Region Of Carotid Bifurcation Research Articles

Morphological feature and mapping inflammation in classified carotid plaques in symptomatic and asymptomatic patients: A hybrid 18F-FDG PET/MR study.

To investigate morphological and inflamed-metabolism features of carotid atherosclerotic plaques between symptomatic and asymptomatic patients with hybrid 18F-FDG PET/MR imaging. A total of 20 symptomatic and 20 asymptomatic patients with carotid plaques underwent hybrid 18F-FDG PET/MR scans. American heart association (AHA) lesion types were classified, and plaque compositions were further determined on consecutive MRI axial sections in both carotid arteries. 18F-FDG uptake in carotid arteries was quantified using region of interest (ROI) methods based on maximum standardized uptake values (SUVmax) and target-to-background ratio (TBR) on corresponding positron emission tomography (PET) images. A total of seventy-one carotid plaques were quantified. AHA type VI was the most common (23, 32.4%), and the region of carotid bifurcation was the most common place presenting lesions (32, 45.1%). Compared with the asymptomatic group, the prevalence of high-risk features including plaque burden, lumen stenosis, maximum necrotic core area, and maximum intra-plaque hemorrhage area increased in the symptomatic group. Carotid TBR values of plaque in symptomatic group (TBR = 2.56 ± 0.34) was significantly higher than that in asymptomatic group (TBR = 1.57 ± 0.14) (P < 0.05). hs-CRP is an independent risk factor for the stability of carotid plaque. The correlation between normalized wall index (NWI) and TBR values was significantly positive in both the symptomatic and the asymptomatic groups (P < 0.01), and both NWI and TBR were significantly correlated with the level of hs-CRP (P < 0.01). Integrated 18F-FDG PET/MR scans presented distinct risk features between symptomatic and asymptomatic patients. Hybrid 18F-FDG PET/MR systems combined with clinical serum hs-CRP may help distinguish vulnerable carotid plaques.

Comparative morphological and molecular studies on the oxygen-chemoreceptive cells in the carotid body and fish gills.

Oxygen-chemoreceptive cells play critical roles for the respiration control. This review summarizes the chemoreceptive cells in the carotid body and fish gills from a morphological and molecular perspective. The cells synthesize and secrete biogenic amines, neuropeptides, and neuroproteins and also express many signaling molecules and transcription factors. In mammals, birds, reptiles, and amphibians, the carotid body primordium is consistently formed in the wall of the third arch artery which gives rise to the common carotid artery and the basal portion of the internal carotid artery. Consequently, the carotid body is located in the carotid bifurcation region, except birds in which the organ is situated at the lateral side of the common carotid artery. The carotid body receives branches of the cranial nerves IX and/or X dependent on the location of the organ. The glomus cell progenitors in mammals and birds are derived from the neighboring ganglion, i.e., the superior cervical sympathetic ganglion and the nodose ganglion, respectively, and immigrate into the carotid body primordium, constituting a solid cell cluster. In other animal species, the glomus cells are dispersed singly or forming small cell groups in intervascular stroma of the carotid body. In fishes, the neuroepithelial cells, corresponding to the glomus cells, are distributed in the gill filaments and lamellae. All oxygen-chemoreceptive cells sensitively respond to acute or chronic hypoxia, exhibiting degranulation, hypertrophy, hyperplasia, and upregulated expression of many genes.

Pulmonary hypertension in patients with hemodynamically significant atherosclerotic lesion of a common carotid artery: new pathophysiological mechanisms of the disease

