isolation-culture-functional-characterization-adult-mouse

Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes

The use of primary cardiomyocytes (CMs) in culture has provided a powerful complement to murine models of heart disease in advancing our understanding of ...

Beth Israel Deaconess Medical Center, Harvard Medical School

sapienza university

Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF.

Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin.

A genetic origin of cerebrovascular accidents has long been suspected on the basis of epidemiologic evidence and familial aggregation. Nevertheless, the final phenotype is largely influenced by concomitant risk factors. We aimed to investigate whether impairment of endothelium-dependent vasodilation can be used as an informative intermediate vascular phenotype in hypertensive patients with familial history of stroke.

Nitric oxide release is impaired in hypertensive individuals with familial history of stroke.

Given its broad use as a screening tool, the electrocardiogram (ECG) has largely become one of the most common diagnostic tests performed in routine clinical practice. As a result, the finding of left bundle-branch block (LBBB) in the absence of a well-defined clinical setting has become relatively frequent and raises questions and often concerns. While in the absence of clinically detectable heart disease LBBB does not necessarily imply poor outcomes, physicians should be aware of the role of LBBB in stratifying risk of cardiovascular events and death in subjects with both ischemic and nonischemic heart disease. This paper reviews historical landmarks, pathophysiologic features, prognostic implications, and clinical management of LBBB in apparently healthy subjects and those with heart disease.

Left bundle-branch block--pathophysiology, prognosis, and clinical management.

The implantable cardioverter defibrillator (ICD) offers life-saving therapies for primary and secondary prevention of sudden cardiac death in high-risk patients. However, ICD detection algorithms consistently misclassify a substantial proportion of supraventricular rhythms, thus carrying the risk for inappropriate therapies. Although single-chamber ICD (Sc-ICD) discrimination tools have been reported to provide high specificity in rejecting sinus tachycardia and atrial fibrillation with a relatively low ventricular rate, accurate recognition of atrial fibrillation with faster ventricular rates, atrial tachycardias, atrial flutter, and some reentrant tachycardias is still an issue. Dual-chamber ICDs (Dc-ICDs) are supposed to overcome specificity issues by enhancing detection algorithms with information derived from the atrial and ventricular timing relationship. The initial promise of Dc-ICDs was to improve detection specificity without compromising sensitivity, and to translate this advantage over Sc-ICDs in a more selective use of aggressive therapies. Despite this solid background, superiority of Dc- over Sc-ICDs has never been convincingly demonstrated. The present review focuses on the efficacy of contemporary ICD arrhythmia discrimination tools and appraises the so far reported evidence supporting the superiority of Dc-ICDs in preventing inappropriate therapies.

Arrhythmia detection in single- and dual-chamber implantable cardioverter defibrillators: the more leads, the better?

Low-dose angiotensin receptor blockers as an alternative to ACE-inhibitors increase the risk of appropriate ICD interventions in heart failure.

Cardiac resynchronization therapy (CRT) promotes left ventricular (LV) reverse remodelling and affects myocardial collagen turnover in heart failure (HF) patients. Osteopontin (OPN) is a matrix glycoprotein required for the activation of fibroblasts upon TGF-Î²1 stimulation. In humans, plasma OPN and OPN-expressing lymphocytes correlate with the severity of HF. We sought to evaluate whether plasma OPN and TGF-Î²1 reflect LV reverse remodelling following CRT.

Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure.

Cardiac remodelling refers to molecular and cellular changes of the myocardium, as well as adapting alterations in size, shape and function of the heart in response to changing loading conditions. It represents the final common pathway of different heart diseases, and is recognized as a crucial aspect of cardiac and myocardial dysfunction and a well established determinant of the clinical course of heart failure.Osteopontin is an extracellular matrix glycoprotein secreted by osteoblasts, osteoclasts, macrophages, T cells, vascular smooth muscle cells, fibroblasts and cardiomyocytes. Osteopontin is not expressed in healthy cardiac tissue, although its expression can be triggered by pressure or volume overload, hypoxia and angiotensin II. Indeed, osteopontin has been reported in macrophages and interstitial tissues early after myocardial infarction and in cardiac macrophage-like cells of inflammatory lesions in experimental models of cardiomyopathy. Pressure overload is associated with osteopontin overexpression as well. Indeed, myocardial osteopontin messenger RNA is upregulated in rats following renovascular hypertension or aortic banding. In humans, a significant correlation exists between increased osteopontin immunoreactivity in cardiac myocytes and impaired left ventricular function or cardiomyocyte hypertrophy in patients with dilated cardiomyopathy.The present article focuses on the role of osteopontin in myocardial hypertrophy and remodelling. In general, evidence supports the concept that osteopontin plays a crucial role in extracellular matrix remodelling following myocardial adaptation to hypertrophic, inflammatory and neurohormonal stimuli in the overloaded heart.

Extracellular matrix remodelling in myocardial hypertrophy and failure : focus on osteopontin.

Defective Ca(2+) handling in failing cardiomyocites predisposes patients with heart failure (HF) to ventricular arrhythmia. We investigated whether gene variants of Ca(2+) handling proteins are associated with the occurrence of ventricular tachycardia/fibrillation (VT/VF) in HF patients implanted with a primary prevention implantable cardioverter-defibrillator (ICD).

Cristina Balla

Cardiovascular Institute

Beth Israel Deaconess Medical Center, Harvard Medical School

Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes