Oxidized Low-density Lipoproteins and Lipopolysaccharides Augment Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine.

Atherosclerosis is a chronic inflammatory disease and hypercholesterolemia is a risk factor. This study aims to compare the potency of lipopolysaccharide (LPS) and oxidized low-density lipoproteins (oxLDL) to induce plaque formation and increase plaque vulnerability in the carotid artery of hypercholesterolemic Yucatan microswine. Atherosclerotic lesions at the common carotid artery junction and ascending pharyngeal artery were induced in hypercholesterolemic Yucatan microswine at 5-6 months of age with balloon angioplasty. LPS or oxLDL were administered intraluminally at the site of injury after occluding the arterial flow temporarily. Pre-intervention ultrasound (US), angiography, and optical coherence tomography (OCT) were done at baseline and just before euthanasia to assess post-op parameters. The images from the US, OCT, and angiography in the LPS and the oxLDL-treated group showed increased plaque formation with features suggestive of unstable plaque, including necrotic core, thin fibrous caps, and a signal poor region more with oxLDL compared to LPS. Histomorphology of the carotid artery tissue near the injury corroborated the presence of severe lesions in both LPS and oxLDL-treated pigs but more in the oxLDL group. Vascular smooth muscle and endothelial cells treated with LPS and oxLDL showed increased folds changes in mRNA transcripts of the biomarkers of inflammation and plaque vulnerability compared to untreated cells. Collectively, the results suggest that angioplasty-mediated intimal injury of the carotid arteries in atherosclerotic swine with local administration of LPS or ox-LDL induces vulnerable plaques compared to angioplasty alone and oxLDL is relatively more potent than LPS in inducing vulnerable plaque.

In vitro measurements of hemodynamic forces and their effects on endothelial cell mechanics at the sub-cellular level.

This paper presents micro-particle tracking velocimetry measurements over cultured bovine aortic endothelial cell monolayers in microchannels. The objective was to quantify fluid forces and cell morphology at the sub-cellular scale for monolayers subjected to steady shear rates of 5, 10, and 20 dyn/cm2. The ultimate goal of this study was to develop an experimental methodology for in vitro detailed study of physiologically realistic healthy and diseased conditions. Cell topography, shear stress, and pressure distributions were calculated from sets of velocity fields made in planes parallel to the microchannel wall. For each experiment, measurements were made in 3 h intervals for 18 h. It was found that there is a three-dimensional change in cell morphology as a result of applied shear stress. That is, cells flatten and become more wedge shaped in the stream direction while conserving volume by spreading laterally, i.e., in the cross-stream direction. These changes in cell morphology are directly related to local variations in fluid loading, i.e., shear stress and pressure. This paper describes the first flow measurements over a confluent layer of endothelial cells that are spatially resolved at the sub-cellular scale with a simultaneous temporal resolution to quantify the response of cells to fluid loading.

Pheochromocytoma crisis presenting with cardiogenic shock.

Pheochromocytoma is a catecholamine-secreting tumor of the adrenal glands whose typical presentation includes the triad of headache, palpitations, and diaphoresis. Pheochromocytoma crisis is an urgent medical condition whose diagnosis and management constitute a challenge for physicians. We present the case of a 55-year-old man who developed cardiogenic shock in the setting of a pheochromocytoma crisis. After stabilizing blood pressure with combined administration of α- and ß-blockers, the tumor was surgically removed. Our diagnostic and therapeutic challenges are discussed.

Cholesterol embolization syndrome following thrombolysis during acute myocardial infarction.

