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. 2019 May 1;9:6801. doi: 10.1038/s41598-019-42592-1

Figure 1.

Figure 1

Tadalafil treatment restores indices of cardiac function in heart failure. (A) Changes in left ventricular dimensions with tachypacing and response to tadalafil treatment (paired data, N = 4 each time point; **p < 0.01 by RM-ANOVA). ‘pre’ denotes before commencement of tachypacing, ‘4wk’ denotes 4-weeks of tachypacing and T1, T2 and T3 denote 1, 2 & 3 weeks of tadalafil treatment. (B) Changes in left ventricular free wall thickness in response to tachypacing and tadalafil treatment (paired data, N = 4 each time point; *, **, *** respectively p < 0.05, 0.01 & 0.001 by RM-ANOVA). (C) Echocardiographic assessment showing short-axis fractional area change in the absence of exogenous catecholamine stimulation: *p < 0.05 vs. 4-week time point (tadalafil arm); **p < 0.01 vs. HF group at 7 weeks; ***p < 0.001 vs. pre-pace function (both groups). Statistics by mixed models analysis. N = HF, 5 at all time points; tadalafil, 20 at pre-pace, 19 at 4-weeks and 18 at 7 weeks. (D) Representative systolic calcium transients for control (black), 4-week paced (green), HF (red) and tadalafil (blue) groups. (E) Summary data for systolic calcium transients; *p < 0.05 vs. control; #p < 0.05 vs. tadalafil. (n/N = 34/16 control, 6/2 following 4 weeks tachypacing, 7/3 HF, 24/6 Tadalafil). (F) Summary data of echocardiographic assessments following 5 µg/kg/min dobutamine infusion: **p < 0.01 vs. HF by one-way ANOVA. N = pre-pacing, 4; 4-weeks, 3; HF, 4; tadalafil, 3. (G) Summary data showing dobutamine induced change in fractional area change derived from paired (repeated measures) data in panel F. Data is expressed as a percentage of the maximum possible response in each group. (H) Summary data showing RR intervals normalized to pre-dobutamine (5 µg.kg/min) RR interval: **p < 0.01 vs. pre-dobutamine RR interval by t-test. N = pre-pacing, 5; 4-weeks, 5; HF, 6; tadalafil, 5. (I) Paired data from 5 animals showing RR interval – dobutamine dose response relationship. *p < 0.05 by mixed models analysis. (J) Kaplan-Meier plot showing fraction of animals free from subjectively assessed signs of HF (N = HF, 42; tadalafil, 27). Tadalafil treatment commenced 28 days after tachypacing (dashed line): ***, denotes p < 0.001 (by Cox regression-based test).