Anthrax lethal toxin induces acute diastolic dysfunction in rats through disruption of the phospholamban signaling network.

Background: Anthrax lethal toxin (LT), secreted by Bacillus anthracis, causes severe cardiac dysfunction by unknown mechanisms. LT specifically cleaves the docking domains of MAPKK (MEKs); thus, we hypothesized that LT directly impairs cardiac function through dysregulation of MAPK signaling mechanisms.

Methods And Results: In a time-course study of LT toxicity, echocardiography revealed acute diastolic heart failure accompanied by pulmonary regurgitation and left atrial dilation in adult Sprague-Dawley rats at time points corresponding to dysregulated JNK, phospholamban (PLB) and protein phosphatase 2A (PP2A) myocardial signaling.

Echocardiographic effects of eplerenone and aldosterone in hypertensive rats.

The effects of aldosterone receptor blockade on echocardiography in spontaneously hypertensive rats (SHR) are not fully characterized. In this study, multiple echocardiographic parameters were compared for 42 weeks between SHR versus Wistar-Kyoto rats (WKY) serving as normotensive controls. In addition, echocardiographic parameters were compared for 28 weeks between the SHR versus SHR treated with eplerenone 100 mg/kg/day or spironolactone 50 mg/kg/day.

Norepinephrine induces systolic failure and inhibits antiapoptotic genes in a polymicrobial septic rat model.

Aims: We examined the effect of norepinephrine (NE) infusion on left ventricular function and apoptotic genes during progression of polymicrobial sepsis.

Methods: Male Sprague-Dawley rats (350-400 g) were made septic by intraperitoneal (i.p.

Enhanced external counterpulsation is a regenerative therapy.

Enhanced external counterpulsation (EECP) is used for the treatment of severe angina and heart failure in patients who are not candidates for revascularization. The clinical benefits of EECP extend well beyond the time period of any hemodynamic effects, but the cause of this prolonged effect is not understood. The prolonged clinical benefits suggest EECP could be a regenerative therapy.

Anthrax toxin: pathologic effects on the cardiovascular system.

Anthrax is a disease caused by infection with spores from the bacteria Bacillus anthracis. After entering the body, the spores germinate into bacteria and secrete a toxin that causes local edema and, in systemic infections, cardiovascular collapse and death. The toxin is a tripartite polypeptide, consisting of protective antigen (PA), lethal factor (LF) and edema factor (EF), which have key roles in the bacterial pathogenesis and disease progression.

Integrins and proximal signaling mechanisms in cardiovascular disease.

Integrins are heterodimeric cell-surface molecules, which act as the principle mediators of molecular dialog between a cell and its extracellular matrix environment. In addition to their structural functions, integrins mediate signaling from the extracellular space into the cell through integrin-associated signaling and adaptor molecules such as FAK (focal adhesion kinase), ILK (integrin-linked kinase), PINCH (particularly interesting new cysteine-histidine rich protein) and Nck2 (non-catalytic (region of) tyrosine kinase adaptor protein-2). Via these molecules, integrin signaling tightly and cooperatively interacts with receptor tyrosine kinases (RTKs) signaling to regulate survival, proliferation and cell shape as well as polarity, adhesion, migration and differentiation.

Guidewire pacing safely and effectively treats bradyarrhythmias induced by rheolytic thrombectomy and precludes the need for transvenous pacing: the Scott & White experience.

Rheolytic thrombectomy (RT) is useful in certain percutaneous coronary interventions but may be associated with transient bradyarrhythmias. Clinicians have devised numerous strategies to deal with these arrhythmias apart from transvenous right ventricular pacing, some of which are described in other parts of this supplement. We report the Scott & White experience utilizing guidewire pacing to quickly and safely pace the heart in the event of bradyarrhythmia.

Lethal and edema toxins of anthrax induce distinct hemodynamic dysfunction.

Fatalities due to anthrax are associated with severe hypotension suggesting that the toxins generated from Bacillus anthracis, lethal toxin (LeTx) and edema toxin (EdTx), have cardiovascular effects. Here, we demonstrate the effects of these toxins and characterize their effects by echocardiography. LeTx leads to a significant reduction in ejection fraction, decreased velocity of propagation (diastolic dysfunction), decreased velocity of circumferential fiber shortening (decreased contractility), and increased LV systolic area (pathophysiology).

Integrins: novel therapeutic targets for cardiovascular diseases.

Integrins are the principle mediators of molecular dialog between a cell and its extracellular matrix environment. The unique combinations of integrin subunits determine which extracellular matrix molecules are recognized by a cell. Recent studies have demonstrated that remodeling in heart and vasculature is linked to alterations in extracellular matrix and integrin expression.

Cyclooxygenase-2 inhibitors: a painful lesson.

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a clinically important class of agents. NSAIDs are commonly used in treatment of conditions such as headache, fever, inflammation and joint pain. Complications often arise from chronic use of NSAIDs.

Aldosterone receptor antagonists and cardiovascular disease: do we need a change of the guard?

Aldosterone is a mineralocorticoid primarily produced in the zona glomerulosa of the adrenal gland. For many years, aldosterone (Aldo) was thought to have its sole site of action in the kidney, where it regulated sodium excretion and potassium reabsorption. It is now known that Aldo is produced in cardiovascular tissues, and has been implicated in the development of ventricular hypertrophy and cardiac fibrosis.

Baseline echocardiographic values for adult male rats.

Background: Because of safety, repeatability, and portability, clinical echocardiography is well established as a standard for cardiac anatomy, cardiac function, and hemodynamics. Similarly, application of echocardiography in commonly used rat experimental models would be worthwhile. The use of noninvasive ultrasound imaging in the rat is a potential replacement for more invasive terminal techniques.

Comparison of lipid and non-lipid markers of atherosclerosis in arterial versus venous blood.

Background: Early studies have suggested that there may be differences in the concentration of lipoprotein particles and their associated apolipoproteins in arterial and venous blood and that this gradient might explain a proclivity to develop atherosclerotic lesions. The aim of this study was to use current methods of analysis to determine levels of these components, including particle densities and several common inflammatory markers in arterial and venous blood.

Methods: Samples of arterial and venous blood were obtained nearly simultaneously in 26 patients undergoing right and left heart catheterization.

Single coronary artery with an ectopic origin and interarterial course: a case report and review of the literature.

A previously unreported variant of a single coronary artery arising between the aorta and pulmonary artery is presented. This variant had many high-risk features, so prophylactic coronary artery bypass grafting was recommended.

Intravenous immunoglobulin-related acute coronary syndrome and coronary angiography in idiopathic thrombocytopenic purpura--a case report and literature review.

In acute coronary syndromes, GPIIb/IIIa platelet inhibitors have demonstrated a reduction in recurrent myocardial ischemia. Conversely, one might expect that enhancing platelet activity in patients in acute coronary syndromes would have the opposite effect. We report a patient with idiopathic thrombocytopenic purpura (ITP) that had recurrent myocardial ischemia associated with administration of intravenous immunogloblin (IVIG).