Table 6.
Reference SC Diet (n = 12) | Buffer SC Diet (n = 12) | MDCO-216 SC Diet (n = 12) | Reference HSHF Diet (n = 15) | Buffer HSHF Diet (n = 19) | MDCO-216 HSHF Diet (n = 22) | |
---|---|---|---|---|---|---|
Heart rate (bpm) | 606 ± 12 | 599 ± 19 | 610 ± 13 | 607 ± 13 | 578 ± 7 | 591 ± 13 |
Pmax (mm Hg) | 99.9 ± 1.5 | 99.4 ± 3.2 | 101 ± 1 | 79.6 ± 2.2 §§§§ | 79.5 ± 2.4 §§§§ | 93.1 ± 1.8 °°°§§*** |
Pes (mm Hg) | 97.7 ± 1.1 | 95.4 ± 3.2 | 95.5 ± 1.1 | 72.0 ± 2.1 §§§§ | 72.5 ± 2.5 §§§§ | 86.2 ± 2.2 §§°°°*** |
dP/dtmax (mmHg/ms) | 9.70 ± 0.80 | 10.6 ± 0.5 | 10.5 ± 0.4 | 7.73 ± 0.39 § | 7.34 ± 0.39 §§§§ | 9.55 ± 0.46 °** |
PRSW (mm Hg) | 87.5 ± 10.6 | 79.5 ± 6.5 | 76.6 ± 3.4 | 52.6 ± 4.5 §§§ | 55.9 ± 4.3 §§ | 73.0 ± 4.0 °°* |
Ees (mmHg/µL) | 8.25 ± 0.69 | 8.24 ± 0.69 | 9.24 ± 0.47 | 4.04 ± 0.34 §§§§ | 4.35 ± 0.33 §§§§ | 7.11 ± 0.34 §§§°°°*** |
Pmin (mm Hg) | 0.065 ± 0.820 | 1.01 ± 0.52 | 1.06 ± 0.58 | 1.88 ± 0.30 § | 2.00 ± 0.26 | 2.06 ± 0.25 |
Ped (mm Hg) | 2.06 ± 0.53 | 2.58 ± 0.44 | 2.58 ± 0.56 | 4.37 ± 0.31 §§§ | 5.18 ± 0.33 §§§§ | 4.04 ± 0.31 §* |
dP/dtmin (mmHg/ms) | −9.81 ± 0.69 | −10.2 ± 0.8 | −10.4 ± 0.4 | −6.94 ± 0.21 §§ | −7.27 ± 0.42 §§ | −9.22 ± 0.31 §°°°*** |
Tau (ms) | 5.52 ± 0.18 | 5.52 ± 0.32 | 5.24 ± 0.21 | 7.10 ± 0.23 §§§§ | 8.07 ± 0.28 §§§§ | 5.48 ± 0.20 °°°*** |
Slope EDPVR (mmHg/µL) | 0.316 ± 0.041 | 0.371 ± 0.056 | 0.291 ± 0.056 | 0.614 ± 0.143 § | 0.454 ± 0.062 | 0.495 ± 0.064 § |
EDV (µL) | 25.4 ± 0.9 | 24.9 ± 0.7 | 26.6 ± 1.4 | 23.5 ± 0.7 | 27.3 ± 1.1 | 23.8 ± 1.1 * |
ESV (µL) | 8.71 ± 1.00 | 9.10 ± 0.40 | 9.76 ± 1.00 | 11.4 ± 0.5 § | 15.1 ± 1.0 §§§§° | 8.78 ± 0.74 °*** |
Stroke volume (µL) | 16.7 ± 0.7 | 15.8 ± 0.5 | 16.9 ± 1.1 | 12.1 ± 0.4 §§§§ | 12.1 ± 0.8 §§ | 15.0 ± 0.6 °°* |
Ejection fraction (%) | 66.3 ± 3.3 | 63.5 ± 1.0 | 63.7 ± 3.0 | 51.7 ± 1.3 §§ | 44.6 ± 2.5 §§§§ | 64.1 ± 2.1 °°*** |
Cardiac output (ml/min) | 10.1 ± 0.5 | 9.46 ± 0.43 | 10.2 ± 0.6 | 7.39 ± 0.35 §§§ | 7.01 ± 0.48 §§ | 8.93 ± 0.44 °** |
Stroke work (mmHg.µL) | 1330 ± 50 | 1260 ± 60 | 1360 ± 90 | 775 ± 39 §§§§ | 765 ± 51 §§§§ | 1120 ± 40 §°°°*** |
dV/dtmax (µL/s) | 859 ± 91 | 730 ± 38 | 768 ± 69 | 542 ± 29 §§ | 587± 41 § | 688 ± 54 ° |
dV/dtmin (µL/s) | −797 ± 61 | −733 ± 42 | −777 ± 68 | −557 ± 47 §§ | −577 ± 44 § | −732 ± 52 °* |
Ea (mmHg/µL) | 6.04 ± 0.39 | 6.11 ± 0.29 | 5.87 ± 0.32 | 6.02 ± 0.24 | 6.66 ± 0.65 | 5.92 ± 0.26 |
Ea/Ees | 0.804 ± 0.109 | 0.808 ± 0.081 | 0.699 ± 0.060 | 1.60 ± 0.12 §§§§ | 1.56 ± 0.11 §§§§ | 0.874 ± 0.061 °°°*** |
Pmax: maximum systolic pressure. Pes: end-systolic pressure. dP/dtmax: peak rate of isovolumetric contraction. PRSW: preload recruitable stroke work. Ees: end-systolic elastance. Pmin: minimum diastolic pressure. Ped: end-diastolic pressure. dP/dtmin: peak rate of isovolumetric relaxation. Tau: time constant of isovolumetric relaxation. EDPVR: end diastolic pressure-volume relationship. EDV: end-diastolic volume. ESV: end-systolic volume. dV/dtmax: peak filling rate. dV/dtmin: peak emptying rate. Ea: arterial elastance. Ea/Ees: ventriculo-arterial coupling ratio. Hemodynamic measurements in the reference groups were performed at the age of 28 weeks, 16 weeks after the start of the HSHF diet. Eight intraperitoneal injections of reconstituted HDLMilano (MDCO-216) (100 mg/kg) or of an equivalent volume of control buffer were executed with a 48-h interval starting at the age of 28 weeks. Mice in the buffer and MDCO-216 groups were analysed one day after the last injection. All data are expressed as means ± SEM. §: p < 0.05; §§: p < 0.01; §§§: p < 0.001; §§§§: p < 0.0001 versus respective SC diet group. °: p <0.05; °°: p < 0.01; °°°: p < 0.001 versus HSHF diet reference. *: p < 0.05; **: p < 0.01; ***: p < 0.001 versus HSHF diet buffer.