Background. Pulmonary hypertension (PH) is a severe pathology that often leads a patient to death or disability. Recently, the development of PH associated with activation of the sympathetic nervous system (SNS) has been of interest. Some results obtained in an acute experiment on rats showed that activation of the carotid bodies of one external carotid artery is a sufficient stimulus to increase the tone of pulmonary arteries. Obviously, this effect is mediated by the sympathetic nervous system. However, the long-term effects of unilateral hypoxia of the carotid bodies on the morphofunctional state of the pulmonary arteries are not described in the literature.&#x0D; Aim. Effect assessment of common carotid artery bifurcation region ischemia due to the atherosclerotic process on the pulmonary arteries in patients.&#x0D; Materials and methods. The retrospective study was conducted in the Burdenko Neurosurgical Center and in the National Medical Research Center for Cardiology. A total of 60 case histories were analyzed in detail. All patients underwent Duplex scanning of the brachiocephalic arteries, as well as transthoracic echocardiography. The study included patients with atherosclerotic plaque in the area of the common carotid artery bifurcation on either one side or both. Exclusion criteria consisted of diseases that lead to the development of PH. The relationship between the presence of hemodynamically significant atheroma and the development of PH was evaluated.&#x0D; Results. Patients were divided into two groups those with hemodynamically significant atherosclerotic plaque in the common carotid artery bifurcation region at least on one side (more than 75% of the vascular obstruction) and hemodynamically insignificant atheromas in the common carotid artery bifurcation region on one or both sides (less than 45%). Among patients from the first group, 52.8% of the patients had signs of PH. Among patients from the second group, only 16.7% of the patients had signs of PH. The difference in the frequency of PH occurrence between the two selected groups is statistically significant (p=0.005). There were no differences in red blood cells number, platelets number, glucose concentration and lipid composition of blood plasma.&#x0D; Conclusion. Activation of SNS due to hemodynamically significant atherosclerotic plaque in the area of the bifurcation of the common carotid artery may be an independent mechanism for the development of PH.&#x0D; Key words: pulmonary hypertension, carotid bodies, atherosclerotic plaque, sympathectomy of pulmonary arteries.

Application of flow diverters in the treatment of aneurysms in the internal carotid artery bifurcation region.

The treatment of aneurysms in the internal carotid bifurcation region (ICABR), including aneurysms of the true internal carotid artery (ICA) terminus, those inclined on the proximal A1 or M1 segments or at the most distal pre-bifurcation (ICA) segment, is often challenging in microsurgical clipping and endovascular surgery. Few reports had discussed flow diversion as a therapeutic option for this group. This was a retrospective study analysing flow diversion in treating ICABR aneurysms. Seven patients harbouring eight aneurysms in the ICABR were treated with flow diversion. Five aneurysms were inclined on the proximal A1 segment, and three were located at the most distal pre-bifurcation segment. Patients' demographics, presentation, procedure technical description, angiographic and clinical follow-up were recorded. PubMed and Ovid MEDLINE were also reviewed for articles published in English, including case series or case reports, for ICABR aneurysms treated with flow diverters. All patients except one underwent angiographic follow-up. The Karman-Byrne occlusion scale was used to determine the occlusion rate. All six patients with documented angiographic follow-up had a class IV occlusion score. No permanent or transient neurological or non-neurological complications were encountered in this study. Treating ICABR aneurysms using flow diversion is feasible, with a promising angiographic occlusion rate. Further studies are needed to analyse long-term clinical and angiographic results.

68Ga]Pentixafor PET/MR imaging of chemokine receptor 4 expression in the human carotid artery

PurposeType 4 chemokine receptor (CXCR4) plays an important role in immune cell migration during the atherosclerosis progression. We aimed to evaluate [68Ga]Pentixafor positron emission tomography (PET) in combination magnetic resonance imaging (MRI) for in vivo quantification of CXCR4 expression in carotid plaques.MethodsSeventy-two patients with lymphoma were prospectively scheduled for whole body [68Ga]Pentixafor PET/MRI with an additional T2-weighted carotid sequence. Volumes of interest (VOIs) were drawn along the carotid bifurcation regions, and the maximum tissue-to-blood ratios (TBR) of [68Ga]Pentixafor uptake were calculated. Lesions were categorized into non-eccentric (n = 27), mild eccentric (n = 67), moderately (n = 41) and severely (n = 19) eccentric carotid atherosclerosis. A different cohort of symptomatic patients (n = 10) with carotid stenosis scheduled for thrombendarterectomy (TEA) was separately imaged with 3T MRI with dedicated plaque sequences (time of flight, T1-, and T2-weighted). MRI findings were correlated with histochemical assessment of intact carotid plaques.ResultsAt hybrid PET/MRI, we observed significantly increased [68Ga]Pentixafor uptake in mildly (mean TBRmax = 1.57 ± 0.27, mean SUVmax = 2.51 ± 0.39), moderately (mean TBRmax = 1.64 ± 0.37, mean SUVmax = 2.61 ± 0.55) and severely eccentric carotids (mean TBRmax = 1.55 ± 0.26, mean SUVmax = 2.40 ± 0.44) as compared to non-eccentric carotids (mean TBRmax = 1.29 ± 0.21, mean SUVmax = 1.77 ± 0.42) (p ≤ 0.05). Histological findings from TEA confirmed that prominent CXCR4 expression was localized within inflamed atheromas and preatheromas. Co-localization of cellular CXCR4 and CD68 expression in the plaque was observed by immunofluorescence staining.ConclusionsIn vivo evaluation of CXCR4 expression in carotid atherosclerotic lesions is feasible using [68Ga]Pentixafor PET/MRI. In atherosclerotic plaque tissue, CXCR4 expression might be used as a surrogate marker for inflammatory atherosclerosis.

