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Two of the most significant characteristics of failing human myocardium are an increased diastolic [Ca2+]i and a prolonged diastolic relaxation. These abnormalities are more pronounced at higher frequencies of stimulation and may be caused by an altered Ca2+ resequestration into the sarcoplasmic reticulum (SR). The force-frequency relationship was(More)
BACKGROUND We investigated whether decreased myofilament calcium contractile activation may, in part, contribute to heart failure. METHODS AND RESULTS Calcium concentration required for 50% activation and Hill coefficient for fibers from nonfailing and failing human hearts at pH 7.1 were not different. Maximum calcium-activated force (F(max)) was also not(More)
Failing human myocardium has been associated with decreased sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity. There remains controversy as to whether the regulation of SR Ca(2+)-ATPase activity is altered in heart failure or whether decreased SR Ca(2+)-ATPase activity is due to changes in SR Ca(2+)-ATPase or phospholamban expression. We therefore(More)
Abnormal intracellular Ca(2+) cycling plays an important role in cardiac dysfunction and ventricular arrhythmias in the setting of heart failure and transient cardiac ischemia followed by reperfusion (I/R). We hypothesized that overexpression of the sarcoplasmic reticulum Ca(2+) ATPase pump (SERCA2a) may improve both contractile dysfunction and ventricular(More)
β-blocker treatmenthas emerged as an effective treatment modality for heart failure.Interestingly, β-blockers can activate both pro-apoptotic and anti-apoptoticpathways. Nevertheless, the mechanism for improved cardiac functionseen with β-blocker treatment remains largely unknown. Carvedilolis a non-selective β-blocker with α-receptor blockade and(More)
METHODS Multicellular preparations from nonfailing and failing human hearts or animals with cardiac hypertrophy were used to study intracellular calcium mobilization. Left ventricular muscle strips were loaded with the intracellular calcium indicator aequorin. Muscle strips were attached to a force transducer and stretched until there was no further(More)
BACKGROUND Excessive alcohol consumption is recognized as a common cause of left ventricular (LV) dysfunction. It is currently thought that 36% of all cases of dilated cardiomyopathy are due to excessive alcohol intake. Suitable animal models are needed to study the pathogenic mechanisms of ethanol-induced LV dysfunction. We have therefore created a new(More)
We investigated the effects of two purported calcium sensitizing agents, MCI-154 and DPI 201–106, and a known calcium sensitizer caffeine on Mg-ATPase (myofibrillar ATPase) and myosin ATPase activity of left ventricular myofibrils isolated from non-failing, idiopathic (IDCM) and ischemic cardiomyopathic (ISCM) human hearts (i.e. failing hearts). The(More)
Global contractile heart failure was induced in turkey poults by furazolidone feeding (700 ppm). Abnormal calcium regulation appears to be a key factor in the pathophysiology of heart failure, but the cellular mechanisms contributing to changes in calcium fluxes have not been clearly defined. Isolated ventricular myocytes from non-failing and failing hearts(More)
Sickle cell anemia affects 100,000 African Americans. Frequent blood transfusions to prevent stroke lead to fatal iron-overload. Iron chelation with deferoxamine (DFO) requires expensive infusions. In the present study, we explore the feasibility of using a new delivery system for DFO, i.e., targeted liposome entrapped DFO (LDFO). Our results reveal that(More)