Cross-talk with β2-adrenoceptors enhances ligand affinity properties from endothelial alpha1D-adrenoceptors that mediates carotid relaxation

Objectives Our main objectives were to investigate the affinity properties of endothelial and muscular α1D-adrenoceptors and to characterize the cross-talk between endothelial α1D- adrenoceptors and β2-adrenoceptors in rat carotid. Methods Relaxation and contraction concentration-response curves for phenylephrine (α1-adrenergic agonist) were obtained in carotid rings in absence or presence of increasing concentrations of BMY7378 (α 1D-adrenergic antagonist), combined or not with increasing concentration of ICI-118,551 (β2-adrenergic antagonist). Schild analysis was used to estimate the affinity constant from pA2 values of BMY7378. Key Findings BMY7378 produced an unsurmountable antagonism on phenylephrine-induced relaxation but a surmountable antagonism on phenylephrine-induced contraction. BMY7378 potency was higher in inhibiting the relaxation than the contraction induced by phenylephrine because the rightward shifts induced by BMY7378 were greater in the relaxation. The apparent pA 2 value for BMY7378 in phenylephrine-induced relaxation was greater than in contraction. When combined with ICI-118,551, BMY7378 yielded a surmountable antagonism on phenylephrine-induced relaxation and presented a pA2 value similar to that obtained in phenylephrine-induced contraction. Conclusions Endothelial α1D-adrenoceptors, which mediates rat carotid relaxation, present high ligand affinity because of the cross-talk with β2-adrenoceptors, which explains the higher potency of phenylephrine in inducing relaxation than contraction and the atypical unsurmountable antagonism produced by BMY7378 on phenylephrine-induced relaxation. © 2013 Royal Pharmaceutical Society.

Carotid artery atherosclerotic profile as a predictor of the aorta atherosclerotic profile in patients with cerebrovascular events

Background: It is well known that the presence of atheroma of the thoracic aorta is a risk factor for cerebrovascular events. We sought to evaluate whether the presence and the morphology of atherosclerotic plaque in the carotid artery detected by duplex ultrasonography is associated with disease in the proximal aorta visualized by transesophageal echocardiogram in patients with a cerebrovascular event. Methods: We carried out a cross-sectional prospective study including 147 consecutive patients with prior stroke or transient ischemic attack (TIA). Neurological evaluations were performed by an expert neurologist using clinical and tomographic diagnostic criteria including the definition of etiology and whether the patient suffered from stroke or TIA. Transthoracic and transesophageal echocardiograms and carotid artery duplex ultrasonography were performed by the same examiner. Patients with and without plaque in the carotid artery were compared using Student's t test or the χ2 test. Regression analysis was used to determine whether the presence of plaque in the carotid artery was predictive of the presence of plaque in the proximal aorta and to analyze the relationship between the echogenicity of carotid and aortic plaques. The significance level was set at p < 0.05. Results: All 147 patients (95 men) were included in the analysis. Patients' ages ranged from 23 to 85 years (65 ± 12.4 years). Most of the patients (58.5%) were Caucasian, while 41.5% were African-Brazilian. Arterial hypertension, diabetes and tobacco use were more frequent among patients with atherosclerotic plaque in the aorta. A normal carotid intima-media thickness halved the risk of atherosclerotic plaque in the aorta [odds ratio (OR) 0.46, 95% confidence interval (CI) 0.23-0.91; p = 0.026]. The presence of carotid plaque increased the risk of aortic plaque by 70-fold (OR 73.2, 95% CI 25.6-2,018.6; p < 0.001) in univariate analysis. The absence of atherosclerotic plaque in the carotid artery reduced the risk of plaque in the aorta to almost 0 (OR 0.014, 95% CI 0.004-0.041; p < 0.001). Considering the 86 patients with both aortic and carotid plaques, the presence of hypoechoic plaque in the carotid artery was a predictor of hypoechoic plaque in the aorta (OR 10.1, 95% CI 3.3-31.2; p < 0.001). Conclusions: The carotid artery atherosclerotic profile defined by ultrasonography is a strong predictor of the atherosclerotic profile of the proximal aorta. This should be taken into consideration before referring patients with acute cerebrovascular events for transesophageal echocardiogram. © 2013 S. Karger AG, Basel.

