Table 1.
Short-term treatment with the REV-ERB agonist SR9009 post-mI/R benefits long-term cardiac structure and function
| mI/R+SR9009 | mI/R+vehicle | Sham | |
|---|---|---|---|
| n | 10 | 10 | 6 |
| Echocardiography baseline | |||
| LVIDd (mm) | 4.02 ± 0.02 | 4.01 ± 0.02 | 4.02 ± 0.03 |
| LVIDs (mm) | 2.41 ± 0.03 | 2.43 ± 0.04 | 2.39 ± 0.03 |
| EF (%) | 76.81 ± 0.60 | 76.21 ± 0.87 | 77.76 ± 0.53 |
| FS (%) | 39.91 ± 0.53 | 39.75 ± 0.64 | 40.69 ± 0.50 |
| HR (bpm) | 472 ± 5 | 472 ± 4 | 468 ± 7 |
| 1 week post-mI/R | |||
| LVIDd (mm) | 4.14 ± 0.04* | 4.49 ± 0.11 | 4.01 ± 0.03 |
| LVIDs (mm) | 2.65 ± 0.05* | 3.23 ± 0.14 | 2.38 ± 0.02 |
| EF (%) | 72.31 ± 0.87* | 60.75 ± 2.24 | 77.55 ± 0.49 |
| FS (%) | 36.15 ± 0.68* | 28.22 ± 1.54 | 40.54 ± 0.44 |
| HR (bpm) | 455 ± 7 | 460 ± 8 | 474 ± 7 |
| 4 weeks post-mI/R | |||
| LVIDd (mm) | 4.35 ± 0.03* | 4.80 ± 0.09 | 4.05 ± 0.03 |
| LVIDs (mm) | 2.90 ± 0.04* | 3.65 ± 0.10 | 2.43 ± 0.03 |
| EF (%) | 68.37 ± 0.82* | 53.84 ± 1.44 | 76.78 ± 0.58 |
| FS (%) | 33.14 ± 0.57* | 23.92 ± 0.79 | 39.81 ± 0.53 |
| HR (bpm) | 468 ± 4 | 469 ± 5 | 485 ± 5 |
| 8 weeks post-mI/R | |||
| LVIDd (mm) | 4.38 ± 0.04* | 4.92 ± 0.11 | 4.05 ± 0.04 |
| LVIDs (mm) | 2.99 ± 0.07* | 3.77 ± 0.12 | 2.39 ± 0.03 |
| EF (%) | 66.44 ± 1.67* | 53.31 ± 1.46 | 78.10 ± 0.48 |
| FS (%) | 31.93 ± 1.15* | 23.61 ± 0.84 | 40.99 ± 0.45 |
| HR (bpm) | 461 ± 9 | 449 ± 4 | 471 ± 3 |
| Hemodynamics and morphometry 8 weeks post-mI/R | |||
| LVESP (mmHg) | 97.11 ± 1.29* | 91.43 ± 1.03 | 98.09 ± 2.14 |
| LVEDP (mmHg) | 1.66 ± 0.84 | 1.83 ± 0.62 | 0.04 ± 0.55 |
| LVESV (μl) | 17.83 ± 1.15* | 28.58 ± 1.70 | 10.85 ± 0.68 |
| LVEDV (μl) | 42.02 ± 1.04* | 48.90 ± 1.30 | 37.19 ± 0.96 |
| SV (μl) | 24.19 ± 0.68* | 20.32 ± 0.79 | 26.34 ± 0.64 |
| CO (mL min−1) | 12.16 ± 0.47* | 9.97 ± 0.32 | 13.33 ± 0.64 |
| +dP/dtmax (mmHg s−1) | 9302 ± 339* | 7275 ± 358 | 10093 ± 819 |
| −dP/dtmin (mmHg s−1) | −8543 ± 223* | −6621 ± 374 | −9262 ± 517 |
| SBP (mmHg) | 95.87 ± 0.86* | 91.12 ± 0.66 | 97.76 ± 1.24 |
| DBP (mmHg) | 58.67 ± 0.79 | 57.28 ± 1.31 | 61.93 ± 1.40 |
| MAP (mmHg) | 70.34 ± 0.61 | 67.88 ± 0.95 | 72.91 ± 1.15 |
| HW (mg) | 125.30 ± 1.77* | 136.10 ± 2.03 | 118.00 ± 1.00 |
| HW:BW (mg g−1) | 4.35 ± 0.09* | 4.64 ± 0.06 | 3.96 ± 0.12 |
| BW (g) | 28.89 ± 0.64 | 29.37 ± 0.48 | 30.02 ± 1.01 |
| HR (bpm) | 503 ± 13 | 495 ± 22 | 506 ± 18 |
LVIDd left ventricle internal dimensions at diastole, LVIDs LV internal dimensions at systole, % EF % ejection fraction, % FS % fractional shortening, HR heart rate, LVESP left ventricle (LV) end systolic pressure, LVEDP LV end diastolic pressure, LVESV LV end systolic volume, LVEDV LV end diastolic volume, SV stroke volume, CO cardiac output, dP/dtmax and dP/dtmin maximum and minimum first derivative of LV pressure, SBP systolic blood pressure, DBP diastolic blood pressure, MAP mean arterial pressure, HW heart weight, BW body weight
n = 8 mI/R+SR9009, mI/R+vehicle, n = 6 sham for hemodynamics. *p < 0.05 mI/R+SR9009 vs. mI/R+vehicle, by Student’s t test. Values are mean ± SEM