Figure 3.
Anakinra reduces TTP-induced myocardial damage. (A) Blood troponin I levels in mice at day 3 for the 4 groups of mice: TTP (VWF + placebo, n = 10), TTP + anakinra (VWF + anakinra, n = 10), and 2 control groups (control [vehicle + placebo], n = 5; and anakinra [vehicle + anakinra], n = 5). One-way ANOVA: P < .001. Troponin concentrations in TTP: 21.15 (16.50-25.78) ng/mL, control: 0.41 (0.24-0.43) ng/mL, anakinra: 0.24 (0.14-0.42) ng/mL, and TTP + anakinra: 4.53 (2.26-6.85) ng/mL. (B) Change in fraction shortening (SF) in mice between day 0 and day 2 for the 4 groups of mice: TTP, n = 12; TTP + anakinra, n = 13; control, n = 10; and anakinra, n = 10. One-way ANOVA: P < .001. Change in SF in TTP: −11.8 (−18.9-−9.3) %; controls: −2.8 (−12.3-4.4) %; anakinra: −0.8 (−1.6-1) %; and TTP + anakinra: −5 (−9.5-−2.5) %. (C) Measurement of the SF on long axis echocardiographic view. (D) Change in [18F]FDG cardiac uptake between day 0 and day 2 for the 4 groups of mice: TTP, n = 5; TTP + anakinra, n = 6; control, n = 6; and anakinra, n = 6. (E) Measurement of [18F]FDG cardiac PET signal. One-way ANOVA: P = .008. Change in [18F]FDG cardiac uptake in TTP: 2.8 (2.5-3.5) × 10−3 %ID/g; control: 0.03 (−0.07-0.1) × 10−3 % ID/g; anakinra 0. 8 (−0.2-1.2) × 10−3 %ID/g; and TTP + anakinra: 0.9 (0.24-1.2) × 10−3 % ID/g. (F) Semiquantitative assessment of myocardial damage in the 4 groups of mice, n = 5 for each group. One-way ANOVA: P < .001; score in TTP: 5 (4-5.88); control: 1 (0.56-1.25); anakinra: 1 (0.8-2.1); and TTP + anakinra: 2.75 (2-3.38). (G) Cardiac histology in hematoxylin and eosin (H&E) staining (∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001).

Anakinra reduces TTP-induced myocardial damage. (A) Blood troponin I levels in mice at day 3 for the 4 groups of mice: TTP (VWF + placebo, n = 10), TTP + anakinra (VWF + anakinra, n = 10), and 2 control groups (control [vehicle + placebo], n = 5; and anakinra [vehicle + anakinra], n = 5). One-way ANOVA: P < .001. Troponin concentrations in TTP: 21.15 (16.50-25.78) ng/mL, control: 0.41 (0.24-0.43) ng/mL, anakinra: 0.24 (0.14-0.42) ng/mL, and TTP + anakinra: 4.53 (2.26-6.85) ng/mL. (B) Change in fraction shortening (SF) in mice between day 0 and day 2 for the 4 groups of mice: TTP, n = 12; TTP + anakinra, n = 13; control, n = 10; and anakinra, n = 10. One-way ANOVA: P < .001. Change in SF in TTP: −11.8 (−18.9-−9.3) %; controls: −2.8 (−12.3-4.4) %; anakinra: −0.8 (−1.6-1) %; and TTP + anakinra: −5 (−9.5-−2.5) %. (C) Measurement of the SF on long axis echocardiographic view. (D) Change in [18F]FDG cardiac uptake between day 0 and day 2 for the 4 groups of mice: TTP, n = 5; TTP + anakinra, n = 6; control, n = 6; and anakinra, n = 6. (E) Measurement of [18F]FDG cardiac PET signal. One-way ANOVA: P = .008. Change in [18F]FDG cardiac uptake in TTP: 2.8 (2.5-3.5) × 10−3 %ID/g; control: 0.03 (−0.07-0.1) × 10−3 % ID/g; anakinra 0. 8 (−0.2-1.2) × 10−3 %ID/g; and TTP + anakinra: 0.9 (0.24-1.2) × 10−3 % ID/g. (F) Semiquantitative assessment of myocardial damage in the 4 groups of mice, n = 5 for each group. One-way ANOVA: P < .001; score in TTP: 5 (4-5.88); control: 1 (0.56-1.25); anakinra: 1 (0.8-2.1); and TTP + anakinra: 2.75 (2-3.38). (G) Cardiac histology in hematoxylin and eosin (H&E) staining (∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001).

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