Early Onset of Atherosclerosis of The Carotid Bifurcation in newborn cadavers

The anatomy of arterial bifurcations affects blood flow and has a significant role in the development of vascular disease. Therefore, it is important to know the structural characteristics of the Common Carotid Artery (CCA) and its branches for early onset of atherosclerosis in newborns. The present study was conducted to evaluate the characteristics of CCA in newborn cadavers. Eight carotid arteries obtained from newborn cadavers were used. The outflow to inflow area ratios was calculated to evaluate vessel diameters. Additionally, scanning electron and light microscopic investigations were conducted with tissue samples. The brachial artery of each cadaver was used as controls. Correlation between area ratios and atherosclerotic endothelial damage was determined. Light microscopic investigations demonstrated that control group sections showed no positivity for Oil red O staining, while carotid bifurcation regions depicted widespread occurrence of intimal lipid accumulations. Scanning electron microscopic examination of control group sections presented regular endothelial topography, while carotid bifurcation region topography exhibited numerous blood cells and separated endothelial cells. Fibrin accumulation on endothelial surface in low area ratios was another important finding in the examination of its endothelial surface degeneration. The above-mentioned morphological findings seemed to be quite parallel to outflow to inflow area ratio data favouring low area and degeneration. The correlation between area ratios and the histological characteristic of cerebral vessels of newborn cadavers indicate that early stages of atherosclerosis began in early embryologic life.

Assessment of shear stress related parameters in the carotid bifurcation using mouse-specific FSI simulations

The ApoE−/− mouse is a common small animal model to study atherosclerosis, an inflammatory disease of the large and medium sized arteries such as the carotid artery. It is generally accepted that the wall shear stress, induced by the blood flow, plays a key role in the onset of this disease. Wall shear stress, however, is difficult to derive from direct in vivo measurements, particularly in mice. In this study, we integrated in vivo imaging (micro-Computed Tomography-µCT and ultrasound) and fluid–structure interaction (FSI) modeling for the mouse-specific assessment of carotid hemodynamics and wall shear stress. Results were provided for 8 carotid bifurcations of 4 ApoE−/− mice. We demonstrated that accounting for the carotid elasticity leads to more realistic flow waveforms over the complete domain of the model due to volume buffering capacity in systole. The 8 simulated cases showed fairly consistent spatial distribution maps of time-averaged wall shear stress (TAWSS) and relative residence time (RRT). Zones with reduced TAWSS and elevated RRT, potential indicators of atherosclerosis-prone regions, were located mainly at the outer sinus of the external carotid artery. In contrast to human carotid hemodynamics, no flow recirculation could be observed in the carotid bifurcation region.

