and molecular modifications occurring in the CB of heroin addicted subjects compared to subjects who died because of trauma. CB sampled from six 27 year old subjects, slides were treated with Mallory Trichrome staining or used for immunohistochemical analysis to detect Neuroglobin (NGB), Hypoxia Inducible Factor-1 (HIF-1α), Vascular Endothelial Growth Factor (VEGF), Inducible Nitric Oxide Synthase (i-NOS), Bax and cleaved Caspase-3 proteins. Mallory Trichrome staining shows an increase in the connective tissue in heroin subjects compared to controls and a parallel reduction in parenchymal area. Immunohistochemical analyses in heroin subjects found a decrease in NGB and an increase in HIF-1α and VEGF compared to controls; i-NOS expression was not statistically significant. Bax and cleaved caspase-3 were positive only in the heroin subjects. These results could confirm the typical hypoxic condition occurring in heroin addicts. Since NGB may function as a reactive oxygen or nitrogen species scavenger and as apoptotic cell death protector, the decrease in its expression may suggest a key role of this globin in human CB impairment due to heroin addiction.

  8. Changes in carotid body and nTS neuronal excitability following neonatal sustained and chronic intermittent hypoxia exposure.

    PubMed

    Mayer, C A; Wilson, C G; MacFarlane, P M

    2015-01-01

    We investigated whether pre-treatment with neonatal sustained hypoxia (SH) prior to chronic intermittent hypoxia (SH+CIH) would modify in vitro carotid body (CB) chemoreceptor activity and the excitability of neurons in the caudal nucleus of the solitary tract (nTS). Sustained hypoxia followed by CIH exposure simulates an oxygen paradigm experienced by extremely premature infants who developed persistent apnea. Rat pups were treated with 5 days of SH (11% O2) from postnatal age 1 (P1) followed by 10 days of subsequent chronic intermittent hypoxia (CIH, 5% O2/5 min, 8 h/day, between P6 and P15) as described previously (Mayer et al., Respir. Physiol. Neurobiol. 187(2): 167-75, 2013). At the end of SH+CIH exposure (P16), basal firing frequency was enhanced, and the hypoxic sensory response of single unit CB chemoafferents was attenuated. Further, basal firing frequency and the amplitude of evoked excitatory post-synaptic currents (ESPC's) of nTS neurons was augmented compared to age-matched rats raised in normoxia. These effects were unique to SH+CIH exposure as neither SH or CIH alone elicited any comparable effect on chemoafferent activity or nTS function. These data indicated that pre-treatment with neonatal SH prior to CIH exposure uniquely modified mechanisms of peripheral (CB) and central (nTS) neural function in a way that would be expected to disturb the ventilatory response to acute hypoxia.

  9. Sympathetic regulation of vascular tone via noradrenaline and serotonin in the rat carotid body as revealed by intracellular calcium imaging.

    PubMed

    Yokoyama, Takuya; Nakamuta, Nobuaki; Kusakabe, Tatsumi; Yamamoto, Yoshio

    2015-01-30

    Hypoxia-induced chemosensory activity in the carotid body (CB) may be enhanced by the sympathetic regulation of vascular tone in the CB. In the present study, we recorded cervical sympathetic nerve activity in rats exposed to hypoxia, and examined noradrenaline (NA)- and serotonin (5-HT)-induced intracellular Ca(2+) ([Ca(2+)]i) responses in smooth muscle cells and pericytes in isolated blood vessels from the CB. Multifiber electrical activity recorded from the cervical sympathetic trunk was increased during the inhalation of hypoxic gas. NA induced [Ca(2+)]i increases in smooth muscle cells in arteriole specimens, whereas 5-HT did not cause any [Ca(2+)]i responses. However, NA did not induce [Ca(2+)]i increases in pericytes in capillaries, whereas 5-HT did and this response was inhibited by the 5-HT2 receptor antagonist, ketanserin. In conclusion, cervical sympathetic nerves enhanced by hypoxia may reduce blood flow in the CB in order to increase chemosensitivity. Thus, hypoxic chemosensitivity in the CB may involve a positive feedback mechanism via sympathetic nerves. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Serotonin-mediated modulation of hypoxia-induced intracellular calcium responses in glomus cells isolated from rat carotid body.

    PubMed

    Yokoyama, Takuya; Nakamuta, Nobuaki; Kusakabe, Tatsumi; Yamamoto, Yoshio

    2015-06-15

    In the present study, we examined serotonin (5-HT)-induced intracellular Ca(2+) ([Ca(2+)]i) responses to hypoxia in glomus cells isolated from carotid body (CB) of the rat. 5-HT did not induce any [Ca(2+)]i responses in clustered glomus cells during normoxia (21% O2), whereas, the perfusion of hypoxic solution (1% O2) induced repetitive increases in [Ca(2+)]i in the same specimens. The frequency and magnitude of hypoxia-induced [Ca(2+)]i changes observed in the glomus cells were enhanced in the presence of 5-HT, and this response was inhibited by the 5-HT2 receptor antagonist, ketanserin. Furthermore, RT-PCR analysis detected the expression of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT3A, and 5-HT3B receptor mRNAs in extracts of the CB. These results suggest that 5-HT increases hypoxia-induced [Ca(2+)]i responses in glomus cells. 5-HT may elevate hypoxic responses in glomus cells in order to increase chemosensory activity of the CB.

  11. The Effect of Sitagliptin on Carotid Artery Atherosclerosis in Type 2 Diabetes: The PROLOGUE Randomized Controlled Trial

    PubMed Central

    Oyama, Jun-ichi; Murohara, Toyoaki; Kitakaze, Masafumi; Ishizu, Tomoko; Sato, Yasunori; Kitagawa, Kazuo; Kamiya, Haruo; Ajioka, Masayoshi; Ishihara, Masaharu; Dai, Kazuoki; Sata, Masataka; Maemura, Koji; Tomiyama, Hirofumi; Higashi, Yukihito; Kaku, Kohei; Matsuhisa, Munehide; Yamashita, Kentaro; Bando, Yasuko K.; Kashihara, Naoki; Ueda, Shinichiro; Inoue, Teruo; Tanaka, Atsushi; Node, Koichi

    2016-01-01

    Background Experimental studies have suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular protective effects. We performed a randomized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone (diet, exercise, and/or drugs, except for incretin-related agents) on the intima-media thickness (IMT) of the carotid artery, a surrogate marker for the evaluation of atherosclerotic cardiovascular disease, in people with type 2 diabetes mellitus (T2DM). Methods and Findings We used a multicenter PROBE (prospective, randomized, open label, blinded endpoint) design. Individuals aged ≥30 y with T2DM (6.2% ≤ HbA1c < 9.4%) were randomly allocated to receive either sitagliptin (25 to 100 mg/d) or conventional therapy. Carotid ultrasound was performed at participating medical centers, and all parameters were measured in a core laboratory. Of the 463 enrolled participants with T2DM, 442 were included in the primary analysis (sitagliptin group, 222; conventional therapy group, 220). Estimated mean (± standard error) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of −0.009 mm (97.2% CI −0.028 to 0.011, p = 0.309). HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy (6.56% ± 0.05% versus 6.72% ± 0.05%, p = 0.008; group mean difference −0.159, 95% CI −0.278 to −0.041). Episodes of serious hypoglycemia were recorded only in the conventional therapy group, and the rate of other adverse events was not different between the two groups. As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis, there were some limitations of interpretation. Conclusions In the PROLOGUE study, there was no evidence that treatment with sitagliptin had an additional effect on the

  12. Post-meal glucose peaks at home associate with carotid intima-media thickness in type 2 diabetes.

    PubMed

    Esposito, Katherine; Ciotola, Miryam; Carleo, Diego; Schisano, Bruno; Sardelli, Luigi; Di Tommaso, Domenico; Misso, Lucio; Saccomanno, Franco; Ceriello, Antonio; Giugliano, Dario

    2008-04-01

    Two-hour postprandial hyperglycemia is related to chronic complications of diabetes and is currently used in the international guidelines to drive the therapy. Our objective was to assess the size and timing of post-meal glucose peaks in the everyday life of type 2 diabetic patients and the relationship with carotid atherosclerosis. This was an observational study performed in 644 outpatients with type 2 diabetes attending diabetes clinics located in the area of the Campania County, South Italy, who provided complete home blood glucose profiles and centralized carotid intima-media thickness (CIMT) assessment. The study was conducted from 2001-2005. Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after the meal. CIMT was assessed by carotid sonography. The level of glycosylated hemoglobin and CIMT progressively increased across quintiles of IGP (P for trend = 0.01 for both). In univariate analysis, all examined glycemic parameters were significantly correlated with CIMT. IGP (r = 0.40; P = 0.006) showed the strongest correlation with CIMT, which remained significant in multiple linear regression analysis (R(2) = 0.26; P = 0.01). IGP was associated with a significant increase of CIMT in tertiles of glycosylated hemoglobin. IGP occurred within 1 h from the start of the meal in 95% of the entire diabetic population. IGPs are frequent in the everyday life of patients with type 2 diabetes, occur for most (95%) within 1 h after meal, timing of IGPs is not influenced by treatment (diet or drugs), and IGPs correlate with CIMT.

  13. Carotid arterial wall inflammation in peripheral artery disease is augmented by type 2 diabetes: a cross-sectional study.

    PubMed

    Bernelot Moens, Sophie J; Stoekenbroek, Robert M; van der Valk, Fleur M; Verweij, Simone L; Koelemay, Mark J W; Verberne, Hein J; Nieuwdorp, Max; Stroes, Erik S G

    2016-11-25

    Patients with peripheral artery disease (PAD) are at increased risk of secondary events, which is exaggerated in the presence of type 2 diabetes mellitus. Diabetes is associated with a systemic pro-inflammatory state. We therefore investigated the cumulative impact of PAD and type 2 diabetes on carotid arterial wall inflammation. As recent data suggest a detrimental role of exogenous insulin on cardiovascular disease, we also included a group of insulin users. (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG PET/CT) imaging showed increased carotid arterial wall inflammation, assessed as target-to-background ratio (TBR), in PAD patients without diabetes (PAD-only: n = 11, 1.97 ± 0.57) compared with matched controls (n = 12, 1.49 ± 0.57; p = 0.009), with a significant further TBR increase in PAD patients with type 2 diabetes (PAD-DM, n = 23, 2.90 ± 1, p = 0.033 vs PAD-only). TBR of insulin users (n = 12, 3.31 ± 1.14) was higher compared with patients on oral medication only (n = 11, 2.44 ± 0.76, p = 0.035), despite comparable PAD severity (Fontaine stages), BMI and CRP. Multivariate regression analysis showed that Hba1c and plasma insulin levels, but not dose of exogenous insulin, correlated with TBR. Concurrent diabetes significantly augments carotid arterial wall inflammation in PAD patients. A further increase in those requiring insulin was observed, which was associated with diabetes severity, rather than with the use of exogenous insulin itself.

  14. Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of disease.

    PubMed

    Matsumoto, Takayuki; Watanabe, Shun; Kawamura, Ryusuke; Taguchi, Kumiko; Kobayashi, Tsuneo

    2014-11-24

    There is a growing body of evidence suggesting that epigallocatechin gallate (EGCG), a major catechin isolated from green tea, has several beneficial effects, such as anti-oxidant and anti-inflammatory activities. However, whether treatment with EGCG can suppress the endothelin-1 (ET-1)-induced contraction in carotid arteries from type 2 diabetic rats is unknown, especially at the chronic stage of the disease. We hypothesized that long-term treatment with EGCG would attenuate ET-1-induced contractions in type 2 diabetic arteries. Otsuka Long-Evans Tokushima fatty (OLETF) rats (43 weeks old) were treated with EGCG (200 mg/kg/day for 2 months, p.o.), and the responsiveness to ET-1, phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) was measured in common carotid artery (CA) from EGCG-treated and -untreated OLETF rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF rats, EGCG attenuated responsiveness to ET-1 in CA compared to untreated groups. However, EGCG did not alter PE-induced contractions in CA from OLETF rats. In endothelium-denuded arteries, EGCG did not affect ET-1-induced contractions in either the OLETF or LETO group. Acetylcholine-induced relaxation was increased by EGCG treatment in CA from the OLETF group. The expressions of ET receptors, endothelial nitric oxide synthase, superoxide dismutases, and gp91(phox) [an NAD(P)H oxidase component] in CA were not altered by EGCG treatment in either group. Our data suggest that, within the timescale investigated here, EGCG attenuates ET-1-induced contractions in CA from type 2 diabetic rats, and one of the mechanisms may involve normalizing endothelial function. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Current and adolescent body fatness and fat distribution: relationships with carotid intima-media thickness and large artery stiffness at the age of 36 years.

    PubMed

    Ferreira, Isabel; Twisk, Jos W R; van Mechelen, Willem; Kemper, Han C G; Seidell, Jacob C; Stehouwer, Coen D A

    2004-01-01

    Body fat and its distribution are determinants of cardiovascular disease but the underlying mechanisms of these adverse effects are poorly understood. We therefore investigated (1) the cross-sectional relationship between estimates of body fatness and its distribution on the one hand and carotid atherosclerosis and stiffness of the carotid, femoral and brachial arteries and the carotido-femoral segment on the other (336 subjects, 175 women); (2) the relationship between estimates of body fatness and its distribution during adolescence (13-16 years) and the same arterial properties at age 36- prospective analyses (subpopulation of 159 subjects, 84 girls). Cross-sectional and prospective analyses within an ongoing observational longitudinal study: The Amsterdam Growth and Health Longitudinal Study. Body fatness and its distribution were assessed by anthropometry and dual-energy X-ray absorptiometry (DXA); arterial properties were assessed non-invasively by ultrasound imaging. Total adiposity and, in men, truncal subcutaneous fat accumulation during adolescence, were positively and independently associated with carotid intima-media thickness at age 36, a pre-clinical indicator of atherosclerosis. Adolescent truncal subcutaneous fat accumulation but not total adiposity was associated with increased arterial stiffness at age 36. At age 36, both abdominal and truncal subcutaneous fat were independently associated with arterial stiffness, while the associations between total adiposity and arterial stiffness appeared to be mediated by other cardiovascular risk factors. Body fatness and body fat distribution are associated with large artery structural and functional properties at age 36 and the roots of these associations may already be present in adolescence.

  16. Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is an Independent Determinant of Carotid Intima-Media Thickness in Patients With Type 2 Diabetes

    PubMed Central

    Takenouchi, Akiko; Tsuboi, Ayaka; Kitaoka, Kaori; Minato, Satomi; Kurata, Miki; Fukuo, Keisuke; Kazumi, Tsutomu

    2017-01-01

    Background Studies demonstrated that visit-to-visit variability in low-density lipoprotein cholesterol (LDLC) is an independent predictor of cardiovascular events in subjects with coronary artery disease. Whether visit-to-visit variability in LDLC levels affects subclinical atherosclerosis is unknown. This study sought to evaluate the role of visit-to-visit variability in LDLC levels on subclinical atherosclerosis. Methods We evaluated 162 type 2 diabetic patients with measurement of carotid intima-media thickness (IMT). Intrapersonal mean and standard deviation (SD) of six measurements of LDLC during 12 months were calculated. Multivariate linear regressions assessed the independent correlates of carotid IMT. Results The mean and SD of LDLC were 112 ± 22 and 15 ± 10 mg/dL, respectively, and 43.2% of patients were on hypolipidemic drugs. Age (standardized β = 0.355, P < 0.001), male sex (standardized β = 0.234, P = 0.002) and SD-LDLC (standardized β = 0.201, P = 0.009) emerged as independent determinants of carotid maximum IMT independently of mean LDLC levels, body mass index (BMI), waist circumference, duration and treatment of diabetes, means and SDs of glycemic and other lipid variables, and uses of hypolipidemic and anti-hypertensive medications (R2 = 0.15). Results did not change when mean IMT was used instead of maximum IMT. After controlling for age and sex, maximum IMT was thicker in patients with the highest compared to those with other three quartiles of SD-LDLC combined (1.14 ± 0.04 (SE) vs. 1.01 ± 0.02 mm, P = 0.01). Independent determinants of SD-LDLC were mean LDLC, use of hypolipidemic drugs, fasting triglyceride and visit-to-visit variability in HbA1c. Conclusions Consistency of LDLC levels may be important to subclinical atherosclerosis in real-world patients with type 2 diabetes. It may be important for patients on lipid-lowering drugs to prevent non-compliance. PMID:28270891

  17. Differential associations of central and brachial blood pressure with carotid atherosclerosis and microvascular complications in patients with type 2 diabetes

    PubMed Central

    2014-01-01

    Background We examined the relationship between central blood pressure (BP), brachial BP with carotid atherosclerosis and microvascular complications in type 2 diabetes mellitus (T2DM). Methods We recruited 201 patients who were evaluated for central BP, brachial BP, carotid ultrasonography, brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI) and microvascular complications. Central BP were calculated using a radial automated tonometric system. Results Agreement between central BP and brachial BP was very strong (concordance correlation coefficient between central and brachial SBP = 0.889, between central and brachial PP = 0.816). Central pulse pressure (PP) was correlated with mean carotid intima-media thickness (CIMT), baPWV and ABI, whereas brachial PP was borderline significantly correlated with CIMT. The prevalence of nephropathy(DN) and retinopathy(DR) according to the brachial PP tertiles increased, the prevalences of microvascular complications were not different across central PP tertiles. In multivariate analysis, the relative risks (RRs) for the presence of DR were 1.2 and 4.6 for the brachial PP tertiles 2 and 3 when compared with the first tertile. Also, the RRs for the presence of DN were 1.02 and 3 for the brachial PP tertiles 2 and 3 when compared with the first tertile. Conclusions Agreement of central BP and brachial BP was very strong. Nonetheless, this study showed that higher brachial PP levels are associated with increased probability for the presence of microvascular complications such as DR/DN. However, there are no associations with central SBP and central PP with microvascular complications. Central BP levels than brachial BP are correlated with surrogate marker of macrovascular complications. PMID:24555866

  18. Carotid artery intima media thickness in relation with atherosclerotic risk factors in patients with type 2 diabetes mellitus.

    PubMed

    Gayathri, R; Chandni, R; Udayabhaskaran, V

    2012-09-01

    The present study was carried out to study the correlation between carotid artery intima media thickness (CIMT) with risk factors for atherosclerosis and atherosclerotic events in Type 2 Diabetes mellitus patients. The predictive value of CIMT as an indicator of early atherosclerosis was determined and the various atherosclerotic risk factors in type 2 diabetes mellitus were studied. Our study showed that CIMT was significantly higher in those type 2 diabetic patients who had atherosclerotic events than in those patients who had no atherosclerotic events. It was also found that waist hip ratio showed a significant positive correlation and independent association with CIMT emphasizing the emerging concept of central obesity. Duration of diabetes, urinary albumin excretion rate, hypertension and glycated hemoglobin had positive correlation with CIMT, but could not assume statistical significance. Age, smoking and dyslipidemia did not show any association with CIMT.

  19. Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: involvement of nitric oxide

    PubMed Central

    Li, Yu-Long; Sun, Shu-Yu; Overholt, Jeffery L; Prabhakar, Nanduri R; Rozanski, George J; Zucker, Irving H; Schultz, Harold D

    2004-01-01

    It has been shown that peripheral chemoreceptor sensitivity is enhanced in both clinical and experimental heart failure (HF) and that impairment of nitric oxide (NO) production contributes to this enhancement. In order to understand the cellular mechanisms associated with the alterations of chemoreceptor function and the actions of NO in the carotid body (CB), we compared the outward K+ currents (IK) of glomus cells in sham rabbits with that in HF rabbits and monitored the effects of NO on these currents. Ik was measured in glomus cells using conventional and perforated whole-cell configurations. IK was attenuated in glomus cells of HF rabbits, and their resting membrane potentials (−34.7 ± 1.0 mV) were depolarized as compared with those in sham rabbits (−47.2 ± 1.9 mV). The selective Ca2+-dependent K+ channel (KCa) blocker iberiotoxin (IbTx, 100 nm) reduced IK in glomus cells from sham rabbits, but had no effect on IK from HF rabbits. In perforated whole-cell mode, the NO donor SNAP (100 μm) increased IK in glomus cells from HF rabbits to a greater extent than that in sham rabbits (P < 0.01), and IbTx inhibited the effects of SNAP. However, in conventional whole-cell mode, SNAP had no effect. Nω-nitro-L-arginine (L-NNA, NO synthase inhibitor) decreased Ik in sham rabbits but not in HF rabbits. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) inhibited the effect of SNAP on Ik. These results demonstrate that IK is reduced in CB glomus cells from HF rabbits. This effect is due mainly to the suppression of KCa channel activity caused by decreased availability of NO. In addition, intracellular cGMP is necessary for the KCa channel modulation by NO. PMID:14673183

  20. Regulation of hypoxia-inducible factor-α isoforms and redox state by carotid body neural activity in rats

    PubMed Central

    Peng, Ying-Jie; Yuan, Guoxiang; Khan, Shakil; Nanduri, Jayasri; Makarenko, Vladislav V; Reddy, Vaddi Damodara; Vasavda, Chirag; Kumar, Ganesh K; Semenza, Gregg L; Prabhakar, Nanduri R

    2014-01-01

    Previous studies reported that chronic intermittent hypoxia (CIH) results in an imbalanced expression of hypoxia-inducible factor-α (HIF-α) isoforms and oxidative stress in rodents, which may be due either to the direct effect of CIH or indirectly via hitherto uncharacterized mechanism(s). As neural activity is a potent regulator of gene transcription, we hypothesized that carotid body (CB) neural activity contributes to CIH-induced HIF-α isoform expression and oxidative stress in the chemoreflex pathway. Experiments were performed on adult rats exposed to CIH for 10 days. Rats exposed to CIH exhibited: increased HIF-1α and decreased HIF-2α expression; increased NADPH oxidase 2 and decreased superoxide dismutase 2 expression; and oxidative stress in the nucleus tractus solitarius and rostral ventrolateral medulla as well as in the adrenal medulla (AM), a major end organ of the sympathetic nervous system. Selective ablation of the CB abolished these effects. In the AM, sympathetic activation by the CB chemoreflex mediates CIH-induced HIF-α isoform imbalance via muscarinic acetylcholine receptor-mediated Ca2+ influx, and the resultant activation of mammalian target of rapamycin pathway and calpain proteases. Rats exposed to CIH presented with hypertension, elevated sympathetic activity and increased circulating catecholamines. Selective ablation of either the CB (afferent pathway) or sympathetic innervation to the AM (efferent pathway) abolished these effects. These observations uncover CB neural activity-dependent regulation of HIF-α isoforms and the redox state by CIH in the central and peripheral nervous systems associated with the chemoreflex. PMID:24973414

  1. Hypoxia induces voltage-dependent Ca2+ entry and quantal dopamine secretion in carotid body glomus cells.

    PubMed Central

    Ureña, J; Fernández-Chacón, R; Benot, A R; Alvarez de Toledo, G A; López-Barneo, J

    1994-01-01

    We have investigated the changes of cytosolic [Ca2+] and the secretory activity in single glomus cells dispersed from rabbit carotid bodies during exposure to solutions with variable O2 tension (Po2). In normoxic conditions (Po2 = 145 mmHg; 1 mmHg = 133 Pa), intracellular [Ca2+] was 58 +/- 29 nM, and switching to low Po2 (between 10 and 60 mmHg) led to a reversible increase of [Ca2+] up to 800 nM. The response to hypoxia completely disappeared after removal of external Ca2+ or with the addition of 0.2 mM Cd2+ to the external solution. These same solutions also abolished both the Ca2+ current of the cells and the increase of internal [Ca2+] elicited by high external K+. Elevations of cytosolic [Ca2+] in response to hypoxia or to direct membrane depolarization elicited the release of dopamine, which was detected by amperometric techniques. Dopamine secretion occurred in episodes of spike-like activity that appear to represent the release from single secretory vesicles. From the mean charge of well-resolved secretory events, we estimated the average number of dopamine molecules per vesicle to be approximately 140,000, a value about 15 times smaller than a previous estimate in chromaffin granules of adrenomedullary cells. These results directly demonstrate in a single-cell preparation the secretory response of glomus cells to hypoxia. The data indicate that the enhancement of cellular excitability upon exposure to low Po2 results in Ca2+ entry through voltage-gated channels, which leads to an increase in intracellular [Ca2+] and exocytotic transmitter release. PMID:7937863

  2. Triglyceride to high-density lipoprotein cholesterol ratio and carotid intima-medial thickness in Chinese adolescents with newly diagnosed type 2 diabetes mellitus.

    PubMed

    Li, Xin; Deng, You-Ping; Yang, Miao; Wu, Yu-Wen; Sun, Su-Xin; Sun, Jia-Zhong

    2016-03-01

    To investigate the relationship between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and carotid intima-medial thickness (CIMT) in Chinese youth and adolescents with newly diagnosed type 2 diabetes mellitus (T2DM). Ninety-eight subjects aged 10-24 yr with newly-diagnosed T2DM had general inflammation, anthropometric, laboratory and CIMT data collected, and were divided into three groups based on TG/HDL-C tertiles. There were no significant differences in gender, age, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and carotid arterial diameter (CAD) among the groups based on TG/HDL-C tertiles. Across TG/HDL-C tertiles, there was a significant progressive increase in body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), homeostasis model assessment-estimated insulin resistance (HOMA-IR), TG, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and CIMT (all P < 0.01 or P < 0.05), while HDL-C was decreased significantly across the groups (P < 0.01). In general linear regression model, TG/HDL-C was an independent determinant of CIMT even after adjusting for BMI, SBP, DBP, TG, TC, LDL-C, HDL-C, HbA1c and HOMA-IR. TG/HDL-C ratio, the marker of small dense LDL particles, is an independent determinant of CIMT in Chinese youth and adolescents with newly diagnosed T2DM, and may be a simple and helpful tool in predicting the increased CIMT in such patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. The relationship of miR-146a gene polymorphism with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus.

    PubMed

    Shen, Jing; Zhang, Min; Sun, Mingfang; Tang, Kang; Zhou, Bo

    2015-12-01

    Atherosclerosis (AS) is regarded as the major cause of disability and death in diabetic patients. However, its precise pathogenesis is not entirely clear. Recent genome-wide association studies (GWAS) have revealed AS is related to some epigenetic changes. This study aimed to investigate the possible associations of miR-146a and transcriptional coactivator p300 polymorphisms with carotid atherosclerosis in type 2 diabetes mellitus. This case-control study included 596 type 2 diabetes mellitus patients with carotid atherosclerosis and 379 patients without carotid atherosclerosis. Genotyping of miR-146a and p300 polymorphisms was performed by allelic discrimination assay with TaqMan-MGB probes. The CC genotype of rs2910164 in miR-146a was found to be associated with an increased risk of carotid vulnerable plaque in the Chinese type 2 diabetes mellitus patients, but this association was not found in the type 2 diabetes mellitus patients with carotid atherosclerosis or in the plaque load group. In addition, no significant difference in transcriptional coactivator p300 genotype distribution was observed between the type 2 diabetes mellitus patients with and without carotid atherosclerosis, plaque stability or plaque load, respectively. Stratified analyses revealed that the miR-146aCC genotype was associated with an increased risk of vulnerable plaque in subjects who were older, females, those with diabetes duration of more than 10 years, and those with hypertension. The gene-gene interactions between the miR-146a rs2910164 and p300 rs20551 polymorphisms were further analysed, but no combined effects of these two genes on enhancing the risk of carotid atherosclerosis, plaque stability, or plaque load were detected. The miR-146a rs2910164 polymorphism might be associated with carotid vulnerable plaque risk in Chinese type 2 diabetes mellitus patients, particularly in older patients, females, those with diabetes duration of more than 10 years and those with hypertension

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

    PubMed

    Niewinski, Piotr; Janczak, Dariusz; Rucinski, Artur; Tubek, Stanislaw; Engelman, Zoar J; Jazwiec, Przemyslaw; Banasiak, Waldemar; Sobotka, Paul A; Hart, Emma C J; Paton, Julian F R; Ponikowski, Piotr

    2014-03-01

    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.

