Rabbit Elastase Aneurysm: Imaging and Histology Correlates for Inflammation and Healing.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage remains a devastating event with poorly understood pathophysiology. Previous studies have suggested that aneurysm wall inflammation may play a part in the development and potential rupture of aneurysms. The rabbit elastase aneurysm model is a well-established model, which produces aneurysms closely mimicking human cerebral aneurysms in flow dynamics and histopathology. The primary aim of this study was to correlate inflammatory changes after aneurysm formation using sequential vessel wall imaging with histopathologic analysis. A secondary aim was to evaluate the potential effect of gender and anti-inflammatory treatment with aspirin on this inflammatory response. METHODS: Twenty-seven New Zealand rabbits underwent surgery to create an aneurysm using elastase infusion at the right common carotid artery origin. Vessel wall imaging and histopathologic analysis was obtained at different time points after aneurysm creation. The rabbits were also randomized by gender and to treatment groups with or without aspirin. RESULTS: Histopathologic analysis revealed 3 distinct phases after aneurysm formation. These phases were an initial inflammatory phase, followed by a regeneration phase, and finally a connective tissue deposition phase. Vessel wall imaging demonstrated 2 distinct imaging patterns. No appreciable differences were seen in histology or imaging when comparing gender or treatment with aspirin. CONCLUSIONS: Inflammatory changes induced by the rabbit elastase aneurysm model can be correlated with histopathologic findings and observed on noninvasive vessel wall imaging. This may provide a method to study the inflammatory pathway as it pertains to aneurysmal development and subsequent rupture.

Biomarkers for vascular ageing in aorta tissues and blood samples.

OBJECTIVES: Functional and quantitative alterations and senescence of circulating and expanded endothelial progenitor cells (EPC), as well as systemic and tissue modifications of angiogenetic and inflammatory molecules, were evaluated for predicting age-related vessel wall remodeling, correlating them to intima media thickness (IMT) in the common carotid artery (CCA), a biomarker of early cardiovascular disease and aortic root dilation. POPULATIONS AND METHODS: A homogenous Caucasian population was included in the study, constituted by 160 healthy subjects (80 old subjects, mean age 72 ±â€¯6.4, range 66-83 years; and 80 younger blood donors, mean age 26.2 ±â€¯3.4, range 21-33 years), and 60 old subjects (mean age 73 ±â€¯1.4 (range 66-83) years) with aortic root dilatation and hypertension, and 60 old people (70 ±â€¯2.8 (age range 66-83)) with sporadic ascending aorta aneurysm (AAA). In addition, 20 control individuals (10 men and 10 women, mean age: 65 ±â€¯8), were also included in the study for evaluating the gene expression's levels, in aorta tissues. Appropriate techniques, practises, protocols, gating strategies and statistical analyses were performed in our evaluations. RESULTS: Interestingly, old people had a significantly reduced functionality and a high grade of senescence (high SA-ß-Gal activity and high levels of TP53, p21 and p16 genes) of EPC expanded than younger subjects. The values of related parameters progressively augmented from the old subjects, in good healthy shape, to subjects with hypertension and aorta dilation, and AAA. Moreover, they significantly impacted the endothelium than the alterations in EPC number. No changes, but rather increased systemic levels of VEGF and SDF-1 were also assessed in old people vs. younger donors. Old people also showed significantly increased systemic levels of inflammatory cytokines, and a reciprocal significant reduction of systemic s-Notch 1 than younger subjects. These parameters, also including the number EPC alterations, resulted to be significantly sustained in old people bearers of an inflammatory combined genotype. Consistent with these data, a reduced expression of Notch-1 gene, accompanied by a sustained expression of inflammatory genes (i.e. TLR4, IL-1ß, IL-6 and IL-17) were detected in aortic tissues from old control people and AAA cases. Finally, we detected the biological effects induced by all the detected alterations on vessel wall age-related remodeling, by evaluating the IMT in the population studied and correlating it to these alterations. The analysis demonstrated that the unique independent risk predictors for vascular ageing are age, the EPC reduced migratory activity and senescence, high grade of expression of genes inducing EPC senescence and chronic tissue and systemic inflammation. CONCLUSIONS: Thus, we propose these parameters, of easy determination in biological samples (i.e. blood and tissue samples) from alive human population, as optimal biomarkers for vascular ageing.