Parametric uncertainty and global sensitivity analysis in a model of the carotid bifurcation: Identification and ranking of most sensitive model parameters

In computational cardiovascular models, parameters are one of major sources of uncertainty, which make the models unreliable and less predictive. In order to achieve predictive models that allow the investigation of the cardiovascular diseases, sensitivity analysis (SA) can be used to quantify and reduce the uncertainty in outputs (pressure and flow) caused by input (electrical and structural) model parameters.In the current study, three variance based global sensitivity analysis (GSA) methods; Sobol, FAST and a sparse grid stochastic collocation technique based on the Smolyak algorithm were applied on a lumped parameter model of carotid bifurcation. Sensitivity analysis was carried out to identify and rank most sensitive parameters as well as to fix less sensitive parameters at their nominal values (factor fixing). In this context, network location and temporal dependent sensitivities were also discussed to identify optimal measurement locations in carotid bifurcation and optimal temporal regions for each parameter in the pressure and flow waves, respectively.Results show that, for both pressure and flow, flow resistance (R), diameter (d) and length of the vessel (l) are sensitive within right common carotid (RCC), right internal carotid (RIC) and right external carotid (REC) arteries, while compliance of the vessels (C) and blood inertia (L) are sensitive only at RCC. Moreover, Young’s modulus (E) and wall thickness (h) exhibit less sensitivities on pressure and flow at all locations of carotid bifurcation. Results of network location and temporal variabilities revealed that most of sensitivity was found in common time regions i.e. early systole, peak systole and end systole.

A two-decade experience of head and neck paragangliomas in a whole population-based single centre cohort.

Paragangliomas are rare neuroendocrine tumours arising from neural crest-derived tissue. In the head and neck region typical locations are the carotid bifurcation, vagal nerve or jugulotympanic region. Paragangliomas are normally benign, and malignant transformation is rare. During the past decade the understanding of the genetic and molecular aetiology has had an important clinical impact on the management of PGs. This is a retrospective review of all histologically verified paragangliomas diagnosed and managed at an academic tertiary care referral centre between 1990 and 2010. Data on age, sex, symptoms, tumour location, management and follow-up were recorded. There were 64 patients with 74 tumours. Thirty-six per cent of the tumours were located in the carotid body region, 48 % in the jugulotympanic region and 15 % in the vagal nerve. One tumour was located in the dorsal neck. Most (95 %) of the patients were treated primarily with surgery and with curative intent. Definitive radiation therapy was primarily given to two patients. Recurrent or residual tumours were treated with surgery in three patients and with radiation therapy in nine patients. The typical long-term post-operative sequel was vocal cord paralysis. Local recurrence was found in 6 % of patients. Symptoms and findings related to paragangliomas are variable and management should be individualized. Surgery remains the primary choice of the current treatment options, but often is challenging and warrants a multidisciplinary approach. We present an algorithm on the management of head and neck paragangliomas based on current knowledge.

“Carotid body tumour: A case report”

Carotid body tumours are rare, slowly growing benign neoplasm arising from paraganglionic cells at the region of carotid bifurcation. They are the rare tumours of head and neck region derived from neural crest. We report here a case of carotid body tumour which was successfully treated surgically. Key Word: Carotid body tumour ; Paraganglioma ; Chemodectoma

Automatic segmentation of the carotid artery bifurcation region with a region-growing approach

The original contribution is to propose an intensity-based segmentation algorithm for extracting the carotid artery bifurcation region and validate the proposed solution on real patients’ CTA data. The proposed homogeneity criteria allow the production of locally smooth segmentations and prevent excessive growth into neighboring tissues of similar densities. The obtained segmentation results are compared to manual findings of a radiologist and measured with the Dice similarity coefficient (D si ). This technique has been shown to be a reliable tool as effective as top state-of-the-art methods (D si =93.6%±3.5% ).

Carotid Intima‐Media Thickness Progression in HIV‐Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation

