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Reversal of cardiac dysfunction and subcellular alterations by metoprolol in heart failure due to myocardial infarction
Author(s) -
Babick Andrea,
Elimban Vijayan,
Zieroth Shelley,
Dhalla Naranjan S.
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24373
Subject(s) - metoprolol , medicine , heart failure , cardiology , phospholamban , endocrinology , ejection fraction , cardiac function curve , myocardial infarction , diastole , blood pressure , chemistry
In order to examine the reversibility of heart failure due to myocardial infarction (MI) by β‐adrenoceptor blockade, 12 weeks infarcted rats were treated with or without metoprolol (50 mg/kg/day) for 8 weeks. The depressed left ventricular (LV) systolic pressure, positive and negative rates of changes in pressure development, ejection fraction, fractional shortening and cardiac output, as well as increased LV end‐diastolic pressure in 20 weeks MI animals were partially reversed by metoprolol. MI‐induced decreases in septum (systolic) thickness as well as increase in LV posterior wall thickness and LV internal diameter were partially or fully reversible by metoprolol. Treatment of MI animals with metoprolol partially reversed the elevated levels of plasma norepinephrine and dopamine without affecting the elevated levels of epinephrine. Although sarcoplasmic reticular (SR) Ca 2+ ‐uptake, as well as protein content for SR Ca 2+ ‐pump and phospholamban, were reduced in the infarcted hearts; these changes were partially reversible with metoprolol. Depressed myofibrillar Ca 2+ ‐stimulated ATPase activity, as well as mRNA levels for SR Ca 2+ ‐pump, phospholamban and α‐myosin heavy chain, were unaffected whereas increased mRNA level for β‐myosin heavy chain was partially reversed by metoprolol. The results suggest that partial improvement of cardiac performance by β‐adrenoceptor blockade at advanced stages of heart failure may be due to partial reversal of changes in SR Ca 2+ ‐pump function whereas partial to complete reverse cardiac remodeling may be due to partial reduction in the elevated levels of plasma catecholamines. J. Cell. Physiol. 228: 2063–2070, 2013. © 2013 Wiley Periodicals, Inc.