title: Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects.
abstract: BACKGROUND
  A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.
  
  
  RESULTS
  Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.
  
  
  CONCLUSIONS
  Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, New York, United States of America.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Rajagopalan
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, New York, United States of America.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Kaie
authors.initials: K
authors.lastname: Ojamaa
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, New York, United States of America.
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Chen
authors.affiliation: CNR Clinical Physiology Institute, Pisa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pingitore
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, New York, United States of America.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Pol
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Debra
authors.initials: D
authors.lastname: Saunders
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Krithika
authors.initials: K
authors.lastname: Balasubramanian
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Rheal A
authors.initials: RA
authors.lastname: Towner
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, New York, United States of America.
authors.forename: A Martin
authors.initials: AM
authors.lastname: Gerdes
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000097:blood
chemical_list: D014284:Triiodothyronine