  5. Association Between IL-18 and Carotid Intima-Media Thickness in Patients with Type II Diabetic Nephropathy

    PubMed Central

    Zhang, Yuanyuan; Feng, Haomiao; Wei, Zhiyong

    2017-01-01

    Background We specifically designed this study to determine the relationship between levels of IL-8 and carotid intima-media thickness (cIMT) in patients with type 2 diabetes mellitus (T2DM). Material/Methods A total of 149 diabetic patients at different stages of diabetic nephropathy and 72 matched controls were recruited in this study. A wide range of parameters were measured: IL-18 (by ELISA), urinary albumin excretion rates (UAER), and carotid intima-media thickness (cIMT, by pulse wave velocity [PWV]). All the diabetic patients were treated by alprostadil. Results ELISA indicated that the level of IL-18 in the patient group was significantly higher compared with that in the control group. The level of IL-18 apparently increased in the higher cIMT group in T2DM patients. Serum IL-18 levels were positively correlated with cIMT in patients with T2DM, the level of IL-18 was negatively correlated with cIMT, and IL-18 levels were positively correlated to age. Moreover, IMT was positively correlated with hemoglobin A1C (HbA1C) and IL-18 levels were significantly associated with cIMT (all P<0.05). Conclusions IL-18 levels were positively correlated with atherosclerotic burden in patients with T2DM and it may be considered as a significant therapeutic target. PMID:28125566

  6. Inverse relationship between the body mass index and severity of carotid siphon calcifications (another obesity paradox): Results from the Atahualpa Project.

    PubMed

    Del Brutto, Oscar H; Mera, Robertino M

    2017-04-01

    The importance of the obesity paradox in the intracranial vasculature has not been explored. We assessed whether the body mass index (BMI) correlates with severity of carotid siphon calcifications (CSC) in community-dwelling adults. Using a population-based study design, Atahualpa residents aged ≥40 years underwent head computed tomography (CT) for assessment of CSC. We evaluated the association between BMI and severity of CSC (dependent variable) using regression models adjusted for demographics and cardiovascular risk factors. Of 830 people enrolled in the Atahualpa Project, 651 (78%) were included. Mean BMI was 27.3 ± 5 kg/m(2), with 39% being overweight and 27% obese. CT revealed high calcium content in the carotid siphon in 25% participants. In an adjusted model, individuals with normal weight had a trend for presenting with more severe CSC than those overweight (p = 0.06), and those ones had significantly more severe CSC than obese participants (p = 0.04). Predictive margins of BMI were higher in individuals with low calcium content in the carotid siphon. A contour plot with Shepard interpolation showed that the paradox disappeared in older individuals and in those with severe obesity, irrespective of age. BMI inversely associates with severity of CSC. This paradox is relevant in younger individuals and in those without severe obesity, irrespective of age. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Adrenergic mechanisms and chemoreception in the carotid body of the cat and rabbit.

    PubMed

    Folgering, H; Ponte, J; Sadig, T

    1982-04-01

    1. The effect of beta-adrenergic and dopaminergic agonists and antagonists on the chemoreceptor response to graded hypoxia and hypercapnia was tested in nineteen cats and ten rabbits anaesthetized either with chloralose-urethane or pentobarbitone sodium, paralysed with pancuronium bromide and artificially ventilated.2. The inhibitory action of dopamine was confirmed. The inhibition following intra-arterial bolus injection was blocked by haloperidol; dopamine then excited and this excitation was blocked with propranolol. Adrenaline or noradrenaline caused a transient inhibition followed by a marked excitation. The inhibition was blocked with haloperidol and the excitation blocked with propranolol or metoprolol. Isoprenaline excited without inhibition and this was blocked with propranolol or metoprolol.3. A novel finding was that the chemoreceptor response to hypoxia was markedly reduced or even abolished with propranolol or metoprolol. The response was enhanced with a constant infusion of isoprenaline, adrenaline or noradrenaline in proportion to the degree of hypoxia, an effect mimicked by raising CO(2). The chemoreceptor response to hypoxia was similarly enhanced by haloperidol and depressed by a constant infusion of dopamine in proportion to the degree of hypoxia.4. The effect of these drugs on the chemoreceptor response to hypercapnia was less constant. In the majority of tests the aminergic agonists and antagonists caused a parallel shift of the CO(2) response curves in the same direction as the O(2) response curves and by amounts proportional to the degree of hypoxia. In some tests these drugs caused a change in the slope of the CO(2) response curves but only if P(a, O2) was less than 60 mmHg.5. One interpretation of these results is that hypoxia exerts a presynaptic action, causing the release of noradrenaline and dopamine from Type I cells, and that these substances act upon aminergic receptors on the sensory fibre, causing a change in potential and

  8. A revisit to O2 sensing and transduction in the carotid body chemoreceptors in the context of reactive oxygen species biology.

    PubMed

    Gonzalez, C; Agapito, M T; Rocher, A; Gomez-Niño, A; Rigual, R; Castañeda, J; Conde, S V; Obeso, A

    2010-12-31

    Oxygen-sensing and transduction in purposeful responses in cells and organisms is of great physiological and medical interest. All animals, including humans, encounter in their lifespan many situations in which oxygen availability might be insufficient, whether acutely or chronically, physiologically or pathologically. Therefore to trace at the molecular level the sequence of events or steps connecting the oxygen deficit with the cell responses is of interest in itself as an achievement of science. In addition, it is also of great medical interest as such knowledge might facilitate the therapeutical approach to patients and to design strategies to minimize hypoxic damage. In our article we define the concepts of sensors and transducers, the steps of the hypoxic transduction cascade in the carotid body chemoreceptor cells and also discuss current models of oxygen- sensing (bioenergetic, biosynthetic and conformational) with their supportive and unsupportive data from updated literature. We envision oxygen-sensing in carotid body chemoreceptor cells as a process initiated at the level of plasma membrane and performed by a hemoprotein, which might be NOX4 or a hemoprotein not yet chemically identified. Upon oxygen-desaturation, the sensor would experience conformational changes allosterically transmitted to oxygen regulated K+ channels, the initial effectors in the transduction cascade. A decrease in their opening probability would produce cell depolarization, activation of voltage dependent calcium channels and release of neurotransmitters. Neurotransmitters would activate the nerve endings of the carotid body sensory nerve to convey the information of the hypoxic situation to the central nervous system that would command ventilation to fight hypoxia.

  9. Association of retinopathy and intima media thickness of common carotid artery in type 2 diabetic patients

    PubMed Central

    Momeni, Ali; Dyani, Mohamad Ali; Ebrahimi, Elnaz; Sedehi, Morteza; Naderi, Afsaneh

    2015-01-01

    Background: This study was carried out in order to evaluate the relationship between retinopathy and carotid intima-media thickness (CIMT). Materials and Methods: In a cross-sectional study, 154 diabetic patients who had a history of diabetic disease were evaluated in two equal groups of 77 patients with and without retinopathy, respectively. CIMT was evaluated in all of the patients. Results: Mean age of the patients was 59.65 ± 9.37 years. Mean CIMT of all patients was 0.84 ± 0.18. CIMT of patients with retinopathy was significantly greater than patients without retinopathy (P < 0.001). CIMT also correlated with age, duration of diabetes, systolic blood pressure, blood urea nitrogen, and serum creatinine. Conclusion: CIMT may be used as a simple, available and noninvasive method for screening of macro and microvascular complication of diabetic patients. PMID:26109997

  10. Bilateral Carotid Artery Injury Response in Side Impact Using a Vessel Model Integrated with a Human Body Model

    PubMed Central

    Danelson, Kerry A.; Gayzik, F. Scott; Yu, Mao M.; Martin, R. Shayn; Duma, Stefan M.; Stitzel, Joel D.

    2009-01-01

    In a far-side crash configuration, the occupant can experience severe excursion from the seat space. Given this challenge, there are research efforts focused on alternate restraints, such as four-point belts. A potential implication of this geometry would be interaction of the belt with the occupant’s neck. This study examines the response of the carotid arteries using a Finite Element Model (FEM) in a far-side crash configuration with a reversed three-point restraint. A FEM of the carotid artery and neck fascia was developed and integrated with the Total Human Model for Safety (THUMS) version 1.44. This model was subjected to four test conditions simulating far-side crashes. Load conditions included a low velocity impact of approximately 4 m/s and a higher velocity impact of approximately 10 m/s. For each velocity, the model was restrained with a belt placed low on the neck and a belt placed higher on the neck. Strain data in each element of the carotid arteries was analyzed. The overall response of the vessel was examined to determine locations of high strain values. Low belt placement resulted in more head excursion, stretching the carotid on the non-struck side. High belt placement resulted in compression of the artery on the struck side due to direct loading of the vessel from the belt. Strain values in the carotid artery elements increased with increasing speed of impact. The lower and higher speed tests with a low belt configuration resulted in a maximum principal strains, at maximal belt engagement, of 0.223 and 0.459, respectively. Corresponding values for the high belt configuration were 0.222 and 0.563. In both belt configurations, the non-struck side vessel stretched more than the struck side vessel; however, the non-struck side vessel experienced higher compressive forces. Strain values measured during the simulations can be compared to a value of 0.31 to intimal failure in previous experimental tests. These results quantitatively illustrate the two

  11. Association between carotid intima-media thickness, buccodental status, and glycemic control in pediatric type 1 diabetes.

    PubMed

    Gómez-Díaz, Rita A; Ramírez-Soriano, Eleazar; Tanus Hajj, Janet; Bautista Cruz, Elia; Jiménez Galicia, Cesar; Villasis-Keever, Miguel Angel; Aguilar-Salinas, Carlos A; Wacher, Niels H

    2012-11-01

    To evaluate the association between carotid intima-media thickness, buccodental status, and glycemic control in patients with type 1 diabetes. Cross-sectional study with consecutive cases attended in an outpatient clinic (n = 69). Medical and clinical dental history, HbA1c, lipid profile, treatment period, and daily insulin dosage were recorded. Sociodemographic data and anthropometrical measurements were obtained by standardized questionnaire. Doppler real-time ultrasound was performed by a single experienced vascular radiologist blinded to the study. Assessment of buccodental status was done by the Maxillofacial Unit of the Pediatrics Hospital, and an oral scrape culture was collected. The mean age was 11.7 ± 3.0 years, with diabetes 5.1 ± 3.3 years. Mean HbA1c was 8.5 ± 1.7%. Primary teeth were present in 52.2% and bacterial plaque in 94.2%. Buccodental conditions featured caries (63.8%), gingivitis (84%), and enamel demineralization (26.1%): white spot lesions (18.8%) and cavitated lesions (7.3%). Bacteria associated with caries were found in 44.1%. Patients in the highest HbA1c tertile (>8.5%) had greater frequency of buccodental conditions and were positive for Streptococcus mutans and Candida albicans; also, cIMT increased and vessel compliance decreased compared to those in the lowest tertile (<7.0%) (p < 0.05). More buccodental conditions and carotid intima-media thickness increase appeared in the patients with HbA1c level > 8.5%, suggesting onset of atherosclerosis. The correlation between buccodental status and HbA1c values may indicate the connection between inflammatory states of atherosclerosis and type 1 diabetes. © 2012 John Wiley & Sons A/S.

  12. Serum endogenous secretory RAGE level is an independent risk factor for the progression of carotid atherosclerosis in type 1 diabetes.

    PubMed

    Katakami, Naoto; Matsuhisa, Munehide; Kaneto, Hideaki; Matsuoka, Taka-aki; Sakamoto, Ken'ya; Yasuda, Tetsuyuki; Umayahara, Yutaka; Kosugi, Keisuke; Yamasaki, Yoshimitsu

    2009-05-01

    Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) system plays an important role in the development of atherosclerosis. It has been recently reported that endogenous secretory RAGE (esRAGE) and total soluble RAGE (sRAGE) levels are associated with diabetic complications. The aim of the present study is to longitudinally evaluate the association between esRAGE and sRAGE levels and the progression of carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis. Japanese type 1 diabetic patients (n=47, aged 24.0+/-3.1 years) were enrolled into a 4-year follow-up study and annual measurements of serum esRAGE and sRAGE levels and IMTs were performed. At baseline, mean-IMT was inversely correlated with circulating esRAGE levels (r=-0.317, p=0.0292), whereas there was not statistical significance between mean-IMT and sRAGE levels. Mean-IMT significantly increased during the follow-up period (from 0.63+/-0.10 to 0.67+/-0.10mm, p=0.0022). Annual increase in mean-IMT (=(mean-IMT after 4 years-mean-IMT at baseline)/4) was positively correlated with the arithmetic average of systolic blood pressure (r=0.310, p=0.0332) and triglyceride (r=0.337, p=0.0201), and inversely correlated with circulating esRAGE levels (r=-0.360, p=0.0124) and sRAGE levels (r=-0.406, p=0.0042) during the follow-up period. Furthermore, stepwise multivariate regression analyses revealed that continuous low levels of circulating esRAGE and sRAGE were determinants of the progression of mean-IMT independently of conventional risk factors. Circulating esRAGE level as well as sRAGE level was an independent risk factor for the progression of carotid IMT in type 1 diabetic subjects.

  13. Effects of the removal of extracellular Ca2+ on [Ca2+]i responses to FCCP and acetate in carotid body glomus cells of adult rabbits.

    PubMed

    Sato, M

    1997-09-12

    The effects of the removal of extracellular Ca2+ on the responses of cytosolic concentrations of Ca2+ ([Ca2+]i) to acidic stimuli, a protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and an organic acid acetate, were examined in clusters of cultured carotid body glomus cells of adult rabbits using fura-2 microfluorometry. Application of FCCP (1 microM) induced an increase in [Ca2+]i (mean +/- S.E.M., 108 +/- 14%). After withdrawal of the protonophore the increased [Ca2+]i returned slowly to a resting level. The [Ca2+]i response was attenuated by an inorganic Ca2+ channel antagonist Ni2+ (2 mM) by 81 +/- 4%, and by an L-type voltage-gated Ca2+ channel antagonist D600 (10 microM) by 53 +/- 13%. The removal of extracellular Ca2+ eliminated the [Ca2+]i response in 71% of the tested cells (n = 17), and depressed it by 68 +/- 6% in the rest. Recovery following stimulation with FCCP in the absence of Ca2+ reversibly produced a rapid and large rise in [Ca2+]i, referred to as a [Ca2+]i rise after Ca2+-free/FCCP. The magnitude of a [Ca2+]i rise after Ca2+-free/FCCP (285 +/- 28%, P < 0.05) was larger than that of an increase in [Ca2+]i induced by FCCP in the presence of Ca2+ and had a correlation with the intensity of the suppression of the [Ca2+]i response by Ca2+ removal. A [Ca2+]i rise after Ca2+-free/FCCP was inhibited mostly by D600. Similarly, recovery following exposure to acetate in the absence of Ca2+ caused a rise in [Ca2+]i, referred to as a [Ca2+]i rise after Ca2+-free/acetate which was sensitive to D600. The magnitude of the [Ca2+]i rise was larger than that of a change in [Ca2+]i caused by acetate in the presence of Ca2+. These results suggest that FCCP-induced increase in [Ca2+]i was, in most cells, due to Ca2+ influx via L-type voltage-gated Ca2+ channels and, in some cells, due to both Ca2+ influx and Ca2+ release from internal Ca2+ pool. The removal of extracellular Ca2+ might modify [Ca2+]i responses to acidic stimuli, causing [Ca2+]i

  14. Nuclear magnetic resonance lipoprotein abnormalities in newly-diagnosed type 2 diabetes and their association with preclinical carotid atherosclerosis.

    PubMed

    Amor, Antonio J; Catalan, Marta; Pérez, Antonio; Herreras, Zoe; Pinyol, Montserrat; Sala-Vila, Aleix; Cofán, Montserrat; Gilabert, Rosa; Ros, Emilio; Ortega, Emilio

    2016-04-01

    Atherogenic dyslipidemia is common in type 2 diabetes (T2DM) and predicts cardiovascular disease, but information on the association of its components with atherosclerosis is scarce. We aimed to assess differences in the lipoprotein profile in newly-diagnosed T2DM and matched control individuals and their associations with preclinical carotid atherosclerosis. In a case-control study, we evaluated lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy and determined carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) by B-mode ultrasonography. We assessed 96 T2DM patients (median age 63 years, 44% women, 19% smokers, 54% hypertension, 38% dyslipidemia) and 90 non-diabetic controls matched for age, sex, and cardiovascular risk factors. In T2DM VLDL-particles (mainly large and enriched in cholesterol and triglycerides) were increased, and large HDL-particles (enriched in triglycerides and depleted in cholesterol) were reduced (p < 0.05; all comparisons). Regarding associations with preclinical atherosclerosis, VLDL triglyceride content (odds ratio [OR], 8.975; 95% confidence interval [CI], 2.330-34.576), total number of VLDL particles (OR, 2.713; CI, 1.601-4.598) and VLDL size (OR, 2.044; CI, 1.320-3.166), and the ratio cholesterol/triglycerides in HDL (OR, 0.638; CI, 0.477-0.852) were associated with plaque burden (≥3 plaques) independently of confounders, including conventional lipid levels. NMR-assessed advanced lipoprotein profile identifies lipid abnormalities associated with newly-diagnosed T2DM and preclinical atherosclerosis that are not captured by the traditional lipid profile. At this early stage of diabetes, NMR lipoproteins could be useful to identify candidates for a more comprehensive cardiovascular risk prevention strategy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Comparison of Flow Impairment during Carotid Artery Stenting Using Two Types of Eccentric Filter Embolic Protection Devices

    PubMed Central

    NII, Kouhei; TSUTSUMI, Masanori; MAEDA, Hitoshi; AIKAWA, Hiroshi; INOUE, Ritsuro; ETO, Ayumu; SAKAMOTO, Kimiya; MITSUTAKE, Takafumi; HANADA, Hayatsura; KAZEKAWA, Kiyoshi

    2016-01-01

    We investigated the angiographic findings and the clinical outcomes after carotid artery stenting (CAS) using two different, eccentric filter embolic protection devices (EPDs). Between July 2010 and August 2015, 175 CAS procedures were performed using a self-expandable closed-cell stent and a simple eccentric filter EPD (FilterWire EZ in 86 and Spider FX in 89 procedures). The angiographic findings (i.e., flow impairment and vasospasm) at the level of EPDs, neurologic events, and post-operative imaging results were compared between the FilterWire EZ and the Spider FX groups. The CAS was angiographically successful in all 175 procedures. However, the angiographs were obtained immediately after CAS-detected flow impairment in the distal internal carotid artery (ICA) in 11 (6.3%) and ICA spasms at the level of the EPD in 40 cases (22.9%). The incidence of these complications was higher with FilterWire EZ than Spider FX (ICA flow impairment of 10.5% vs. 2.2%, P = 0.03; vasospasm 30.2% vs. 15.7%, P = 0.03). There were nine neurologic events (5.1%); five patients were presented with transient ischemic attacks, three had minor strokes, and one had a major stroke. New MRI lesions were seen in 25 (29.1%) FilterWire-group and in 36 (40.4%) Spider-group patients. The neurologic events and new MRI lesions were not associated with the type of EPD used. Although the ICA flow impairment may result in neurologic events, there was no significant association between the FilterWire EZ and the Spider FX CAS with respect to the incidence of neurologic events by the prompt treatment such as catheter aspiration. PMID:27319302

  16. Acetate enhances the chemosensory response to hypoxia in the cat carotid body in vitro in the absence of CO2-HCO3-.

    PubMed

    Iturriaga, R

    1996-01-01

    To determine if intracellular acidosis enhances hypoxic chemoreception in the absence of CO2-HCO3- at pH 7.4, the effects of sodium acetate (30 mM) were studied on the chemosensory responses of the cat carotid body to hypoxic, stagnant and cytotoxic hypoxia. Carotid bodies were perfused and superfused in vitro with Tyrode's solution, free of CO2-HCO3-, buffered with HEPES-NaOH, pH 7.40, at 36.5 +/d- 0.5 degrees C and equilibrated at PO2 of 125 Torr (perfusate) and < 20 Torr (superfusate). In the absence of acetate, hypoxia (PO2 25 Torr), flow interruption and NaCN (0.01-100 micrograms) augmented the chemosensory discharges. However, in the presence of acetate, the half-excitation time of these responses decreased and their amplitude increased. Thus, acetate enhances the chemosensory response to hypoxic, stagnant and cytotoxic hypoxia. It is suggested that that intracellular acidosis induced by acetate contributes to this potentiation by correcting the alkaline pHi caused by the absence of HCO3-(-)HCO2 in the perfusate.

  17. Effects of modulators of AMP-activated protein kinase on TASK-1/3 and intracellular Ca2+ concentration in rat carotid body glomus cells

    PubMed Central

    Kim, Donghee; Kang1,2, Dawon; Martin, Elizabeth A.; Kim, Insook; Carroll, John L.

    2014-01-01

    Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca2+ concentration ([Ca2+]i). Recent studies suggest that AMP-activated protein kinase (AMPK) mediates these effects of hypoxia by inhibiting the background K+ channels such as TASK. Here we studied the effects of modulators of AMPK on TASK activity in cell-attached patches. Activators of AMPK (1 mM AICAR and 0.1–0.5 mM A769662) did not inhibit TASK activity or cause depolarization during acute (10 min) or prolonged (2–3 hr) exposure. Hypoxia inhibited TASK activity by ~70% in cells pretreated with AICAR or A769662. Both AICAR and A769662 (15–40 min) failed to increase [Ca2+]i in glomus cells. Compound C (40 µM), an inhibitor of AMPK, showed no effect on hypoxia-induced inhibition of TASK. AICAR and A769662 phosphorylated AMPKα in PC12 cells, and Compound C blocked the phosphorylation. Our results suggest that AMPK does not affect TASK activity and is not involved in hypoxia-induced elevation of intracellular [Ca2+] in isolated rat carotid body glomus cells. PMID:24530802

  18. Carotid duplex

    MedlinePlus

    ... moved around your neck. The pressure should not cause any pain. You may also hear a "whooshing" sound. This is normal. ... clotting (thrombosis) Narrowing in the arteries (stenosis) Other ... an abnormal sound called a bruit over the carotid neck arteries. ...

  19. Carotid Endarterectomy

    MedlinePlus

    ... is not a cure. Your arteries can become blocked again if your underlying condition, such as high ... or cut, on your neck to expose the blocked section of the carotid artery. Your surgeon will ...

  20. Carotid Artery Screening

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Carotid Artery Screening What is carotid artery screening? Who should ... information about carotid artery screening? What is carotid artery screening? Screening examinations are tests performed to find ...

  1. Multiple strokes and bilateral carotid dissections: a fulminant case of newly diagnosed Ehlers-Danlos syndrome type IV.

    PubMed

    Dohle, C; Baehring, J M

    2012-07-15

    Ehlers-Danlos Syndrome is a rare group of inheritable disorders resulting in abnormal collagen production, leading to skin fragility, joint hypermobility and easy bruising. Six major subtypes have been identified, of which Type IV most often leads to neurovascular complications, may lead to inner organ rupture and overall has the worst prognosis. Early recognition followed by genetic testing is key, since this diagnosis will guide decision making in the management of complications, influence the choice of antiplatelet medications versus anticoagulants and allow for potentially affected family members to be identified, undergo genetic testing and reproductive counseling. We here report the case of a 50 year old woman with a fulminant presentation of Ehlers Danlos Syndrome Type IV, including bilateral carotid and vertebral artery dissection, multiple strokes and liver rupture. Of note, this patient did not have a known history or obvious clinical features of connective tissue disease. Genetic testing confirmed the diagnosis. Review of her family history revealed multiple family members with a history of aortic dissection or aneurysm rupture. This case illustrates that Ehlers Danlos Syndrome Type IV is an important differential diagnosis even in adult patients without a known history of connective tissue disease and no prior complications.

  2. [Syncope and carotid paraganglioma].

    PubMed

    Bizueto-Rosas, Héctor; Salazar-Reyes, Anabel; Moran-Reyes, Ely Guadalupe; González-Arcos, Gregorio; Hernández-Pérez, Noemí A; Solorio-Rosette, Hugo F; Soto-Hernández, Gabriel

    2014-01-01

    Syncope is a medical emergency, which is more or less frequent. Its prevalence increases with age. It is defined as the loss of consciousness and postural tone resulting from a transient alteration of cerebral flow. It appears suddenly, but it does not leave behind any sequela or after-effects. Out of two groups, the neutrally mediated (or neuromediated) syncope, especially the one called carotid sinus hypersensitivity, is related to the carotid sinus paraganglioma. It is triggered by sinus pressure, which results in sudden death by overstimulation. In the next article, we show the case of a sexagenarian female patient with a disabling syncope and a 7 cm carotid body paraganglioma, which did not allow her the minimum movement of lateral dorsiflexion or extension of the neck. For this reason, the patient had to remain hospitalized, in a dorsal decubitus position with semiflexion of the neck. Before the surgery was practiced, a temporary pacemaker was used, and after the resection of the carotid body paraganglioma, in accordance to the patient's studies of cardiac electrophysiology, she was discharged without electrical nerve stimulation.

  3. Clinical and dietary predictors of common carotid artery intima media thickness in a population with type 1 and type 2 diabetes: A cross-sectional study

    PubMed Central

    Petersen, Kristina S; Keogh, Jennifer B; Meikle, Peter J; Garg, Manohar L; Clifton, Peter M

    2017-01-01

    AIM To determine the clinical and dietary predictors of common carotid artery intima media thickness (CCA IMT) in a cohort of subjects with type 1 and type 2 diabetes. METHODS Participants with type 1 (n = 23) and type 2 diabetes (n = 127) had mean and mean maximum CCA IMT measured using B mode ultrasound. Dietary intake was measured using a food frequency questionnaire. Clinical and dietary predictors of mean and mean maximum CCA IMT were determined using linear regression analysis adjusted for potential confounders. RESULTS The main predictors of mean and mean maximum CCA IMT were age and weight. After multivariate adjustment there were no dietary predictors of CCA IMT. However, in subjects that were not prescribed a lipid lowering medication alcohol consumption was positively associated with CCA IMT after multivariate adjustment. No difference existed in CCA IMT between subjects with type 1 or type 2 diabetes once age was adjusted for. CONCLUSION CCA IMT was predominantly predicted by age and weight in these subjects with diabetes. The finding that CCA IMT was not different between people with type 1 and type 2 diabetes warrants further investigation in a larger cohort. PMID:28138361

  4. The association of carotid intima media thickness with retinol binding protein-4 and total and high molecular weight adiponectin in type 2 diabetic patients.

    PubMed

    Mansouri, Masoumeh; Heshmat, Ramin; Tabatabaei-Malazy, Ozra; Sharifi, Farshad; Badamchizadeh, Zohreh; Alatab, Sudabeh; Omidfar, Kobra; Fakhrzadeh, Hossein; Larijani, Bagher

    2012-08-02

    The aim of this study was to investigate whether carotid intima media thickness (CIMT) is associated with serum level of retinol- binding protein-4 (RBP4) and total and high molecular weight (HMW) adiponectin in type 2 diabetes (T2DM) without clinical symptom of atherosclerotic disease. 101 type 2 diabetic patients (mean age, 53.63 ± 8.42 years) and 42 body mass index (BMI) matched control (mean age 50.1 ± 8.4) were recruited. The CIMT was assessed by using B-mode ultrasonography, while serum levels of RBP4 and total and HMW adiponectin were measured by using enzyme linked immunosorbant assay (ELISA). Linear regression analysis was performed with CIMT as dependent variable and adipokines and cardio metabolic risk factors as independent variables. The CIMT was higher in diabetic group compared to control group (p <0.05). The mean concentration of RBP4 and total and HMW adiponectin did not differ between two groups.Age (B = 0.44 P <0.05), blood pressure (B = 0.37 P = <0.05), waist circumference (B = -0.21 P <0.05) and TG (B = 0.1 P <0.05) were identified as independent predictors for CIMT in diabetic group, while RBP4 and adiponectin were not associated with CIMT neither in diabetic group nor in control group. In conclusion, the present study showed that serum levels of RBP4 or total and HMW adiponectin were not potential predictors of CIMT in type 2 diabetic patients who exposed to this risk factor at least for nine years.

  5. Microsurgical anatomy of the human carotid body (glomus caroticum): Features of its detailed topography, syntopy and morphology.