Ultrasound evaluation of common carotid artery blood flow in the Labrador retriever

Background: Doppler ultrasound (DUS) examination provides quantitative and qualitative information concerning the blood flow in veins and arteries, enabling their morphological evaluation and the collection of hemodynamic data. Dogs and cats as well as humans may display neurological signs of brain hypoperfusion secondary to common carotid alterations. Hence, DUS examination might aid in the differential diagnosis of neurological disorders of ischemic origin, among other causes. The objective of this study was to register normal values for systolic peak velocity, minimum diastolic velocity, diameter and resistance index of both common carotid arteries of 12 healthy Labrador retriever dogs between 2 and 5 years of age. By gathering these values, we might be able to improve the sensitivity of hemodynamic studies in clinically important brain disorders. Results: There were no statistical differences between the values for the right and left vessels: the systolic peak velocity was 75.8 ± 16 cm/s, minimum diastolic velocity was 12.2 ± 4 cm/s, common carotid diameter was 0.545 ± 0.063 cm, and resistance index was 0.83 ± 0.07. Conclusions: The results of this study might be used to establish normal parameters for Labrador retriever dogs and thus help in the diagnosis of neurological disorders associated with alterations of the carotid arteries. Similar studies must be performed to evaluate the same parameters in other dog breeds of different sizes and skull conformations. © 2013 Svicero et al.; licensee BioMed Central Ltd.

Horner-s Syndrome following common carotid artery translocation in a horse: case report

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of clinical and inflammatory markers of subclinical carotid atherosclerosis in postmenopausal women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pseudoaneurysm of the internal carotid artery presenting with massive (recurrent) epistaxes: a life-threatening complication of craniofacial trauma

Vascular lesions can be serious complications resulting of blunt or penetrating trauma(1,2). Internal carotid artery lesion is one of most serious and relatively frequent in all mechanisms of craniofacial trauma. Several clinical manifestations can occur as central neurologic and cranial nerves deficits as well as several degrees of bleeding (from mild symptomatic to fatal). Recurrent and massive epistaxis can occur after trauma due to pseudaoneurysms of the external and internal carotid artery (ICA)(3,4). Considering its life-threatening course, the assisting physician has a relatively narrow time to detect and treat these lesions.We present two cases of recurrent and massive epistaxis secondary to ICA pseudoaneurysm following blunt and perforating trauma. Evolution was fatal in the first case with delayed treatment and uneventfully in the second which was treated by occlusion of the pseudoaneurysm and ICA via endovascular intervention.

Internal carotid artery pseudoaneurysm after tonsillectomy treated by endovascular approach. A case report

Surgery on the head and neck region may be complicated by vascular trauma, caused by direct injury on the vascular wall. Lesions of the arteries are more dangerous than the venous one. The traumatic lesion may cause laceration of the artery wall, spasm, dissection, arteriovenous fistula, occlusion or pseudoaneurysm. We present a case of a child with a giant ICA pseudoaneurysm after tonsillectomy, manifested by pulsing mass and respiratory distress, which was treated by endovascular approach, occluding the lesion and the proximal artery with Histoacryl. We reinforce that the endovascular approach is the better way to treat most of the traumatic vascular lesions.

The I405V and Taq1B polymorphisms of the CETP gene differentially affect sub-clinical carotid atherosclerosis

Background: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. Methods: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-a concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. Results: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT, which was equal and above the 66th percentile and positively interacted with age. However, no associations with the V allele or CETP and PLTP activities were observed. Conclusions: None of the studied parameters, including CETP activity, explained the different relationships between these polymorphisms and cIMT, suggesting that other non-determined factors were affected by the genotypes and related to carotid atherosclerotic disease.

Oxidized low-density lipoproteins and their antibodies: Relationships with the reverse cholesterol transport and carotid atherosclerosis in adults without cardiovascular diseases

Background: Metabolic predictors and the atherogenicity of oxidized LDL (oxLDL) and the specific antibodies against oxLDL (oxLDL Ab) are unclear and controversial. Methods: In 107 adults without atherosclerotic manifestations, we measured oxLDL and oxLDL Ab, and also the activities of CETP. PLTP, lipases and the carotid intima-media thickness (cIMT). Comparisons were performed for the studied parameters between the lowest and the highest tertile of oxLDL and oxLDL Ab, and the relationships between studied variables were evaluated. Results: Subjects with higher oxLDL Ab present reduced hepatic lipase activity and borderline increased cIMT. In the highest oxLDL tertile, besides the higher levels of total cholesterol, LDL-C and apoB100, we found reduced CETP activity and higher cIMT. A significant correlation between oxLDL Ab and cIMT, independent of oxLDL, and a borderline correlation between oxLDL and cIMT independent of oxLDL Ab were found. In the multivariate analysis, apoAl was a significant predictor of oxLDL Ab, in contrast to regulation of oxLDL by apoB100, PLTP and inverse of CETP. Conclusions: In adults without atherosclerotic disease, the metabolic regulation and carotid atherosclerosis of oxLDLAb and oxLDL groups, characterized a dual trait in oxLDL Ab, as a contributor to carotid atherosclerosis, much less so than oxidized LDL, and with a modest atheroprotective role. (C) 2012 Elsevier B.V. All rights reserved.

Endonasal endoscopic exposure of the internal carotid artery: An anatomical study

Objectives/Hypothesis: The aim of this work was to define the anatomical landmarks, limitations, and difficulties of obtaining internal carotid artery (ICA) exposure via endonasal endoscopic approaches (EEA).

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA(1) levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.