BackgroundShear stress gradients and inflammation have been causally associated with atherosclerosis development in carotid bifurcation regions. The mechanism underlying higher levels of carotid intima-media thickness observed among HIV-infected individuals remains unknown.Methods and ResultsWe measured carotid intima-media thickness progression and development of plaque in the common carotid, bifurcation region, and internal carotid artery in 300 HIV-infected persons and 47 controls. The median duration of follow-up was 2.4 years. When all segments were included, the rate of intima-media thickness progression was greater in HIV-infected subjects compared with controls after adjustment for traditional risk factors (0.055 vs. 0.024 mm/year, P=0.016). Rate of progression was also greater in the bifurcation region (0.067 vs. 0.025 mm/year, P=0.042) whereas differences were smaller in the common and internal regions. HIV-infected individuals had a greater incidence of plaque compared with controls in the internal (23% vs. 6.4%, P=0.0037) and bifurcation regions (34% vs. 17%, P=0.014). Among HIV-infected individuals, the rate of progression in the bifurcation region was more rapid compared with the common carotid, internal, or mean intima-media thickness; in contrast, progression rates among controls were similar at all sites. Baseline hsCRP was elevated in HIV-infected persons and was a predictor of progression in the bifurcation region.ConclusionsAtherosclerosis progresses preferentially in the carotid bifurcation region in HIV-infected individuals. hsCRP, a marker of inflammation, is elevated in HIV and is associated with progression in the bifurcation region. These data are consistent with a model in which the interplay between hemodynamic shear stresses and HIV-associated inflammation contribute to accelerated atherosclerosis. (J Am Heart Assoc. 2012;1:jah3-e000422 doi: 10.1161/JAHA.111.000422.)Clinical Trial RegistrationURL: http://clinicaltrials.gov. Unique identifier: NCT01519141

Magnetic Resonance Imaging of Carotid Atherosclerotic Plaque in Clinically Suspected Acute Transient Ischemic Attack and Acute Ischemic Stroke

Carotid atherosclerotic plaque rupture is thought to cause transient ischemic attack (TIA) and ischemic stroke (IS). Pathological hallmarks of these plaques have been identified through observational studies. Although generally accepted, the relationship between cerebral thromboembolism and in situ atherosclerotic plaque morphology has never been directly observed noninvasively in the acute setting. Consecutive acutely symptomatic patients referred for stroke protocol magnetic resonance imaging/angiography underwent additional T1- and T2-weighted carotid bifurcation imaging with the use of a 3-dimensional technique with blood signal suppression. Two blinded reviewers performed plaque gradings according to the American Heart Association classification system. Discharge outcomes and brain magnetic resonance imaging results were obtained. Image quality for plaque characterization was adequate in 86 of 106 patients (81%). Eight TIA/IS patients with noncarotid pathogenesis were excluded, yielding 78 study patients (38 men and 40 women with a mean age of 64.3 years, SD 14.7) with 156 paired watershed vessel/cerebral hemisphere observations. Thirty-seven patients had 40 TIA/IS events. There was a significant association between type VI plaque (demonstrating cap rupture, hemorrhage, and/or thrombosis) and ipsilateral TIA/IS (P<0.001). A multiple logistic regression model including standard Framingham risk factors and type VI plaque was constructed. Type VI plaque was the dominant outcome-associated observation achieving significance (P<0.0001; odds ratio, 11.66; 95% confidence interval, 5.31 to 25.60). In situ type VI carotid bifurcation region plaque identified by magnetic resonance imaging is associated with ipsilateral acute TIA/IS as an independent identifier of events, thereby supporting the dominant disease pathophysiology.

Prevalence of carotid and pulp calcifications: a correlation using digital panoramic radiographs

To compare the prevalence of pulp calcification with that of carotid calcification using digital panoramic dental radiographs. Digital panoramic radiographs of patients at a dental oncology clinic were included if (1) the carotid artery bifurcation region was visible bilaterally and (2) the patient had non-restored or minimally restored molars and/or canines. An endodontist evaluated the images for pulpal calcifications in the selected teeth. An oral and maxillofacial radiologist independently evaluated the same images for calcifications in the carotid bifurcation region. Odds-ratio and Pearson chi(2) were used for data analysis. Presence of pulpal calcification was also evaluated as a screening test for the presence of carotid calcification. A total of 247 panoramic radiographs were evaluated. 32% (n = 80) had pulpal calcifications and 25% (n = 61) had carotid calcifications with 12% (n = 29) having both carotid and pulp calcifications. A significantly higher prevalence of both pulp and carotid calcification was found in subjects older than age 60 years compared to younger age groups. Accuracy of pulpal calcification in screening for carotid calcification was 66.4%. Both pulp and carotid calcifications were more prevalent in older individuals. The presence of pulp calcification was not a strong predictor for the presence of carotid calcification.