    PubMed

    Schulz, Sissy-Amelie; Wöhler, Aliona; Beutner, Dirk; Angelov, Doychin N

    2016-03-01

    The human glomus caroticum (GC) is not readily accessible during ordinary anatomical teaching courses because of insufficient time and difficulties encountered in the preparation. Accordingly, most anatomical descriptions of its location, relationship to neighboring structures, size and shape are supported only by drawings, but not by photographs. The aim of this study is to present the GC with all associated roots and branches. Following microscope-assisted dissection and precise photo-documentation, a detailed analysis of location, syntopy and morphology was performed. We carried out this study on 46 bifurcations of the common carotid artery (CCA) into the external (ECA) and internal (ICA) carotid arteries and identified the GC in 40 (91%) of them. We found significant variations regarding the location of the GC and its syntopy: GC was associated with CCA (42%), ECA (28%) and ICA (30%) lying on the medial or lateral surface (82% or 13%, respectively) or exactly in the middle (5%) of the bifurcation. The short and long diameter of its oval form varied from 1.0 × 2.0 to 5.0 × 5.0mm. Connections with the sympathetic trunk (100%), glossopharyngeal (93%), vagus (79%) and hypoglossal nerve (90%) could be established in 29 cadavers. We conclude that precise knowledge of this enormous variety might be very helpful not only to students in medicine and dentistry during anatomical dissection courses, but also to surgeons working in this field. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide.

    PubMed

    Centeno, José M; Marrachelli, Vannina G; Miranda, Luis; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Miranda, Francisco J; Alborch, Enrique

    2013-02-15

    The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabetic than in control rabbits. Endothelium removal did not modify the relaxation to BNP in control rabbits but increased this relaxation in diabetic rabbits. In control rabbits, indomethacin inhibited the BNP-induced relaxation in the presence and in the absence of endothelium. In diabetic rabbits, indomethacin did not modify the BNP-induced relaxation in arteries with endothelium and inhibited it in arteries without endothelium. In the presence of BNP the carotid artery released thromboxane A2 and prostacyclin, and the release of endothelial prostacyclin was inhibited in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to BNP, and these inhibitions were lower in diabetic than in control rabbits. In conclusion, our results provide a new understanding concerning the mechanisms of the diabetes-induced hyporeactivity of the carotid artery to BNP, that at least include the loss of endothelial prostacyclin and a reduced participation of ATP-sensitive K(+) channels (KATP) and voltage-sensitive K(+) channels (KV). Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Impaired systolic blood dipping and nocturnal hypertension: an independent predictor of carotid intima-media thickness in type 1 diabetic patients.

    PubMed

    Atabek, Mehmet Emre; Akyürek, Nesibe; Eklioglu, Beray Selver; Alp, Hayrullah

    2014-01-01

    Type 1 diabetes in children predicts a broad range of later health problems including an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate whether nocturnal hypertension and impaired nocturnal dipping affect atherosclerosis in children and adolescents with type 1 diabetes and to investigate the relationship between atherogenic risk factors and carotid intima-media thickness (CIMT). One hundred fifty-nine type 1 diabetic patients and 100 healthy controls were included in the study. We investigated metabolic and anthropometric parameters such as body mass index (BMI), waist circumference, fasting glucose and insulin, serum lipids, 24h ambulatory blood pressure monitoring (ABPM), and CIMT and compared these with those in control subjects (CS). No difference was found between type 1 diabetic patients and CS in age, weight, waist/hip ratio, triglyceride, HDL-cholesterol level. However in children with type 1 diabetes, total cholesterol (p=0.016),and LDL-cholesterol (p=0.002) levels and CIMT (P<0.001) were greater than those of controls. It was determined that 10% of type 1 diabetic patients had dyslipidemia. In 23.2% of type 1 diabetic patients, ABPM showed arterial hypertension. CIMT was significantly higher in the hypertensive group than in the non-hypertensive group (P=0.003). Twenty-three (14.4%) diabetic patients had nocturnal hypertension. CIMT was significantly greater in the nocturnal hypertensive group (p=0.023). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) dipping was significantly different in diabetic patients (P<0.001). CIMT was correlated positively with Hba1c (r=0.220, p=0.037), and negatively with SBP dipping (r=-0.362, p=0.020) in the diabetic patients. In stepwise regression analysis, Hba1c and SBP dipping emerged as a significant predictor of CIMT (β=0.300, p=0.044, β=0.398 p=0.009) contributing to 15.58% of its variability. These results provide additional evidence for the presence of

  8. Carotid-femoral pulse wave velocity is associated with N-terminal pro-B-type natriuretic peptide level in patients with atrial fibrillation.

    PubMed

    Chen, Lin Y; Tai, Bee C; Foo, David C; Wong, Raymond C; Adabag, A Selcuk; Benditt, David G; Ling, Lieng H

    2011-01-01

    To determine the extent to which conduit artery stiffness is associated with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF). Cross-sectional study. National University Hospital, Singapore. Cases (n=117) were patients with AF onset <65 years of age without heart failure or structural heart disease. Controls (n=274) were patients without AF who were seen at the general cardiology clinic. Transthoracic echocardiography, carotid-femoral pulse wave velocity (CFPWV) measured using applanation tonometry and blood draw for plasma NT-proBNP at enrolment for all patients. Plasma NT-proBNP. In patients with AF, CFPWV was associated with NT-proBNP after adjusting for hypertension and factors that were univariately associated with NT-proBNP: age at enrolment, type of AF, body mass index, left ventricular mass index, left atrial volume index, mitral E/E', mitral deceleration time and use of β-blockers (β=0.234; 95% CI 0.100 to 0.367; p=0.001). In contrast, CFPWV was not associated with NT-proBNP in controls. In patients with AF, the adjusted mean NT-proBNP level in the highest quartile of CFPWV (350 pg/ml; 95% CI 237 to 517 pg/ml) was fivefold higher than the lowest quartile (69 pg/ml; 95% CI 47 to 103 pg/ml) (p=0.001). CFPWV is associated with NT-proBNP level in AF. Since elevated NT-proBNP is a marker of adverse cardiovascular outcomes, arterial stiffness may be associated with worse prognosis in patients with AF.

  9. The influence of acute hypoxia and carotid body denervation on thermoregulation during non-rapid eye movement sleep in the developing lamb.

    PubMed

    Symonds, M E; Andrews, D C; Johnson, P

    1999-11-01

    We investigated the influence of ambient temperature on the thermoregulatory response to hypoxia in developing lambs before (at 4 and 14 days of age) and after (17 and 30 days of age) carotid body denervation (CBD). Lambs were studied during non-rapid eye movement sleep at thermoneutral (23-15 C) and cool (10-5 C) ambient temperatures, during normoxia and acute hypoxia (inspired oxygen content of 13 %). Measurements of oxygen consumption, arterial partial pressures of O2 and CO2, colonic temperature, incidence of shivering and plasma concentrations of thyroid hormones, cortisol, insulin and glucose were made under each condition. Oxygen consumption was higher at cool compared with thermoneutral ambient temperatures and decreased during hypoxia during cooling at all stages. At 4 days of age, only one lamb shivered during cooling in normoxia, but 4 out of 12 lambs shivered during hypoxia and colonic temperature fell, significantly, by 0.2 C. At 14 days, 8 out of 12 lambs shivered during cooling, of which 6 continued to shiver during hypoxia but colonic temperature did not change significantly. Plasma triiodothyronine concentrations increased on cooling at 4 and 14 days, an affect that was inhibited by hypoxia at 4, but not 14 days of age. At 17 days of age, i.e. post-CBD, plasma thyroid hormone concentrations and oxygen consumption were lower during cold exposure compared with intact lambs at 14 days of age. In CBD lambs, imposing further hypoxia resulted in colonic temperature falling 0. 6 C during cooling, with only 2 out of 10 lambs shivering. Plasma glucose and insulin, but not cortisol, concentrations decreased during hypoxia, irrespective of age or CBD. It is concluded that hypoxia has an important influence on metabolism and thermoregulation, which is modulated by age and environmental conditions. Compromised carotid body function, in lambs older than 2 weeks of age, can result in severe hypoxia and thermoregulatory dysfunction even with modest environmental

  10. Effects of active and passive smoking on the development of cardiovascular disease as assessed by a carotid intima-media thickness examination in patients with type 2 diabetes mellitus.

    PubMed

    Jiang, Fei; Wang, Jie; Zhang, Rong; Chen, Miao; Peng, Danfeng; Sun, Xue; Yan, Jing; Luo, Yi; Tang, Shanshan; Hu, Cheng; Jia, Weiping

    2015-05-01

    Carotid intima-media thickness has been widely used as a surrogate end-point for cardiovascular disease, myocardial infarction, and stroke. This study aimed to assess the effects of active and passive smoking exposure on the development of cardiovascular disease in patients with type 2 diabetes mellitus. Seven hundred twenty-two patients with type 2 diabetes mellitus were recruited for the study. A standardized questionnaire on smoking status, pack-years of smoking, and the number of years of smoking cessation was provided to the patients, and their responses were collected for analysis. The carotid intima-media thickness, carotid plaque, and the internal diameter of the common carotid artery were determined by high-resolution B-mode ultrasonography. Compared to non-smokers, passive female smokers had a higher risk of cardiovascular disease (odds ratio = 3.50, 95% confidence interval: 1.29-9.49, P = 0.009); they also had a significantly larger common carotid artery (P = 0.041) and risk of carotid plaque (odds ratio = 2.20, 95% confidence interval: 1.1980-4.0505, P = 0.01). Both active and passive male smokers had a significantly greater carotid intima-media thickness than non-smokers (P = 0.003 and P = 0.005, respectively). Male active smokers had a significantly higher risk of carotid plaque (odds ratio = 2.88, 95% confidence interval: 1.4788-5.6094, P = 0.001). In conclusion, cumulative active and passive smoking exposures are significant risk factors for carotid atherosclerosis in patients with type 2 diabetes mellitus. Our results highlight the importance of endorsing a smoke-free environment for patients with type 2 diabetes mellitus.

  11. Relation of Epicardial Fat Thickness with Carotid Intima-Media Thickness in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Cetin, Mustafa; Cakici, Musa; Polat, Mustafa; Suner, Arif; Zencir, Cemil; Ardic, Idris

    2013-01-01

    Aims. The aim of this study was to investigate the relationship of echocardiographic epicardial fat thickness (EFT) with carotid intima-media thickness (CIMT), in patients with type 2 diabetes mellitus (T2DM). Methods and Results. A total of 139 patients with T2DM (mean age 54.3 ± 9.2 and 49.6% male) and 40 age and sex-matched control subjects were evaluated. Echocardiographic EFT and ultrasonographic CIMT were measured in all subjects. Patients with T2DM had significantly increased EFT and CIMT than those of the controls (6.0 ± 1.5 mm versus 4.42 ± 1.0 mm, P < 0.001 and 0.76 ± 0.17 mm versus 0.57 ± 0.14 mm, P < 0.001, resp.). EFT was correlated with CIMT, waist circumference, BMI, age, duration of T2DM, HbA1c in the type 2 diabetic patients. Linear regression analysis showed that CIMT (β = 3.52, t = 3.72, P < 0.001) and waist circumference (β = 0.36, t = 2.26, P = 0.03) were found to be independent predictors of EFT. A cutoff high risk EFT value of 6.3 mm showed a sensitivity and specificity of 72.5% and 71.7%, respectively, for the prediction of subclinical atherosclerosis. Conclusion. We found that echocardiographic EFT was significantly higher in patients with T2DM. Our study also showed that EFT was strongly correlated with waist circumference and CIMT as being independent of sex. PMID:23762053

  12. Relation of epicardial fat thickness with carotid intima-media thickness in patients with type 2 diabetes mellitus.

    PubMed

    Cetin, Mustafa; Cakici, Musa; Polat, Mustafa; Suner, Arif; Zencir, Cemil; Ardic, Idris

    2013-01-01

    Aims. The aim of this study was to investigate the relationship of echocardiographic epicardial fat thickness (EFT) with carotid intima-media thickness (CIMT), in patients with type 2 diabetes mellitus (T2DM). Methods and Results. A total of 139 patients with T2DM (mean age 54.3 ± 9.2 and 49.6% male) and 40 age and sex-matched control subjects were evaluated. Echocardiographic EFT and ultrasonographic CIMT were measured in all subjects. Patients with T2DM had significantly increased EFT and CIMT than those of the controls (6.0 ± 1.5 mm versus 4.42 ± 1.0 mm, P < 0.001 and 0.76 ± 0.17 mm versus 0.57 ± 0.14 mm, P < 0.001, resp.). EFT was correlated with CIMT, waist circumference, BMI, age, duration of T2DM, HbA1c in the type 2 diabetic patients. Linear regression analysis showed that CIMT (β = 3.52, t = 3.72, P < 0.001) and waist circumference (β = 0.36, t = 2.26, P = 0.03) were found to be independent predictors of EFT. A cutoff high risk EFT value of 6.3 mm showed a sensitivity and specificity of 72.5% and 71.7%, respectively, for the prediction of subclinical atherosclerosis. Conclusion. We found that echocardiographic EFT was significantly higher in patients with T2DM. Our study also showed that EFT was strongly correlated with waist circumference and CIMT as being independent of sex.

  13. Importance of plasma N-terminal pro B-type natriuretic peptide, epicardial adipose tissue, and carotid intima-media thicknesses in asymptomatic obese children.

    PubMed

    Saritas, Turkay; Tascilar, Emre; Abaci, Ayhan; Yozgat, Yilmaz; Dogan, Mustafa; Dundaroz, Ruşen; Hasimi, Adnan; Yesilkaya, Ediz; Lenk, M Koray; Kilic, Ayhan

    2010-08-01

    This study aimed to analyze the variations of N-terminal pro B-type natriuretic peptide, epicardial adipose tissue thickness, and carotid intima-media thickness in childhood obesity. The study participants consisted of 50 obese children in the study group and 20 nonobese children referred for evaluation of murmurs who proved to have an innocent murmur and were used as control subjects. All the subjects underwent transthoracic echocardiographic examination for determination of left ventricular systolic function and mass index, myocardial tissue rates, and myocardial performance index. Epicardial adipose tissue thickness and carotid intima-media thickness also were measured during echocardiography. Serum N-terminal pro B-type natriuretic peptide levels were measured at the time of evaluation. The left ventricle mass index was 40.21 + or - 10.42 g/m(2) in the obese group and 34.44 + or - 4.51 g/m(2) in the control group (p > 0.05). The serum N-terminal pro B-type natriuretic peptide level was 109.25 + or - 48.53 pg/ml in the study group and 51.96 + or - 22.36 pg/ml and in the control group (p = 0.001). The epicardial adipose tissue thickness was 5.57 + or - 1.45 mm in the study group and 2.98 + or - 0.41 mm in the control group (p = 0.001), and the respective carotid intima-media thicknesses were 0.079 + or - 0.019 cm and 0.049 + or - 0.012 cm (p = 0.001). The left ventricular systolic and diastolic functions showed no statistically significant correlations with N-terminal pro B-type natriuretic peptide levels, carotid intima-media thickness, or epicardial adipose tissue thickness values. The results show that measurement of serum N-terminal pro B-type natriuretic peptide level, carotid intima-media thickness, and epicardial adipose tissue thickness in asymptomatic obese children is not needed.

  14. Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects.

    PubMed

    Niskanen, L; Karvonen, M K; Valve, R; Koulu, M; Pesonen, U; Mercuri, M; Rauramaa, R; Töyry, J; Laakso, M; Uusitupa, M I

    2000-06-01

    We have recently demonstrated that subjects having Pro7 in the signal peptide ofneuropeptide Y (NPY) have higher serum cholesterol and apolipoprotein B levels than individuals with wild-type (Leu7Leu7) signal peptide sequence. We investigated the association of Leu7Pro polymorphism with common carotid intima media thickness (IMT) assessed by ultrasonograph in patients with type 2 diabetes (n = 81; 41 men and 40 women; mean age, 67.1 yr) and nondiabetic subjects (n = 105; 48 men and 57 women; mean age, 65.5 yr) and genotyped for the Leu7Pro polymorphism in prepro-NPY. The frequency of Pro7 in prepro-NPY was 9.9% (8 of 81) in diabetic patients and 14.3% (15 of 105) in control subjects (P = 0.360). The mean common carotid IMT was 1.04 +/- 0.02 mm in nondiabetic subjects without the Leu7Pro polymorphism and 1.14 +/- 0.04 mm in nondiabetic subjects with in (P = 0.156) and 1:18 +/- 0.03 and 1.58 +/- 0.21mm in diabetic patients without and with the Leu7Pro polymorphism (P = 0.004), respectively. In the analysis of covariance of the entire group, the mean common carotid IMT was independently associated with the Leu7Pro polymorphism (F = 5.165; P = 0.024) after adjustment for known risk factors. Thus, the presence of the Pro7 substitution in the prepro-NPY associates with increased carotid atherosclerosis.

  15. Carotid-Femoral Pulse Wave Velocity Is Associated With Cerebral White Matter Lesions in Type 2 Diabetes

    PubMed Central

    Laugesen, Esben; Høyem, Pernille; Stausbøl-Grøn, Brian; Mikkelsen, Anders; Thrysøe, Samuel; Erlandsen, Mogens; Christiansen, Jens S.; Knudsen, Søren T.; Hansen, Klavs W.; Kim, Won Y.; Hansen, Troels K.; Poulsen, Per L.

    2013-01-01

    OBJECTIVE Patients with type 2 diabetes have a high incidence of cardiovascular events including stroke. Increased arterial stiffness (AS) predicts cardiovascular events in the general population. Cerebral white matter lesions (WMLs) are associated with an increased risk of stroke. It is unknown whether AS in patients with type 2 diabetes is associated with WMLs. RESEARCH DESIGN AND METHODS We examined 89 patients recently diagnosed with type 2 diabetes (<5 years) and 89 sex- and age-matched controls. AS was assessed with carotid-femoral pulse wave velocity (PWV). WMLs were identified using magnetic resonance imaging and graded qualitatively with the Breteler scale (no/slight changes = 0, moderate changes = 1, severe changes = 2) and semiquantitatively. RESULTS The diabetic population had excellent glycemic control (HbA1c, 6.5% [6.2–6.8]; median [interquartile range {IQR}]) and had, compared with the controls, lower office blood pressure (BP) (127 ± 12/79 ± 8 vs. 132 ± 14/84 ± 10 mmHg) and total cholesterol (4.3[3.9–4.7] vs. 5.6 [5.1–6.4]; mmol/L; median [IQR]), (P < 0.01 for all). Despite this, PWV was higher in the patients with diabetes compared with controls (9.3 ± 2.0 vs. 8.0 ± 1.6 m/s; P < 0.0001). PWV was associated with Breteler score (OR 1.36 [95% CI 1.17–1.58]; P < 0.001) and WML volume (OR 1.32 [95% CI 1.16–1.51]; P < 0.001) per 1 m/s increase in PWV. These associations remained significant when adjusted for age, sex, diabetes, 24-h mean arterial BP, BMI, heart rate, and use of antihypertensives and statins (Breteler score: OR 1.28 [95% CI 1.03–1.60]; P < 0.05 and WML volume: OR 1.30 [95% CI 1.06–1.58]; P < 0.05). CONCLUSIONS PWV was higher among patients with well-controlled type 2 diabetes compared with controls and was independently associated with WMLs. PWV may represent a clinically relevant parameter in the evaluation of cerebrovascular disease risk in type 2 diabetes. PMID:23129135

  16. Early Diagnosis and Treatment of Coronary Heart Disease in Symptomatic Subjects With Advanced Vascular Atherosclerosis of the Carotid Artery (Type III and IV b Findings Using Ultrasound)

    PubMed Central

    Adams, Ansgar; Bojara, Waldemar; Schunk, Klaus

    2017-01-01

    Background A study was conducted as to whether the early diagnosis of coronary heart disease (CHD) in symptomatic patients with advanced atherosclerosis of the carotid artery was more successful using ultrasound technology than exercise electrocardiography (ECG). Methods Within the scope of an occupational screening program using subjects from diverse employment sectors, people were given the opportunity to determine their risk of heart attack. During the study, the total plaque area (TPA), the maximum plaque thickness in the carotid artery and the PROCAM scores of 3,513 healthy men and 2,088 healthy women between the ages of 20 and 65 were determined. During the subsequent follow-up study, 36 subjects developed symptoms such as exertional dyspnea, atypical angina pectoris (AP) or typical AP. Four patients displayed no symptoms. The initial cardiac diagnostic testing was conducted on 31 patients using an exercise ECG, four patients were assessed using a coronary angiogram, and five further patients were assessed using a computed tomography (CT) coronary angiogram. An ultrasound examination of the carotid artery of 39 patients revealed a type IV b finding and in one patient, the examination revealed a type III finding. Results In 17 patients, the PROCAM score was < 10%, 13 patients had a score of 10-20% and 10 patients had a score of > 20%. In the final analysis, only two patients had entirely smooth coronary arteries, seven had coronary sclerosis, seven had a 30% stenosis, one had a 30-40% stenosis, one had a 40% stenosis, and 22 patients had a stenosis ≥ 50%, and in extreme cases, a left main coronary artery stenosis with three-vessel disease was shown. The exercise ECG only achieved a true positive result in four patients, and in 21 patients, the result was false negative. Conclusions Symptomatic patients with advanced atherosclerosis of the carotid artery (type III and type IV b findings) had a high risk for CHD. The diagnosis of CHD is better achieved by

  17. Functional abolition of carotid body activity restores insulin action and glucose homeostasis in rats: key roles for visceral adipose tissue and the liver.

    PubMed

    Sacramento, Joana F; Ribeiro, Maria J; Rodrigues, Tiago; Olea, Elena; Melo, Bernardete F; Guarino, Maria P; Fonseca-Pinto, Rui; Ferreira, Cristiana R; Coelho, Joana; Obeso, Ana; Seiça, Raquel; Matafome, Paulo; Conde, Sílvia V

    2017-01-01

    We recently described that carotid body (CB) over-activation is involved in the aetiology of insulin resistance and arterial hypertension in animal models of the metabolic syndrome. Additionally, we have demonstrated that CB activity is increased in animal models of insulin resistance, and that carotid sinus nerve (CSN) resection prevents the development of insulin resistance and arterial hypertension induced by high-energy diets. Here, we tested whether the functional abolition of CB by CSN transection would reverse pre-established insulin resistance, dyslipidaemia, obesity, autonomic dysfunction and hypertension in animal models of the metabolic syndrome. The effect of CSN resection on insulin signalling pathways and tissue-specific glucose uptake was evaluated in skeletal muscle, adipose tissue and liver. Experiments were performed in male Wistar rats submitted to two high-energy diets: a high-fat diet, representing a model of insulin resistance, hypertension and obesity, and a high-sucrose diet, representing a lean model of insulin resistance and hypertension. Half of each group was submitted to chronic bilateral resection of the CSN. Age-matched control rats were also used. CSN resection normalised systemic sympathetic nervous system activity and reversed weight gain induced by high-energy diets. It also normalised plasma glucose and insulin levels, insulin sensitivity lipid profile, arterial pressure and endothelial function by improving glucose uptake by the liver and perienteric adipose tissue. We concluded that functional abolition of CB activity restores insulin sensitivity and glucose homeostasis by positively affecting insulin signalling pathways in visceral adipose tissue and liver.

  18. Reciprocal photolabile O2 consumption and chemoreceptor excitation by carbon monoxide in the cat carotid body: evidence for cytochrome a3 as the primary O2 sensor.

    PubMed

    Lahiri, S; Buerk, D G; Chugh, D; Osanai, S; Mokashi, A

    1995-07-03

    High carbon monoxide (CO) gas tensions (> 500 Torr) at normoxic PO2 (125-140 Torr) stimulates carotid chemosensory discharge in the perfused carotid body (CB) in the absence but not in the presence of light. According to a metabolic hypothesis of O2 chemoreception, the increased chemosensory discharge should correspond to a photoreversible decrease of O2 consumption, unlike a non-respiratory hypothesis. We tested the respiratory vs. non-respiratory hypotheses of O2 chemoreception in the cat CB by measuring the effect of high CO. Experiments were conducted using CBs perfused and superfused in vitro with high CO in normoxic, normocapnic cell-free CO2-HCO3- buffer solution at 37 degrees C. Simultaneous measurements of the rate of O2 disappearance with recessed PO2 microelectrodes and chemosensory discharge were made after flow interruption with and without CO in the perfusate. The control O2 disappearance rate without CO was -3.66 +/- 0.43 (S.E.) Torr/s (100 measurements in 12 cat CBs). In the dark, high CO reduced the O2 disappearance rate to -2.35 +/- 0.33 Torr/s, or 64.2 +/- 9.0% of control (P < 0.005, 34 measurements). High CO was excitatory in the dark, with an increase in baseline neural discharge from 129.2 +/- 47.0 to 399.3 +/- 49.1 impulses per s (P < 0.0001), and maximum discharge rate of 659 +/- 76 impulses/s (N.S. compared to control) during flow interruption. During perfusion with high CO in the light, there were no significant differences in baseline neural discharge or in the maximum neural discharge after flow interruption, and little effect on O2 metabolism (88.8 +/- 11.5% of control, N.S., 29 measurements).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Association of the ACE rs4646994 and rs4341 polymorphisms with the progression of carotid atherosclerosis in slovenian patients with type 2 diabetes mellitus

    PubMed Central

    Merlo, S; Novák, J; Tkáčová, N; Nikolajević Starčević, J; Šantl Letonja, M; Makuc, J; Cokan Vujkovac, A; Letonja, J; Bregar, D; Zorc, M; Rojko, M; Mankoč, S; Kruzliak, P

    2015-01-01

    Abstract The current study was designed to reveal possible associations between the angiotensin-converting-enzyme (ACE) gene polymorphisms (rs4646994 and rs4341) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) in a 4-year-long follow-up study. Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. Genotyping of ACE polymorphisms was performed using KASPar assays, and ultrasound examinations were performed twice (at the enrollment and at follow-up). With regard to the progression of atherosclerosis in subjects with T2DM, statistically significant differences were demonstrated in the change of the sum of carotid plaques thickness for the rs4646994 polymorphism. We did not demonstrate an association between the tested polymorphisms (rs4646994 and rs4341) and either carotid intima media thickness (CIMT) or CIMT progression in a 3.8-year period. In our study, we demonstrated that subjects with T2DM with the DD genotype of the rs4646994 [ACE insertion/deletion (I/D)] polymorphism had faster progression of atherosclerosis in comparison to subjects with other genotypes. PMID:27785395

  20. Carotid femoral pulse wave velocity in type 2 diabetes and hypertension: capturing arterial health effects of step counts

    PubMed Central

    Dasgupta, Kaberi; Rosenberg, Ellen; Joseph, Lawrence; Trudeau, Luc; Garfield, Natasha; Chan, Deborah; Sherman, Mark; Rabasa-Lhoret, Rémi; Daskalopoulou, Stella S.