Quantitative measurement of regional cerebral blood flow and oxygen metabolism in a rat model of cerebral hypoperfusion.

This study was aimed at evaluating the regional changes in the cerebral metabolic rate of oxygen (CMRO2) in relation to the cerebral blood flow (CBF) in the bilateral common carotid artery occlusion (BCAO) rat model. Ligation of the bilateral common carotid arteries (or a sham operation in control animals) was performed in 10-week-old male Wistar rats. O-15 PET images were acquired in the subacute phase (1 week after the surgery) and chronic phase (6 weeks after the surgery) with the animals under anesthesia, using a small-animal PET system and the O-15 gas steady-state inhalation method with arterial blood sampling developed in our previous study. Histopathological staining by Klüver-Barrera method and immunocytochemistry staining by glial fibrillary acidic protein were performed. Cognitive function was tested by using the apparatus of Y-maze. Significantly lower CBF and higher oxygen extraction fraction were observed in broad areas of the cerebrum in the subacute phase in the BCAO rats, with recovery in the chronic phase. A stable decrease of the CMRO2 in the subacute phase of arterial occlusion and later was observed in the BCAO rat model, mainly in the anterior cerebral artery territory. Atrophy and rarefaction of corpus callosum were found in the BCAO in the chronic phase. Activity of astrocytes in the BCAO was prominent in the both phases. Working memory was impaired in the BCAO in the chronic phase. Regional changes in cerebral perfusion and oxygen metabolism in the subacute and chronic phases of arterial occlusion were clarified in a rat model of BCAO by quantitative O-15 PET based on the steady-state method.

Effect of Positive End-Expiratory Pressure on Overlap Between Internal Jugular Vein and Carotid Artery in Mechanically Ventilated Patients with Laryngeal Mask Airway (LMA) Insertion - A Prospective Randomized Trial.

BACKGROUND In the present study, we aimed to determine the effect of different positive end-expiratory pressure (PEEP) levels on the cross-sectional area (CSA) of the right internal jugular vein (RIJV) and the overlap index between the RIJV and the right common carotid artery (RCCA) in mechanically ventilated patients with laryngeal mask airway (LMA) insertion. MATERIAL AND METHODS A total of 60 patients who were scheduled for elective surgery under general anesthesia with LMA insertion were enrolled. After LMA insertion, the image of RIJV and RCCA were taken after applying 4 different PEEPs in a random order: 0 (P0), 5 (P5), 10 (P10), and 15 (P15) cm H2O. The CSA, transverse and anteroposterior (AP) diameters of the RIJV, and the overlap index were measured. RESULTS Compared to group P0, the overlap indexes of P10 (P=0.0032) and P15 (P<0.001) were significantly increased, but without a significant trend toward further increases in group P15. PEEP at 10 and 15 cm H2O increased CSA, transverse and AP diameter of the RIJV in comparison to group P0 (all P<0.001). There was a statistically significant increase in CSA of the RIJV in P15 compared with P10 by 12.2% (P<0.001), but did not reach the relevant cut-off value (ΔCSA ≥15%). CONCLUSIONS The application of PEEP at 10 cm and 15 cm H2O in patients receiving mechanical ventilation with LMA insertion significantly increases the size of the RIJV. However, the overlap index between the RIJV and the RCCA increased as well.

Cerebral oxygenation associated with INSURE versus LISA procedures in surfactant-deficient newborn piglet RDS model.

BACKGROUND: Nasal continuous-positive airway pressure (nCPAP) with the INSURE (INtubation-SURfactant-Extubation) or LISA (Less-Invasive Surfactant Administration) procedures are increasingly being chosen as the initial treatment for neonates with surfactant deficiency. Our objective was to compare the effects on cerebral oxygenation of different methods for surfactant administration: INSURE and LISA, using a nasogastric tube (NT) or a LISAcath® catheter, in spontaneously breathing SF-deficient newborn piglets. METHODS: Eighteen newborn piglets with SF-deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to INSURE, LISA-NT, or LISAcath® groups. We assessed pulmonary (gas exchange, lung mechanics, lung histology) and hemodynamic (mean arterial blood pressure, heart rate) changes, cerebral oxygenation (cTOI) and cerebral fractional tissue extraction (cFTOE), with near-infrared spectroscopy, carotid blood flow and brain histology. RESULTS: SF-deficient piglets developed respiratory distress (FiO2 = 1, pH <7.2, PaCO2 >70 mmHg, PaO2 <70 mmHg, Cdyn <0.5 mL/cmH2 O/kg). Rapid improvements in pulmonary status were observed in all surfactant-treated groups without hemodynamic alterations. In the INSURE group, a transient decrease in cTOI occurred during and immediately after surfactant administration, while cTOI only decreased during surfactant administration in the LISA-NT group and did not change significantly in the LISAcath® group. Brain injury scores were low in all surfactant-treated groups. CONCLUSION: In spontaneously breathing SF-deficient newborn piglets, short-lasting decreases in cerebral oxygenation are associated with surfactant administration by the INSURE method or LISA using an NT, while no cerebral oxygenation changes occurred with LISA using a LISAcath®. Notably, none of treatments studied seems to have a negative impact on the neonatal brain.

