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. 2020 Jan 17;141(9):751–767. doi: 10.1161/CIRCULATIONAHA.119.042559

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© 2020 The Authors.

Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

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Figure 3. — Bufalin and lycorine reverse established fibrosis and improve heart function in hypertensive mice. A, Therapeutic in vivo study using a murine model of systemic hypertension. Bufalin, lycorine, or dimethyl sulfoxide (DMSO) was injected intraperitoneally every other day for 6 consecutive weeks starting 2 weeks after the implantation of minipumps filled with angiotensin II (Ang II). B, Significant amelioration of cardiac fibrosis in established diastolic heart failure on treatment with bufalin and lycorine by 50% (2-way ANOVA, Tukey multiple-comparisons test, n=19/8/7/17/18/16). C, Representative images of hemodynamic pressure-volume loops. Both compounds were able to partly reverse diastolic dysfunction; bufalin recovered hemodynamic parameters (dP/dtmin, tau, and end-diastolic pressure-volume relationship [EDPVR]) compared with the Ang II group. D through F, Strong trend of reduction of myocardial performance index (MPI; 1-way ANOVA, n=19/8/7/17/18/16) and prolongation of deceleration time (2-way ANOVA, Tukey multiple-comparisons test, n=19/8/7/17/18/16) by the lead compounds and decreased peak E/A (2-way ANOVA, Tukey multiple-comparisons test, n=18/8/7/14/15/15) on treatment with compounds. G,Strong trend in reduction of peak E/E’ on treatment with both bufalin and lycorine (2-way ANOVA, Tukey multiple-comparisons test, n=14/8/7/14/14/15). H, Significant improvement of load-independent EDPVR by bufalin and lycorine on systemic hypertension (2-way ANOVA, Tukey multiple-comparisons test, n=14/8/7/14/14/15). I, Significant increase in left ventricular (LV) mass by Ang II infusion in animals treated with the solvent only (controls) but not in mice treated with bufalin or lycorine (2-way ANOVA, Tukey multiple-comparisons test, n=19/8/7/16/17/16). All values from B through I are presented as mean±SEM. ESPVR indicates end-systolic pressure-volume relationship; and ns, not significant. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.