    2017-01-01

    Objective: Optimal medication use obscures the impact of physical activity on traditional cardiometabolic risk factors. We evaluated the relationship between step counts and carotid-femoral pulse wave velocity (cfPWV), a summative risk indicator, in patients with type 2 diabetes and/or hypertension. Research design and methods: Three hundred and sixty-nine participants were recruited (outpatient clinics; Montreal, Quebec; 2011–2015). Physical activity (pedometer/accelerometer), cfPWV (applanation tonometry), and risk factors (A1C, Homeostatic Model Assessment–Insulin Resistance, blood pressure, lipid profiles) were evaluated. Linear regression models were constructed to quantify the relationship of steps/day with cfPWV. Results: The study population comprised 191 patients with type 2 diabetes and hypertension, 39 with type 2 diabetes, and 139 with hypertension (mean ± SD: age 59.6 ± 11.2 years; BMI 31.3 ± 4.8 kg/m2; 54.2% women). Blood pressure (125/77 ± 15/9 mmHg), A1C (diabetes: 7.7 ± 1.3%; 61 mmol/mol), and low-density lipoprotein cholesterol (diabetes: 2.19 ± 0.8 mmol/l; without diabetes: 3.13 ± 1.1mmol/l) were close to target. Participants averaged 5125 ± 2722 steps/day. Mean cfPWV was 9.8 ± 2.2 m/s. Steps correlated with cfPWV, but not with other risk factors. A 1000 steps/day increment was associated with a 0.1 m/s cfPWV decrement across adjusted models and in subgroup analysis by diabetes status. In a model adjusted for age, sex, BMI, ethnicity, immigrant status, employment, education, diabetes, hypertension, medication classes, the mean cfPWV decrement was 0.11 m/s (95% confidence interval −0.2, −0.02). Conclusions: cfPWV is responsive to step counts in patients who are well controlled on cardioprotective medications. This ability to capture the ‘added value’ of physical activity supports the emerging role of cfPWV in arterial health monitoring. PMID:28129250

  1. Ultrasonic Measurement of Common Carotid Intima-Media Thickness in Type 2 Diabetic and Non-Diabetic Patients

    PubMed Central

    Alizadeh, Ahmad; Roudbari, Ali; Heidarzadeh, Abtin; Babaei Jandaghi, Ali; Bani Jamali, Maryam

    2012-01-01

    Background Diabetes mellitus is a widespread disease. Its vascular complications can be characterized by arteriosclerosis formation in carotid arteries. Due to its delayed diagnosis resulting in more complications in Iran, it seems that screening diabetic patients is mandatory. Objectives The aim of this study was to compare the intima-media thickness (IMT) of carotid artery in diabetic and non-diabetic patients. Patients and Methods This is a cross-sectional study, which included 80 participants (40 diabetics and 40 non-diabetics). By using ultrasound, bilateral IMTs of the distal carotid were measured and the data were analyzed using ANOVA and multivariate regression tests in SPSS 14. Results The mean IMT was 0.97 in diabetic patients and 0.63 in non-diabetics (P < 0.001). Age and gender had significant positive effects on the increase of IMT (P < 0.05 and P < 0.005, respectively for age and gender). Past medical history of coronary heart disease (CHD) and cerebrovascular accident (CVA) in diabetes is associated significantly with an increase in IMT (P =0.019 and 0.027 respectively). Other confounding variables such as smoking, history of hypertension (HTN) and hyperlipoproteinemia (HLP) in diabetic patients showed no significant relationship with the increase of IMT. Conclusions Although measuring the IMT of the carotid artery by sonography is a useful tool for screening diabetic patients, more studies are needed for determining how to use these measurements in promoting the patients outcomes. PMID:23329968

  2. The Mitochondrial SDHD Gene Is Required for Early Embryogenesis, and Its Partial Deficiency Results in Persistent Carotid Body Glomus Cell Activation with Full Responsiveness to Hypoxia

    PubMed Central

    Piruat, José I.; Pintado, C. Oscar; Ortega-Sáenz, Patricia; Roche, Marta; López-Barneo, José

    2004-01-01

    The SDHD gene encodes one of the two membrane-anchoring proteins of the succinate dehydrogenase (complex II) of the mitochondrial electron transport chain. This gene has recently been proposed to be involved in oxygen sensing because mutations that cause loss of its function produce hereditary familiar paraganglioma, a tumor of the carotid body (CB), the main arterial chemoreceptor that senses oxygen levels in the blood. Here, we report the generation of a SDHD knockout mouse, which to our knowledge is the first mammalian model lacking a protein of the electron transport chain. Homozygous SDHD−/− animals die at early embryonic stages. Heterozygous SDHD+/− mice show a general, noncompensated deficiency of succinate dehydrogenase activity without alterations in body weight or major physiological dysfunction. The responsiveness to hypoxia of CBs from SDHD+/− mice remains intact, although the loss of an SDHD allele results in abnormal enhancement of resting CB activity due to a decrease of K+ conductance and persistent Ca2+ influx into glomus cells. This CB overactivity is linked to a subtle glomus cell hypertrophy and hyperplasia. These observations indicate that constitutive activation of SDHD+/− glomus cells precedes CB tumor transformation. They also suggest that, contrary to previous beliefs, mitochondrial complex II is not directly involved in CB oxygen sensing. PMID:15572694

  3. Association between HbA1c and carotid atherosclerosis among elderly Koreans with normal fasting glucose

    PubMed Central

    Lee, Seung Won; Kim, Hyeon Chang; Lee, Yong-ho; Song, Bo Mi; Choi, Hansol; Park, Ji Hye; Rhee, Yumie; Kim, Chang Oh

    2017-01-01

    Aim We examined whether glycated haemoglobin (HbA1c) is associated to carotid atherosclerosis in an elderly Korean population with normal fasting glucose. Methods Using data from the Korean Urban Rural Elderly study, we conducted a cross-sectional analysis of 1,133 participants (335 men and 798 women) with a mean age of 71.8 years. All participants had fasting blood glucose less than 100mg/dL (5.6 mmol/L) and HbA1c level below 6.5% (48 mmol/mol). They were also free from a history of cardiovascular disease, known type 2 diabetes mellitus or use of anti-diabetes medications. Carotid atherosclerosis was assessed by intima-media thickness (IMT) using ultrasonography. The association between HbA1c and carotid IMT was investigated using multivariable linear regression analysis. Results HbA1c levels were independently and positively associated with carotid IMT (β = 0.020, p = 0.045) after adjusting for sex, age, body mass index, systolic blood pressure, diastolic blood pressure, triglyceride, LDL cholesterol, smoking and alcohol intake. However, fasting insulin and glucose levels were not associated with carotid IMT. Conclusion HbA1c levels were positively associated with carotid atherosclerosis, as assessed by carotid IMT, in an elderly population with normoglycemia. Our study suggested that higher HbA1c level is an effective and informative marker of carotid atherosclerosis in an elderly population. PMID:28178313

  4. Carotid bypass for carotid occlusion.

    PubMed

    Hage, Ziad A; Behbahani, Mandana; Amin-Hanjani, Sepideh; Charbel, Fady T

    2015-07-01

    The 2-year risk of ipsilateral ischemic stroke following internal carotid artery occlusion (ICAO) in a patient undergoing maximal medical therapy is 5-8% per year. While medical therapy may reduce the risk of stroke, it does not completely eliminate it. Since the 1985 extracranial-intracranial (EC-IC) bypass study, additional trials have been conducted to further investigate the usefulness of EC-IC bypass surgery in more selected patients with cerebral ischemia and impaired hemodynamic reserve. These important studies will be briefly reviewed in this article, as well as a discussion regarding the utility of bypass surgery for ICAO in current clinical practice. In addition, a short discussion regarding the pathophysiology of carotid occlusion will be presented. We will also highlight our own institutional patient selection criteria based on the latest methods for hemodynamic assessment, as well as our intraoperative flow assisted surgical techniques (FAST), and post-operative patient follow-up.

  5. CT angiography ofthe carotid arteries.

    PubMed

    Prokop, M; Waaijer, A; Kreuzer, S

    2004-01-01

    The introduction of multislice scanning has made CT angiography (CTA) a serious competitor to MR angiography (MRA) as a second line method for the evaluation of the carotid arteries. For optimum display of the morphology of stenoses, it is necessary to apply the thinnest possible section collimation (ideally [symbol: see text] 1.25mm). While the scan range is limited for single slice CTA, it is possible to cover the whole supraaortic circulation from the aortic arch to the intracranial vessels using multislice scanning. Timing of contrast injection is important, however, the injection technique for carotid CTA is more forgiving than for other body regions. Image evaluation is mainly based on axial sections and curved planar reformations (CPR). Other techniques only serve as an adjunct to better be able to demonstrate the findings. Most potential pitfalls can be avoided by using the appropriate technique. CTA has been shown to have a pooled sensitivity of 95% and specificity of 98% for the detection of >70% stenoses, even if only older single-slice techniques are used. Differentiation between lipid, fibrous and calcified plaques may be possible, especially with multislice scanning. Multislice CTA can in addition detect tandem stenoses in the region of the carotid origin from the aorta, the carotid siphon, and the intracranial portion of the carotids. CT is able to provide a comprehensive evaluation of patients with acute stroke by using a combined approach of pre-contrast CT to detect hemorrhage and manifest infarction, CT brain perfusion measurements to differentiate between penumbra and infarct and CTA to detect the occluded vessel as well as potential concomitant carotid abnormalities. In summary, carotid CTA has come of age and can be used to quantify stenoses more precisely than ultrasound, to detect tandem stenoses and for the workup of acute stroke patients. The learning objectives include learning how to chose acquisition parameters for carotid CTA, how to

  6. Carotid artery stenting versus carotid endarterectomy.

    PubMed

    Nanna, Michael G; Gomes, Paulina; Njoh, Roland F; Ward, Charisse; Attaran, Robert R; Mena, Carlos

    2016-09-01

    Stroke remains a significant contributor to morbidity and mortality in developed countries. Carotid artery stenosis is a major cause of stroke. Advances in medical therapy, surgical technique and endovascular maturation has resulted in options for the treatment of carotid stenosis. Here, we present a review of carotid artery stenting and carotid endarterectomy as it applies to trials comparing and contrasting the two treatment options. We also explore the intricacies surrounding reimbursement of these treatment strategies in the USA.

  7. Modulation of junctional conductance between rat carotid body glomus cells by hypoxia, cAMP and acidity.

    PubMed

    Abudara, V; Eyzaguirre, C

    1998-05-04

    Short-term cultures of glomus cells (up to seven days), were employed to study intercellular electrical communications. Bidirectional electric coupling was established under current clamping after impaling two adjacent glomus cells with microelectrodes, and alternate stimulation and recording. Their resting potential (Vm) and input resistance (Ro) were thus measured. Both coupled cells were then voltage clamped at a level between their Vms. Current pulses applied to either cell elicited a transjunctional voltage (Vj) and current (Ij), used to calculate the junctional conductance (Gj). Gj was 1.52+/-0.29 nS (mean+/-S.E.; n=147). Vj linearly influenced Gj, suggesting ohmic junctions. Gj was not affected by Vm in 50% of the cases. However, there was Vm-dependence in the others, but voltage changes had to be large (>+/-40 mV from the Vm). Therefore, physiologically or pharmacologically induced glomus cell depolarization or hyperpolarization may not significantly affect intercellular coupling unless there are large variations in Vm. Hypoxia (induced by Na2S2O4 1 mM or 100% N2) decreased Gj in 60-80% of the pairs while producing tighter coupling in the rest. Similar effects were obtained when the medium was acidified with lactic acid 1-10 mM. Cobalt chloride (3 mM) prevented, diminished or reversed the changes in Gj observed during low PO2, suggesting that [Ca2+]i changes are important in hypoxic uncoupling. However, non-specific cationic effects of Co2+ have not been ruled out. Applications of the membrane-permeant dB-cAMP 1 mM tightened coupling in almost all cell pairs. This is important because endogenous cAMP increases during hypoxia. Our results suggest that multiple factors modulate junctional conductance between glomus cells. Changes in Gj by 'natural' stimuli and/or cAMP may play an important role in chemoreception, especially in titrating the release of transmitters toward the carotid nerve terminals. Copyright 1998 Elsevier Science B.V.

  8. Gene Expression Profiling Supports the Neural Crest Origin of Adult Rodent Carotid Body Stem Cells and Identifies CD10 as a Marker for Mesectoderm-Committed Progenitors.

    PubMed

    Navarro-Guerrero, Elena; Platero-Luengo, Aida; Linares-Clemente, Pedro; Cases, Ildefonso; López-Barneo, José; Pardal, Ricardo

    2016-06-01

    Neural stem cells (NSCs) are promising tools for understanding nervous system plasticity and repair, but their use is hampered by the lack of markers suitable for their prospective isolation and characterization. The carotid body (CB) contains a population of peripheral NSCs, which support organ growth during acclimatization to hypoxia. We have set up CB neurosphere (NS) cultures enriched in differentiated neuronal (glomus) cells versus undifferentiated progenitors to investigate molecular hallmarks of cell classes within the CB stem cell (CBSC) niche. Microarray gene expression analysis in NS is compatible with CBSCs being neural crest derived-multipotent progenitor cells able to sustain CB growth upon exposure to hypoxia. Moreover, we have identified CD10 as a marker suitable for isolation of a population of CB mesectoderm-committed progenitor cells. CD10 + cells are resting in normoxia, and during hypoxia they are activated to proliferate and to eventually complete maturation into mesectodermal cells, thus participating in the angiogenesis necessary for CB growth. Our results shed light into the molecular and cellular mechanisms involved in CBSC fate choice, favoring a potential use of these cells for cell therapy. Stem Cells 2016;34:1637-1650. © 2016 AlphaMed Press.

  9. Carotid artery anatomy (image)

    MedlinePlus

    There are four carotid arteries, two on each side of the neck: right and left internal carotid arteries, and right and left external carotid arteries. The carotid arteries deliver oxygen-rich blood from the heart to the head and brain.

  10. Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats.

    PubMed

    Moreira, Josimar D; Pernomian, Larissa; Gomes, Mayara S; Moreira, Rafael P; do Prado, Alejandro F; da Silva, Carlos H T P; de Oliveira, Ana M

    2016-07-15

    Diabetes mellitus is associated with reactive oxygen and nitrogen species accumulation. Behavioral stress increases nitric oxide production, which may trigger a massive impact on vascular cells and accelerate cardiovascular complications under oxidative stress conditions such as Diabetes. For this study, type-1 Diabetes mellitus was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration-response curves for angiotensin II were obtained in endothelium-intact carotid rings from diabetic rats that underwent to acute restraint stress for 3h. The contractile response evoked by angiotensin II was increased in carotid arteries from diabetic rats. Acute restraint stress did not alter angiotensin II-induced contraction in carotid arteries from normoglycaemic rats. However acute stress combined with Diabetes increased angiotensin II-induced contraction in carotid rings. Western blot experiments and the inhibition of nitric oxide synthases in functional assays showed that neuronal, endothelial and inducible nitric oxide synthase isoforms contribute to the increased formation of peroxynitrite and contractile hyperreactivity to angiotensin II in carotid rings from stressed diabetic rats. In summary, these findings suggest that the increased superoxide anion generation in carotid arteries from diabetic rats associated to the increased local nitric oxide synthases expression and activity induced by acute restrain stress were responsible for exacerbating the local formation of peroxynitrite and the contraction induced by angiotensin II. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Spatial Distribution of Small Water Body Types across Indiana Ecoregions

    EPA Science Inventory

    Due to their large numbers and biogeochemical activity, small water bodies (SWB), such as ponds and wetlands, can have substantial cumulative effects on hydrologic, biogeochemical, and biological processes; yet the spatial distributions of various SWB types are often unknown. Usi...

  12. Spatial Distribution of Small Water Body Types across Indiana Ecoregions

    EPA Science Inventory

    Due to their large numbers and biogeochemical activity, small water bodies (SWB), such as ponds and wetlands, can have substantial cumulative effects on hydrologic, biogeochemical, and biological processes; yet the spatial distributions of various SWB types are often unknown. Usi...

  13. Impact of carotid atherosclerosis detection on physician and patient behavior in the management of type 2 diabetes mellitus: a prospective, observational, multicenter study.

    PubMed

    Jeong, In-Kyung; Kim, Sin-Gon; Cho, Dong Hyeok; Kim, Chong Hwa; Kim, Chul Sik; Lee, Won-Young; Won, Kyu-Chang; Kim, Doo-Man

    2016-11-14

    This study compared carotid ultrasound (CUS) and traditional risk calculations in determining cardiovascular disease (CVD) risk in patients with type 2 diabetes mellitus (DM) and investigated whether awareness of CVD affects patient and/or physician behavior. In this prospective, observational, multicenter study, 797 participants with type 2 diabetes were assessed using CUS, the United Kingdom Prospective Diabetes Study Risk Engine (UKPDSRE) calculator, and the Framingham Risk Score (FRS) algorithm. Health-related behaviors and physician treatments were compared at baseline and at 6 months after assessment. According to CUS, 43.5 % of the participants were at high risk (compared to 10.6 % and 4.3 % using the UKPDSRE and FRS approaches, respectively). Interestingly, 31.5 % of the patients with low risk scores according to the UKPDSRE calculator and 35.8 % of the patients with low risk scores according to the FRS algorithm were found to be at high risk according to CUS. The proportion of patients who achieved target LDL-C levels significantly increased after CUS. Moreover, increased awareness of atherosclerosis through CUS findings significantly altered physician treatment patterns and patient health-related behaviors. Carotid atherosclerosis was detected in more than 30 % of all participants with low or intermediate risk stratification scores. Improved awareness of atherosclerosis through CUS findings had a positive impact on both patient and physician behavior, resulting in improved CV risk management.

  14. Ultrasound analysis of gray-scale median value of carotid plaques is a useful reference index for cerebro-cardiovascular events in patients with type 2 diabetes

    PubMed Central

    Ariyoshi, Kyoko; Okuya, Shigeru; Kunitsugu, Ichiro; Matsunaga, Kimie; Nagao, Yuko; Nomiyama, Ryuta; Takeda, Komei; Tanizawa, Yukio

    2015-01-01

    Aims/Introduction Measurements of plaque echogenicity, the gray-scale median (GSM), were shown to correlate inversely with risk factors for cerebro-cardiovascular disease (CVD). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is a potential predictor of CVD risk. In the present study, we assessed the usefulness of carotid plaque GSM values and EPA/AA ratios in atherosclerotic diabetics. Materials and Methods A total of 84 type 2 diabetics with carotid artery plaques were enrolled. On admission, platelet aggregation and lipid profiles, including EPA and AA, were examined. Using ultrasound, mean intima media thickness and plaque score were measured in carotid arteries. Plaque echogenicity was evaluated using computer-assisted quantification of GSM. The patients were then further observed for approximately 3 years. Results Gray-scale median was found to be a good marker of CVD events. On multivariate logistic regression analysis, GSM <32 and plaque score ≥5 were significantly associated with past history and onset of CVD during the follow-up period, the odds ratios being 7.730 (P = 0.014) and 4.601 (P = 0.046), respectively. EPA/AA showed a significant correlation with GSM (P = 0.012) and high-density lipoprotein cholesterol (P = 0.039), and an inverse correlation with platelet aggregation (P = 0.046) and triglyceride (P = 0.020). Although most patients with CVD had both low GSM and low EPA/AA values, an association of EPA/AA with CVD events could not be statistically confirmed. Conclusions The present results suggest the GSM value to be useful as a reference index for CVD events in high-risk atherosclerotic diabetics. Associations of the EPA/AA ratio with known CVD risk factors warrant a larger and more extensive study to show the usefulness of this parameter. PMID:25621138

  15. Ultrasound analysis of gray-scale median value of carotid plaques is a useful reference index for cerebro-cardiovascular events in patients with type 2 diabetes.

    PubMed

    Ariyoshi, Kyoko; Okuya, Shigeru; Kunitsugu, Ichiro; Matsunaga, Kimie; Nagao, Yuko; Nomiyama, Ryuta; Takeda, Komei; Tanizawa, Yukio

    2015-01-01

    Measurements of plaque echogenicity, the gray-scale median (GSM), were shown to correlate inversely with risk factors for cerebro-cardiovascular disease (CVD). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is a potential predictor of CVD risk. In the present study, we assessed the usefulness of carotid plaque GSM values and EPA/AA ratios in atherosclerotic diabetics. A total of 84 type 2 diabetics with carotid artery plaques were enrolled. On admission, platelet aggregation and lipid profiles, including EPA and AA, were examined. Using ultrasound, mean intima media thickness and plaque score were measured in carotid arteries. Plaque echogenicity was evaluated using computer-assisted quantification of GSM. The patients were then further observed for approximately 3 years. Gray-scale median was found to be a good marker of CVD events. On multivariate logistic regression analysis, GSM <32 and plaque score ≥5 were significantly associated with past history and onset of CVD during the follow-up period, the odds ratios being 7.730 (P = 0.014) and 4.601 (P = 0.046), respectively. EPA/AA showed a significant correlation with GSM (P = 0.012) and high-density lipoprotein cholesterol (P = 0.039), and an inverse correlation with platelet aggregation (P = 0.046) and triglyceride (P = 0.020). Although most patients with CVD had both low GSM and low EPA/AA values, an association of EPA/AA with CVD events could not be statistically confirmed. The present results suggest the GSM value to be useful as a reference index for CVD events in high-risk atherosclerotic diabetics. Associations of the EPA/AA ratio with known CVD risk factors warrant a larger and more extensive study to show the usefulness of this parameter.

  16. Carotid artery stenting: current and emerging options

    PubMed Central

    Morr, Simon; Lin, Ning; Siddiqui, Adnan H

    2014-01-01

    Carotid artery stenting technologies are rapidly evolving. Options for endovascular surgeons and interventionists who treat occlusive carotid disease continue to expand. We here present an update and overview of carotid stenting devices. Evidence supporting carotid stenting includes randomized controlled trials that compare endovascular stenting to open surgical endarterectomy. Carotid technologies addressed include the carotid stents themselves as well as adjunct neuroprotective devices. Aspects of stent technology include bare-metal versus covered stents, stent tapering, and free-cell area. Drug-eluting and cutting balloon indications are described. Embolization protection options and new direct carotid access strategies are reviewed. Adjunct technologies, such as intravascular ultrasound imaging and risk stratification algorithms, are discussed. Bare-metal and covered stents provide unique advantages and disadvantages. Stent tapering may allow for a more fitted contour to the caliber decrement between the common carotid and internal carotid arteries but also introduces new technical challenges. Studies regarding free-cell area are conflicting with respect to benefits and associated risk; clinical relevance of associated adverse effects associated with either type is unclear. Embolization protection strategies include distal filter protection and flow reversal. Though flow reversal was initially met with some skepticism, it has gained wider acceptance and may provide the advantage of not crossing the carotid lesion before protection is established. New direct carotid access techniques address difficult anatomy and incorporate sophisticated flow-reversal embolization protection techniques. Carotid stenting is a new and exciting field with rapidly advancing technologies. Embolization protection, low-risk deployment, and lesion assessment and stratification are active areas of research. Ample room remains for further innovations and developments. PMID:25349483

  17. Developmental charts for children with osteogenesis imperfecta, type I (body height, body weight and BMI).

    PubMed

    Graff, Krzysztof; Syczewska, Malgorzata

    2017-03-01

    Osteogenesis imperfecta (OI) is a rare genetic disorder of type I collagen. Type I is the most common, which is called a non-deforming type of OI, as in this condition, there are no major bone deformities. This type is characterised by blue sclera and vertebral fractures, leading to mild scoliosis. The body height of these patients is regarded as normal, or only slightly reduced, but there are no data proving this in the literature. The aim of this study is the preparation of the developmental charts of children with OI type I. The anthropometric data of 117 patients with osteogenesis imperfecta were used in this study (61 boys and 56 girls). All measurements were pooled together into one database (823 measurements in total). To overcome the problem of the limited number of data being available in certain age classes and gender groups, the method called reverse transformation was used. The body height of the youngest children, aged 2 and 3 years, is less than that of their healthy peers. Children between 4 and 7 years old catch up slightly, but at later ages, development slows down, and in adults, the median body height shows an SDS of -2.7. These results show that children with type I OI are smaller from the beginning than their healthy counterparts, their development slows down from 8 years old, and, ultimately, their body height is impaired. What is Known: • The body height of patients with osteogenesis imperfecta type I is regarded as normal, or only slightly reduced, but in the known literature, there is no measurement data supporting this opinion. What is New: • Children with type I osteogenesis imperfecta are smaller from the beginning than their healthy counterparts, their development slows down from 8 years old and, ultimately, their final body height is impaired. • The developmental charts for the body height, body weight and BMI of children with type I osteogenesis imperfecta are shown.

  18. Muscle fibre type composition and body composition in hammer throwers.

    PubMed

    Terzis, Gerasimos; Spengos, Konstantinos; Kavouras, Stavros; Manta, Panagiota; Georgiadis, Giorgos

    2010-01-01

    Aim of the present study was to describe the muscle fibre type composition and body composition of well-trained hammer throwers. Six experienced hammer throwers underwent the following measurements: one repetition maximum in squat, snatch, and clean, standing broad jump, backward overhead shot throw and the hammer throw. Dual x-ray absorptiometry was used for body composition analysis. Fibre type composition and cross sectional area was determined in muscle biopsy samples of the right vastus lateralis. Eight physical education students served as a control group. One repetition maximum in squat, snatch and clean for the hammer throwers was 245 ± 21, 132 ± 13 and 165 ± 12kg, respectively. Lean body mass was higher in hammer throwers (85.9 ± 3. 9kg vs. 62.7 ± 5.1kg (p < 0.01). The percentage area of type II muscle fibres was 66.1 ± 4% in hammer throwers and 51 ± 8% in the control group (p < 0.05). Hammer throwers had significantly larger type IIA fibres (7703 ± 1171 vs. 5676 ± 1270μm(2), p < 0.01). Hammer throwing performance correlated significantly with lean body mass (r = 0.81, p < 0.05). These data indicate that hammer throwers have larger lean body mass and larger muscular areas occupied by type II fibres, compared with relatively untrained subjects. Moreover, it seems that the enlarged muscle mass of the hammer throwers contributes significantly to the hammer throwing performance. Key pointsWell-trained hammer throwers had increased lean body mass, higher type IIA muscle fibres cross sectional areas, as well as higher bone mineral density, compared to controls.Increased lean body mass was closely related with hammer throwing performance.The relative high percentage of type IIX muscle fibres in vastus lateralis in hammer throwers warrants further investigation.

  19. Muscle Fibre Type Composition and Body Composition in Hammer Throwers

    PubMed Central

    Terzis, Gerasimos; Spengos, Konstantinos; Kavouras, Stavros; Manta, Panagiota; Georgiadis, Giorgos

    2010-01-01

    Aim of the present study was to describe the muscle fibre type composition and body composition of well-trained hammer throwers. Six experienced hammer throwers underwent the following measurements: one repetition maximum in squat, snatch, and clean, standing broad jump, backward overhead shot throw and the hammer throw. Dual x-ray absorptiometry was used for body composition analysis. Fibre type composition and cross sectional area was determined in muscle biopsy samples of the right vastus lateralis. Eight physical education students served as a control group. One repetition maximum in squat, snatch and clean for the hammer throwers was 245 ± 21, 132 ± 13 and 165 ± 12kg, respectively. Lean body mass was higher in hammer throwers (85.9 ± 3. 9kg vs. 62.7 ± 5.1kg (p < 0.01). The percentage area of type II muscle fibres was 66.1 ± 4% in hammer throwers and 51 ± 8% in the control group (p < 0.05). Hammer throwers had significantly larger type IIA fibres (7703 ± 1171 vs. 5676 ± 1270μm2, p < 0.01). Hammer throwing performance correlated significantly with lean body mass (r = 0.81, p < 0.05). These data indicate that hammer throwers have larger lean body mass and larger muscular areas occupied by type II fibres, compared with relatively untrained subjects. Moreover, it seems that the enlarged muscle mass of the hammer throwers contributes significantly to the hammer throwing performance. Key points Well-trained hammer throwers had increased lean body mass, higher type IIA muscle fibres cross sectional areas, as well as higher bone mineral density, compared to controls. Increased lean body mass was closely related with hammer throwing performance. The relative high percentage of type IIX muscle fibres in vastus lateralis in hammer throwers warrants further investigation. PMID:24149393

  20. Type-D personality and body image in men: the role of exercise status.

    PubMed

    Borkoles, Erika; Polman, Remco; Levy, Andrew

    2010-01-01

    The 'Distressed' or Type-D personality is described by the interaction between high levels of negative affectivity and social inhibition. This study investigated the prevalence of Type-D personality in men of different exercise status, the association between Type-D and body image perceptions, and the moderating effect of exercise status. Participants were 564 British males aged between 18 and 55 years. Of these 200 were classified as sedentary, 148 as active and 216 as weight trainers. Participants completed the DS14 and Multidimensional Body-Self Relations Questionnaire. Results showed that more individuals were classified as Type-D in the sedentary group (45%) than the two active groups, and in the weight training (24.5%) than the active (14.2%) group. Both Type-D and a sedentary lifestyle were associated with a significantly poorer body image. However, exercise mode was not associated with body image differences. Sedentary Type-D men scored significantly lower in Body Areas Satisfaction and higher in Self-Classified Weight than both active groups. Regular exercise might provide a pathway for Type-D men to develop a more positive body image.