Longitudinal Movement of the Common Carotid Artery Wall: New Information on Cardiovascular Aging.

Putative changes in the multiphasic pattern of longitudinal movement of the common carotid artery wall in the normal aging process are unknown. The aim of this study was to explore the phases, and resulting patterns, of the longitudinal movement of the intima-media complex of the human common carotid artery with respect to age and gender. One hundred thirty-five healthy non-smoking patients of different ages were investigated using in-house-developed ultrasound methods. The patterns of longitudinal movement seen in middle-aged and older patients were markedly different from those commonly seen in young patients, including the appearance of two additional phases of motion and, thus, new complex patterns. The displacement and maximum velocity of one of the phases, occurring at the time of aortic valve closure, increased quadratically with age in both men and women.

[Properties of decellularized rabbit carotid artery with two different cross-linked technologies: A comparative study].

OBJECTIVE: To compare the properties between decellularized rabbit carotid artery with different cross-linked technologies.
 Methods: The decellularized rabbit carotid arteries were randomly divided into a photo-oxidation group and a procyanidins group. One group was cross-linked with photo-oxidation and the other group was cross-linked with procyanidins. The in vitro or in vivo properties of the two groups were evaluated by testing heat-shrinking temperature, max tensile strength and the max elongation or by testing tissue structure, inflammatory reaction and calcification degree.
 Results: The heat-shrinking temperature, max tensile strength and the max elongation were similar in the two groups (P>0.05). The tissue structure and inflammatory reaction were also similar in the two groups. Although the result of Von-Kossa calcium salt stain was slightly different, the calcium content was lower in the procyanidins group than that in the photo-oxidation group (P<0.05).
 Conclusion: The grafts by two cross-linked technologies show excellent mechanical capability, lower immunogenicity, good biological stability and anti-calcification ability. The procyanidins group shows a better anti-calcification property than the photo-oxidation group.

Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice.

Pituitary adenylate cyclase-activating peptide (PACAP; 1-38 and 1-27) and vasoactive intestinal peptide (VIP) are related neuropeptides of the secretin/glucagon family. Overlapping signaling through G-protein-coupled receptors mediates their vasomotor activity. We previously showed that PACAP deficiency (PACAP-KO) shifts the mechanisms of vascular response and maintains arterial relaxation through the VIP backup mechanism and (mainly) its VPAC1R, but their age-dependent modulation is still unknown. We hypothesized that backup mechanisms exist, which maintain the vasomotor activity of these peptides also in older age. Thus, we investigated the effects of exogenous VIP and PACAP peptides in isolated carotid arteries of 2- and 15-month-old wild-type (WT) and PACAP-KO mice. All peptides induced relaxation in the arteries of young WT mice, whereas in young PACAP-KO mice PACAP1-27 and VIP, but not PACAP1-38, induced relaxation. Unlike VIP, PACAP-induced vasomotor responses were reduced in aging WT mice. However, in the arteries of aging PACAP-KO mice, PACAP1-27- and VIP-induced responses were reduced, but PACAP1-38 showed a greater vasomotor response compared to that of young PACAP-KO animals. There were no significant differences between the vasomotor responses of aging WT and PACAP-KO mice. Our data suggest that, in the absence of PACAP both in young and old ages, the vascular response is mediated through backup mechanisms, most likely VIP, maintaining proper vascular relaxation in aging-induced PACAP insufficiency.

