Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Figure 1.. Characterization of myocardial infarction (MI)-induced heart failure model. Representative ECG (A) from one Sham animal (i) and one MI animal (ii). The negative QS complex characteristic of transmural MI is highlighted in ii. Progression of ejection fraction (EF, %) of MI and Sham-operated groups 1, 8, and 12 weeks after surgery are demonstrated in B. Data are reported as means±SE. **P<0.01 vs respective Sham group at the same week (one-way ANOVA followed by Bonferroni multiple comparison post-test).

Figure 2.. Circulating thyroid hormone concentration of Sham and infarcted (MI) groups. Circulating T4 (A) and T3 (B) concentration of Sham-operated and MI groups at weeks 1, 8, and 12 post-surgery was measured by radioimmunoassay. T3/T4 ratio is reported in C. Data are reported as means±SE. **P<0.01 vs respective control group at the same week; #P<0.05 and ##P<0.01 vs MI group one week after surgery; ψP<0.05 vs MI group 8 weeks after surgery (one-way ANOVA followed by Bonferroni multiple comparison post-test).

Figure 3.. Temporal effects of myocardial infarction (MI; black squares) on type 2 deiodinase (D2) activity. Progression of D2 activity in brown adipose tissue (BAT) (A) and correlation between the triiodothyronine/thyroxine (T3/T4) ratio and D2 activity in BAT (B) at 1, 8, and 12 weeks of sham-operated (Sham) or infarcted rats over the 12 weeks of the experimental protocol. Data are reported as means±SE. **P<0.01 vs respective control group; #P<0.05 vs MI group in the first week. B, Point of intersection between the D2 activity in BAT and the T3/T4 ratio for each animal studied.

Figure 4.. Effect of propranolol treatment on heart function and the infarct area. Ejection fraction (EF) was assessed by echocardiography in Sham-operated and myocardial infarction (MI) groups treated with water or β-blocker propranolol at weeks 1 (A) and 12 (B). Picrosirius staining performed in representative heart sections obtained from all groups (lower part). The infarct area (scar tissue) in LV is delimited by broken lines. As shown in Table 1, in these representative hearts, propranolol treatment reduced the infarct size at the first week post-MI (31 vs 40%), but not 12 weeks post-MI (45 vs 48%) compared to MI treated with vehicle, respectively. Note the thickening of the scar in propranolol-treated infarcted rats, especially at week 1. Representative histopathological slides from the hearts are shown in the same sequence as panels A and B. LV: left ventricle; RV: right ventricle. Scale bar=0.5 cm. Data are reported as means±SE. *P<0.05 and **P<0.01 vs respective control group at the same week. #P<0.05 and ##P<0.01 vs MI+Water group (one-way ANOVA followed by Bonferroni multiple comparison post-test).

Figure 5.. Effect of propranolol on circulating triiodothyronine (T3) levels. Circulating T3 concentration of Sham-operated and myocardial infarction (MI) groups treated with water or propranolol at weeks 1 (A) and 12 (B) was assessed by radioimmunoassay. Data are reported as means±SE. **P<0.01 vs respective control group at the same week (one-way ANOVA followed by Bonferroni multiple comparison post-test).

Figure 6.. Effect of propranolol on brown adipose tissue (BAT) type 2-deiodinase activity (D2) post-myocardial infarction (MI). BAT D2 activity was assessed in Sham-operated and MI groups treated with water or propranolol at weeks 1 (A) and 12 (B). Data are reported as means±SE. **P<0.01 vs respective control group; ##P<0.01 vs MI group in the first week (one-way ANOVA followed by Bonferroni multiple comparison post-test).