  1. Is plasticity within the retrotrapezoid nucleus responsible for the recovery of the PCO2 set‐point after carotid body denervation in rats?

    PubMed Central

    Basting, Tyler M.; Abe, Chikara; Viar, Kenneth E.; Stornetta, Ruth L.

    2016-01-01

    Key points Arterial PCO2 is kept constant via breathing adjustments elicited, at least partly, by central chemoreceptors (CCRs) and the carotid bodies (CBs).The CBs may be active in a normal oxygen environment because their removal reduces breathing. Thereafter, breathing slowly returns to normal. In the present study, we investigated whether an increase in the activity of CCRs accounts for this return.One week after CB excision, the hypoxic ventilatory reflex was greatly reduced as expected, whereas ventilation and blood gases at rest under normoxia were normal.Optogenetic inhibition of Phox2b‐expressing neurons including the retrotrapezoid nucleus, a cluster of CCRs, reduced breathing proportionally to arterial pH. The hypopnoea was greater after CB excision but only in a normal or hypoxic environment. The difference could be simply explained by the loss of fast feedback from the CBs.We conclude that, in rats, CB denervation may not produce CCR plasticity. We also question whether the transient hypoventilation elicited by CB denervation means that these afferents are active under normoxia. Abstract Carotid body denervation (CBD) causes hypoventilation and increases the arterial PCO2 set‐point; these effects eventually subside. The hypoventilation is attributed to reduced CB afferent activity and the PCO2 set‐point recovery to CNS plasticity. In the present study, we investigated whether the retrotrapezoid nucleus (RTN), a group of non‐catecholaminergic Phox2b‐expressing central respiratory chemoreceptors (CCRs), is the site of such plasticity. We evaluated the contribution of the RTN to breathing frequency (F R), tidal volume (V T) and minute volume (V E) by inhibiting this nucleus optogenetically for 10 s (archaerhodopsinT3.0) in unanaesthetized rats breathing various levels of O2 and/or CO2. The measurements were made in seven rats before and 6–7 days after CBD and were repeated in seven sham‐operated rats. Seven days post‐CBD, blood gases and

  2. Molecular identification and functional role of voltage-gated sodium channels in rat carotid body chemoreceptor cells. Regulation of expression by chronic hypoxia in vivo.

    PubMed

    Caceres, Ana I; Obeso, Ana; Gonzalez, Constancio; Rocher, Asuncion

    2007-07-01

    We have assessed the expression, molecular identification and functional role of Na+ channels (Na(v)) in carotid bodies (CB) obtained from normoxic and chronically hypoxic adult rats. Veratridine evoked release of catecholamines (CA) from an in vitro preparation of intact CBs obtained from normoxic animals, the response being Ca2+ and Na+-dependent and sensitive to tetrodotoxin (TTX). TTX inhibited by 25-50% the CA release response evoked by graded hypoxia. Immunoblot assays demonstrated the presence of Na(v)alpha-subunit (c. 220 kDa) in crude homogenates from rat CBs, being evident an up-regulation (60%) of this protein in the CBs obtained from chronically hypoxic rats (10% O2; 7 days). This up-regulation was accompanied by an enhanced TTX-sensitive release response to veratridine, and by an enhanced ventilatory response to acute hypoxic stimuli. RT-PCR studies demonstrated the expression of mRNA for Na(v)1.1, Na(v)1.2, Na(v)1.3, Na(v)1.6 and Na(v)1.7 isoforms. At least three isoforms, Na(v)1.1, Na(v)1.3 and Na(v)1.6 co-localized with tyrosine hydroxylase in all chemoreceptor cells. RT-PCR and immunocytochemistry indicated that Na(v)1.1 isoform was up-regulated by chronic hypoxia in chemoreceptor cells. We conclude that Na(v) up-regulation represents an adaptive mechanism to increase chemoreceptor sensitivity during acclimatization to sustained hypoxia as evidenced by enhanced ventilatory responses to acute hypoxic tests.

  3. Carotid baroreflex control of heart rate is enhanced, while control of mean arterial pressure is preserved during whole body heat stress in young healthy men.

    PubMed

    Krnjajic, Davor; Allen, Dustin R; Butts, Cory L; Keller, David M

    2016-10-01

    Whole body heat stress (WBH) results in numerous cardiovascular alterations that ultimately reduce orthostatic tolerance. While impaired carotid baroreflex (CBR) function during WBH has been reported as a potential reason for this decrement, study design considerations may limit interpretation of previous findings. We sought to test the hypothesis that CBR function is unaltered during WBH. CBR function was assessed in 10 healthy male subjects (age: 26 ± 3; height: 185 ± 7 cm; weight: 82 ± 10 kg; BMI: 24 ± 3 kg/m(2); means ± SD) using 5-s trials of neck pressure (+45, +30, and +15 Torr) and neck suction (-20, -40, -60, and -80 Torr) during normothermia (NT) and passive WBH (Δ core temp ∼1°C). Analyses of stimulus response curves (four-parameter logistic model) for CBR control of heart rate (CBR-HR) and mean arterial pressure (CBR-MAP), as well as separate two-way ANOVA of the hypotensive and hypertensive stimuli (factor 1: thermal condition, factor 2: chamber pressure), were performed. For CBR-HR, maximal gain was increased during WBH (-0.73 ± 0.11) compared with NT (-0.39 ± 0.04, mean ± SE, P = 0.03). In addition, the CBR-HR responding range was increased during WBH (33 ± 5) compared with NT (19 ± 2 bpm, P = 0.03). Separate analysis of hypertensive stimulation revealed enhanced HR responses during WBH at -40, -60, and -80 Torr (condition × chamber pressure interaction, P = 0.049) compared with NT. For CBR-MAP, both logistic analysis and separate two-way ANOVA revealed no differences during WBH. Therefore, in response to passive WBH, CBR control of heart rate (enhanced) and arterial pressure (no change) is well preserved. Copyright © 2016 the American Physiological Society.

  4. BDNF and AMPA receptors in the cNTS modulate the hyperglycemic reflex after local carotid body NaCN stimulation.

    PubMed

    Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Melnikov, V; Virgen-Ortiz, A; Lemus, M; Pineda-Lemus, M; de Álvarez-Buylla, E

    2017-07-01

    The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation. Copyright © 2017. Published by Elsevier B.V.

  5. Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body

    PubMed Central

    Kang, Dawon; Wang, Jiaju; Hogan, James O; Vennekens, Rudi; Freichel, Marc; White, Carl; Kim, Donghee

    2014-01-01

    The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K+ current and causes cell depolarization, Ca2+ influx via voltage-dependent Ca2+ channels and a rise in intracellular [Ca2+] ([Ca2+]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K+ channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K+, Na+ and Cs+ but not to Cl− or Ca2+. The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca2+ channel with FPL64176 activated the 20 pS channel when 1 mm Ca2+ was present in the external solution. Ca2+ (10 μm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca2+]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be −28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K+ conductance and then activates a Na+-permeable, non-selective cation channel via depolarization-induced rise in [Ca2+]i. Our results suggest that inhibition of K+ efflux and stimulation of Na+ influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia. PMID:24591572

  6. Carotid baroreflex responsiveness in heat-stressed humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.

    2000-01-01

    The effects of whole body heating on human baroreflex function are relatively unknown. The purpose of this project was to identify whether whole body heating reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid-vasomotor and carotid-cardiac baroreflex responsiveness were assessed in normothermia and during whole body heating. Whole body heating increased sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01) and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01), whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2 to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness were assessed by identifying the maximal gain of MAP and heart rate to R wave-triggered changes in carotid sinus transmural pressure. Whole body heating significantly decreased the responsiveness of the carotid-vasomotor baroreflex (from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/- 0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid-cardiac baroreflex curves were shifted downward and upward, respectively, to accommodate the decrease in blood pressure and increase in heart rate that accompanied the heat stress. Moreover, the operating point of the carotid-cardiac baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the functional reserve for the carotid baroreflex to increase heart rate during a hypotensive challenge, may contribute to increased susceptibility to orthostatic intolerance during a heat stress.

  7. Carotid baroreflex responsiveness in heat-stressed humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.

    2000-01-01

    The effects of whole body heating on human baroreflex function are relatively unknown. The purpose of this project was to identify whether whole body heating reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid-vasomotor and carotid-cardiac baroreflex responsiveness were assessed in normothermia and during whole body heating. Whole body heating increased sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01) and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01), whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2 to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness were assessed by identifying the maximal gain of MAP and heart rate to R wave-triggered changes in carotid sinus transmural pressure. Whole body heating significantly decreased the responsiveness of the carotid-vasomotor baroreflex (from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/- 0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid-cardiac baroreflex curves were shifted downward and upward, respectively, to accommodate the decrease in blood pressure and increase in heart rate that accompanied the heat stress. Moreover, the operating point of the carotid-cardiac baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the functional reserve for the carotid baroreflex to increase heart rate during a hypotensive challenge, may contribute to increased susceptibility to orthostatic intolerance during a heat stress.

  8. A collaborative exercise on DNA methylation based body fluid typing.

    PubMed

    Jung, Sang-Eun; Cho, Sohee; Antunes, Joana; Gomes, Iva; Uchimoto, Mari L; Oh, Yu Na; Di Giacomo, Lisa; Schneider, Peter M; Park, Min Sun; van der Meer, Dieudonne; Williams, Graham; McCord, Bruce; Ahn, Hee-Jung; Choi, Dong Ho; Lee, Yang Han; Lee, Soong Deok; Lee, Hwan Young

    2016-10-01

    A collaborative exercise on DNA methylation based body fluid identification was conducted by seven laboratories. For this project, a multiplex methylation SNaPshot reaction composed of seven CpG markers was used for the identification of four body fluids, including blood, saliva, semen, and vaginal fluid. A total of 30 specimens were prepared and distributed to participating laboratories after thorough testing. The required experiments included four increasingly complex tasks: (1) CE of a purified single-base extension reaction product, (2) multiplex PCR and multiplex single-base extension reaction of bisulfite-modified DNA, (3) bisulfite conversion of genomic DNA, and (4) extraction of genomic DNA from body fluid samples. In tasks 2, 3 and 4, one or more mixtures were analyzed, and specimens containing both known and unknown body fluid sources were used. Six of the laboratories generated consistent body fluid typing results for specimens of bisulfite-converted DNA and genomic DNA. One laboratory failed to set up appropriate conditions for capillary analysis of reference single-base extension products. In general, variation in the values obtained for DNA methylation analysis between laboratories increased with the complexity of the required experiments. However, all laboratories concurred on the interpretation of the DNA methylation profiles produced. Although the establishment of interpretational guidelines on DNA methylation based body fluid identification has yet to be performed, this study supports the addition of DNA methylation profiling to forensic body fluid typing. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Cross-sectional associations between dietary intake and carotid intima media thickness in type 2 diabetes: baseline data from a randomised trial

    PubMed Central

    Chiavaroli, Laura; Mirrahimi, Arash; Ireland, Christopher; Mitchell, Sandra; Sahye-Pudaruth, Sandhya; Coveney, Judy; Olowoyeye, Omodele; Patel, Darshna; de Souza, Russell J; Augustin, Livia S A; Bashyam, Balachandran; Pichika, Sathish Chandra; Blanco Mejia, Sonia; Nishi, Stephanie K; Leiter, Lawrence A; Josse, Robert G; McKeown-Eyssen, Gail E; Moody, Alan R; Kendall, Cyril W C; Sievenpiper, John L; Jenkins, David J A

    2017-01-01

    Objective To assess associations between dietary intake and carotid intima media thickness (CIMT) by carotid ultrasound (CUS), a surrogate marker of cardiovascular disease (CVD) risk, in those with type 2 diabetes. Design Cross-sectional analysis of baseline data from 325 participants from three randomised controlled trials collected in the same way. Setting Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Canada. Participants 325 participants with type 2 diabetes, taking oral antidiabetic agents, with an HbA1c between 6.5% and 8.0% at screening, without a recent cardiovascular event. Main outcome measures CIMT by CUS and associations with dietary intake from 7-day food records, as well as anthropometric measures and fasting serum samples. Results CIMT was significantly inversely associated with dietary pulse intake (β=−0.019, p=0.009), available carbohydrate (β=−0.004, p=0.008), glycaemic load (β=−0.001, p=0.007) and starch (β=−0.126, p=0.010), and directly associated with total (β=0.004, p=0.028) and saturated (β=0.012, p=0.006) fat intake in multivariate regression models adjusted for age, smoking, previous CVD event, blood pressure medication, antidiabetic medication and ultrasonographer. Conclusions Lower CIMT was significantly associated with greater consumption of dietary pulses and carbohydrates and lower total and saturated fat intake, suggesting a potential role for diet in CVD risk management in type 2 diabetes. Randomised controlled trials are anticipated to explore these associations further. Trial registration number NCT01063374. PMID:28336747

  10. [Digital subtract arteriographic characteristics of carotid artery, vertebral artery, subclavian artery and renal artery in type 2 diabetic patients with lower extremities peripheral arterial disease].

    PubMed

    Chen, Da-Wei; Lu, Wu-Sheng; Wang, Chun; Jiao, He; Tian, Hao-Ming; Ran, Xing-Wu

    2012-09-01

    To investigate angiographical characteristics of carotid, vertebral, subclavian, and renal arteries in the type 2 diabetic patients with lower extremities peripheral arterial disease (LEPAD). There were 104 type 2 diabetic patients with LEPAD recruited in this study, who received digital subtract arteriography (DSA). Ankle-brachial index (ABI) assessment was also performed in 50 participants. Dependent upon the stenosis degree of vertebral artery, subclavian artery and renal artery measured by DSA, the patients were divided into normal group (stenosis < or = 50%) or pathological group(stenosis > 50% or blocked lesions). The angiographic features of carotid, vertebral, subclavian, and renal arteries were analyzed and the relationship between arterial stenosis and ABI was explored. DSA results of 104 patients showed that the most common lesion in the arteries was plaque. The stenosis degrees of 51%-74% and 75%-99% were most commonly observed in renal artery, with incidence of 22.1% and 5.8%, respectively. Arterial occlusion was most commonly observed in vertebral artery, with incidence of 27.9%. The patients with stenosis or occlusion of arteries had lower ABI (P = 0.000), and the patients with stenosis or occlusion of vertebral and renal arteries also had lower ABI (P = 0.003 and 0.02, respectively), compared with those without stenosis. ABI < 0.9 indicated higher risk of stenosis or occlusion of vertebral and renal arteries (P = 0.008 and 0.047 respectively). Between the patients with subclavian arterial stenosis and those without this artery stenosis, there was no statistical significant difference observed in ABI level. Type 2 diabetic patients with LEPAD can affect multiple arteries, showing plaque formation, multi-segmental stenosis and occlusion of arteries. The patients with ABI < 0.9 have higher risk of multiple arterial stenosis or occlusion lesions.

  11. Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Merlo, Sebastjan; Starčević, Jovana Nikolajević; Mankoč, Sara; Šantl Letonja, Marija; Cokan Vujkovac, Andreja; Zorc, Marjeta; Petrovič, Daniel

    2016-01-01

    Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM. PMID:26881237

  12. Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Merlo, Sebastjan; Starčević, Jovana Nikolajević; Mankoč, Sara; Šantl Letonja, Marija; Cokan Vujkovac, Andreja; Zorc, Marjeta; Petrovič, Daniel

    2016-01-01

    Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.

  13. Carotid Artery Disease

    MedlinePlus

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  14. Carotid artery surgery - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100124.htm Carotid artery surgery - series—Normal anatomy To use the sharing ... out of 4 Overview There are four carotid arteries, with a pair located on each side of ...

  15. Evaluation of body adiposity index as a predictor of aortic stiffness in multi-ethnic Asian population with type 2 diabetes.

    PubMed

    Moh, Mei Chung; Sum, Chee Fang; Lam, Benjamin Chih Chiang; Ng, Xiao Wei; Su, Chang; Tavintharan, Subramaniam; Yeoh, Lee Ying; Wong, Melvin Ding Sheng; Lee, Simon Biing Ming; Tang, Wern Ee; Lim, Su Chi

    2015-03-01

    Cardiovascular disease is the leading cause of morbidity and mortality in type 2 diabetes mellitus. We evaluated the predictive ability of the recently developed body adiposity index for aortic stiffness, an intermediate endpoint of cardiovascular disease, in a cross-sectional multi-ethnic Asian type 2 diabetes mellitus cohort (N = 1408). AS was estimated using carotid-femoral pulse wave velocity measured by applanation tonometry. Body adiposity index was computed as hip circumference/(height)(1.5) - 18. Compared to body mass index, waist circumference and visceral fat area, body adiposity index displayed the weakest association with pulse wave velocity (r = 0.077, 0.096, 0.134 and 0.058, respectively; all p < 0.05). Interestingly, the relationship between measurements of obesity and pulse wave velocity was ethnic dependent - body mass index, body adiposity index, waist circumference and visceral fat area consistently predicted pulse wave velocity only in Indians but not others. In multi-variable analysis, body mass index was a significant determinant of pulse wave velocity in all ethnicities. In conclusion, body adiposity index is a weak predictor of aortic stiffness (when compared with body mass index) in Asians with type 2 diabetes mellitus. © The Author(s) 2014.

  16. Surgical removal of embolic material after its unexpected migration through extracranial-intracranial anastomosis in the treatment of Barrow Type D carotid-cavernous fistula: case report.

    PubMed

    Oh, Jae-Sang; Kim, Dong-Sung; Shim, Jai-Joon; Yoon, Seok-Mann

    2017-03-03

    Endovascular occlusion via the transvenous route is the favored treatment for indirect carotid-cavernous fistulas (CCFs). However, transarterial embolization can be used as an alternative method in patients with an inaccessible venous route. The authors present the case of a 49-year-old woman with a 2-month history of chemosis and proptosis in her right eye. Angiography demonstrated a Barrow Type D CCF. Transarterial Onyx embolization through the accessory meningeal artery was performed after an unsuccessful transvenous approach. Unexpected Onyx migrations to the cerebral arteries were detected while injecting the embolic material. Three hours after failed attempts to retrieve the Onyx cast endovascularly, it was microsurgically removed from the right middle cerebral artery. To the authors' knowledge, this is the first report of the surgical removal of Onyx from a normal cerebral artery.

  17. [Outcomes of carotid endarterectomy and stenting in patients with carotid artery stenosis].

    PubMed

    Gavrilenko, A V; Ivanov, V A; Piven', A V; Kuklin, A V; Kravchenko, A A; Miklashevich, É R; Abugov, S A

    2012-01-01

    Analysed in the article are the outcomes of treating a total of 156 patients diagnosed with carotid artery stenosis. Of these, carotid endarterectomy was performed in 82 patients and stenting of carotid arteries was carried out in the remaining 74 patients. The incidence rate of perioperative stroke in the carotid endarterectomy group amounted to 3.6%, being in the stenting group 4.8%, P = 0.57. Multifactorial analysis was used to reveal risk factors for each method. Thus, in the carotid endarterectomy group, the risk factors for cerebrovascular complications appeared to be contralateral occlusion in patients with a history of stroke endured within less than six previous months (P<0.05), as well as the age over 75 years amongst the patients requiring placement of a temporary intraluminal bypass graft (P<0.05). For carotid stenting, risk factors of cerebrovascular complications included a hypoechogenic heterogeneous type of an atherosclerotic plaque (P<0.05) and ulceration of its surface (P<0.05). The presence of the patient's baseline functional class III angina of effort appeared to be a risk factor for the development of cardiovascular complications for carotid endarterectomy (P<0.05). No cardiovascular risk factors for carotid stenting were revealed. Based on the assessment of the risk factors thus detected, the authors worked out an algorithm of choosing an optimal treatment policy for patients presenting with carotid artery stenosis.

  18. Association of Risk Estimates of Three Different Cardiovascular Risk Assessment Tools with Carotid Intima Media Thickness in Patients with Type 2 Diabetes.

    PubMed

    Herath, Herath Mudiyanselage Meththananda; Weerarathna, Thilak Priyantha; Dulanjalee, Ranasinghe Bethmi Arachige Thilini; Jayawardana, Madumekala Rupasinghe; Edirisingha, Udara Priyadarshani; Rathnayake, Madushanka

    2016-07-01

    Risk assessment tools used to calculate the Cardiovascular Disease (CVD) risk such as the Framingham Risk Score (FRS), United Kingdom Prospective Diabetes study (UKPDS) risk engine and the World Health Organization (WHO) risk score have not been tested on their ability to detect subclinical atherosclerosis in most developing countries. To study the association between the calculated CVD risk scores using each of these tools and Carotid Intima Medial Thickness (CIMT), a surrogate marker of atherosclerosis, in a group of patients with Type 2 diabetes (T2DM) in Sri Lanka. We calculated CVD risk scores of 68 randomly selected patients with T2DM with no history or symptoms of CVD and measured their CIMT using B-mode ultrasonography (USS). Carotid USS was considered positive when the maximum carotid IMT was 0.9mm or when arteriosclerotic plaques were detected. The 10-year CVD risk was calculated using the FRS, the UKPDS risk engine and the WHO risk score. Pearson correlation was used to study the association between CVD risk scores with CIMT. Of the 68 patients studied, 50% were males and their mean age (SD) was 56.9 (±9.6) years. The mean age at onset and duration of diabetes were 44.3(±9.1) and 12.2(±7.6) years respectively. Of the scoring methods, UKPDS tool had weak, but significantly positive (r = 0.26, p < 0.05) and FRS had positive but not significant association (r= 0. 21) with CIMT. There was a negative association between CIMT and WHO risk score (r= - 0.07). Of the three CVD risk assessment tools, both UKPDS risk engine and FRS have almost equal ability (former being marginally superior) in predicting underlying atherosclerotic vascular disease in patients with T2DM. Negative association of the WHO risk score with CIMT argues against its utility for CVD screening. These findings highlight the need for developing more sensitive and reliable CVD risk assessment tools for developing countries.

  19. Association of Risk Estimates of Three Different Cardiovascular Risk Assessment Tools with Carotid Intima Media Thickness in Patients with Type 2 Diabetes

    PubMed Central

    Weerarathna, Thilak Priyantha; Dulanjalee, Ranasinghe Bethmi Arachige Thilini; Jayawardana, Madumekala Rupasinghe; Edirisingha, Udara Priyadarshani; Rathnayake, Madushanka

    2016-01-01

    Introduction Risk assessment tools used to calculate the Cardiovascular Disease (CVD) risk such as the Framingham Risk Score (FRS), United Kingdom Prospective Diabetes study (UKPDS) risk engine and the World Health Organization (WHO) risk score have not been tested on their ability to detect subclinical atherosclerosis in most developing countries. Aim To study the association between the calculated CVD risk scores using each of these tools and Carotid Intima Medial Thickness (CIMT), a surrogate marker of atherosclerosis, in a group of patients with Type 2 diabetes (T2DM) in Sri Lanka. Materials and Methods We calculated CVD risk scores of 68 randomly selected patients with T2DM with no history or symptoms of CVD and measured their CIMT using B-mode ultrasonography (USS). Carotid USS was considered positive when the maximum carotid IMT was 0.9mm or when arteriosclerotic plaques were detected. The 10-year CVD risk was calculated using the FRS, the UKPDS risk engine and the WHO risk score. Pearson correlation was used to study the association between CVD risk scores with CIMT. Results Of the 68 patients studied, 50% were males and their mean age (SD) was 56.9 (±9.6) years. The mean age at onset and duration of diabetes were 44.3(±9.1) and 12.2(±7.6) years respectively. Of the scoring methods, UKPDS tool had weak, but significantly positive (r = 0.26, p < 0.05) and FRS had positive but not significant association (r= 0. 21) with CIMT. There was a negative association between CIMT and WHO risk score (r= - 0.07). Conclusion Of the three CVD risk assessment tools, both UKPDS risk engine and FRS have almost equal ability (former being marginally superior) in predicting underlying atherosclerotic vascular disease in patients with T2DM. Negative association of the WHO risk score with CIMT argues against its utility for CVD screening. These findings highlight the need for developing more sensitive and reliable CVD risk assessment tools for developing countries. PMID

  20. Evaluation of carotid intima-media thickness and carotid arterial stiffness in children with adenotonsillar hypertrophy.

    PubMed

    Çiftel, Murat; Demir, Berrin; Kozan, Günay; Yılmaz, Osman; Kahveci, Hasan; Kılıç, Ömer

    2016-02-01

    Adenotonsillar hypertrophy can produce cardiopulmonary disease in children. However, it is unclear whether adenotonsillar hypertrophy causes atherosclerosis. This study evaluated carotid intimamedia thickness and carotid arterial stiffness in children with adenotonsillar hypertrophy. The study included 40 children with adenotonsillar hypertrophy (age: 5-10 years) and 36 healthy children with similar age and body mass index. Systolic blood pressure, diastolic blood pressure, and pulse pressure were measured in all subjects. Carotid intima-media thickness, carotid arterial systolic diameter, and carotid arterial diastolic diameter were measured using a high-resolution ultrasound device. Based on these measurements, carotid arterial strain, carotid artery distensibility, beta stiffness index, and elasticity modulus were calculated. Carotid intima-media thickness was greater in children with adenotonsillar hypertrophy (0.36±0.05 mm vs. 0.34±0.04 mm, P=0.02) compared to healthy controls. Beta stiffness index (3.01±1.22 vs. 2.98±0.98, P=0.85), elasticity modulus (231.39±99.23 vs. 226.46±83.20, P=0.88), carotid arterial strain (0.17±0.06 vs. 0.17±0.04, P=0.95), and carotid artery distensibility (13.14±3.88 vs. 12.92±3.84, P=0.75) were similar between children with adenotonsillar hypertrophy and the healthy controls. The present study revealed increased carotid intima-media thickness in children with adenotonsillar hypertrophy. The risk of subclinical atherosclerosis may be higher in children with adenotonsillar hypertrophy.

  1. Changes in carotid intima-media thickening in patients with type 2 diabetes mellitus: Subanalysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation.

    PubMed

    Mita, Tomoya; Katakami, Naoto; Shiraiwa, Toshihiko; Yoshii, Hidenori; Gosho, Masahiko; Shimomura, Iichiro; Watada, Hirotaka

    2017-03-01

    Figure 1 shows differences in treatment-induced delta change in carotid IMT relative to baseline, according to various pre-defined risk factors for atherosclerosis. These data suggest that treatment with DPP-4 inhibitors seem to prevent the progression of carotid atherosclerosis regardless of disease burden.

  2. The effect of diabetes self-management education on body weight, glycemic control, and other metabolic markers in patients with type 2 diabetes mellitus.

    PubMed

    Yuan, Chuang; Lai, Christopher W K; Chan, Lawrence W C; Chow, Meyrick; Law, Helen K W; Ying, Michael

    2014-01-01

    To comprehensively evaluate the effect of a short-term diabetes self-management education (DSME) on metabolic markers and atherosclerotic parameters in patients with type 2 diabetes. 76 patients with type 2 diabetes were recruited in this study. They were divided into the intervention group (n = 36) and control group (n = 40). The patients in the intervention group received a 3-month intervention, including an 8-week education on self-management of diabetes mellitus and subsequent 4 weeks of practice of the self-management guidelines. The patients in the control group received standard advice on medical nutrition therapy. Metabolic markers, carotid intima-media thickness (CIMT), and carotid arterial stiffness (CAS) of the patients in both groups were assessed before and after the 3-month intervention. There was a significant reduction in hemoglobin A1c (HbA1c, -0.2 ± 0.56% versus 0.08 ± 0.741%; P < 0.05) and body weight (-1.19 ± 1.39 kg versus -0.61 ± 2.04 kg; P < 0.05) in the intervention group as compared to the control group. However, no significant improvements were found in other metabolic markers, CIMT and CAS (P > 0.05). DSME can improve HbA1c and body weight in patients with type 2 diabetes.

