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Digitoxin Attenuates Heart Failure, Reduces Myocardial Hypertrophy, and Preserves the Calcium-Binding Proteins in
Camila T Picollo1, Alexandra A Dos Santos1, Ednei L Antonio1
1Cardiology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Insights
Digitoxin treatment improved heart function and structure in rats with myocardial infarction (MI)-induced heart failure. This study shows digitoxin mitigates cardiac remodeling and contractile impairment in heart failure models.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Myocardial infarction (MI) leads to heart failure with impaired cardiac structure and function.
- Digitoxin has previously shown survival benefits in heart failure models.
Purpose of the Study:
- To evaluate digitoxin's effects on myocardial structure, ventricular function, and calcium kinetics proteins in a rat model of heart failure due to MI.
- To investigate the long-term impact of digitoxin on cardiac remodeling and contractile function.
Main Methods:
- Seventy-two rats with MI were randomized into sham, digitoxin, infarction, and infarction + digitoxin groups.
- Assessments included echocardiography, hemodynamics, papillary muscle mechanics, collagen content, cardiomyocyte nuclear volume, and Western blot analysis.
- Digitoxin was administered orally via rat chow for 120 days.
Main Results:
- MI induced inotropic impairment, pulmonary congestion, increased nuclear volume, myocardial collagen, and Na+/Ca2+ exchanger levels.
- MI decreased SERCA2 and phosphorylated phospholamban levels.
- Digitoxin treatment improved cardiac remodeling, inotropism, ventricular performance, pulmonary congestion, collagen accumulation, nuclear volume, and normalized calcium kinetics proteins.
Conclusions:
- Long-term digitoxin treatment attenuates congestive heart failure in rats with MI.
- Digitoxin mitigates myocardial remodeling and contractile impairment.
- Digitoxin preserves myocardial levels of proteins involved in calcium kinetics.
Abstract:
We previously showed that digitoxin prolongs the survival of rats with heart failure due to myocardial infarction (MI). In this study, we evaluated the effect of digitoxin on myocardial structure, ventricular function, and proteins involved in calcium kinetics. Seventy-two rats with MI >35% of the left ventricle were randomly assigned to 4 treatment groups: sham (n = 15), digitoxin (n = 11), infarction (n = 20), and infarction + digitoxin (n = 26). The rats were assessed 120 days after surgery by echocardiogram, hemodynamics, papillary muscle mechanics, collagen content, cardiomyocyte nuclear volume, and Western blot analysis of proteins involved in calcium kinetics. Digitoxin was administered via the rat chow. Two-way analysis of variance was used for comparisons. Myocardial infarction caused inotropic impairment, pulmonary congestion, increase of nuclear volume, myocardial collagen, and Na+/Ca2+ exchanger levels, and decreased SERCA2 and phosphorylated phospholamban levels. Treatment with digitoxin showed improvements in cardiac remodeling, inotropism, ventricular performance, pulmonary congestion, collagen accumulation, nuclear volume, and proteins involved in calcium kinetics. In rats with heart failure due to MI, long-term treatment with digitoxin attenuates congestive heart failure, mitigates myocardial remodeling and contractile impairment, and preserves myocardial levels of proteins involved in calcium kinetics.
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