Time‑dependent and independent effects of thyroid hormone administration following myocardial infarction in rats

Abstract

Cardiac function is reduced following myocardial infarction (MI) due to myocardial injury and alterations in the viable non‑ischemic myocardium, a process known as cardiac remodeling. The current treatments available for patients with acute MI (AMI) reduce infarct size, preserve left ventricular (LV) function and improve survival; however, these treatments do not prevent remodeling, which can lead to heart failure. The aim of the present study was to investigate the effects of thyroid hormone (TH) treatment following MI in an in vivo rat model. A total of 199 rats were separated into 3 groups: Sham operated and 2 different coronary artery ligation (CAL) groups. Rats subjected to CAL were randomly divided into a further 2 groups 24 h following surgery. The first group received standard rat chow (designated the CAL group), while the second group received food containing 0.05% thyroid powder (designated the CALTH group). The mean daily intake of TH per rat was estimated at 3.0 µg T3 and 12 µg T4. Echocardiography was used to monitor the rats. Large‑scale analysis confirmed the favorable effects of TH treatment following CAL on various parameters of cardiac function. TH treatment reduced LV dilation, and increased global and regional LV function. The development of cardiac hypertrophy was induced and, thus, wall stress was limited. Furthermore, TH treatment improved cardiac geometry, which manifested as an increased sphericity index. Myocardial function, as well as LV dilatation, following CAL and TH treatment was not closely associated with the extent of injury, indicating a novel therapeutic intervention that may alter the course of LV remodeling that typically leads to post‑MI heart failure. Data modelling and regressions may be developed to enable the simulation of the pathophysiological processes that occur following MI, and to predict with accuracy the effects of novel or current treatments that act via the modulation of tissue injury, LV dilation, LV geometry and hypertrophy.

Figure 1.

Diagrammatic representation of the experimental procedures followed during the present study. Rats were divided into 3 groups: Those that underwent an SO; those that were subjected to CAL without any TH treatment; and those that were subjected to CALTH. The SO and CAL experimental groups were monitored for 2, 4 and 13 weeks, respectively. The CALTH group was monitored for 2 and 13 weeks. SO, sham operation; CAL, coronary artery ligation; TH, thyroid hormone; CALTH, coronary artery ligation with thyroid hormone.

Figure 2.

Effects of intervention in SO and CAL populations that did not receive thyroid hormone, irrespective of time. (A) LV ejection fraction (%), (B) LV systolic velocity and (C) SI manifested to a significantly higher level in the SO group when compared with the CAL group. On the other hand, (D) LV end diastolic diameter, (E) LV end systolic diameter, (F) wall tension index and (G) LV weight were significantly higher in the CAL group when compared within the SO group. *P<0.05, as indicated. SO, sham operation; CAL, coronary artery ligation; LV, left ventricular; SI, sphericity index; SO, sham operation; w, weight.

Figure 3.

Time-independent effects of thyroid hormone in the CAL group. Significant reductions in the untreated group compared with the treated group were observed for (A) LV ejection fraction (%), (D) LV posterior wall thickness, (E) systolic velocity, (G) sphericity index and (H) heart rate. On the other hand, significantly higher values were observed in the untreated group when compared with the treated group, for (B) LV end diastolic diameter, (C) LV end systolic diameter and (F) wall tension index. *P<0.05, as indicated. SO, sham operation; CAL, coronary artery ligation; LV, left ventricular; EF, ejection fraction; d, diameter; v, velocity; WTI, wall tension index; SI, sphericity index; HR, heart rate; NO, indicates CAL samples not treated with thyroid hormone; YES, indicates CAL samples that did receive thyroid hormone.

Figure 4.

Time-dependent effects of TH in the CAL group. Significant differences were observed with respect to (A) LV ejection fraction, (B) LV end diastolic diameter, (C) LV end systolic diameter, (D) LV posterior wall thickness, (E) wall tension index, (F) sphericity index, (G) systolic velocity, (H) heart rate and (I) LV weight. *P<0.05 and **P<0.01, as indicated. SV, systolic velocity; CAL, coronary artery ligation; LV, left ventricular; TH, thyroid hormone; d, diameter; WTI, wall tension index; w, weight; I, CAL group with no TH treatment at 2 weeks; II, CAL group with no TH treatment at 4 weeks; III, CAL group with no TH treatment at 13 weeks; IV, CAL group with TH treatment at 2 weeks; V, CAL group with TH treatment at 13 weeks.