  3. Management of Carotid Bifurcation Tumors: 30-Year Experience.

    PubMed

    Torrealba, Jose Ignacio; Valdés, Francisco; Krämer, Albrecht H; Mertens, Renato; Bergoeing, Michel; Mariné, Leopoldo

    2016-07-01

    The carotid bifurcation can host a variety of tumors requiring complex surgical management. Treatment requires resection and, in some cases, vascular reconstruction that may compromise the cerebral circulation. The most frequent lesion at this location is the carotid body tumor (CBT). CBT are classified according to Shamblin in 3 types depending on the degree of carotid vessels encasement. Our main objective was to report our clinical experience managing carotid bifurcation tumors throughout the last 30 years. Between 1984 and 2014, we treated 30 patients with 32 carotid bifurcation tumors. There were 21 women and 9 men (2.3:1), with a mean age of 45.5 years (18-75). The most frequent presentation was an asymptomatic neck swelling or palpable mass localized at the carotid triangle (86.7%). Thirty of 32 tumors were resected. Since 1994, computed tomography scan has been the most frequently used diagnostic imaging tool (80%), followed by magnetic resonance imaging. Angiography was used mainly during the first 10 years of the study period. Mean size of the tumor was 44.6 mm (20-73 mm). Nineteen (63%) were classified as Shamblin II and 6 (20%) as Shamblin's III. All specimens were analyzed by a pathologist; 28 tumors (93%) were confirmed as paragangliomas, 2 (7%) were diagnosed as schwannomas. Two patients underwent preoperative embolization of the CBT; 5 patients (17%) required simultaneous carotid revascularization, all of them Shamblin III. Mean hospitalization time was 4.5 days (1-35 days). Transient extracranial nerve deficit was observed in 7 patients (23.3%). Three patients (Shamblin III) required red blood cells transfusion. One patient (Shamblin III) underwent a planned en bloc excision of the vagus nerve. There was no perioperative mortality or procedure-related stroke. No malignancy or tumor recurrence were observed during follow-up. CBTs can be diagnosed on clinical grounds requiring vascular imaging confirmation. These infrequent lesions are

  4. [Carotid artery intima-media thickness (cIMT) in young type 1 diabetic patients in relation to comorbid additional autoimmune diseases and microvascular complications].

    PubMed

    Klonowska, Bożenna; Charemska, Dorota; Jabłońska, Jolanta; Banach, Agnieszka; Kącka, Anna; Szynkarczuk, Edyta; Konopka, Malwina; Jarocka-Cyrta, Elżbieta; Załuski, Dariusz; Głowińska-Olszewska, Barbara

    2016-01-01

    Atherosclerosis, which is the cause of diseases of the cardiovascular system, and frequent and serious complications of type 1 diabetes (T1DM), has an autoimmune origin. Some diseases of this type, as rheumatoid arthritis, but also Hashimoto thyroiditis or celiac disease are associated with a higher incidence of heart disease. So far no studies evaluated the preclinical phase of development of atherosclerosis (cIMT) in young patients with T1DM and the comorbid additional autoimmune diseases. was evaluation of cIMT (carotid intima media thickness) carotid arteries and the risk factors of atherosclerosis in young patients with type 1 diabetes according to the comorbid autoimmune diseases and a comparison group of patients with known vascular complications and a group of healthy people. The study involved a group of 90 adolescents and young adults with T1DM in middle age 17,1±3years, with an average disease duration of 10,5±3,3 years. Diabetes patients were divided into 4 groups - diabetes without complications - C, diabetes with celiac disease - CC, diabetes with Hashimoto's thyroiditis - CH, diabetes with vascular complications - CN. The control group (K) consisted of 22 healthy age-matched volunteers. In statistical analysis rated: average A1C of all the years of illness, BMI, blood pressure, lipid values, duration of illness, presence of diabetes complications, daily insulin dose and cIMT thickness of the common carotid artery. cIMT of T1DM patients was significantly higher: 0,470 mm than in healthy: 0,409 mm. In the group with vascular complications of diabetes was found the highest rate of cIMT: 0,501 mm in comparison to the group of diabetes without complications: 0,462 mm, diabetes with celiac disease: 0,462 mm, and diabetes with Hashimoto's thyroiditis: 0,453 mm. HbA1c was highest in the group CN: 9,84±1,5%, compared to CH: 9,04± 1,2%, CC: 8,84±1,8% and C without complications: 8,55±1,2%. BMI was highest in the group CN: 23,3± 4,4kg/m2and CH: 22,6 ± 2

  5. Serum carboxy-terminal telopeptide of type I collagen levels are associated with carotid atherosclerosis in patients with cardiovascular risk factors.

    PubMed

    Kondo, Takeshi; Endo, Itsuro; Aihara, Ken-Ichi; Onishi, Yukiyo; Dong, Bingzi; Ohguro, Yukari; Kurahashi, Kiyoe; Yoshida, Sumiko; Fujinaka, Yuichi; Kuroda, Akio; Matsuhisa, Munehide; Fukumoto, Seiji; Matsumoto, Toshio; Abe, Masahiro

    2016-04-25

    Carboxy-terminal telopeptide of type I collagen (ICTP) is generated through matrix metalloproteinase (MMP)-dependent type I collagen digestion, and has been widely utilized as a biomarker for bone turnover. The fact that atherosclerotic lesions are rich in both type I collagen and MMP-producing macrophages led to the hypothesis that serum ICTP concentrations may serve as a non-invasive clinical biomarker for atherosclerosis. Therefore, the association of serum ICTP concentrations with the maximum intima-media thickness (IMT) of carotid arteries, a surrogate index of systemic atherosclerosis, or brachial-ankle pulse wave velocity (baPWV) in patients with atherosclerotic risk factors was evaluated. A total of 52 male and 65 female (mean age: 62.8 yrs) patients without renal failure, malignancies or bone diseases known to affect serum ICTP concentrations were recruited. Patients with max IMTs ≥1.1 mm showed significantly higher serum ICTP concentrations compared with patients with max IMTs <1.1 mm (3.33 ± 0.97 vs 2.82 ± 0.65 ng/mL, p<0.05). Serum ICTP concentration was also positively correlated with max IMT (p<0.001) or baPWV values (p<0.05). Multivariate analyses also revealed that serum ICTP concentrations were correlated with max IMT (p<0.001; 95% CI 0.200 to 0.454). These results suggest that serum ICTP concentrations can be used as a non-invasive biomarker for systemic atherosclerosis.

  6. Effect of a Mediterranean diet on endothelial progenitor cells and carotid intima-media thickness in type 2 diabetes: Follow-up of a randomized trial.

    PubMed

    Maiorino, Maria Ida; Bellastella, Giuseppe; Petrizzo, Michela; Gicchino, Maurizio; Caputo, Mariangela; Giugliano, Dario; Esposito, Katherine

    2017-03-01

    Background We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Design This was a parallel, two-arm, single-centre trial. Methods Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet ( n = 108) or a low-fat diet ( n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT). Results At the EOT, both the CD34(+)KDR(+) and CD34(+)KDR(+)CD133(+) counts had increased with the Mediterranean diet compared with the low-fat diet ( p < 0.05 for both). At the EOT evaluation, there was a significant ( p = 0.024) difference of -0.025 mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) ( p = 0.032 for both). Changes in the CIMT were inversely correlated with the changes in EPC levels (CD34(+)KDR(+), r = -0.24, p = 0.020; CD34(+)KDR(+)CD133(+), r = -0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet. Conclusion Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.

  7. Data on carotid intima-media thickness and lipoprotein subclasses in type 1 diabetes from the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC).

    PubMed

    Basu, Arpita; Jenkins, Alicia J; Zhang, Ying; Stoner, Julie A; Klein, Richard L; Lopes-Virella, Maria F; Timothy Garvey, W; Lyons, Timothy J

    2016-03-01

    Type 1 diabetes (T1DM) is associated with increased risk of macrovascular complications. We examined longitudinal associations of serum conventional lipids and nuclear magnetic resonance (NMR)-determined lipoprotein subclasses with carotid intima-media thickness (IMT) in adults with T1DM (n=455) enrolled in the Diabetes Control and Complications Trial (DCCT). Data on serum lipids and lipoproteins were collected at DCCT baseline (1983-89) and were correlated with common and internal carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC 'Year 1' (199-1996) and EDIC 'Year 6' (1998-2000). This article contains data on the associations of DCCT baseline lipoprotein profiles (NMR-based VLDL & chylomicrons, IDL/LDL and HDL subclasses and 'conventional' total, LDL-, HDL-, non-HDL-cholesterol and triglycerides) with carotid IMT at EDIC Years 1 and 6, stratified by gender. The data are supplemental to our original research article describing detailed associations of DCCT baseline lipids and lipoprotein profiles with EDIC Year 12 carotid IMT (Basu et al. in press) [1].

  8. Living with Carotid Artery Disease

    MedlinePlus

    ... from the NHLBI on Twitter. Living With Carotid Artery Disease If you have carotid artery disease, you can take steps to manage the ... treatment plan, and getting ongoing care. Having carotid artery disease raises your risk of having a stroke . ...

  9. What Is Carotid Artery Disease?

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Carotid Artery Disease? Carotid artery disease is a disease in ... blood to your face, scalp, and neck. Carotid Arteries Figure A shows the location of the right ...

  10. Diabetic Peripheral Neuropathy Is Associated With Increased Arterial Stiffness Without Changes in Carotid Intima–Media Thickness in Type 2 Diabetes

    PubMed Central

    Kim, Eun Sook; Moon, Sung-dae; Kim, Hun-Sung; Lim, Dong Jun; Cho, Jae Hyoung; Kwon, Hyuk Sang; Ahn, Chul Woo; Yoon, Kun Ho; Kang, Moo Il; Cha, Bong Yun; Son, Ho Young

    2011-01-01

    OBJECTIVE This study was conducted to investigate the association of diabetic peripheral neuropathy (DPN) with both arterial stiffness and intima–media thickness (IMT). RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of 731 subjects with type 2 diabetes. DPN was diagnosed on the basis of neuropathic symptoms, insensitivity to a 10-g monofilament, abnormal pin-prick sensation, and abnormal current perception threshold. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), and IMT was assessed by B-mode ultrasonography. RESULTS Patients with DPN had higher CAVI than those without DPN in multivariate-adjusted models, whereas no differences in IMT were observed between patients with and without DPN after adjustment for age and sex. In the multivariate analysis, CAVI was a significant determinant of DPN (odds ratio 1.36 [95% CI 1.13–1.65], P = 0.001). CONCLUSIONS DPN is significantly associated with arterial stiffness without carotid intimal changes in patients with type 2 diabetes. PMID:21515840

  11. In vitro activation of cyclo-oxygenase in the rabbit carotid body: effect of its blockade on [3H]catecholamine release.

    PubMed Central

    Gómez-Niño, A; Almaraz, L; González, C

    1994-01-01

    The release of prostaglandin E2 (PGE2) from rabbit carotid bodies (CBs) incubated in basal conditions (PO2 approximately 132 mmHg; PCO2 approximately 33 mmHg; pH = 7.42) amounts to 94.4 +/- 10.1 pg (mg protein)-1 (10 min)-1 (mean +/- S.E.M.). Incubation of the CB in a hypoxic solution (PO2 approximately 46 mmHg) produced a significant 40% increase (P < 0.05) in the release of PGE2. Indomethacin (2 microM) prevented the hypoxia-induced release of PGE2. Sensory plus sympathetic denervation of the CB 4 days prior to the experiments did not modify either basal or low PO2-induced PGE2 release, indicating that intraglomic nerve endings are not significant sources for the PGE2 released. Incubation of the CB in an acidic-hypercapnic solution (PO2 approximately 132 mmHg; PCO2 approximately 132 mmHg; pH = 6.60) or in a high K(+)-containing solution (35 mM) was also effective in promoting an increase in the outflow of PGE2 from the organs. The release of [3H]catecholamines ([3H]CA) from the CB elicited by incubating the organs in low PO2 solutions (PO2 ranged between 66 and 13 mmHg) was potentiated by two inhibitors of cyclo-oxygenase, acetylsalicylic acid (ASA, 100 microM) and indomethacin (2 microM). The effect persisted after chronic denervation of the organ. The secretory response elicited by acidic stimuli was also augmented by cyclo-oxygenase inhibitors. Thus, [3H]CA release elicited by incubating the CBs in the acidic-hypercapnic solution increased by 300% in the presence of indomethacin (2 microM), and ASA (100 microM) more than doubled the release induced by dinitrophenol (100 microM), a protonophore that mimics an acidic stimulus. Indomethacin, but not ASA, moderately increased the high K(+)-evoked [3H]CA release. The effect of indomethacin on the release of [3H]CA elicited by acidic and hypoxic stimuli was reversed by PGE2 in a dose-dependent manner (0.3-300 nM). These results show that low PO2 and high PCO2-low pH, the natural stimuli to the CB, as well as high

  12. The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation

    PubMed Central

    Katakami, Naoto; Shiraiwa, Toshihiko; Yoshii, Hidenori; Gosho, Masahiko; Shimomura, Iichiro; Watada, Hirotaka

    2017-01-01

    Background. The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT) in insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods. This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0.10 mm in a post hoc analysis. Results. The percentages of the number of the patients who showed regression of mean-IMT-CCA (28.9% in the sitagliptin group versus 16.4% in the conventional group, P = 0.022) and left max-IMT-CCA (43.0% in the sitagliptin group versus 26.2% in the conventional group, P = 0.007), but not right max-IMT-CCA, were higher in the sitagliptin treatment group compared with those in the non-DPP-4 inhibitor treatment group. In multiple logistic regression analysis, sitagliptin treatment significantly achieved higher target attainment of mean-IMT-CCA ≥0.10 mm and right and left max-IMT-CCA ≥0.10 mm compared to conventional treatment. Conclusions. Our data suggested that DPP-4 inhibitors were associated with the regression of carotid atherosclerosis in insulin-treated T2DM patients. This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396). PMID:28250768

  13. Carotid blowout syndrome in patients treated by larynx cancer.

    PubMed

    Chiesa Estomba, Carlos Miguel; Betances Reinoso, Frank Alberto; Osorio Velasquez, Alejandra; Castro Macia, Olalla; Gonzalez Cortés, Maria Jesus; Araujo Nores, Jesus

    2016-09-29

    Carotid blowout syndrome is an uncommon complication for patient treated by head and neck tumours, related with a high mortality rate. The aim of this study was to study the risk of carotid blowout in a large cohort of patients treated only by larynx cancer. Retrospective analysis of patients older than 18 years, treated by larynx cancer who developed a carotid blowout syndrome in a tertiary academic centre. 197 patients met the inclusion criteria, 192 (98.4%) were male and 5 (1.6%) were female. 6 (3%) patients developed a carotid blowout syndrome, 4 patients had a carotid blowout syndrome located in the internal carotid artery and 2 in the common carotid artery. According to the type of rupture, 3 patients suffer a type I, 2 patients a type III and 1 patient a type II. Five of those patients had previously undergone radiotherapy and all patients underwent total laryngectomy. We found a statistical correlation between open surgical procedures (p=0.004) and radiotherapy (p=0.023) and the development of a carotid blowout syndrome. Carotid blowout syndrome is an uncommon complication in patients treated by larynx tumours. According to our results, patient underwent radiotherapy and patients treated with open surgical procedures with pharyngeal opening have a major risk to develop this kind of complication. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  14. 1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients.

    PubMed

    Giacconi, Robertina; Caruso, Calogero; Lio, Domenico; Muti, Elisa; Cipriano, Catia; Saba, Vittorio; Boccoli, Gianfranco; Gasparini, Nazzarena; Malavolta, Marco; Mocchegiani, Eugenio

    2005-08-01

    Patients with type 2 diabetes mellitus (NIDDM) are at risk for macrovascular disease complications, such as myocardial infarction (MI) or stroke from plaque rupture. Cytokines play a key role in plaque vulnerability. IFN-gamma inhibits collagen synthesis thereby affecting plaque stability. High IL-6, TNF-alpha, and dyslipidemia are risk factors for thrombosis. Abnormal increments of HSP70 in atherosclerotic plaques might lead to plaque instability and rupture caused by chronic inflammation, which up-regulates the expression of pro-inflammatory cytokines (IL-6 and TNF-alpha) in human monocytes. Studies of a polymorphic PstI site lying in the coding region at position 1267 of the HSP70-2 gene have shown that the BB genotype is associated with NIDDM. We screened 60 old NIDDM patients with carotid stenosis and 107 old healthy controls for 1267 HSP70-2 polymorphism in order to establish if an association with plaque frailty exists. Different genotypic distributions were observed between patients and healthy controls. An increased relative risk was associated with the B allele (p = 0.0107; odds ratio = 1.861). HSP70-2, IL-6, IFN-gamma, TNF-alpha gene expressions within the plaques and serum levels of triglyceride, total cholesterol and LDL cholesterol were tested from patients stratified according to their B+ (AB and BB) and B- (AA) genotypes. Plaque morphology (soft or fibrous-calcified) and the incidence of cerebral ischaemia were also assessed. B+ patients showed increased HSP70-2, IL-6, IFN-gamma, TNF-alpha and dyslipidemia as compared to B- carriers. The frequency of soft plaques increased in B+ in comparison to B- patients (67% versus 13%; odds ratio 13.0, p = 0.0006). A higher frequency of cerebral ischaemia (ictus or transient ischaemic attack (TIA)) was present in B+ than in B- genotype (53% versus 20%; odds ratio 4.57, p < 0.05) Hence, 1267 HSP70-2 polymorphism may be of use in identifying B+ NIDDM patients at risk for carotid plaque rupture and cerebral

  15. Age determines the magnitudes of angiotensin II-induced contractions, mRNA, and protein expression of angiotensin type 1 receptors in rat carotid arteries.

    PubMed

    Vamos, Zoltan; Cseplo, Peter; Ivic, Ivan; Matics, Robert; Hamar, Janos; Koller, Akos

    2014-05-01

    In this study, we hypothesized that aging alters angiotensin II (Ang II)-induced vasomotor responses and expression of vascular mRNA and protein angiotensin type 1 receptor (AT1R). Thus, carotid arteries were isolated from the following age groups of rats: 8 days, 2-9 months, 12-20 months, and 20-30 months, and their vasomotor responses were measured in a myograph after repeated administrations of Ang II. Vascular relative AT1R mRNA level was determined by quantitative reverse-transcriptase polymerase chain reaction and the AT1R protein density was measured by Western blot. Contractions to the first administration of Ang II increased from 8 days to 6 months and then they decreased to 30 months. In general, second administration of Ang II elicited reduced contractions, but they also increased from 8 days until 2 months and then they decreased to 30 months. Similarly the AT1R mRNA level increased from 8 days to 12 months and then decreased to 30 months. Similarly the AT1R protein density increased from 8 days until 16 months and then they decreased to 30 months. The pattern of these changes correlated with functional vasomotor data. We conclude that aging (newborn to senescence) has substantial effects on Ang II-induced vasomotor responses and AT1R signaling suggesting the importance of genetic programs.

  16. Quantification of the mechanical behavior of carotid arteries from wild-type, dystrophin-deficient, and sarcoglycan-δ knockout mice

    PubMed Central

    Gleason, Rudolph L.; Dye, Wendy W.; Wilson, Emily; Humphrey, Jay D.

    2008-01-01

    As patients with muscular dystrophy live longer because of improved clinical care, they will become increasingly susceptible to many of the cardiovascular diseases that affect the general population. There is, therefore, a pressing need to better understand both the biology and the mechanics of the arterial wall in these patients. In this paper, we use nonlinear constitutive relations to model, for the first time, the biaxial mechanical behavior of carotid arteries from two common mouse models of muscular dystrophy (dystrophin deficient and sarcoglycan-delta null) and wild-type controls. It is shown that a structurally motivated four-fiber family stress-strain relation describes the passive behavior of all three genotypes better than does a commonly used phenomenological exponential model, and that a Rachev-Hayashi model describes the mechanical contribution of smooth muscle contraction under basal tone. Because structurally motivated constitutive relations can be extended easily to model adaptations to altered hemodynamics, results from this study represent an important step toward the ultimate goal of understanding better the mechanobiology and pathophysiology of arteries in muscular dystrophy. PMID:18842267

  17. Altered expression of adenosine A1 and A2A receptors in the carotid body and nucleus tractus solitarius of adult male and female rats following neonatal caffeine treatment.

    PubMed

    Bairam, Aida; Joseph, Vincent; Lajeunesse, Yves; Kinkead, Richard

    2009-09-01

    Neonatal caffeine treatment (adenosine receptor antagonist, 15 mg/kg/day, between postnatal days 3 and 12) affects respiratory patterns in adult male but not female rats as shown by an increase in the respiratory frequency in the early phase of response to hypoxia and an increase in the tidal volume in the late phase of response. Here, we tested the hypothesis that these changes are correlated with modified expression of adenosine receptors in the chemoreflex pathway. Carotid bodies, nucleus tractus solitarii, and superior cervical ganglia were collected from 3-month-old male and female rats that were either naive (not manipulated during the neonatal period) or treated with caffeine (NCT) or water (NWT) between postnatal days 3 and 12 by gavage. Western blot analysis was used to assess the expression of adenosine A(1) and A(2A) receptors and tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis. In male rats, there was a 37% increase in the level of A(2A) receptor and a 17% decrease in tyrosine hydroxylase in the carotid body of NCT (p<0.001) as compared to NWT rats. In the nucleus tractus solitarius, we found a 13% and 19% decrease in A(1) receptor expression in NWT and NCT rats (p<0.01), respectively, compared to naive rats. In the superior cervical ganglion, there was no change in A(1) receptor, A(2A) receptor, and tyrosine hydroxylase expression. In female rats, the only changes observed were decreases of 12% and 15% in A(1) receptor levels in the nucleus tractus solitarius of NWT and NCT rats (p<0.01), respectively, compared to naive rats. We conclude that NCT induces long-term changes in the adenosine receptor system. These changes may partially explain the modifications of the respiratory pattern induced by NCT in adults. The increased expression of the adenosine A(2A) receptor (specific to male rats), combined with the decreased tyrosine hydroxylase expression in the carotid body, suggests that NCT affects adenosine-dopamine interactions

  18. Altered body composition in type 2 diabetes mellitus

    PubMed Central

    Heshka, Stanley; Ruggiero, Andrea; Bray, George A.; Foreyt, John; Kahn, Stephen E.; Lewis, Cora E.; Saad, Mohammed; Schwartz, Ann V.

    2010-01-01

    Objective To identify differences in amount and distribution of fat and lean soft tissue in subjects with and without type 2 diabetes and to determine whether any differences are affected by race/ethnicity or sex. Design Overweight and obese (body mass index, BMI≥25 kg/m2) Black, White and Hispanic men (490) and women (825) with type 2 diabetes ([mean±SD] age 58.5±6.6; BMI 35.3±5.3) who had a baseline dual energy x-ray absorptiometry whole body scan at the time of enrollment in the Look Ahead clinical trial, and 242 healthy controls, 91 males and 151 females (age 55.3±8.6 y, BMI 30.7±4.2 kg/m2) who were participating in unrelated research and were scanned on the same densitometers. Results Adjusted for covariates, total fat mass was smaller in persons with type 2 diabetes than in controls (−1.4±0.3[SE]; 34.5 vs 35.8 kg, p<0.001) while trunk fat was larger (1.3±0.2[SE]; 19.9 vs 18.6 kg, p<0.001) and leg fat was smaller (−1.5±0.2[SE]; 10.7 vs 12.3 kg, p<0.001). The arms of subjects with type 2 diabetes did not have significantly less fat compared to controls. Adjusted trunk lean mass was larger in type 2 diabetes by 0.6 kg (28.4 vs 27.8 kg, p<0.001) while leg lean was smaller by 0.5 kg (18.1 vs 18.6 kg, p<0.001). Conclusions Type 2 diabetes is associated with less total fat, leg fat and leg lean mass and more truncal fat and lean mass than controls. The physiological processes producing these deviations in tissue distribution and their metabolic significance warrant further investigation. (ClinicalTrials.gov number, NCT00017953) PMID:18227843

  19. Correlation between polymorphism of platelet alloantigen genes HPA-1-5 and type 2 diabetes complication by carotid atherosclerosis in a Chinese population.

    PubMed

    Zhang, Y H; Xu, S F; Zheng, J; Hong, H S; Fan, L M

    2015-05-04

    We investigated the association between the polymorphism of human platelet alloantigen genes HPA-1-HPA-5 and the complication of type 2 diabetes mellitus (T2DM) by carotid atherosclerosis (CA) among Han people in Guiyang District, China. Ninety-nine T2DM patients were selected from the Affiliated Hospital of Guiyang Medical College and divided into a CA(+) group and a CA(-) group. A control group comprised 100 healthy people from the medical examination center of the same hospital. Genomic DNA from all the subjects was isolated by phenol-chloroform extraction and target genes were amplified using sequence-specific primer-polymerase chain reaction, followed by gene type detection of HPA. There were significant differences in allele and genotype frequencies of HPA-1, -2, -3, and -5 among the three groups [CA(+), CA(-), and the control group] (P < 0.05), and significant differences in allele and genotype frequencies of HPA-1, -2, and -3 between groups CA(+) and CA(-) and the control group (P < 0.05). Moreover, there was a significant difference in allele and genotype frequencies of HPA-5 between the CA(+) and CA(-) groups (P < 0.05). Logistic regression analysis showed that risk factors for T2DM patients developing a CA complication were age, duration of diabetes, high blood pressure, smoking, overweight, abnormal blood lipid levels, and polymorphism of HPA-5. There may be a correlation between T2DM and polymorphism of HPA-1-3. Polymorphism of HPA- 5 is probably a risk factor for CA complicating T2DM.

  20. [The meaning of the combination of fibrinogen, micro/macroalbuminuria and atheromatosis in the carotid bloodstream for the evaluation of the abnormal finding of the stress myocardial SPECT in the asymptomatic 2nd type diabetic patients].

    PubMed

    Zamrazil, V; Pálová, S; Holá, D

    2006-02-01

    Stress perfusion myocardial scintigraphy (SPECT) is useful in silent ischemia detection in the group of the asymptomatic type 2. diabetic patients. In our paper we present the combinations of the parameters predictive for stress myocardial SPECT result. We selected parameters (fibrinogen, micro/macroalbuminuria, ateroma in carotid artery bed) that were significantly associated with stress myocardial SPECT result. We analyzed the combinations of these parameters change and evaluated their significance for stress myocardial SPECT result prediction. We evaluated 121 type 2. diabetic patients without patological ECG changes and with normal left ventricle ejection fraction. Thirty one (26%) had abnormal and 90 (74%) equivocal or normal stress myocardial SPECT result. The combination of ateroma presence in carotid bed and fibrinogen in upper tertile was found in 20 patients. Fifteen of them (75%) had the abnormal SPECT result. The combinations of the ateroma absence, negative micro/macroalbuminuria and fibrinogen in the middle or lower tertile were present almost in the half of all the examined diabetic patients. Such combinations were connected with normal or equivocal SPECT result in 93-96% cases. Micro/macroalbuminuria, fibrinogen and ateroma in carotid bed found by sonography are significantly associated with stress myocardial SPECT result. Combinations of these parameters changes lead to the futher stratification that enables the rationale approach in the stress examination indication.

  1. Nasal foreign bodies in children: Types, locations, complications and removal.

    PubMed

    Cetinkaya, Erdem Atalay; Arslan, İlker Burak; Cukurova, İbrahim

    2015-11-01

    To evaluate 1875 cases of nasal foreign body (NFB) removal with regard to type of foreign body (FB), location, complications, techniques for removal, age and gender, and to present the results of the evaluation. Between 2006 and 2013, a total of 1875 NFBs were removed from 1870 children in ENT Services of Antalya Ataturk State Hospital and Izmir Tepecik Training - Research Hospital. A retrospective review was undertaken to evaluate the parameters related to the NFBs and their removal and the data were analyzed. The most frequent NFBs were hard spherical objects and the most common locations to lodge were on the right side just anterior to the middle turbinate. Prolonged exposure increases the complication rate, and button batteries are particularly ominous as they drift into the airway, never observed. We found a higher incidence in patients between ages 2 and 5 years. The distribution of NFBs was 52.9% in boys and 47.1% in girls. NFBs are most commonly hard, round objects. Button batteries and penetrating FBs must be treated immediately. Complications from NFBs are rare but may be potentially serious or even life threatening. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. On the Manev-Type Two-Body Problem

    NASA Astrophysics Data System (ADS)

    Mioc, Vasile; Stoica, Cristina

    1997-12-01

    The two-body problem in Manev-type fields (featured by potentials of the form {A/r+B/r}(2) ; r is the distance between particles, {A} and {B} are real parameters) constitutes a good model for various concrete physical problems of astronomy, astrophysics, relativity, atomic physics, mechanics, etc. We study relative motion in such fields both quantitatively and qualitatively. An analytic solution is obtained in a closed form. A qualitative investigation is performed, representing the motion in the (1/r,dot r) phase plane, where all the solutions are conic sections (or arcs of them). A bifurcation analysis is performed case by case for the whole allowed interplay among field parameters, angular momentum and total energy. Each solution is interpreted in terms of physical motion.