Wedelolactone, a plant coumarin, prevents vascular smooth muscle cell proliferation and injury-induced neointimal hyperplasia through Akt and AMPK signaling.

Wedelolactone (WDL) is a natural compound derived from Chinese herbal medicine Eclipta prostrate L, and has been reported to exhibit various effects potentially beneficial for human health. However, the possible preventive effects of WDL toward vascular remodeling and mechanisms involved have not been investigated to date. In this study, we investigated the effects of WDL on proliferation induced by platelet-derived growth factor (PDGF) in primary rat aortic smooth muscle cells (VSMCs) and on neointimal hyperplasia resulted from balloon injury in rats. WDL exhibited strong inhibitory effects against PDGF-induced VSMC proliferation. Cell cycle analysis revealed that WDL induced G0/G1 arrest and prevented cell cycle from entering S phase. Immunoblot analysis suggested that the cell cycle arrest induced by WDL was through Akt suppression and adenosine 5'-monophosphate-activated protein kinase (AMPK) activation, with a subsequent cyclin-dependent kinase inhibitor p21 induction and cyclin D1 inhibition. We also observed that WDL notably reduced neointima-to-media area ratio of balloon-injured rat common carotid arteries (CCAs) in comparison with those untreated balloon-injured CCAs. The regulation of WDL on protein expressions of Akt, AMPK and cyclin D1 in vivo were also consistent with that in vitro. Taken together, our results suggest WDL exhibits potential preventive effects toward vascular remodeling and neointimal hyperplasia through the reduction of VSMC proliferation via inhibition of Akt and activation of AMPK.

Design of a Pulsatile Fresh Frozen Human Cadaver Circulation Model for Endovascular Training.

BACKGROUND: The objective of this project was to create a model capable of training endovascular skills using a freshly frozen human cadaver (HC). We present the results of our experience creating a cadaveric model for endovascular skills training. We undertook a unique cadaver laboratory-based research project. METHODS: We favor a minimally invasive surgical technique with inflow into the right common carotid artery and outflow through the left common femoral and right superficial femoral arteries. Endovascular access was through the right common femoral artery. RESULTS: Through this technique, the arch, thoracic, abdominal, and iliac vessels are all accessible. We perfuse the model through an open pulsatile flow circuit at varying rates to maximize angiographic image capture while minimizing cadaveric edema thus expanding the models longevity. CONCLUSIONS: A fresh frozen pulsatile human cadaver training model is a feasible and credible training model that has exciting potential for endovascular skills training.

Carotid Doppler flowmetry correlates poorly with thermodilution cardiac output following cardiac surgery.

BACKGROUND: It remains unclear whether measuring carotid arterial flow by the time velocity integral using vascular Doppler ultrasound can be used to monitor cardiac output and volume responsiveness. METHODS: The carotid Doppler flow (time velocity integral and peak flow velocity variation) was assessed in triplicate by an intensivist with formal vascular ultrasound training. Thirty-three patients admitted following coronary by-pass surgery were studied before and after a passive leg-raising manoeuvre to investigate volume responsiveness (more than 10% increase in cardiac output) along with indices of arterial load measuring cardiac output by thermodilution. Pearson's correlation coefficient and area under the curve (AUC) by receiver operating characteristics were calculated. RESULTS: A significant correlation between carotid Doppler flow and cardiac output was demonstrated in post-operative cardiac surgery patients (r = 0.80 [95%CI 0.61-0.89]), including relative changes following passive leg raising (r = 0.79 [95%CI 0.60-0.89]) that showed a mean difference of 2% with wide limits of agreements (-19% to 16%). Changes in carotid Doppler flow following passive leg raising correlated with the baseline arterial resistance but not with compliance or effective elastance. A peak flow variation > 10% before passive leg raising discriminated responders to the manoeuvre with an AUC of 0.81 [95% CI 0.55-0.95]. CONCLUSIONS: Weak correlations between common carotid Doppler flow and cardiac output mean that the methods cannot be used interchangeably in post-operative cardiac surgery patients.

Vascular geometry of the extracranial carotid arteries: an analysis of length, diameter, and tortuosity.

