Figure 1.
End-diastolic MR images of the aortic arch.
Examples of MRI scans through the aortic arch in (left) a control, (middle) mild TAC and (right) severe TAC mouse. Indicated are (IA) the innominate artery, (LCCA) left common carotid artery, (LSA) left subclavian artery, and the transverse aortic constriction (TAC).
Figure 2.
Kaplan-Meier analysis was performed based on survival data of a large cohort of healthy mice (n = 55), mild TAC (n = 5) and severe TAC mice (n = 99) available from our laboratory. Log Rank analysis showed a significant difference in survival between the severe TAC mice as compared to the control and mild TAC mice (P = 0.02).
Table 1.
General animal characteristics.
Figure 3.
Representative end diastolic short-axis and long-axis images from control mice and mice subjected to a mild and severe aortic constriction 10 weeks after surgery (A). Indicated are the left ventricle (LV), right ventricle (RV), the papillary muscles (PM) and decreased apical wall thickness in the mouse with a severe TAC (↓). Corresponding movies can be found in the supplementary material. Wall thickening (WT) in the experimental groups at 2 and 10 weeks after surgery (B). At 2 weeks, WT had decreased in all sections of the heart in mice with a severe TAC as compared to controls (P<0.01 in all cases), but the decrease in mild TAC mice did not reach statistical significance (P>0.05). At 2 weeks, WT in the animals with a mild constriction was significantly different from the mice with a severe constriction in all portions of the heart (P<0.05, in all cases). No changes over time were detected in the control and mild TAC mice (P>0.05, in all cases), whereas WT decreased in all portions of the severe TAC hearts (P<0.05, in all cases).
Figure 4.
LV mass normalized to tibia length (TL) in control, mild and severe TAC mice as a function of time. Cardiac mass slightly increased in response to a mild constriction as compared to controls (*, P<0.05) and progressively increased in response to a severe constriction (‡, P<0.001). Mean and SD per time point are denoted by the corresponding symbol and error bars. The inset shows a photograph of (left) a control, (middle) mild TAC and (right) severe TAC heart 10 weeks (severe TAC) and 13 weeks (control and mild TAC) after surgery.
Figure 5.
Left and right ventricular volumes.
End diastolic volume in control, mild and severe TAC mice (left column), end systolic volume (middle column) and ejection fraction (right column) as a function of time for both the left ventricle (LV) (top row) and right ventricle (RV) (bottom row). End diastolic and end systolic volumes clearly show LV and RV dilation in the severe TAC mice, but not in the mild TAC mice as compared to the control animals. LV ejection fraction was slightly depressed in response to a mild constriction as compared to controls, and showed a progressive decline in time in the group with a severe constriction. RV ejection fraction remained unchanged in mice with a mild constriction of the aorta as compared to control mice, but showed a progressive decline in case of a severe aortic constriction. Mean and SD per time point are denoted by the corresponding symbol and error bars. Statistical differences as compared to the control group are indicated by * (P<0.05), † (P<0.01) and ‡ (P<0.001).
Figure 6.
Left versus right ventricular ejection fraction.
Relationship between left (LV) and right ventricular (RV) ejection fraction (EF) for all mice at all time points. The right ventricular ejection fraction progressively decreased (black arrow) in the severe TAC group only and that the changes in RVEF were preceded by a decline in LVEF apparent from the shift of the majority of the measurement points to the left.
Table 2.
Assessment of pulmonary remodeling and heart weight.
Figure 7.
Left ventricular radial wall thickening and circumferential wall shortening.
Figure 7D shows that radial wall thickening and circumferential wall shortening were identical between the control (0.12±0.03 and −0.10±0.02, respectively) and mild TAC mice (0.12±0.02 and −0.11±0.02, respectively) (P>0.05). Moreover, no effects of time were observed (P>0.05). In contrast, radial wall thickening was significantly decreased in the mice with a severe TAC as compared to control mice (P<0.001) and showed a decrease from 0.09±0.02 in week 2 to 0.06±0.01 in week 10 (P<0.05). Circumferential wall shortening was also significantly decreased in mice with a severe TAC as compared to control mice (P<0.01) and showed a decrease from −0.09±0.01 in week 2 to −0.06±0.01 in week 10 (P<0.05).