Objective-We hypothesized that reactive oxygen species (ROS) contribute to progression of aortic valve (AV) calcification/stenosis. Methods and Results-We investigated ROS production and effects of antioxidants tempol and lipoic acid (LA) in calcification progression in rabbits given 0.5% cholesterol diet ϩ10 4 IU/d Vit.D 2 for 12 weeks. Superoxide and H 2 O 2 microfluorotopography and 3-nitrotyrosine immunoreactivity showed increased signals not only in macrophages but preferentially around calcifying foci, in cells expressing osteoblast/osteoclast, but not macrophage markers. Such cells also showed increased expression of NAD(P)H oxidase subunits Nox2, p22phox, and protein disulfide isomerase. Nox4, but not Nox1 mRNA, was increased. Tempol augmented whereas LA decreased H 2 O 2 signals. Importantly, AV calcification, assessed by echocardiography and histomorphometry, decreased 43% to 70% with LA, but increased with tempol (PՅ0.05). Tempol further enhanced apoptosis and Nox4 expression. In human sclerotic or stenotic AV, we found analogous increases in ROS production and NAD(P)H oxidase expression around calcifying foci. An in vitro vascular smooth muscle cell (VSMC) calcification model also exhibited increased, catalase-inhibitable, calcium deposit with tempol, but not with LA. Conclusions-Our data provide evidence that ROS, particularly hydrogen peroxide, potentiate AV calcification progression. However, tempol exhibited a paradoxical effect, exacerbating AV/vascular calcification, likely because of its induced increase in peroxide generation. Key Words: calcification Ⅲ atherosclerosis Ⅲ antioxidants Ⅲ valves Ⅲ free radicals D egenerative aortic valve (AV) stenosis, the third most prevalent cardiovascular disease in the elderly, 1 shares common risk factors and pathophysiological features with atherosclerosis. [2][3][4][5][6] Although the role of oxidative stress in atherosclerosis is well explored, 7,8 it is unclear whether redox processes contribute to progression of AV calcification. 2,3,9 -11,15,16 Scarce observations provide indirect support for this hypothesis. 10 In vitro studies showed that exogenous superoxide, hydrogen peroxide, or other oxidants increase the number and activity of calcifying vascular cells (CVCs), 11 referred to as a specific subpopulation of cells, derived from (de)differentiation of vascular smooth muscle cells, 12 pericytes, or mesenchymal cells 13 that can produce hydroxyapathite in the vascular wall. 14 In addition, reactive oxygen species (ROS) mediate increase in BMP2 expression and signaling, favoring osteogenesis. 2 On the other hand, calcium resorption by osteoclasts is dependent on ROS derived from its own NAD(P)H oxidase, 15 whereas nitric oxide induces osteoclast detachment and inhibits calcium resorption. 16 Recent data from an experimental mouse model of aortic stenosis suggested locally increased superoxide generation. 3 Observational clinical studies with statins indicated possible decrease in calcification progression in hypercholesterolemic patients, 4 but ...

Objective: To determine the safety and cardiac chronotropic responsiveness to early atropine dobutamine stress echocardiography (DSE) in the elderly. Design: Retrospective study of 258 patients > 70 years who underwent early atropine DSE and 290 patients > 70 years who underwent conventional DSE. In the early atropine protocol, atropine was started at 20 mg/kg/min of dobutamine if heart rate was , 100 beats/min, up to 2 mg. The cardiac chronotropic responsiveness in the elderly was compared with a control group of patients , 70 years matched for sex, myocardial infarction, diabetes, and treatment with b blockers and calcium channel blockers.Results: The dose of dobutamine given to elderly patients was lower during early atropine than during conventional DSE (mean (SD) 29 (7) v 38 (4) mg/kg/min, p = 0.001). Early atropine DSE resulted in diminished incidence of ventricular extrasystoles, non-sustained ventricular tachycardia, bradycardia, and hypotension compared with conventional DSE. In comparison with patients , 70 years, elderly patients required lower doses of dobutamine and atropine and achieved a higher percentage of predicted maximum heart rate (92 (9)% v 88 (10)%, p = 0.0001). Except for more common hypotension (16% v 10%, p = 0.004), no other difference in adverse effects was observed between patients > 70 and , 70 years. Conclusions: Early atropine DSE is a safe strategy in the elderly resulting in lower incidence of minor adverse effects than with the conventional protocol. Elderly patients presented adequate cardiac chronotropic responsiveness to early injections of atropine, requiring lower doses of drugs to reach test end points.

Patients with FH and no obstructive CAD have blunted MBF reserve and lower FMD values as compared with healthy volunteers. Both FMD and MBF reserve were normalized after atorvastatin treatment.

Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Several heart conditions have been associated with CKD, including myocardial and pericardial diseases. This paper describes a case of Dialysis-related constrictive pericarditis in a patient diagnosed with sudden hypotension during a hemodialysis session. A 65-year-old man diagnosed with hypertension, diabetes, obesity, and cirrhosis on hemodialysis for two years complained of symptoms during one of his sessions described as malaise, lipothymia, and confusion. The patient had a record of poor compliance with the prescribed diet and missed dialysis sessions. He was sluggish during the physical examination, and presented hypophonetic heart sounds, a blood pressure of 50/30mmHg, and a prolonged capillary refill time. The patient was referred to the intensive care unit and was started on antibiotics and vasoactive drugs. His workup did not show signs of infection, while electrocardiography showed low QRS-wave voltage. His echocardiogram showed signs consistent with a thickened pericardium without pericardial effusion. Cardiac catheterization showed equalization of diastolic pressures in all heart chambers indicative of constrictive pericarditis. The patient underwent a pericardiectomy. Examination of surgical specimens indicated he had marked fibrosis and areas of dystrophic calcification without evidence of infection, consistent with Dialysis-related constrictive pericarditis. Hypotension for unknown causes must be considered in the differential diagnosis of dialysis patients.