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Changes in mechanical and electrical coupling affect cardiac function following volume overload reversal
Author(s) -
Guggilam Anuradha,
Hutchinson Kirk R,
West Thomas A,
Galantowicz Maarten L,
Lord Kevin C,
Lucchesi Pamela A
Publication year - 2011
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.25.1_supplement.1096.6
Subject(s) - contractility , volume overload , connexin , cardiology , medicine , pressure overload , vinculin , diastole , immunohistochemistry , heart failure , myocyte , endocrinology , gap junction , phosphorylation , biology , microbiology and biotechnology , blood pressure , intracellular , cardiac hypertrophy , focal adhesion
This study determined the mechanisms that account for delayed functional improvement following reversal of LV volume overload during compensated heart failure. Methods Rats were subjected to sham or aortocaval fistula (ACF) surgery for 4wks; a subset then received a reversal procedure. LV morphology and function were assessed 4wks post reversal in sham, ACF and ACF+Rev groups by echocardiography or in vivo pressure‐volume analysis. Myocyte contractility was assessed with an IonOptix system. Protein expression and localization were examined by immunoblotting and immunohistochemistry. Results At 4wks post ACF‐reversal, LV end‐systolic and end‐diastolic diameters were normalized to sham. In contrast, LV systolic dysfunction (fractional shortening, ESPVR) persisted in the ACF+Rev group. Isolated LV myocytes from ACF+Rev exhibited increased contractility compared to ACF. In ACF and ACF+Rev LV tissues, β‐catenin and N‐cadherin protein expression were unchanged, but immunohistochemistry revealed reduced β‐catenin and vinculin in the intercalated disc region (ICD), nuclear translocation of β‐catenin and decreased connexin‐43 expression and ICD localization. Conclusion Loss of connexin‐43 and vinculin, and relocalization of β‐catenin from the ICD may result in impaired electrical and force transmission contributing to the persistent cardiac dysfunction in vivo following ACF reversal.