The protective effect of isosteviol sodium on cardiac function and myocardial remodelling in transverse aortic constriction rat

Figures

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  Figure 1. STVNa amelioration of cardiac myocyte hypertrophy. A, Representative left ventricular myocardial sections stained with Haematoxylin and Eosin; B, The data of cardiomyocyte area (CMA) in the sham group, TAC (transverse aortic constriction) group, and STV (L, M, H doses) (STVNa treatment) or Sil (sildenafil treatment) groups both for 3 wk (n = 5) and 9 wk (n = 5), wk, week. Data are mean ± SEM. ***P < .001 vs sham group, ### P < .001 vs TAC group

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  Figure 2. In vivo cardiac function improvement by STVNa treatment. A, Summary data for LVP, left ventricular pressure; dp/dt, peak rate of pressure decline (diastolic indexes) and pressure ascend (systolic indexes); MAP, mean arterial pressure; HR, heart rate in 3‐wk groups (A) and 9‐wk groups (B). Pressure‐volume relationship measured by preload reduction (C). EDPVR, the slope of end‐diastolic pressure‐volume relationship represents cardiac stiffness and ESPVR, the slope of end‐systolic pressure‐volume relationship represents end‐systolic elastics. STVNa decreased cardiac stiffness induced by TAC and increased cardiac contractility, but sildenafil did not have significant effect on cardiac contractility. *P < .05 ***P < .001 vs sham group; # P < .05, ## P < .01, ### P < .001 vs TAC group, + P < .05 vs TAC + STV (H) group, n = 5

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  Figure 3. STVNa reversing the alteration of cardiac electric cardiograms. A, QRS interval measured in ms, R amplitude measured in mV. TAC for 9 wk induced an increase of QRS duration and R amplitude which was reversed by STVNa and sildenafil treatment. B, QT and QTc dispersions measured in ms High QT dispersion indicates a high risk of cardiac arrhythmia and is reduced by STVNa but not sildenafil treatment. C, Representative QT/RR plot in the TAC group (blue) and TAC treated with STVNa high dose (red). In 9‐wk groups, QTd increased in the TAC group and could be reversed by STVNa treatment. *P < .05, **P < .01 vs sham group; # P < .05, ## P < .01 vs TAC group, + P < .05 vs TAC + STV group, n = 5

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  Figure 4. STVNa treatment did not increase oxygen consumption. A, Representative image of calcium transient, a fluo‐4 AM (1 μmol/L) loaded acutely on isolated rat myocardial cells, indicating that STVNa (1 mmol/L) improved cardiac function without increasing intracellular calcium level. The bottom bar graph shows the summary data for intracellular calcium level and the rate of decay of the intracellular calcium transient measured by F/F0, The time and T50 were increased according to calcium fluorescence images. Ctrl, control cells; STV, STVNa‐treated cells; n = 3. B, Representative ECG recording in sham (blue), TAC (red) and STVNa (high‐dose group) treatment group (green)

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  Figure 5. STVNa prevents cardiac fibrosis induced by pressure overload. A, Representative F‐actin‐stained photomicrographs (×630, oil). Ventricular cross‐sections were stained with FITC‐conjugated phalloidin (green). B, Fibrosis measured in ventricular cross‐sections stained with Picrosirius Red stain (red) 3 and 9 wk after TAC surgery. Scale bar = 100 mm, n = 5. C, STVNa inhibition of the TGF‐β1‐stimulated fibrotic response in isolated neonatal rat cardiac fibroblasts. *P < .05, **P < .01, ***P < .001 vs sham group or control; ### P < .001 vs TAC group or TGF‐β1‐treated group

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  Figure 6. HRV analysis of aortic constriction rats with or without drug treatment. A, Group data of SDNN (standard derivation of RR interval) measured in ms and rMSSD value for sham, TAC, TAC treated with STVNa (TAC + STV) and TAC‐treated sildenafil (TAC + Sil) groups. B, Representative traces of the power spectral density of HRV in the sham group, 9‐wk TAC group, and TAC with STVNa or sildenafil treatment groups. PSD, Power spectral density expressed in normalized units (n. u.). *P < .05 vs sham group; # P < .05 vs TAC group