Figure 5.

Time-dependent effects of TH in the CAL group with respect to scar parameters. Significant differences were observed with respect to (A) scar weight in the CAL group without TH treatment between 2 and 13 weeks. Significant differences were observed between the CAL group without TH treatment at 13 weeks and the CAL group with TH treatment at 2 weeks, as well as between the CAL group without TH treatment at 13 weeks and the CAL group with TH treatment at 13 weeks. (B) Significant differences were observed with respect to scar area in the CAL group without TH treatment between 2 and 13 weeks. In addition, significant differences were observed between the CAL group without TH treatment at 13 weeks and the CAL group with TH treatment at 13 weeks. *P<0.05, as indicated. TH, thyroid hormone; CAL, coronary artery ligation; w, weight; A, area; I, CAL group with no TH treatment at 2 weeks; II, CAL group with no TH treatment at 4 weeks; III, CAL group with no TH treatment at 13 weeks; IV, CAL group with TH treatment at 2 weeks; V, CAL group with TH treatment at 13 weeks.

Figure 6.

Time-independent regressions for SA with respect to estimated variables in rats without thyroid hormone intervention. The time-independent regression of SA with respect to the estimated variables indicated correlations between the ultrasound-estimated variables and the surgically estimated parameters. In particular, SA, LV weight and LV EF% had markedly linear behavior with respect to the following variables: (A) LV EF% vs. SA (R²=0.84), (B) LVEDD vs. SA (R²=0.76), and (C) LVESD vs. SA (R²=0.83), irrespective of the intervention and time of sacrifice. It was also observed that (D) LV EF% manifested linear behavior with LVEDD (R²=0.82); (E) LV EF% did not manifest significant linear behavior with respect to LV weight (R²=0.12); neither did (F) sphericity index vs. SA (R²=0.46) or (G) systolic velocity vs. SA (R²=0.55). LV, left ventricular; EF, ejection fraction; SA, scar area; LVEDD, LV end diastolic diameter; LVESD, LV end systolic diameter.

Figure 7.

Time-independent regressions for SA with respect to estimated variables in rats with TH intervention. The time-independent regression of SA with respect to the estimated variables indicated correlations between the ultrasound-estimated variables and the surgically estimated parameters. In contrast to the results without TH treatment, SA, LV weight and LV EF% did not exert significant linear behavior with respect to the following variables: (A) LV EF% vs. SA (R²=0.48), (B) LVEDD vs. SA (R²=0.41), and (C) LVESD vs. SA (R²=0.40), irrespective of the intervention and time of sacrifice. It was also noted that LV EF% did not have significant linear behavior with respect to (D) LVEDD (R²=0.58) or (E) LV weight (R²=0.02) (E), and (F) neither did sphericity index vs. SA (R²=0.33) or (G) systolic velocity vs. SA (R²=0.54). LV, left ventricular; TH, thyroid hormone; EF, ejection fraction; SA, scar area; LVEDD, LV end diastolic diameter; LVESD, LV end systolic diameter.

Figure 8.

Representative echocardiographic images of parasternal short-axis view at the level of the papillary muscles during (A) the end-diastolic phase as well as the (B) end-systolic phase from rats subjected to SO. Echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during the (C) end-diastolic phase as well as (D) the end-systolic phase from rats subjected to CAL without TH are presented. Finally, echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during (E) the end-diastolic phase as well as (F) the end-systolic phase from rats subjected to CALTH. LV dilatation is evident in the groups with coronary artery ligation. The CALTH group is characterized by a greater development of LV hypertrophy and improved LV systolic function when compared with CAL without thyroid hormone. TH, thyroid hormone; LV, left ventricular; SO, sham operation; CAL, coronary artery ligation; CALTH, coronary artery ligation with thyroid hormone treatment.