Increased carotid intima-media thickness in patients with pheochromocytoma in comparison to essential hypertension

Catecholamines due to various mechanisms may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial wall. The aim of this study was to compare intima-media thickness (IMT) of the common carotid artery (CCA) and carotid bifurcation (CB) in patients with pheochromocytoma, essential hypertension and healthy controls. Carotid ultrasound studies were carried out in 30 patients with pheochromocytoma matched for age and gender with 80 patients with essential hypertension and 40 normotensive controls. Significantly higher IMT was found in patients with pheochromocytoma and essential hypertension compared to controls when measured in the CCA (0.931+/-0.223, 0.825+/-0.146 and 0.738+/-0.113 mm; P<0.001; P<0.05), and only in patients with pheochromocytoma compared to controls in the region of CB (1.359+/-0.593, 1.095+/-0.311 and 0.968+/-0.247 mm; P<0.001; P=0.13). Higher IMT in patients with pheochromocytoma compared to patients with essential hypertension was also statistically significant in both carotid regions (both P<0.01). This difference remained significant after adjustment for all relevant clinical and biochemical covariates in the CCA (P=0.014) but disappeared in the region of CB (P=0.079). In summary, patients with pheochromocytoma have increased common carotid IMT when compared to patients with essential hypertension. This finding could be caused by the deleterious effects of the excess of catecholamines on the vascular wall growth and thickening.

FRS2α2F/2F mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve

The docking protein FRS2α is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intracellular signaling pathways. We show that the carotid body is absent in FRS2α 2F/2F mice, in which the Shp2-binding sites of FRS2α are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2α 2F/2F mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2α 2F/2F mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some glomus cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides glomus cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.

Correlation between carotid area calcifications and periodontitis: a retrospective study of digital panoramic radiographic findings in pretreatment cancer patients

The objective of this study was to examine the prevalence of carotid area calcifications retrospectively detected on digital panoramic radiographs of pretreatment cancer subjects, and to correlate the finding of such calcifications with radiographic evidence of periodontal bone loss in the same subjects. Digital panoramic radiographs of 201 subjects were evaluated for calcifications projected in the carotid artery bifurcation area as well as for alveolar bone loss as a result of periodontal disease. Inclusion criteria were unobscured carotid artery bifurcation regions bilaterally and sufficient index teeth present with a definable cemento-enamel junction and alveolar crest. Radiographs were independently observed for carotid area calcifications and for periodontal status. Image enhancements permitted for detection of calcifications projected in the carotid area included window/level, inverse, and emboss. Periodontal measurements were made on index teeth using proprietary imaging software and a mouse-driven measurement algorithm. A 3-factor analysis of variance was performed with 3 between-subjects comparisons. Percentage of bone loss was the dependent variable. Independent variables were age, subject sex, and the presence or absence of carotid area calcifications. Differences measured in percentage of bone loss between sexes were not statistically significant. While bone loss did increase with age, comparison of the mean bone loss of each age category revealed no statistical significance. There was a highly significant correlation between carotid artery area calcifications visible on panoramic radiographs and percent alveolar bone loss. Radiographs showing unilateral and bilateral calcifications had a mean percent bone loss of 24.2% +/- 12.6% and 25.7% +/- 13.0% respectively, compared to those with no calcification at 10.4% +/- 9.9%. Nearly 1 in 4 subjects in this study evidenced calcifications projected in the carotid bifurcation region. The finding of such calcifications was significantly related to the calculated percentage of alveolar bone loss.

Chronic intermittent hypoxia (IH) increases blood pressure in carotid denervated rats

