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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac myocyte function is dependent on the synchronized movements of Ca(2+) into and out of the cell, as well as between the cytosol and sarcoplasmic reticulum. These movements determine cardiac rhythm and regulate excitation-contraction coupling. Ca(2+) cycling is mediated by a number of critical Ca(2+)-handling proteins and transporters, such as L-type Ca(2+) channels (LTCCs) and sodium/calcium exchangers in the sarcolemma, and sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), ryanodine receptors, and cardiac phospholamban in the sarcoplasmic reticulum. The entry of Ca(2+) into the cytosol through LTCCs activates the release of Ca(2+) from the sarcoplasmic reticulum through ryanodine receptor channels and initiates myocyte contraction, whereas SERCA2a and cardiac phospholamban have a key role in sarcoplasmic reticulum Ca(2+) sequesteration and myocyte relaxation. Excitation-contraction coupling is regulated by phosphorylation of Ca(2+)-handling proteins. Abnormalities in sarcoplasmic reticulum Ca(2+) cycling are hallmarks of heart failure and contribute to the pathophysiology and progression of this disease. Correcting impaired intracellular Ca(2+) cycling is a promising new approach for the treatment of heart failure. Novel therapeutic strategies that enhance myocyte Ca(2+) homeostasis could prevent and reverse adverse cardiac remodeling and improve clinical outcomes in patients with heart failure.
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PMID:Altered sarcoplasmic reticulum calcium cycling--targets for heart failure therapy. 2309 87

Cardiac contractility modulation (CCM) is the application of nonexcitatory electrical signals to the myocardium, during the absolute refractory period of the action potential, to elicit a positive inotropic effect without increasing myocardial oxygen consumption. These effects are independent of QRS duration; consequently, CCM device therapy might benefit symptomatic patients with reduced left ventricular ejection fraction who are not candidates for cardiac resynchronization therapy. Preclinical studies have demonstrated a rapid positive inotropic effect of CCM, which seems to be mediated by modulation of cardiomyocyte Ca(2+) fluxes and alterations in the phosphorylation of cardiac phospholamban. In vivo translational and clinical studies that utilized double biphasic voltage pulses to the right ventricular aspect of the interventricular septum have demonstrated positive global effects on cardiac reverse remodelling and contractility. Long-term application of CCM seems to improve patients' exercise tolerance and quality of life. These benefits are apparently accomplished with an acceptable safety profile; however, to date, no data have demonstrated reductions in hospitalizations for heart failure or mortality. CCM is currently available in Europe and ongoing studies are attempting to identify the ideal target population and accumulate additional outcome data.
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PMID:Cardiac contractility modulation therapy in advanced systolic heart failure. 2393 81