  3. Carotid endarterectomy and carotid artery stenting utilization trends over time.

    PubMed

    Skerritt, Matthew R; Block, Robert C; Pearson, Thomas A; Young, Kate C

    2012-03-29

    Carotid endarterectomy (CEA) has been the standard in atherosclerotic stroke prevention for over 2 decades. More recently, carotid artery stenting (CAS) has emerged as a less invasive alternative for revascularization. The purpose of this study was to investigate whether an increase in stenting parallels a decrease in endarterectomy, if there are specific patient factors that influence one intervention over the other, and how these factors may have changed over time. Using a nationally representative sample of US hospital discharge records, data on CEA and CAS procedures performed from 1998 to 2008 were obtained. In total, 253,651 cases of CEA and CAS were investigated for trends in utilization over time. The specific data elements of age, gender, payer source, and race were analyzed for change over the study period, and their association with type of intervention was examined by multiple logistic regression analysis. Rates of intervention decreased from 1998 to 2008 (P < 0.0001). Throughout the study period, endarterectomy was the much more widely employed procedure. Its use displayed a significant downward trend (P < 0.0001), with the lowest rates of intervention occurring in 2007. In contrast, carotid artery stenting displayed a significant increase in use over the study period (P < 0.0001), with the highest intervention rates occurring in 2006. Among the specific patient factors analyzed that may have altered utilization of CEA and CAS over time, the proportion of white patients who received intervention decreased significantly (P < 0.0001). In multivariate modeling, increased age, male gender, white race, and earlier in the study period were significant positive predictors of CEA use. Rates of carotid revascularization have decreased over time, although this has been the result of a reduction in CEA despite an overall increase in CAS. Among the specific patient factors analyzed, age, gender, race, and time were significantly associated with the utilization of

  4. Muscle adiposity and body fat distribution in type 1 and type 2 diabetes: varying relationships according to diabetes type.

    PubMed

    Dubé, M C; Joanisse, D R; Prud'homme, D; Lemieux, S; Bouchard, C; Pérusse, L; Lavoie, C; Weisnagel, S J

    2006-12-01

    To compare the relationships between markers of total and regional adiposity with muscle fat infiltration in type 1 diabetic and type 2 diabetic subjects and their respective nondiabetic controls, and to document these relationships in type 1 diabetic subjects. Cross-sectional study. In total, 86 healthy, with type 1 diabetes, type 2 diabetes or control subjects. Each diabetic group was matched for age, sex and body mass index with its respective nondiabetic control group. Measures of body composition (hydrodensitometry), fat distribution (waist circumference, abdominal and mid-thigh computed tomography scans) and blood lipid profiles were assessed. Low attenuation mid-thigh muscle surface correlated similarly with markers of adiposity and body composition in all groups, regardless of diabetes status, except for visceral adipose tissue and waist circumference. Indeed, relationships between visceral adiposity and muscle adiposity were significantly stronger in type 2 vs type 1 diabetic subjects (P<0.05 for comparison of slopes). In addition, in well-controlled type 1 diabetic subjects (mean HbA(1c) of 6.8%), daily insulin requirements tended to correlate with low attenuation mid-thigh muscle surface, a specific component of fat-rich muscle (r=0.36, P=0.08), but not with glycemic control (HbA(1c)). This study suggests that the relationship of central adiposity and muscle adiposity is modulated by diabetes status and is stronger in the insulin resistant diabetes type (type 2 diabetes). In well-controlled nonobese type 1 diabetic subjects, the relationship between muscle fat accumulation and insulin sensitivity was also maintained.

  5. Angiotensin II Promotes the Development of Carotid Atherosclerosis in Type 2 Diabetes Patients via Regulating the T Cells Activities: A Cohort Study

    PubMed Central

    Wang, Kai; Jin, Feng; Zhang, Zhanpu; Sun, Xiaochuan

    2016-01-01

    Background Specific T cell phenotype has been reported to potentially contribute to the development of angiotensin II (Ang II)-induced several vascular disorders. Type 2 diabetes mellitus (T2DM) is intimately associated with cardiovascular disease. The present study aimed to investigate the relationship between T cell phenotypes and Ang II in T2DM patients combined with carotid atherosclerosis (CA). Material/Methods This study was performed on 50 patients with T2DM in our hospital. Based on the presence of CA, they were divided into CA group (presence of CA, n=30) or T2DM group (absence of CA, n=20). Additionally, 10 healthy participants were selected as controls. Basic characteristics of all participants were collected and recorded. Peripheral blood mononuclear cells (PBMCs) isolated from patients and controls with or without Ang II and Ang II receptor blocker (ARB) treatment were used to detect Th1, Th2, and Th17 cell proportions, mRNA levels of T-bet, GATA3, and RORγt as well as the expression of IFN-γ, IL-4, and IL-17 by flow cytometry, ELISA, and Real-Time PCR. Results Ang II levels were notably higher in patients in the CA group than those in the T2DM and control group (p<0.05). Th1 and Th17 positive cells, mRNA levels of T-bet and RORγt as well as the expression of IFN-γ and IL-17 were significantly increased in the CA group compared with the T2DM group and control group (p<0.05). Moreover, the activities of T cells and related cytokines were significantly increased of healthy controls after Ang II treatment (p<0.05), while these changes were notably weakened by ARB treatment (p<0.05). Conclusions Ang II promotes the development of CA in T2DM patients by regulating T cells activities. PMID:27782101

  6. Body Type and Sex of Receiver: Their Effects on Source Credibility.

    ERIC Educational Resources Information Center

    Eckman, Bruce K.; Rancer, Andrew S.

    This study focused on whether actual or stereotypic associations with a speaker's body type would affect his or her credibility. Effects on the source-credibility ratings submitted by a total of 165 students were investigated for three different sources' body types. A significant main effect was found for body type but not for the blocked…

  7. Quantification of carotid vessel atherosclerosis

    NASA Astrophysics Data System (ADS)

    Chiu, Bernard; Egger, Micaela; Spence, J. D.; Parraga, Grace; Fenster, Aaron

    2006-03-01

    Atherosclerosis is characterized by the development of plaques in the arterial wall, which ultimately leads to heart attacks and stroke. 3D ultrasound (US) has been used to screen patients' carotid arteries. Plaque measurements obtained from these images may aid in the management and monitoring of patients, and in evaluating the effect of new treatment options. Different types of measures for ultrasound phenotypes of atherosclerosis have been proposed. Here, we report on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US images obtained at two different time points. We evaluated our technique using manual segmentations of the wall and lumen of the carotid artery from images acquired in two US scanning sessions. To incorporate the effect of intraobserver variability in our evaluation, manual segmentation was performed five times each for the arterial wall and lumen. From this set of five segmentations, the mean wall and lumen surfaces were reconstructed, with the standard deviation at each point mapped onto the surfaces. A correspondence map between the mean wall and lumen surfaces was then established, and the thickness of the atherosclerotic plaque at each point in the vessel was estimated to be the distance between each correspondence pairs. The two-sample Student's t-test was used to judge whether the difference between the thickness values at each pair corresponding points of the arteries in the two 3D US images was statistically significant.

  8. HbA1c is significantly associated with arterial stiffness but not with carotid atherosclerosis in a community-based population without type 2 diabetes: The Dong-gu study.

    PubMed

    Lee, Young-Hoon; Shin, Min-Ho; Choi, Jin-Su; Rhee, Jung-Ae; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Ryu, So-Yeon; Choi, Seong-Woo; Kim, Bok-Hee; Oh, Gyung-Jae; Kweon, Sun-Seog

    2016-04-01

    We examined the associations between HbA1c levels and various atherosclerotic vascular parameters among adults without diabetes from the general population. A total of 6500 community-dwelling adults, who were free of type 2 diabetes and ≥50 years of age, were included. High-resolution B-mode ultrasound was used to evaluate carotid artery structure, including intima-media thickness (IMT), plaque, and luminal diameter. Brachial-ankle pulse wave velocity (baPWV), which is a useful indicator of systemic arterial stiffness, was determined using an automatic waveform analysis device. No significant associations were observed between HbA1c, carotid IMT, plaque, or luminal diameter in a fully adjusted model. However, the odds ratio (95% confidence interval) for high baPWV (defined as the highest quartile) increased by 1.43 (1.19-1.71) per 1% HbA1c increase after adjusting for conventional risk factors in a multivariate logistic regression analysis. In addition, HbA1c was independently associated with baPWV in a multivariate linear regression analysis. High-normal HbA1c level was independently associated with arterial stiffness, but not with carotid atherosclerotic parameters, in the general population without diabetes. Our results suggest that the functional atherosclerotic process may already be accelerated according to HbA1c level, even at a level below the diagnostic threshold for diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Photoacoustic imaging of carotid artery atherosclerosis

    NASA Astrophysics Data System (ADS)

    Kruizinga, Pieter; van der Steen, Antonius F. W.; de Jong, Nico; Springeling, Geert; Robertus, Jan Lukas; van der Lugt, Aad; van Soest, Gijs

    2014-11-01

    We introduce a method for photoacoustic imaging of the carotid artery, tailored toward detection of lipid-rich atherosclerotic lesions. A common human carotid artery was obtained at autopsy, embedded in a neck mimicking phantom and imaged with a multimodality imaging system using interstitial illumination. Light was delivered through a 1.25-mm-diameter optical probe that can be placed in the pharynx, allowing the carotid artery to be illuminated from within the body. Ultrasound imaging and photoacoustic signal detection is achieved by an external 8-MHz linear array coupled to an ultrasound imaging system. Spectroscopic analysis of photoacoustic images obtained in the wavelength range from 1130 to 1250 nm revealed plaque-specific lipid accumulation in the collagen structure of the artery wall. These spectroscopic findings were confirmed by histology.

  10. The relationship between carotid blood pressure reactivity to mental stress and carotid intima-media thickness.

    PubMed

    Spartano, Nicole L; Augustine, Jacqueline A; Lefferts, Wesley K; Gump, Brooks B; Heffernan, Kevin S

    2014-10-01

    Brachial blood pressure (BP) reactivity to stress predicts large artery damage and future cardiovascular (CV) events. Central BP is an emerging risk factor associated with target organ damage (TOD). Currently, little is known about the central BP response to mental stress and its association to TOD. Twenty-five healthy, non-obese adults completed a computerized mental stress test. Brachial and carotid systolic (S)BP reactivity to stress were calculated as SBP during stress minus resting SBP. Resting carotid intima-media thickness (IMT) was also measured. Carotid SBP reactivity to stress was significantly associated with carotid IMT, independent of age, sex, body mass index, non-high density lipoprotein cholesterol and brachial SBP reactivity to stress (r = 0.386, p < 0.05). The relationship between carotid SBP reactivity and carotid IMT suggests that the central BP response to stress may prove to be an early risk marker for potential subclinical TOD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Carotid artery disease

    MedlinePlus

    ... a stroke recover most or all of their functions. Others die of the stroke itself or from complications. About half of people ... patients with extracranial carotid and vertebral artery disease: executive summary: ... American Association of Neuroscience Nurses, American Association ...

  12. Carotid dissection (image)

    MedlinePlus

    ... This leaking of blood into the artery wall (dissection) may cause a clot to form, reducing blood ... the neck, which means stroke secondary to carotid dissection may occur in young people as well as ...

  13. Body adiposity index, body fat content and incidence of type 2 diabetes.

    PubMed

    Schulze, M B; Thorand, B; Fritsche, A; Häring, H U; Schick, F; Zierer, A; Rathmann, W; Kröger, J; Peters, A; Boeing, H; Stefan, N

    2012-06-01

    The aim of this study was to compare estimates of body fat content, i.e. body adiposity index (BAI), BMI and waist and hip circumferences, with respect to their ability to predict the percentage of body fat (PBF; confirmed by magnetic resonance tomography) and incident type 2 diabetes. Associations between anthropometric measurements and PBF were evaluated in the Tübingen Lifestyle Intervention Program (TULIP; 138 men, 222 women), and between these measurements and incident type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (9,729 men, 15,438 women) and the Cooperative Health Research in the Region of Augsburg (KORA) study (5,573 men, 5,628 women), using correlation and multivariate Cox regression analyses. BMI more strongly correlated with PBF (men: r = 0.81, women: r = 0.84) than BAI (r = 0.68 and 0.81, respectively), while waist circumference among men (r = 0.84) and hip circumference among women (r = 0.88) showed the strongest correlations. BAI overestimated PBF among men (mean difference -3.0%), and this error was dependent on the value of PBF. BAI was more weakly associated with diabetes risk (RRs for 1 SD, EPIC-Potsdam men: 1.62 [95% CI 1.52, 1.72], women: 1.67 [95% CI 1.55, 1.80]; KORA men: 1.62 [95% CI 1.48, 1.78], women: 1.82 [95% CI 1.65, 2.02]) compared with BMI (RRs, EPIC-Potsdam men: 1.95 [95% CI 1.83, 2.09], women 1.88 [95% CI 1.76, 2.02], KORA men 1.75 [95% CI 1.62, 1.89], women 2.00 [95% CI 1.81, 2.22]), while waist circumference showed the strongest associations (RRs: 2.17 [95% CI 2.01, 2.35], 2.33 [95% CI 2.15, 2.53], 1.81 [95% CI 1.66, 1.96] and 2.29 [95% CI 2.05, 2.57] for EPIC-Potsdam men and women and KORA men and women, respectively). Waist circumference in men and hip circumference in women are better predictors of PBF than BAI and BMI. BAI was not as strong a predictor of diabetes as BMI, while waist circumference was the strongest predictor.

  14. The effect of cardiovascular risk factors on the longitudinal evolution of the carotid intima medial thickness in children with type 1 diabetes mellitus

    PubMed Central

    2011-01-01

    Background Type 1 diabetes mellitus is a generally accepted atherogenic risk factor. The aim of this prospective longitudinal study was to evaluate changes in carotid intima media thickness (cIMT) in children and adolescents with type 1 diabetes mellitus (T1DM) using standardized methods. Methods We re-evaluated cIMT in 70 (38 f) of initial 150 (80 f) patients with T1DM after 4 years. At re-evaluation, mean (± SD) age was 16.45 ± 2.59 y, mean diabetes duration was 9.2 ± 3.24 y and patients had a mean HbA1c of 8.14 ± 1.06%. Results Mean cIMT z-scores increased significantly during 4 years (0.58 ± 0.75, p < 0.001) as well as BMI-z-score (0.41 ± 0.81, p < 0.01), systolic blood pressure (0.77 ± 1.15, p < 0.01) and HbA1c (0.90 ± 1.07, < 0.001). In a linear regression model systolic blood pressure z-score at first measurement (0.02, CI: 0.01, 0.04) was a significant predictor for the mean effect on cIMT z-score. In a logistic regression model significant risk factors for an increase in IMT of ≥1.5 z-scores were BMI z-scores (OR: 3.02, CI:1.11, 10.14), diabetes duration (OR:1.32, CI:1.04, 1.77) and systolic blood pressure (OR: 1.14, CI: 1.04, 1.27) at first measurement each. Conclusions Longitudinal cIMT measurements revealed progression in subclinical atherosclerosis during a four year period in diabetic children and adolescents. Systolic blood pressure and BMI were related to cIMT increment. Control of these risk factors by lifestyle and medical intervention may prevent progression of cIMT in diabetic children. PMID:21679428

  15. Adiponectin and carotid intimal medial thickness in subjects with and without glucose intolerance (CURES-82).

    PubMed

    Gokulakrishnan, K; Indulekha, K; Ganesan, S; Anuradha, S; Mohan, V

    2010-02-01

    This study assessed the association of serum adiponectin with carotid intimal medial thickness (IMT) in Asian Indians with different grades of glucose intolerance. Subjects with normal glucose tolerance (NGT) (n = 520), impaired glucose tolerance (IGT) (n = 115), and type 2 diabetes mellitus (T2DM) (n = 540) were recruited from the Chennai Urban Rural Epidemiology Study, in south India. Adiponectin levels were measured using radioimmunoassay. Carotid IMT was assessed by high resolution B-mode ultrasonography. Insulin resistance was calculated using the homeostasis assessment model. Subjects with glucose intolerance (i.e., IGT and T2DM) were older compared to subjects with NGT. Waist circumference, systolic blood pressure, and serum triglycerides were higher among subjects with IGT and T2DM compared to subjects with NGT (P < 0.001). Subjects with glucose intolerance had significantly higher mean carotid IMT values and lower adiponectin compared to subjects with NGT (P < 0.001). Serum adiponectin levels were significantly correlated with IMT among NGT (P = 0.005) and IGT (P = 0.005) subjects but not in subjects with diabetes. Linear regression analysis revealed adiponectin to be negatively associated with IMT (P < 0.001) even after adjusting for age, gender, body mass index, insulin resistance, and glucose intolerance (P < 0.001). Carotid IMT is associated with lower serum adiponectin levels independent of conventional cardiovascular risk factors in urban South Indians.

  16. [Carotid ultrasonography: evaluation of carotid ultrasonography].

    PubMed

    Taniuchi, Ryosui

    2007-02-01

    Carotid ultrasonography is a laboratory procedure showing how arteriosclerosis screening can diagnose carotid artery occlusion and high-grade stenosis. It is useful for inspection in general practice because of its non-invasiveness, development of sonography equipment, laboratory methods and the establishment of an evaluation method. We generally use a linear array probe of around 7-8MHz for carotid observation and combine the B mode method, color and power Doppler method, and pulsed Doppler method for inspection. At vessel analysis, the intima-media thickness, the property of plaque and stenotic ratio are evaluated. We observe the direction of bloodstream and presence of stricture by Doppler color flow imaging and measure flow velocity and the wave pattern by pulsed Doppler method and, with the B mode method, evaluate the extent or degree of stricture. This can be depicted well using a convex array probe and sector array probe when the mental change caused by disease is deep, and depiction is difficult by linear array probe.

  17. Dependence of carotid chemosensory responses on metabolic substrates.

    PubMed

    Spergel, D; Lahiri, S; Wilson, D F

    1992-11-20

    The dependence of the carotid chemosensory response to hypoxia on metabolic substrate and the hypothesis that lactic acidosis is essential for O2 chemoreception were tested. Effects of 3 types of substrate (glucose, glutamate and a mixture of amino acids) on the response to hypoxia (perfusate flow interruption) were measured (n = 33 carotid bodies). The response to nicotine (n = 25) was used to determine whether these effects were exclusive to the hypoxic response. The cat carotid body was perfused and superfused in vitro with modified Tyrode solution (pO2 > 400 Torr, pCO2 < 1 Torr, pH = 7.4) at 36 degrees C containing a given substrate for at least 15 min prior to flow interruption or nicotine injection. Without substrate, responses to flow interruption (n = 4) and nicotine (n = 2) were irreversibly depressed. With glucose, responses to flow interruption (n = 13) and nicotine (n = 8) increased in a concentration-dependent fashion. Glutamate (42 mM) alone (n = 11) or a mixture of amino acids (4.2 mM) plus 5.5 mM glucose (n = 12) substituted for 11 mM glucose (n = 10). Thus, glutamate (42 mM), or a mixture of amino acids (4.2 mM) or a high concentration of glucose (11 mM) can support chemosensory responses to flow interruption and nicotine. Since glutamate undergoes oxidative deamination to alpha-ketoglutarate without lactic acid production, O2 chemoreception does not depend on lactic acidosis.

  18. Youth overweight and metabolic disturbances in predicting carotid intima-media thickness, type 2 diabetes, and metabolic syndrome in adulthood: the Cardiovascular Risk in Young Finns study.

    PubMed

    Koskinen, Juha; Magnussen, Costan G; Sabin, Matthew A; Kähönen, Mika; Hutri-Kähönen, Nina; Laitinen, Tomi; Taittonen, Leena; Jokinen, Eero; Lehtimäki, Terho; Viikari, Jorma S A; Raitakari, Olli T; Juonala, Markus

    2014-07-01

    Our objective was to assess cardiovascular risk and metabolic complications in adulthood in subjects with or without overweight and metabolic disturbances (i.e., elevated blood pressure, glucose, triglycerides, low HDL cholesterol, and high LDL cholesterol) and their combinations as youth. Using data from the population-based Cardiovascular Risk in Young Finns study, we examined the utility of four age- and sex-specific youth phenotypes (group I: normal weight, no metabolic disturbances; group II: normal weight, one or more metabolic disturbances; group III: overweight/obese, no metabolic disturbances; group IV: overweight/obese, one or more metabolic disturbances) in predicting adult high carotid intima-media thickness (IMT), type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS). The study included 1,617 participants 9-24 years of age at baseline who were followed up 21-25 years later. IMT (mean ± SEM) was higher among participants in groups II (0.627 ± 0.005 mm, P = 0.05), III (0.647 ± 0.010 mm, P = 0.005), and IV (0.670 ± 0.010 mm, P < 0.0001) compared with group I (0.616 ± 0.003 mm). In addition, subjects in group IV had significantly higher IMT compared with those in group II (P = 0.002). Participants in groups II, III, and IV were at increased risk of the development of MetS in adulthood compared with those in the control group. For group II participants, the difference was attenuated after risk factor adjustments. Additionally, participants in group III and IV were at increased risk of the development of T2DM compared with those in groups I and II. While metabolic risk factors associated with overweight increase future risk for MetS, T2DM, and increased IMT, overweight in isolation is also a risk factor. Therefore, overweight should be prevented and treated wherever possible. © 2014 by the American Diabetes Association.

  19. pH regulation in adult rat carotid body glomus cells. Importance of extracellular pH, sodium, and potassium [published erratum appears in J Gen Physiol 1993 Jan;101(1):following 144

    PubMed Central

    1992-01-01

    The course of intracellular pH (pHi) was followed in superfused (36 degrees C) single glomus (type I) cells of the freshly dissociated adult rat carotid body. The cells had been loaded with the pH-sensitive fluorescent dye 2',7'-(2-carboxyethyl)-5 (and -6)-carboxyfluorescein. The high K(+)-nigericin method was used for calibration. The pHi of the glomus cell at pHo 7.40, without CO2, was 7.23 +/- 0.02 (n = 70); in 5% CO2/25 mM HCO3-, pHi was 7.18 +/- 0.08 (n = 9). The pHi was very sensitive to changes in pHo. Without CO2, delta pHi/delta pHo was 0.85 (pHo 6.20-8.00; 32 cells), while in CO2/HCO3- this ratio was 0.82 irrespective of whether pHo (6.80-7.40; 14 cells) was changed at constant PCO2 or at constant [HCO3-]o. The great pHi sensitivity of the glomus cell to pHo is matched only by that of the human red cell. An active Na+/H+ exchanger (apparent Km = 58 +/- 6 mM) is present in glomus cells: Na+ removal or addition of the amiloride derivative 5- (N,N-hexamethylene)-amiloride induced pHi to fall by as much as 0.9. The membrane of these cells also contains a K+/H+ exchanger. Raising [K+]o from 4.7 to 25, 50, or 140 mM reversibly raised pHi by 0.2, 0.3, and 0.6, respectively. Rb+ had no effect, but in corresponding concentrations of Tl+ alkalinization was much faster than in K+. Reducing [K+]o to 1.5 mM lowered pHi by 0.1. These pHi changes were shown not to be due to changes in membrane voltage, and were even more striking in the absence of Na+. Intrinsic buffering power (amount of strong base required to produce, in the nominal absence of CO2, a small pHi rise) increased from 3 to approximately 21 mM as pHi was lowered, but remained nearly unchanged below pHi 6.60. The fitted expression assumed the presence of one "equivalent" intracellular buffer (pK 6.41, 41 mM). The exceptional pHi sensitivity to pHo suggests that the pHi of the glomus cell is a link in the chemoreceptor's response to external acidity. PMID:1294152

  20. Glomus tissue in the vicinity of the human carotid sinus.

    PubMed Central

    Garfia, A

    1980-01-01

    Three of 60 cadavers have shown, in the adventitia or in the adipose tissue from the human carotid sinus region, small islands of tissue richly and typically vascularized and with nerve endings contacting cells like the tissue of the principal carotid body. In two of the cases such 'miniglomera' were single but in the third there were several all on the same side. A modified en bloc silver nitrate reduction stain was used to demonstrate the microvascular arrangements and the nerve endings by light microscopy of serial tangential sections of the carotid bifurcation. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7364653

  1. Screening for Carotid Artery Stenosis

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of screening for carotid artery stenosis: Health professionals ... blood flow through the arteries. Potential Benefits and Harms of Carotid Artery Stenosis Screening and Treatment The ...

  2. Body image and body type preferences in St. Kitts, Caribbean: a cross- cultural comparison with U.S. samples regarding attitudes towards muscularity, body fat, and breast size.

    PubMed

    Gray, Peter B; Frederick, David A

    2012-09-06

    We investigated body image in St. Kitts, a Caribbean island where tourism, international media, and relatively high levels of body fat are common. Participants were men and women recruited from St. Kitts (n = 39) and, for comparison, U.S. samples from universities (n = 618) and the Internet (n = 438). Participants were shown computer generated images varying in apparent body fat level and muscularity or breast size and they indicated their body type preferences and attitudes. Overall, there were only modest differences in body type preferences between St. Kitts and the Internet sample, with the St. Kitts participants being somewhat more likely to value heavier women. Notably, however, men and women from St. Kitts were more likely to idealize smaller breasts than participants in the U.S. samples. Attitudes regarding muscularity were generally similar across samples. This study provides one of the few investigations of body preferences in the Caribbean.

  3. Spatial Distribution of Small Water Body Types in Indiana Ecoregions

    EPA Science Inventory

    Due to their large numbers and biogeochemical activity, small water bodies (SWBs), such as ponds and wetlands, can have substantial cumulative effects on hydrologic and biogeochemical processes. Using updated National Wetland Inventory data, we describe the spatial distribution o...

  4. Spatial Distribution of Small Water Body Types in Indiana Ecoregions

    EPA Science Inventory

    Due to their large numbers and biogeochemical activity, small water bodies (SWBs), such as ponds and wetlands, can have substantial cumulative effects on hydrologic and biogeochemical processes. Using updated National Wetland Inventory data, we describe the spatial distribution o...

  5. [Grafting of carotid arteries].

    PubMed

    Belov, Iu V; Stepanenko, A B; Gens, A P; Bazylev, V V; Seleznev, M N; Savichev, D D

    2005-01-01

    Over 5-years, 167 reconstructive surgeries for stenosis of internal carotid arteries (ICA) were performed in 124 patients. Mean age of the patients was 63.5 years. One hundred and twenty-nine carotid endarterectomies (CEAE) in 86 patients and 38 reconstructive operations of ICA in 38 patients were performed. There were no lethal outcomes in short- and long-term postoperative period. In short-term period after prosthesis of ICA restenosis was revealed in 3% patients, after eversion CEAE in 3% patients the embolism was seen, after standard CEAE restenosis were diagnosed in 8% patients and thrombosis -- in 3%. In long-term period after grafting of ICA the strokes were seen in 3%, stenosis -- in 6% patients, after eversion endarterectomy -- in 0 and 3% patients, and after standard CEAE -- in 3 and 24% patients, respectively. It is concluded that grafting of ICA is adequate surgical method of reconstruction and stroke prevention in specific variants of carotid atherosclerosis.

  6. Carotid surgery following previous carotid endarterectomy is safe and effective.

    PubMed

    Abou-Zamzam, Ahmed M; Moneta, Gregory L; Landry, Gregory J; Yeager, Richard A; Edwards, James M; McConnell, Donald B; Taylor, Lloyd M; Porter, John M

    2002-01-01

    With the perceived high risk of repeat carotid surgery, carotid angioplasty and stenting have been advocated recently as the preferred treatment of recurrent carotid disease following carotid endarterectomy. An experience with the operative treatment of recurrent carotid disease to document the risks and benefits of this procedure is presented. A review of a prospectively acquired vascular registry over a 10-year period (Jan. 1990-Jan. 2000) was undertaken to identify patients undergoing repeat carotid surgery following previous carotid endarterectomy. All patients were treated with repeat carotid endarterectomy, carotid interposition graft, or subclavian-carotid bypass. The perioperative stroke and death rate, operative complications, life-table freedom from stroke, and rates of recurrent stenosis were documented. During the study period 56 patients underwent repeat carotid surgery, comprising 6% of all carotid operations during this period. The indication for operation was symptomatic disease recurrence in 41 cases (73%) and asymptomatic recurrent stenosis >/=80% in 15 cases (27%). The average interval from the prior carotid endarterectomy to the repeat operation was 78 months (range 3 weeks-297 months). The operations performed included repeat carotid endarterectomy with patch angioplasty in 31 cases (55%), interposition grafts in 19 cases (34%), and subclavian-carotid bypass in 6 cases (11%). There were three perioperative strokes with one resulting in death for a perioperative stroke and death rate of 5.4%. One minor transient cranial nerve (CN IX) injury occurred. Mean follow-up was 29 months (range, 1-116 months). Life-table freedom from stroke was 95% at 1 year and 90% at 5 years. Recurrent stenosis (>/=80%) developed in three patients (5.4%) during follow-up, including one internal carotid artery occlusion. Two patients (3.6%) underwent repeat surgery. Repeat surgery for recurrent cerebrovascular disease following carotid endarterectomy is safe and

  7. Prolificacy and Its Relationship with Age, Body Weight, Parity, Previous Litter Size and Body Linear Type Traits in Meat-type Goats

    PubMed Central

    Haldar, Avijit; Pal, Prasenjit; Datta, M.; Paul, Rajesh; Pal, Saumen K.; Majumdar, Debasis; Biswas, Chanchal K.; Pan, Subhransu

    2014-01-01

    Data on age and body weight at breeding, parity, previous litter size, days open and some descriptive body linear traits from 389 meat-type, prolific Black Bengal goats in Tripura State of India, were collected for 3 and 1/2 years (2007 to 2010) and analyzed using logistic regression model. The objectives of the study were i) to evaluate the effect of age and body weight at breeding, parity, previous litter size and days open on litter size of does; and ii) to investigate if body linear type traits influenced litter size in meat-type, prolific goats. The incidence of 68.39% multiple births with a prolificacy rate of 175.07% was recorded. Higher age (>2.69 year), higher parity order (>2.31), more body weight at breeding (>20.5 kg) and larger previous litter size (>1.65) showed an increase likelihood of multiple litter size when compared to single litter size. There was a strong, positive relationship between litter size and various body linear type traits like neck length (>22.78 cm), body length (>54.86 cm), withers height (>48.85 cm), croup height (>50.67 cm), distance between tuber coxae bones (>11.38 cm) and distance between tuber ischii bones (>4.56 cm) for discriminating the goats bearing multiple fetuses from those bearing a single fetus. PMID:25049997

  8. Carotid Artery Stenting 2013: Thumbs up

    PubMed Central

    Wagdi, Philipp

    2013-01-01

    It has been customary for interventional cardiologists involved in carotid artery stenting, to underline non-inferiority of the percutaneous technique versus surgical carotid endarterectomy. To that end, all cause morbidity and mortality figures of both methods are compared. Surgery has, in most large randomized studies, had an edge over stenting in terms of cerebrovascular adverse events. This may have partly been due to occasional indiscriminate indication for stenting in lesions and/or vessels with unfavourable characteristics (severe target vessel tortuosity and calcification, Type III aortic arch, and so on). On one hand, the author pleads for improvement of the excellent results of endarterectomy, by subjecting all patients planned for surgery to a thorough preoperative cardiological work up, including generous invasive investigation, thus reducing the incidence of perioperative myocardial infarction, heart failure and cardiac death. On the other hand, we are convinced that the results of carotid stenting should then be compared to best practice surgery. The rate of neurological adverse event rate after carotid endarterectomy at our institution lies under 0.7% at 30 days postoperatively. Specifically, the goal should be that carotid stenting underbids surgical endarterectomy, also and mainly, in terms of cerebral and cerebrovascular adverse events. Cardiac morbidity and mortality as well as laryngeal nerve palsy should no more be the main arguments for the percutaneous approach. This should easily be possible if patient selection for carotid revascularisation would be approached according to morphological criteria, in analogy with the “Syntax”-score used to optimise revascularisation strategies in coronary artery disease.

  9. Carotid Artery Screening

    MedlinePlus

    ... or radiologist then places the transducer on the skin in various locations, sweeping over the area of interest or angling the sound beam from a different location to better see an area of concern. Doppler sonography and Carotid IMT US are performed using the ...

  10. 16 CFR 1112.11 - What are the types of third party conformity assessment bodies?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... assessment bodies? 1112.11 Section 1112.11 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS REQUIREMENTS PERTAINING TO THIRD PARTY CONFORMITY ASSESSMENT BODIES General Requirements Pertaining to Third Party Conformity Assessment Bodies § 1112.11 What are the types of third party...

  11. A cohort study of duplex Doppler examinations of the carotid artery in primary open angle glaucoma

    PubMed Central

    Marmion, Vincent J; Aldoori, Munther I; Woodcock, John P

    2014-01-01

    Objectives To explore the possibility of pathological change in the common carotid artery at the bifurcation and in the internal carotid artery beyond the bifurcation which could contribute to a reduced diastolic pressure as observed in primary open angle glaucoma. Design Duplex ultrasonic examinations of carotid bifurcations were conducted on 80 patients. Carotid artery defects were allocated into three types: no demonstrable flow defects, internal carotid artery abnormalities and disease in the carotid bulb. Setting Bristol Royal Infirmary Vascular Laboratory. Participants Eighty patients (mean age 69.6 years) providing a total of 160 sides to the analysis. Main outcome measures An estimated central retinal artery pressure, intraocular pressure and field loss were recorded for each side measured. Results Doppler investigations revealed significant levels of pathological change in the internal carotid distinct from changes at the carotid bulb. The disease revealed in the internal carotid artery was significantly associated with intraocular pressure (p = 0.032), with an effect small to medium in magnitude. The Q2 measure, derived from mean arterial pressure and intraocular pressure, was also substantively associated with disease in the internal carotid artery. Both intraocular pressure and the Q2 measure effectively discriminated between groups, with field loss providing rather less discriminating capability. There was a strong trend towards a higher intraocular pressures and a greater visual field loss with internal carotid artery disease. Conclusions Pathological changes in the extra cranial carotid artery in primary open angle glaucoma exceed those in the arteries classified as normal. The presence of disease specifically in the internal carotid artery emphasised the need for a mechanism for the evaluation of the internal carotid apart from the carotid bulb. A basis for clarifying the presence of an ischaemic zone is proposed. PMID:25289141

  12. Carotid Baroreflex Function During Prolonged Exercise

    NASA Technical Reports Server (NTRS)

    Raven, P. B.

    1999-01-01

    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  13. Carotid Baroreflex Function During Prolonged Exercise

    NASA Technical Reports Server (NTRS)

    Raven, P. B.

    1999-01-01

    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  14. Carotid endarterectomy in patients with contralateral carotid artery occlusion.

    PubMed

    Dalainas, Ilias; Nano, Giovanni; Bianchi, Paolo; Casana, Renato; Malacrida, Giovanni; Tealdi, Domenico G

    2007-01-01

    The aim of this study was to evaluate the 30-day outcome of carotid endarterectomy in patients with contralateral carotid artery occlusion and compare it to that in patients with patent contralateral carotid artery. We compared 2,959 carotid endarterectomies performed in patients with patent contralateral internal carotid artery to 373 carotid endarterectomies performed in patients with occlusion of the contralateral carotid artery in the same institute between 1988 and 2004. Patient demographics, surgical and anesthesiological strategy, perioperative neurological and cardiac events, and deaths were compared. The patients were grouped and analyzed according to the presence or absence of symptoms and to their gender. No significant difference was shown in perioperative cardiological and neurological events and deaths in patients with contralateral carotid occlusion versus patients without contralateral carotid occlusion. Females had significant more neurological events than males, in both the asymptomatic (P < 0.001) and symptomatic (P = 0.02) groups. Concomitant occlusion of the contralateral carotid artery was not associated with increased risk of perioperative cardiological or neurological adverse events. However, female gender was associated with higher risk for adverse neurological events.

  15. Cost varies with procedure type in pediatric GI foreign bodies.

    PubMed

    Kennedy, Rachel S; Starker, Rebecca A; Feldman, Kelly A; Tashiro, Jun; Perez, Eduardo A; Mendoza, Fernando G; Sola, Juan E

    2017-03-01

    In pediatric cases of ingested foreign bodies, gastrointestinal foreign bodies (GIFB) have distinct factors contributing to longer and more costly hospitalizations. Patients admitted with ingested foreign bodies were identified in the Kids' Inpatient Database (1997-2009). Overall, 7480 cases were identified. Patients were most commonly <5years of age (44%), male (54%), and Caucasian (57%). A total of 2506 procedures were performed, GI surgical procedures (57%) most frequently, followed by GI endoscopy (24%), esophagoscopy (11%), and bronchoscopy - in cases of inhaled objects (9%). On multivariate analysis, length of stay increased when cases were associated with intestinal obstruction (OR=1.7), esophageal perforation (OR=40.0), intestinal perforation (OR=4.4), exploratory laparotomy (OR=1.9), and gastric (OR=2.9), small bowel (OR=1.5), or colon surgery (OR=2.5), all p<0.02. Higher total charges (TC) were associated with intestinal obstruction (OR=2.0), endoscopy of esophagus (OR=1.8), stomach (OR=2.1), or colon (OR=3.3), and exploratory laparotomy (OR=3.6) or surgery of stomach (OR=5.6), small bowel (OR=6.4), or colon (OR=3.4), all p<0.001. Surgical or endoscopic procedures are performed in approximately one third of GIFB cases. Associated psychiatric disorder or self-inflicted injury is seen in more than 20% of GIFB patients. Resource utilization is determined heavily by associated diagnoses and treatment procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. [Treatment of carotid cavernous fistulas].

    PubMed

    Solymosi, L

    2004-11-01

    The diagnosis and treatment of carotid cavernous fistulas (CCF) is an interdisciplinary challenge for both ophthalmologists and interventional neuroradiologists. According to the clinical signs and symptoms the tentative diagnosis is made by the ophthalmologist. It is the task of the neuroradiologist to ascertain this diagnosis by intra-arterial angiography. If a fistula is suspected this invasive diagnostic procedure is indispensable, not only to establish the diagnosis but also to classify those types of fistula with an unfavourable spontaneous course possibly resulting in intracranial haemorrhage. The indication for therapy is based on the clinical symptoms and the angiographic findings. In a number of cases no therapy is required. Since a fistula may change over time, these patients have to be under close ophthalmological surveillance. In many patients a conservative therapeutic approach with manual compression of the carotid artery is sufficient as a fIrst step. Invasive treatment is performed via the endovascular approach in almost all cases. Direct CCF are predominantly treated transarterially with detachable balloons and/or coils. Recently, intracranial stents have been used increasingly. The embolisation of indirect CCF is most effective using the transvenous access with coils. There are several approaches to the cavernous sinus. The interventional occlusion of CCF is nowadays a very effective treatment associated with a comparatively high cure rate and low incidence of complications. By close cooperation between ophthalmologists and neuroradiologists the patients can be protected against visual loss, the development of a secondary glaucoma, and, most importantly, against intracranial haemorrhage.

  17. Impact of body mass index on the predictive ability of body fat distribution for type 2 diabetes risk in Koreans.

    PubMed

    Kim, C-H; Kim, H-K; Kim, E-H; Bae, S-J; Park, J-Y

    2012-11-01

    The optimal anthropometric measure of obesity or body fat distribution that best predicts the risk of Type 2 diabetes in Asians is unclear. Moreover, it has not been determined whether BMI modifies the effect of body fat distribution on diabetes risk in Asians. We analysed the anthropometric and laboratory data of 7658 non-diabetic Korean adults (5061 men and 2597 women, aged 20-79 years) who underwent routine medical check-ups at 5-year intervals. BMI, waist circumference, waist-to-height ratio, and bioelectrical impedance (to calculate fat mass and per cent body fat) were measured at baseline. Of the 7658 participants, 278 subjects (3.6%) developed diabetes over 5 years. Each of the anthropometric measures of general obesity (BMI, fat mass, per cent body fat) and central body fat distribution (waist circumference and waist-to-height ratio) was a good predictor of Type 2 diabetes. However, when the areas under the receiver-operating characteristic curves were compared, BMI (0.697; 95% CI, 0.669-0.725), waist circumference (0.709, 0.682-0.736) and waist-to-height ratio (0.718, 0.692-0.743) were better predictors of diabetes risk than fat mass (0.672, 0.643-0.700) or per cent body fat (0.657, 0.628-0.686). In the low- (< 23 kg/m(2)) and mid- (23-27 kg/m(2)) BMI groups, the addition of waist-to-height ratio or waist circumference to BMI could improve the prediction of diabetes risk. BMI, waist circumference and waist-to-height ratio were good predictors of Type 2 diabetes risk in Koreans. In non-obese or less obese subjects, measures of central body fat distribution can help improve the prediction of Type 2 diabetes risk when added to measures of general obesity. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  18. Wall shear stress evolution in carotid artery bifurcation

    NASA Astrophysics Data System (ADS)

    Bernad, S. I.; Bosioc, A. I.; Totorean, A. F.; Petre, I.; Bernad, E. S.

    2017-07-01

    The steady flow in an anatomically realistic human carotid bifurcation was simulated numerically. Main parameters such as wall shear stress (WSS), velocity profiles and pressure distributions are investigated in the carotid artery, namely in bifurcation and sinusoidal enlargement regions. Flow in the carotid sinus is dominated by a single secondary vortex motion accompanied by a strong helical flow. This type of flow is induced primarily by the curvature and asymmetry of the in vivo geometry. Low wall shear stress concentration occurs at both the anterior and posterior aspects of the proximal internal bulb.

  19. Polymorphisms +45T>G and +276G>T of the adiponectin gene does not affect plasma adiponectin level and carotid intima-media thickness in patients with diabetes mellitus type 2.

    PubMed

    Nikolajević-Starčević, J; Pleskovič, A; Santl Letonja, M; Jenko Pražnikar, Z; Petrovič, D

    2014-10-01

    Despite increasing evidence of adiponectin's anti-inflammatory and antiatherogenic effects, its role in atherogenesis remains uncertain. The aim of the present study is to investigate the association between +45T>G and +276G>T polymorphisms of the adiponectin gene and both plasma adiponectin levels and carotid intima-media thickness in patients with diabetes mellitus type 2. 301 diabetic patients, divided into three categories on the basis on BMI were enrolled in the study. Carotid intima-media thickness (CIMT) was assessed ultrasonographically. Plasma adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Genotypes were determined by real-time PCR. Adiponectin level and prevalence of the G allele of 45T>G polymorphism decreased significantly with increasing BMI category. G allele of +45T>G polymorphism was associated with higher plasma adiponectin level only after adjustment for age, sex and BMI. No statistically significant difference in CIMT and +276T>G genotypes distribution was observed between BMI categories. None of the polymorphisms as well as plasma adiponectin level was associated with CIMT after adjustment for covariates. The G allele of the +45T>G polymorphism is not independently associated with plasma adiponectin level and is not associated with CIMT. +276G>T polymorphism is not associated with plasma adiponectin levels and CIMT in diabetic patients.

  20. Sport type and interpersonal and intrapersonal predictors of body dissatisfaction in high school female sport participants.

    PubMed

    Karr, Trisha M; Davidson, Denise; Bryant, Fred B; Balague, Gloria; Bohnert, Amy M

    2013-03-01

    Through multiple group structural equation modeling analyses, path models were used to test the predictive effects of sport type and both interpersonal (i.e., mothers' body dissatisfaction, family dynamics) and intrapersonal factors (i.e., athletic self-efficacy, body mass index [BMI]) on high school female sport participants' (N=627) body dissatisfaction. Sport types were classified as esthetic/lean (i.e., gymnastics), non-esthetic/lean (i.e., cross-country), or non-esthetic/non-lean (i.e., softball). Most participants reported low body dissatisfaction, and body dissatisfaction did not differ across sport types. Nevertheless, mothers' body dissatisfaction was positively associated with daughters' body dissatisfaction for non-esthetic/lean and non-esthetic/non-lean sport participants, and high family cohesion was predictive of body dissatisfaction among non-esthetic/lean sport participants. Across sport types, higher BMI was associated with greater body dissatisfaction, whereas greater athletic self-efficacy was associated with lower body dissatisfaction. These findings highlight the complex relationship between interpersonal and intrapersonal factors and body dissatisfaction in adolescent female sport participants. Copyright © 2012. Published by Elsevier Ltd.

  1. Are Carotid Stent Fractures Clinically Significant?

    SciTech Connect

    Garcia-Toca, Manuel; Rodriguez, Heron E.; Naughton, Peter A.; Keeling, Aiofee; Phade, Sachin V.; Morasch, Mark D.; Kibbe, Melina R.; Eskandari, Mark K.

    2012-04-15

    Purpose: Late stent fatigue is a known complication after carotid artery stenting (CAS) for cervical carotid occlusive disease. The purpose of this study was to determine the prevalence and clinical significance of carotid stent fractures. Materials and Methods: A single-center retrospective review of 253 carotid bifurcation lesions treated with CAS and mechanical embolic protection from April 2001 to December 2009 was performed. Stent integrity was analyzed by two independent observers using multiplanar cervical plain radiographs with fractures classified into the following types: type I = single strut fracture; type II = multiple strut fractures; type III = transverse fracture; and type IV = transverse fracture with dislocation. Mean follow-up was 32 months. Results: Follow-up imaging was completed on 106 self-expanding nitinol stents (26 closed-cell and 80 open-cell stents). Eight fractures (7.5%) were detected (type I n = 1, type II n = 6, and type III n = 1). Seven fractures were found in open-cell stents (Precise n = 3, ViVEXX n = 2, and Acculink n = 2), and 1 fracture was found in a closed-cell stent (Xact n = 1) (p = 0.67). Only a previous history of external beam neck irradiation was associated with fractures (p = 0.048). No associated clinical sequelae were observed among the patients with fractures, and only 1 patient had an associated significant restenosis ({>=}80%) requiring reintervention. Conclusions: Late stent fatigue after CAS is an uncommon event and rarely clinically relevant. Although cell design does not appear to influence the occurrence of fractures, lesion characteristics may be associated risk factors.

  2. Aerodynamics on a transport aircraft type wing-body model

    NASA Technical Reports Server (NTRS)

    Schmitt, V.

    1982-01-01

    The DFLR-F4 wing-body combination is studied. The 1/38 model is formed by a 9.5 aspect ratio transonic wing and an Airbus A 310 fuselage. The F4 wing geometrical characteristics are described and the main experimental results obtained in the S2MA wind tunnel are discussed. Both wing-fuselage interferences and viscous effects, which are important on the wing due to a high rear loading, are investigated by performing 3D calculations. An attempt is made to find their limitations.

  3. Management of carotid 'blowout' with endovascular stent grafts.

    PubMed

    Warren, Frank M; Cohen, James I; Nesbit, Gary M; Barnwell, Stanley L; Wax, Mark K; Andersen, Peter E

    2002-03-01

    Since 1992, endovascular techniques for vascular occlusion and stenting have evolved significantly. Endovascular occlusion of the carotid artery has been used in the management of carotid "blowout." Although it seems logical to expand this application to the use of arterial stents to repair rather than occlude the artery when cerebral cross-circulation is inadequate, concerns remain regarding the placement of a foreign body in a contaminated field. The purpose of the present report is to describe our experience with endovascular stents for control of carotid hemorrhage. Retrospective case review. Retrospective review of three cases of acute or threatened carotid hemorrhage managed with endovascular stent placement. Two patients presented with acute carotid blowout, and one patient with a probable sentinel bleed. All patients previously had been heavily treated with surgery and irradiation: Two had developed pharyngocutaneous fistulas, and one had an open wound filled with tumor that surrounded the carotid artery. All were thought to be at significant risk for stroke if the carotid artery was occluded. In all three patients, stent placement resolved the acute hemorrhage. Mean duration of follow-up was 8.3 months. In two patients, the stent became exposed, ultimately thrombosed or extruded, or both. The third patient had no residual sequelae of stenting but died 3 months later. When an unacceptable risk of cardiovascular accident makes occlusion unwise, acute carotid hemorrhage can be successfully managed with directed placement of endovascular stents, but the long-term sequelae of placing these foreign bodies in a field with ongoing contamination make this a temporizing rather than permanent measure for use while more definitive long-term solutions are pursued.

  4. Adolescent build plotting on body composition chart and the type of diabetes mellitus.

    PubMed

    Park, Hye Won; Kim, Yong Hyuk; Cho, Myunghyun; Kwak, Byung Ok; Kim, Kyo Sun; Chung, Sochung

    2012-11-01

    Although the prevalence of type 2 diabetes is increasing, there are cases difficult to categorize into certain type in pediatric diabetic patients. The aims of this study were to detect and choose a proper treatment modality for atypical cases of diabetes mellitus, using the body composition chart. We conducted a retrospective study from August 2005 to 2012 with patients who visited Konkuk University Medical Center, and were diagnosed with diabetes mellitus. The medical records were reviewed for the anthropometric data and indices of body composition. The subjects were grouped by the type of diabetes and gender. We constructed a body composition chart plotting fat free mass index and fat mass index (FMI). Body mass index and all body composition indices were higher in type 2 diabetes, in each gender in analysis with Mann-Whitney test. Significant determinant of diabetes type was revealed as FMI and contributing factors on FMI were analyzed with regression analysis. Six atypical cases were identified by a body composition chart including non-obese type 2 diabetes showing suboptimal growth with lower BMI related to relatively lower insulin secretion and type 1 diabetes with insulin resistance resulted from obesity. Body composition chart analysis might be useful in characterization of diabetes type and detection of atypical cases and early adjustment of diabetes management strategy.

  5. Adolescent Build Plotting on Body Composition Chart and the Type of Diabetes Mellitus

    PubMed Central

    Park, Hye Won; Kim, Yong Hyuk; Cho, Myunghyun; Kwak, Byung Ok; Kim, Kyo Sun

    2012-01-01

    Although the prevalence of type 2 diabetes is increasing, there are cases difficult to categorize into certain type in pediatric diabetic patients. The aims of this study were to detect and choose a proper treatment modality for atypical cases of diabetes mellitus, using the body composition chart. We conducted a retrospective study from August 2005 to 2012 with patients who visited Konkuk University Medical Center, and were diagnosed with diabetes mellitus. The medical records were reviewed for the anthropometric data and indices of body composition. The subjects were grouped by the type of diabetes and gender. We constructed a body composition chart plotting fat free mass index and fat mass index (FMI). Body mass index and all body composition indices were higher in type 2 diabetes, in each gender in analysis with Mann-Whitney test. Significant determinant of diabetes type was revealed as FMI and contributing factors on FMI were analyzed with regression analysis. Six atypical cases were identified by a body composition chart including non-obese type 2 diabetes showing suboptimal growth with lower BMI related to relatively lower insulin secretion and type 1 diabetes with insulin resistance resulted from obesity. Body composition chart analysis might be useful in characterization of diabetes type and detection of atypical cases and early adjustment of diabetes management strategy. PMID:23166422

  6. Lower urinary tract function in dementia of Lewy body type

    PubMed Central

    Sakakibara, R; Ito, T; Uchiyama, T; Asahina, M; Liu, Z; Yamamoto, T; Yamanaka, Y; Hattori, T

    2005-01-01

    Methods: We examined 11 patients (eight men, three women; age range 65–81; disease duration 2–14 years) with probable DLB. Urodynamic studies consisted of: measurement of postvoid residual in all patients, uroflowmetry in five, and electromyography (EMG) cystometry in seven. Results: All patients had symptoms of LUT: urinary incontinence (urgency type/functional type due to dementia and immobility/both urgency and stress type in 7/2/1 patients, respectively); night-time frequency; urgency; and daytime frequency and voiding difficulty. Seven had postvoid residuals, and three had residual urine volume >100 ml. Decreased urinary flow was seen in all five and detrusor overactivity in 5/7 patients who underwent flowmetry and EMG cystometry, respectively. Low compliance detrusor (storage phase, n = 2; with bethanechol supersensitivity), an underactive detrusor (n = 4), an acontractile detrusor (n = 1), and detrusor–sphincter dyssynergia (voiding phase) (n = 1) were also seen; 2/3 patients who underwent motor unit potential analysis had neurogenic changes. Conclusion: LUT dysfunction is a common feature in DLB, not only due to dementia and immobility, but also to central and peripheral types of somato-autonomic dysfunction. PMID:15834036

  7. Carotid-cardiac baroreflex influence on forearm vascular resistance during low level LBNP

    NASA Technical Reports Server (NTRS)

    Ludwig, David

    1990-01-01

    Twelve healthy males were tested at low levels of lower body negative pressure (LBNP) with and without artificial stimulation of the carotid-cardiac baroreceptors. The carotid-cardiac baroreceptors were stimulated by applying a pressure of 10 mmHg to the carotid artery via a pressurized neck chamber. During the procedure, forearm blood flow (FBF) and forearm vascular resistance (FVR) were measured using a Whitney mercury silastic strain gauge technique. FBF decreased while FVR increased with increased intensity of LBNP. Both FBF and FVR were unaffected by carotid-cardiac baroreceptor stimulation.

  8. Management of Carotid Artery Trauma

    PubMed Central

    Lee, Thomas S.; Ducic, Yadranko; Gordin, Eli; Stroman, David

    2014-01-01

    With increased awareness and liberal screening of trauma patients with identified risk factors, recent case series demonstrate improved early diagnosis of carotid artery trauma before they become problematio. There remains a need for unified screening criteria for both intracranial and extracranial carotid trauma. In the absence of contraindications, antithrombotic agents should be considered in blunt carotid artery injuries, as there is a significant risk of progression of vessel injury with observation alone. Despite CTA being used as a common screening modality, it appears to lack sufficient sensitivity. DSA remains to be the gold standard in screening. Endovascular techniques are becoming more widely accepted as the primary surgical modality in the treatment of blunt extracranial carotid injuries and penetrating/blunt intracranial carotid lessions. Nonetheless, open surgical approaches are still needed for the treatment of penetrating extracranial carotid injuries and in patients with unfavorable lesions for endovascular intervention. PMID:25136406

  9. Vascular tone and reactivity to serotonin in the internal and external carotid vascular beds of the dog.

    PubMed

    Vidrio, H; Hong, E

    1976-04-01

    The effects of intra-arterial infusions of serotonin on internal and external carotid blood flow were determined in anesthetized dogs by electromagnetic flow measurements. Serotonin decreased flow in the internal carotid and increased it in the external carotid. Both responses were blocked by the serotonin antagonist methysergide. The alpha adrenergic antagonist zolertine, the ganglionic blocking agent chlorisondamine and the vasodilator diazoxide blocked external carotid dilator responses but did not modify constriction in the internal carotid. Blockade of external carotid responses by the three drugs was also demonstrated in experiments in which this bed was perfused at a constant rate. These results indicate that the internal and external carotid vascular beds of the dog react in opposite ways to serotonin, that both responses are mediated through the same type of serotonin receptors and that the dilator responses of the external carotid are dependent on vascular tone.

  10. Obesity and carotid artery remodeling

    PubMed Central

    Kozakova, M; Palombo, C; Morizzo, C; Højlund, K; Hatunic, M; Balkau, B; Nilsson, P M; Ferrannini, E

    2015-01-01

    Background/Objective: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP). Subjects/Methods: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24–159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age). Results: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 μm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 μm, P=0.001, P<0.05 and P=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, P<0.0001). As compared with gender- a