To determine if denervation of the carotid sinus region to eliminate arterial chemoreceptor inputs alters the mean arterial pressure (MAP) response to exposures to IH, the carotid sinus nerves were sectioned bilaterally in rats and the carotid bifurcation region painted with phenol. After a one week recovery period, rats were instrumented with telemetry transmitters. After a one week recovery period, the denervation was considered adequate if a 10 min reduction in inspired O2 to 10% resulted in a fall in MAP instead of the increase in MAP observed in carotid sinus nerve intact rats. Carotid denervated rats (n=7) and carotid intact rats (13) were exposed to IH (7 days for 8 hr/day, 3 min room air alternating with 3 min 10% O2). During the period of the day when exposed to IH, there was a significant effect of IH on MAP (p=.003). In intact rats MAP on control days was significantly different from the IH exposure days (p=.001) but not in denervated rats (p=.067). During the dark period of the day there was a significant effect of IH on MAP (p=.001) but no difference between intact and denervated rats. The change in MAP during the control period (average of control days 3–7) compared to during IH exposure (average of days 3–7) was 6.1±0.5mmHg in intact rats and −2.29±0.7mmHg in denervated rats during the period of the day when exposed to IH (p ≤ .001) and 5.9±0.2mmHg in intact rats and 4.2±0.6mmHg in denervated rats during the dark period of the day (p=.028). In conclusion, the arterial chemoreceptors prevent falls in MAP during exposure to IH, and mechanisms independent of the arterial chemoreceptors are capable of increasing MAP following exposure to IH.

Cardiovascular responses to carotid chemoreceptor stimulation in the dog: their modulation by urinary bladder distension.

Respiratory, heart rate and hindlimb vascular responses were studied in response to increasing levels of stimulation of the carotid body chemoreceptors, together with an examination of the modulation of their effects by distension of the urinary bladder in the dog anaesthetized with a mixture of chloralose and urethane. The vascularly isolated carotid bifurcation regions were perfused with blood, stimulation of the carotid bodies being carried out by three different levels of hypoxic isocapnic blood (PO2 approximately 58, 40 and 22 mmHg) obtained from a donor animal. A vascularly isolated hindlimb was autoperfused at constant blood flow through its femoral artery. In spontaneously breathing animals, increasingly intense hypoxic stimulation of the carotid bodies caused a progressive augmentation of respiratory minute volume. Superimposition of distension of the bladder increased ventilation further, by the same amount during hypoxic as during normoxic blood perfusion of the chemoreceptors. Prevention of the effects of lung stretch afferent stimulation by artificial ventilation modified the heart rate and hindlimb vascular responses to excitation of the carotid bodies by revealing or accentuating the primary cardiovascular responses, bradycardia and vasoconstriction. In contrast, no such respiratory modulation was apparent in the cardiovascular responses to bladder distension. When, under conditions of artificial ventilation and in the absence of changes in the arterial baroreceptor input, the primary cardio-inhibitory and vasoconstrictor responses to carotid chemoreceptor stimulation predominated, the heart slowed progressively as the stimulus was increased. At the same time the cardio-accelerator effects of bladder distension progressively diminished, indicating an interaction between the cardiac reflex responses evoked by the two inputs. In contrast, the reflex vascular responses resulting from stimulation of the two inputs were additive, at least for PO2 levels of carotid body perfusate down to approximately 40 mmHg. In conclusion these experiments demonstrate the differential nature of the integration of respiratory and cardiovascular responses evoked by stimulation of the carotid chemoreceptors and bladder distension.

Chemoreflexes in rabbits

Criteria defining chemoreflexes (called responses) in rabbits have been established in relation to right atrial injection of 16 chemicals, and compared with previously-defined chemoreflexes of cats. A vagally mediated ‘pulmonary’ response elicited at latencies <1.6 sec consists only of an increased frequency of breathing due primarily to decrease of expiratory duration. A vagally mediated ‘cardiac’ response at latencies of 2–3 sec consists of bradycardia, hypotension and a respiratory component of decreased tidal volume. A ‘non-vagal excitatory’ response probably from the carotid bifurcation region consists predominantly of increased tidal volume, commencing at latencies >2 sec. Stimuli eliciting ‘pulmonary’ responses were acetic, propionic, butyric, glycolic, lactic, glyoxilic and pyruvic acids, sodium dithionite and phenyl diguanide, and all also elicited the ‘non-vagal excitatory’ response. Phenyl diguanide additionally elicited the ‘cardiac’ response. No responses were elicited either by amino-substituted acids (glycine, β- and L-alanine, 2-amino-butyric acid and GABA) or sodium salts of lactic and acetic acids, except occasionally β-alanine and GABA elicited a ‘non-vagal excitatory’ response.