Young Mice Exhibit Increased Relative Ventricular Remodeling After AMI —A Longitudinal CMR Study

Figures

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  FIGURE 1. Study design. (A) 21 mice underwent longitudinal CMR imaging before LAD‐ligation as well as 2, 7, and 28 days after MI; hearts were excised for histology after the final scan. (B) Histology only was performed in a separate group of 17 animals.

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  FIGURE 2. Baseline parameters for cardiac performance and heart contractility. Data were acquired from young and old animals 5 days prior to MI‐induction. While ventricle volume differs significantly, no age‐related changes were detected for ejection fraction and heart contractility. Welch's t‐test, *p < 0.05, **p < 0.01, ****p < 0.001, n = 7–9.

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  FIGURE 3. Impact of myocardial infarction on LVEF. (A) Young animals demonstrated a significant decline after LAD‐ligation (Baseline vs. D2; D2 vs. D7) that persists until D28. (B) In contrast, LVEF in old animals remains constant after the pronounced drop at D2. One‐way ANOVA with Sidak'ss post hoc test, #p < 0.001 Baseline versus D2, p < 0.0001 Baseline versus D7 and D28; $p < 0.0001 Baseline versus D2, D7, D28; **p < 0.005 (C) Comparison of baseline‐normalized data revealed no significant differences between both groups at any time point. Linear mixed‐effects model, three‐way ANOVA, followed by Sidak post hoc test, n = 7–11.

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  FIGURE 4. Changes of the ventricle volume following MI, normalized to baseline conditions. (A, B) End‐diastolic and end‐systolic volume increased after LAD‐ligation. Notably, comparison of both groups showed a more distinct incline of the volume in young animals. (C) Moreover, MI results in a reduction of the stroke volume that slightly recovers over time in both young and aged animals. (D) Representative CMR images of the long axis in young and aged animals at distinct time points, showing reduced ventricle volume after MI. Linear mixed‐effects model, three‐way ANOVA, followed by Sidak post hoc test, ***p < 0.001, n = 7–11.

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  FIGURE 5. Effect of MI‐induced remodeling on heart tissue mass. (A, B) Both groups demonstrated an inclined diastolic mass after MI‐induction. (C) However, detected heart weight was significantly higher in old mice if compared to their younger counterparts. One‐way ANOVA, Sidak's post hoc test (A, B), Linear mixed‐effects model, three‐way ANOVA, followed by Sidak post hoc test, n = 7–11, *p < 0.05, **p < 0.005, ***p < 0.001.

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  FIGURE 6. Measurement of heart contractility by strain analysis. To evaluate contraction capacity, feature tracking analysis was performed and (A) GCS, (B) GLS, (C) GRSLAX and (D) GRSSAX were calculated. Following MI, contraction capacity of the heart dramatically decreased in both groups for all detected strain variants. In young animals, MI results in lower contractility values if compared to pre‐infarct conditions. Linear mixed‐effects model, three‐way ANOVA, followed by Sidak post hoc test, *p < 0.05, n = 7–11.

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  FIGURE 7. Analysis of scar tissue of infarcted hearts. (A) Quantitative evaluation showed a decline in scar tissue from D7 to D28, yet no differences between young and old animals were detected. Students t‐test, n = 6–10. (B) Representative images of heart slices labeled with Masson Trichrome and (C) heart slices labeled for Collagen V showed increased signal intensity at scar areas. (D) Higher magnification of the scar tissue revealed cell‐free areas at Day 7 post MI, predominantly in heart sections of aged animals. Scale bar 1 mm. Two‐way ANOVA, followed by Tukey post hoc test, n = 7–11.