title: Thyroid hormone at supra-physiological dose optimizes cardiac geometry and improves cardiac function in rats with old myocardial infarction.
abstract: Thyroid hormone (TH) is critical in cardiac cell differentiation (regulating contractile proteins and cell geometry) and this effect could be potentially exploited therapeutically in reversing the process of de-differentiation which underlies postischemic cardiac remodeling. Acute myocardial infarction was induced in male Wistar rats by ligating left coronary artery (AMI, n=8), while sham operated animals served as control (SHAM, n=8). 13 weeks after AMI, TH was administered in a group of animals for 4 weeks (AMI-THYR, n=9). TH significantly increased beta-MHC and decreased alpha-MHC expression in the myocardium. This response was accompanied by changes in cardiac geometry: sphericity index, (SI, long to short axis ratio) was found to be 1.95 (SEM, 0.02) in SHAM, 1.51(0.03) in AMI and 1.64(0.03) in AMI-THYR, p<0.05. As a consequence, cardiac function was significantly improved: left ventricular ejection fraction (EF%) was 74.5% (SEM, 2.8) in SHAM vs 29.5% (2.1) in AMI, and 40.0% in AMI-THYR, p<0.05. Furthermore, +dp/dt and -dp/dt were 4250 (127) and 2278 (55) in SHAM vs 2737(233) and 1508 (95) in AMI vs 3866 (310) and 2137(111) in AMI -THYR, respectively, p<0.05. TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure.
authors.affiliation: Department of Pharmacology, University of Athens, 75 Mikras Asias Ave.,11527 Goudi, Athens, Greece. cpantos@cc.uoa.gr
authors.forename: C
authors.initials: C
authors.lastname: Pantos
authors.forename: I
authors.initials: I
authors.lastname: Mourouzis
authors.forename: N
authors.initials: N
authors.lastname: Tsagoulis
authors.forename: K
authors.initials: K
authors.lastname: Markakis
authors.forename: G
authors.initials: G
authors.lastname: Galanopoulos
authors.forename: N
authors.initials: N
authors.lastname: Roukounakis
authors.forename: P
authors.initials: P
authors.lastname: Perimenis
authors.forename: A
authors.initials: A
authors.lastname: Liappas
authors.forename: D V
authors.initials: DV
authors.lastname: Cokkinos
mesh_terms: D000818:Animals; D004452:Echocardiography; D006333:Heart Failure / Q000517:prevention & control; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000502:physiology* / Q000627:therapeutic use*; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D020033:Protein Isoforms; D013963:Thyroid Hormones; D018995:Myosin Heavy Chains