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Comparative Study
. 2014 Dec;20(12):1012-9.
doi: 10.1016/j.cardfail.2014.10.003. Epub 2014 Nov 25.

Thyroid hormone replacement therapy attenuates atrial remodeling and reduces atrial fibrillation inducibility in a rat myocardial infarction-heart failure model

Youhua Zhang  1 , Eduard I Dedkov  2 , Bianca Lee 3rd  2 , Ying Li  2 , Khusbu Pun  2 , A Martin Gerdes  2
Affiliations
Comparative Study

Thyroid hormone replacement therapy attenuates atrial remodeling and reduces atrial fibrillation inducibility in a rat myocardial infarction-heart failure model

Youhua Zhang et al. J Card Fail. 2014 Dec.

Abstract

Background: Heart failure (HF) is associated with increased atrial fibrillation (AF) risk. Accumulating evidence suggests the presence of myocardial tissue hypothyroidism in HF, which may contribute to HF development. In a recent report we demonstrated that hypothyroidism, like hyperthyroidism, leads to increased AF inducibility. The present study was designed to investigate the effect of thyroid hormone (TH) replacement therapy on AF arrhythmogenesis in HF.

Methods and results: Myocardial infarction (MI) was produced in rats by means of coronary artery ligation. Rats with large MIs (>40%) were randomized into L-thyroxine (T4; n = 14) and placebo (n = 15) groups 2 weeks after MI. Rats received 3.3 mg T4 (in 60-day release form) or placebo pellets for 2 months. Compared with the placebo, T4 treatment improved cardiac function and decreased left ventricular internal diameters as well as left atrial diameter. T4 treatment attenuated atrial effective refractory period prolongation (45 ± 1.5 ms in placebo group vs 37 ± 1.6 ms in T4 group; P < .01) and reduced AF inducibility (AF/atrial flutter/tachycardia were inducible in 11/15 rats [73%] in the placebo- vs 4/14 rats [29%] in the T4-treated group; P < .05). Arrhythmia reduction was associated with decreased atrial fibrosis but was not associated with connexin 43 changes.

Conclusions: To our knowledge this is the first study demonstrating that TH replacement therapy in HF attenuates atrial remodeling and reduces AF inducibility after MI-HF. Clinical studies are needed to confirm such benefits in human patients.

Keywords: Atrial fibrillation; arrhythmogenesis; heart failure; thyroid hormone.

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Conflict of interest statement

Conflicts of interests for ALL authors: None

Figures

Figure 1
Figure 1
Echocardiographic parameters. Values are means±SEM. For each parameter, P value is indicated. LVFS, left ventricular fractional shortening; LADd, left atrial diameter in diastole; MI, myocardial infarction; AWTd, left ventricular anterior wall thickness in diastole; AWTs, left ventricular anterior wall thickness in systole; LVDd, left ventricular diameter in diastole; LVDs, left ventricular diameter in systole; PWTd, left ventricular posterior wall thickness in diastole; PWTs, left ventricular posterior wall thickness in systole.
Figure 2
Figure 2
Left ventricular hemodynamics. Data presentation and P value are indicated as in Figure 1. LVSP, left ventricular systolic pressure; LVEDP, left ventricular end-diastolic pressure; +dp/dt, positive change in pressure over time; -dP/dt, negative change in pressure over time.
Figure 3
Figure 3
Atrial fibrillation (AF) inducibility test. The original ECG traces show an example of typical AF after the burst pacing. Atrial electrograms (RA1, RA2) demonstrate rapid, irregular atrial activations with varying electrogram morphology (top panel). Note that different atrial electrical activation pattern recorded from high right atrium (RA1) and lower right atrium (RA2) during AF in this animal. The bottom panel shows an example of induced atrial flutter/tachycardia after burst pacing. The atrial activation is regular and slower (compared to AF in top panel). Note that atrial cycle lengths are the same in the RA1 and RA2. RA: right atrial electrogram.
Figure 4
Figure 4
Atrial fibrillation (AF) incidence and duration in the studied groups. Note that a logarithmic scale is used for the AF duration data. Data presentation and P value are indicated as in Figure 1.
Figure 5
Figure 5
Left atrial fibrosis content. Representative photomicrographs of left atrial histological slides (Masson Trichrome stain) from 1 rat in each group are shown on top. Data presentation and P value are indicated as in Figure 1.
Figure 6
Figure 6
Left atrial myocytes connexin (Cx) 43 expression. Representative photomicrographs of left atrial myocytes Cx43 immunostaining (red) combined with laminin immunostaining (green) outlining the myocardial tissue from 1 rat in each group are shown on top. Data presentation and P value are indicated as in Figure 1.
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