BACKGROUND: Stable access is essential for successful intracranial interventions. Quantifying variations in extracranial carotid arteries may help in the selection and development of access catheters. This study describes the vascular dimensions from the aortic arch to the skull base. METHODS: CT angiography analysis was performed on 100 patients. The lengths, diameters, and tortuosity of the common carotid artery (CCA) and internal carotid artery (ICA) were measured from the aortic arch to the skull base. RESULTS: The mean±SD length of the carotid artery from the aortic arch to the skull base was 22.2±2.2 cm for the right side and 20.8±1.9 cm for the left side (p<0.0001). The length of the right CCA was 13.6±1.2 cm and the length of the left CCA was 12.4±1.4 cm (p<0.0001). The length of the right ICA was 8.6±1.4 cm compared with 8.4±1.4 cm for the left ICA (p=0.3). The ICA length in men and women was 8.9±1.3 cm and 8.2±1.3 cm, respectively (p=0.0001), and the CCA length in men and women was 13.6±1.5 cm and 12.3±1.6 cm, respectively (p<0.0001). The lengths of the CCA and ICA in patients aged ≥60 years were 13.3±1.7 cm and 8.9±1.5 cm, respectively compared with 12.8±1.7 cm and 8.2±1.1 cm, respectively, for patients aged <60 years (p=0.04 for CCA, p=0.0002 for ICA). Tortuosity of the CCA and ICA was 1.2±0.2 and 1.3±0.1, respectively, in patients aged ≥60 years compared with 1.1±0.1 for both the ICA and CCA in patients aged <60 years (p<0.0001 for both). There was a consistent ratio of CCA/ICA length of 1.6±0.3 on the right and 1.5±0.3 on the left (p<0.0001). The arterial diameters did not show any significant difference. CONCLUSIONS: The distance from the aortic arch to the skull base is longer on the right than on the left side. Both the CCA and ICA are longer in men and in patients aged ≥60 years. The tortuosity of both segments significantly increases with age.

Long-lasting endothelium-dependent relaxation of isolated arteries caused by an extract from the bark of Combretum leprosum.

OBJECTIVE: To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals. METHODS: Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations. RESULTS: In all rings tested, Combretumleprosum extract (1.5µg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances. CONCLUSIONS: Combretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors.

Long-lasting endothelium-dependent relaxation of isolated arteries caused by an extract from the bark of Combretum leprosum / Extrato das cascas de Combretum leprosum causa relaxamento dependente de endotélio de longa duração em artérias isoladas

Objective To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals.Methods Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations.Results In all rings tested, Combretumleprosum extract (1.5μg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances.ConclusionsCombretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors.

Objetivo Descrever e caracterizar os relaxamentos induzidos por um extrato das cascas de Combretum leprosum em anéis de artérias de diferentes espécies de animais.Métodos Anéis (3 a 4mm) de artérias de coelho, rato e porco foram montados em cubas para órgão isolado (Krebs, 37°C, 95%O2/5%CO2) para registro das contrações isométricas. Após um período de estabilização (2 a 3 horas), as contrações foram induzidas com fenilefrina (0,1 a 0,3µM) ou U46619 (10 a 100nM); no platô dessas contrações, adicionamos o extrato Combretum leprosum. Diferentes protocolos foram realizados para determinar potência, duração, reversibilidade e mecanismo dos relaxamentos induzidos pelo extrato.Resultados Em todas as preparações testadas, o extrato de Combretum leprosum (1,5µg/mL) provocou relaxamentos dependentes de endotélio. Em aorta torácica de coelho ou rato, os relaxamentos foram revertidos pela vitamina B12a ou L-NG-nitro-arginina. Em anéis de aorta abdominal de coelho e de artérias coronárias de porco, o extrato causou relaxamentos sensíveis e resistentes à L-NG-nitro-arginina. Em aorta torácica de coelho, o extrato foi relativamente muito potente (EC50=0,20μg/mL) e quando causou relaxamentos; intrigantemente o endotélio continuou a produzir fatores relaxantes por um longo período após remoção do extrato. A magnitude dos relaxamentos induzidos pelo extrato foi significativamente reduzida em ausência Ca2+ extracelular; ademais, o vermelho de rutênio (10μM), um bloqueador de canais TRPs, foi capaz de reverter os relaxamentos induzidos pelo extrato. Análises preliminares indicaram que o extrato continha compostos com reatividade química semelhante à polifenóis.Conclusão O extrato de Combretum leprosum contem compostos bioativos capazes de promover estimulação dependente de Ca2+ das células endoteliais a qual resulta numa produção prolongada de fatores relaxantes.

