Long-term thyroid hormone administration reshapes left ventricular chamber and improves cardiac function after myocardial infarction in rats.
Thyroid hormone (TH) is critical for tissue differentiation at early stages of development, induces physiological hypertrophy and regulates the expression of important contractile proteins such as myosin heavy chain (MHC) isoform and calcium cycling proteins. Furthermore, TH seems to control the response to stress by regulating important cardioprotective molecules such as heat shock proteins (HSPs). Thus, the present study investigated whether TH administration immediately after acute myocardial infarction can favourably remodel the post-infarcted myocardium. Acute myocardial infarction was induced in rats by coronary artery ligation (AMI, n=10), while SHAM-operated animals served as controls (SHAM, n = 8). TH was administered for 13 weeks (AMI-THYR, n = 9). Cardiac contractile function and left ventricular (LV) chamber remodelling was assessed by serial echocardiography and in Langendorff heart preparations. AMI significantly reduced LV ejection fraction (EF%); 30.0 (s.e.m, 2.3) Vs. 73.8 (1.8) in SHAM, P < 0.05. In addition, +dp/dt and -dp/dt (in mmHg/s) were 4,051 (343) and 2,333 (118) respectively for SHAM Vs. 2,102 (290) and 1,368 (181) for AMI, P < 0.05. With TH treatment, EF% was increased to 49.5 (2.7) in AMI-THYR, P < 0.05, while +dp/dt and -dp/dt (in mmHg/s) were 3,708 (231) and 2,035 (95) for AMI-THYR, P < 0.05 Vs. AMI. A marked elevation of the expression of beta-MHC and a reduced ratio of SERCA/Phospholamban were found in viable myocardium of AMI hearts, which was prevented by TH. Furthermore, heat shock protein 70 myocardial content was decreased in AMI hearts and was significantly increased after TH treatment. An ellipsoidal reshaping of LV chamber was observed with TH; cardiac sphericity index, (ratio of long/short axis, SI), was 1.98 (0.03) for SHAM, 1.52 (0.05) for AMI and 1.72(0.02) for AMI-THYR, P < 0.05. In conclusion, long-term TH administration immediately after AMI results in sustained improvement of cardiac haemodynamics.
Pantos
Constantinos
C
Dept. of Pharmacology, University of Athens, 75 Mikras Asias Ave., Goudi, 11527, Athens, Greece. cpantos@cc.uoa.gr
Mourouzis
Iordanis
I
Markakis
Konstantinos
K
Tsagoulis
Nikolaos
N
Panagiotou
Matthew
M
Cokkinos
Dennis V
DV
D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry; D018995:Myosin Heavy Chains / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects
D018840:HSP70 Heat-Shock Proteins; D013963:Thyroid Hormones; D018995:Myosin Heavy Chains