Digitoxin Attenuates Heart Failure, Reduces Myocardial Hypertrophy, and Preserves the Calcium-Binding Proteins in Infarcted Rats.

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.

• Authors: Camila T Picollo, Alexandra A Dos Santos, Ednei L Antonio, Jairo M A Silva, Danilo Bocalini, Andrey Jorge Serra, Silvia S M Ihara, Paulo J F Tucci
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 25 Issue 3 Pg. 265-272 (05 2020) ISSN: 1940-4034 [Electronic] United States
• PMID: 31714152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• Cardiotonic Agents
• Digitoxin
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Signaling
• Calcium-Binding Proteins (metabolism)
• Cardiotonic Agents (pharmacology)
• Digitoxin (pharmacology)
• Disease Models, Animal
• Female
• Heart Failure (metabolism, pathology, physiopathology, prevention & control)
• Hypertrophy, Left Ventricular (metabolism, pathology, prevention & control)
• Kinetics
• Myocardial Contraction (drug effects)
• Myocardial Infarction (drug therapy, metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• Rats, Wistar
• Ventricular Function, Left (drug effects)
• Ventricular Remodeling (drug effects)