Common carotid artery peak systolic velocity ratio predicts high-grade common carotid stenosis.

OBJECTIVE: Screening for common carotid artery (CCA) stenosis with duplex ultrasound (DUS) velocity criteria alone can be limited by within-patient and between-patients hemodynamic variability. This study aimed to evaluate inter-CCA velocity ratio criteria to predict high-grade CCA stenosis. METHODS: This was a retrospective review of consecutive patients who underwent computed tomography angiography and DUS peak systolic velocity (PSV) measurements of bilateral CCAs, independently recorded, between 2008 and 2014. Patients with dampened CCA waveforms on DUS composed group B. The remainder without dampened waveforms constituted group A. Inter-CCA PSV ratios were calculated by dividing the higher CCA PSV by the lower one of the other side, so the ratios would always be ≥1. Ratios were subsequently paired with each respective unilateral CCA diameter stenosis and differential bilateral CCA diameter stenosis. A quadratic regression model was fitted to predict unilateral and differential stenosis. Receiver operating characteristic curve was used to determine optimal ratios for ≥50% and ≥80% CCA stenosis. The study excluded patients with carotid artery occlusion. RESULTS: From a total of 201 patients, 193 patients were included in group A and 8 in group B. Within group A, 31 patients had ≥50% unilateral stenosis and 17 had ≥50% differential stenosis. All stenoses ≥50% were identified on the same side with the higher PSV. Inter-CCA PSV ratio predicted ≥50% unilateral (r(2) = 0.536; P < .001) and differential stenosis (r(2) = 0.581; P < .001). In group B, all patients had ≥60% stenosis that was near or involved the vessel origin. An increasing inter-CCA PSV ratio showed a trend toward contralateral high-grade stenosis (r(2) = 0.596; P = .1). Receiver operating characteristic curves showed an optimal threshold CCA ratio ≥2.16 for ≥50% unilateral stenosis with 92% accuracy, 62% sensitivity, and 98% specificity (area under curve = 0.854; 95% confidence interval, 0.759-0.948) and a ratio ≥2.62 for ≥50% differential stenosis with 97% accuracy, 83% sensitivity, and 98% specificity (area under curve = 0.94; 95% confidence interval, 0.835-1). CONCLUSIONS: DUS-based CCA PSV ratio can accurately predict unilateral and differential high-grade CCA stenosis. Also, in patients with unilateral dampened waveforms, it implied contralateral severe proximal stenosis. This parameter should be further validated in prospective studies and may serve as an adjunct screening tool to detect high-grade CCA stenosis.

Novel classification of the posterior auricular artery based on angiographical appearance.

PURPOSE: To investigate the length variation of the posterior auricular artery and propose a novel classification of the posterior auricular artery based on angiographical appearance. PATIENTS AND METHODS: A series of 234 consecutive patients who had undergone conventional cerebral angiography was analyzed. The posterior auricular artery was examined on the lateral projection of the external carotid or common carotid arteriography. The posterior auricular artery was classified into four groups by length, using the external auditory canal and the top of the helix as radiographical landmarks. Our proposed classification is as follows: Type A, posterior auricular artery terminates between its origin and the center of the external auditory canal; Type B, posterior auricular artery terminates between the center of the external auditory canal and the top of the helix; Type C, posterior auricular artery terminates between the top of the helix and the vertex; and Type D, posterior auricular artery reaches up to the vertex. RESULTS: A total of 424 (right, 214; left, 210) posterior auricular arteries were analyzed in 111 men and 123 women aged 11 to 91 years (mean, 61.0 years) examined for aneurysms in 78 cases, occlusive vascular diseases in 56, intracranial hemorrhages in 41, tumors in 35, and others in 24. Types A, B, C, and D were found in 15.1%, 34.9%, 48.8%, and 1.2% of the patients, respectively. CONCLUSION: A novel classification of the posterior auricular artery identifies four types based on its length on cerebral angiography.

Direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics.

The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n=10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg(-1)·min(-1)), and 3) glucose-dependent insulinotropic polypeptide (GIP, 1.5 pmol·kg(-1)·min(-1)). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P<0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P<0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels.

Triglyceride glucose index and common carotid wall shear stress.