BACKGROUND: Cholesterol embolization syndrome (CES) is the result of atherosclerotic plaque erosion and subsequent dislodgement of cholesterol crystals from the core of the plaque to the peripheral arteries. The source of emboli is usually located in the aorta, whereas the most commonly affected organs are the skin and the kidneys. CASE REPORT: The case of a 69-year-old male with cyanotic painful discoloration of his toes following thrombolysis for acute myocardial infarction 1 month previously is presented. Both transesophageal echocardiography and magnetic resonance aortography showed a diffuse ulcerated atherosclerotic plaque in the course of descending thoracic aorta, while a skin biopsy of the cyanotic toes revealed cholesterol crystals in the lumen of the small diameter arteries. CONCLUSION: Cholesterol embolizations from the aorta are difficult to treat and may end in renal failure. Since treatment options are limited without proven efficacy, increased awareness by the clinicians is needed.

Brugada syndrome associated with supraventricular tachycardia: diagnostic and therapeutic strategies.

We report the case of a patient with Brugada syndrome and a history of palpitations who presented with an episode of syncope and developed supraventricular tachycardia in the electrophysiological study. The patient was treated with radiofrequency ablation for the supraventricular tachycardia and an implantable cardioverter defibrillator for the Brugada syndrome. At 18 months following implantation of the defibrillator an electrical storm with ventricular fibrillation episodes occurred followed by appropriate discharges of the defibrillator.

Non-diabetic hyperglycaemia correlates with angiographic coronary artery disease prevalence and severity.

AIM: The role of glycaemia as a coronary artery disease (CAD) risk factor is controversial, and the optimal glucose level is still a matter of debate. For this reason, we assessed the prevalence and severity of angiographic CAD across hyperglycaemia categories and in relation to haemoglobin A(1c) (HbA(1c)) levels. METHODS: We studied 273 consecutive patients without prior revascularization undergoing coronary angiography for suspected ischaemic pain. CAD severity was assessed using three angiographic scores: the Gensini's score; extent score; and arbitrary index. Patients were grouped, according to 2003 American Diabetes Association criteria, into those with normal fasting glucose (NFG), impaired fasting glucose (IFG) and diabetes mellitus (DM). RESULTS: CAD prevalence was 2.5-fold higher in both the IFG and DM groups compared with the NFG group. Deterioration of glycaemic profile was a multivariate predictor of angiographic CAD severity (extent score: P=0.027; arbitrary index: P=0.007). HbA(1c) levels were significantly higher among CAD patients (P=0.016) and in those with two or more diseased vessels (P=0.023) compared with the non-CAD group. HbA(1c) levels remained predictive of CAD prevalence even after adjusting for conventional risk factors, including DM (adjusted OR: 1.853; 95% CI: 1.269-2.704). CONCLUSION: Non-diabetic hyperglycaemia, assessed either categorically by fasting glucose categories or continuously by HbA(1c) levels, correlates with the poorest angiographic outcomes.

Predicting the risk of rupture of abdominal aortic aneurysms by utilizing various geometrical parameters: revisiting the diameter criterion.

The authors estimated noninvasively the wall stress distribution for actual abdominal aortic aneurysms (AAAs) in vivo on a patient-to-patient basis and correlated the peak wall stress (PWS) with various geometrical parameters. They studied 39 patients (37 men, mean age 73.7 +/- 8.2 years) with an intact AAA (mean diameter 6.3 +/- 1.7 cm) undergoing preoperative evaluation with spiral computed tomography (CT). Real 3-dimensional AAA geometry was obtained from image processing. Wall stress was determined by using a finite-element analysis. The aorta was considered isotropic with linear material properties and was loaded with a static pressure of 120.0 mm Hg. Various geometrical parameters were used to characterize the AAAs. PWS and each of the geometrical characteristics were correlated by use of Pearson's rank correlation coefficients. PWS varied from 10.2 to 65.8 N/cm2 (mean value 37.1 +/- 9.9 N/cm2). Among the geometrical parameters, the PWS was well correlated with the mean centerline curvature, the maximum centerline curvature, and the maximum centerline torsion of the AAAs. The correlation of PWS with maximum diameter was nonsignificant. Multiple regression analysis revealed that the mean centerline curvature of the AAA was the only significant predictor of PWS and subsequent rupture risk. This noninvasive computational approach showed that geometrical parameters other than the maximum diameter are better indicators of AAA rupture.