Figure 8.

Representative echocardiographic images of parasternal short-axis view at the level of the papillary muscles during (A) the end-diastolic phase as well as the (B) end-systolic phase from rats subjected to SO. Echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during the (C) end-diastolic phase as well as (D) the end-systolic phase from rats subjected to CAL without TH are presented. Finally, echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during (E) the end-diastolic phase as well as (F) the end-systolic phase from rats subjected to CALTH. LV dilatation is evident in the groups with coronary artery ligation. The CALTH group is characterized by a greater development of LV hypertrophy and improved LV systolic function when compared with CAL without thyroid hormone. TH, thyroid hormone; LV, left ventricular; SO, sham operation; CAL, coronary artery ligation; CALTH, coronary artery ligation with thyroid hormone treatment.

Figure 8.

Representative echocardiographic images of parasternal short-axis view at the level of the papillary muscles during (A) the end-diastolic phase as well as the (B) end-systolic phase from rats subjected to SO. Echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during the (C) end-diastolic phase as well as (D) the end-systolic phase from rats subjected to CAL without TH are presented. Finally, echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during (E) the end-diastolic phase as well as (F) the end-systolic phase from rats subjected to CALTH. LV dilatation is evident in the groups with coronary artery ligation. The CALTH group is characterized by a greater development of LV hypertrophy and improved LV systolic function when compared with CAL without thyroid hormone. TH, thyroid hormone; LV, left ventricular; SO, sham operation; CAL, coronary artery ligation; CALTH, coronary artery ligation with thyroid hormone treatment.

Figure 8.

Representative echocardiographic images of parasternal short-axis view at the level of the papillary muscles during (A) the end-diastolic phase as well as the (B) end-systolic phase from rats subjected to SO. Echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during the (C) end-diastolic phase as well as (D) the end-systolic phase from rats subjected to CAL without TH are presented. Finally, echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during (E) the end-diastolic phase as well as (F) the end-systolic phase from rats subjected to CALTH. LV dilatation is evident in the groups with coronary artery ligation. The CALTH group is characterized by a greater development of LV hypertrophy and improved LV systolic function when compared with CAL without thyroid hormone. TH, thyroid hormone; LV, left ventricular; SO, sham operation; CAL, coronary artery ligation; CALTH, coronary artery ligation with thyroid hormone treatment.

Figure 8.

Representative echocardiographic images of parasternal short-axis view at the level of the papillary muscles during (A) the end-diastolic phase as well as the (B) end-systolic phase from rats subjected to SO. Echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during the (C) end-diastolic phase as well as (D) the end-systolic phase from rats subjected to CAL without TH are presented. Finally, echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during (E) the end-diastolic phase as well as (F) the end-systolic phase from rats subjected to CALTH. LV dilatation is evident in the groups with coronary artery ligation. The CALTH group is characterized by a greater development of LV hypertrophy and improved LV systolic function when compared with CAL without thyroid hormone. TH, thyroid hormone; LV, left ventricular; SO, sham operation; CAL, coronary artery ligation; CALTH, coronary artery ligation with thyroid hormone treatment.

Figure 8.

Representative echocardiographic images of parasternal short-axis view at the level of the papillary muscles during (A) the end-diastolic phase as well as the (B) end-systolic phase from rats subjected to SO. Echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during the (C) end-diastolic phase as well as (D) the end-systolic phase from rats subjected to CAL without TH are presented. Finally, echocardiographic images of the parasternal short-axis view at the level of the papillary muscles during (E) the end-diastolic phase as well as (F) the end-systolic phase from rats subjected to CALTH. LV dilatation is evident in the groups with coronary artery ligation. The CALTH group is characterized by a greater development of LV hypertrophy and improved LV systolic function when compared with CAL without thyroid hormone. TH, thyroid hormone; LV, left ventricular; SO, sham operation; CAL, coronary artery ligation; CALTH, coronary artery ligation with thyroid hormone treatment.