OBJECTIVES: Alterations in wall shear stress contribute to both clinical and subclinical atherosclerosis. Several conditions such as hypertension, diabetes, and obesity can impair shear stress, but the role of insulin resistance has never been investigated. The present study was designed to investigate whether insulin resistance assessed by TyG Index associates with wall shear stress in the common carotid artery. METHODS: One hundred six individuals were enrolled. Blood pressure, lipids, glucose, and cigarette smoking were evaluated. TyG Index was calculated as log[fasting triglycerides × fasting glucose / 2]. Subjects underwent blood viscosity measurement and echo-Doppler evaluation of carotid arteries to calculate wall shear stress. The association between TyG Index and carotid wall shear stress was assessed by simple and multiple regression analyses. RESULTS: TyG Index was significantly and inversely associated with carotid wall shear stress both in simple (r = -0.44, P < 0.001) and multiple regression analyses accounting for age, sex, and major cardiovascular risk factors. The association was further confirmed after exclusion of subjects with diabetes, dyslipidemia, fasting blood glucose greater than 100 mg/dL, and triglycerides greater than 150 mg/dL. CONCLUSIONS: The present findings suggest that increasing insulin resistance, as assessed by TyG Index, associates with atherosclerosis-prone shear stress reduction in the common carotid artery.

Creation of sidewall aneurysm in rabbits: aneurysm patency and growth follow-up.

INTRODUCTION: To explore the patency and growth of surgical sidewall aneurysms in rabbits. MATERIALS AND METHODS: Forty sidewall aneurysms were created in the right common carotid artery (RCCA). Intravenous digital subtraction angiography (DSA) through the ear vein was performed immediately after creation. Three weeks later, intra-arterial DSA through the femoral artery was performed. Aneurysm sizes (neck, width, height and volume) were measured and calculated immediately after creation and 3 weeks later. Aneurysm patency after creation was evaluated. Differences in aneurysm sizes immediately after creation and 3 weeks later were compared using the Student's t test. RESULTS: Aneurysms and the parent artery remained patent in 38 (95%) of the 40 rabbits 3 weeks after creation. Two other rabbits (5%) showed aneurysm occlusion. There was a significant difference in aneurysm neck size 3 weeks after creation (3.6±0.9 mm vs 2.4±0.4 mm, p<0.0001). The aneurysm became wider 3 weeks later (5.8±1.5 mm vs 4.3±1.2 mm, p<0.0001). Aneurysm length was also larger than immediately after creation (6.1±1.3 mm vs 4.3±1.4 mm, p<0.0001). The aneurysm volume was larger than that created immediately (127.5±89.4 mm(3) vs 51.0±34.9 mm(3), p<0.0001). CONCLUSIONS: The patency rate of sidewall aneurysms in rabbits is high. The aneurysm keeps growing for at least 3 weeks after creation.

The multifunctional Ca²âº/calmodulin-dependent kinase IIδ (CaMKIIδ) regulates arteriogenesis in a mouse model of flow-mediated remodeling.

OBJECTIVE: Sustained hemodynamic stress mediated by high blood flow promotes arteriogenesis, the outward remodeling of existing arteries. Here, we examined whether Ca²âº/calmodulin-dependent kinase II (CaMKII) regulates arteriogenesis. METHODS AND RESULTS: Ligation of the left common carotid led to an increase in vessel diameter and perimeter of internal and external elastic lamina in the contralateral, right common carotid. Deletion of CaMKIIδ (CaMKIIδ-/-) abolished this outward remodeling. Carotid ligation increased CaMKII expression and was associated with oxidative activation of CaMKII in the adventitia and endothelium. Remodeling was abrogated in a knock-in model in which oxidative activation of CaMKII is abolished. Early after ligation, matrix metalloproteinase 9 (MMP9) was robustly expressed in the adventitia of right carotid arteries of WT but not CaMKIIδ-/- mice. MMP9 mainly colocalized with adventitial macrophages. In contrast, we did not observe an effect of CaMKIIδ deficiency on other proposed mediators of arteriogenesis such as expression of adhesion molecules or smooth muscle proliferation. Transplantation of WT bone marrow into CaMKIIδ-/- mice normalized flow-mediated remodeling. CONCLUSION: CaMKIIδ is activated by oxidation under high blood flow conditions and is required for flow-mediated remodeling through a mechanism that includes increased MMP9 expression in bone marrow-derived cells invading the arterial wall.