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Cellular Mechanisms of Cardiac Dysfunction in Volume Overload Induced Heart Failure
Author(s) -
Guggilam Anuradha,
Galantowicz Maarten L,
West Aaron T,
Zhang Xiaojin,
Lucchesi Pamela A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb662
Subject(s) - myocyte , volume overload , heart failure , medicine , cardiology , serca , pressure overload , stimulation , contraction (grammar) , endocrinology , cardiac myocyte , chemistry , biochemistry , cardiac hypertrophy , atpase , enzyme
Left ventricular (LV) volume overload (VO) in valve regurgitation patients can be only treated by surgical intervention. The cellular mechanisms involved in cardiac dysfunction are not well known. The aim of this study was to understand the mechanical properties of myocytes isolated from VO‐induced heart failure and the possible mechanisms of dysfunction. Male Sprague‐Dawley rats underwent aorta‐caval fistula (ACF) surgery to induce VO heart failure or sham procedure. The rats with ACF went into failure at ~21wks post‐surgery. LV myocytes were isolated. Myocyte cell‐shortening fraction (CS) and Ca[i]2+ transients were measured at different frequency field stimulations to study cellular mechanical properties and molecular components of excitation‐contraction (EC) coupling. SERCA, pRYR and pPLB were reduced in ACF hearts while NCX was unchanged. Regardless of the stimulation frequency, CS of ACF myocytes was significantly lower than those of sham myocytes (~45% reduction). Interestingly, rapid stimulation at higher frequencies did not alter the Ca2+ area of relengthening in ACF myocytes, suggesting the activity of RYR and SERCA are intact despite reduction in protein levels. These data suggest that EC coupling is not a causative factor for cardiac dysfunction seen in VO and may possibly be due to reduced Ca2+ sensitivity or decreased force generation in elongated myocytes of ACF rats.