The cardioprotective efficacy of TVP 1022 against ischemia/reperfusion injury and cardiac remodeling in rats

Figure 1. TVP1022 attenuated the enlargement in LV dimensions 14 days post‐MI. (A) Representative apical level echocardiographic two‐dimensional (2D) mode end‐diastolic cines of the sham, MI+Vehicle and TVP1022 (40 mg/kg) groups (additional groups are depicted in Fig. S2A), white tracing – LV cavity; Echocardiographic 2D measurements obtained at the apical (B and C) and PM (D and E) levels. Left ventricular EDA (B and D) and ESA (C and E) [% change from baseline] measured in the different groups: MI+Vehicle (n = 22), MI+TVP1022 (20 mg/kg) (n = 14), MI+TVP1022, (40 mg/kg) (n = 19), MI+TVP1022 (IV‐only) (n = 8) and sham (n = 8). *P < 0.05 versus MI+Vehicle, #P < 0.05 versus sham.

Figure 2. TVP1022 attenuated the decline in LV function 14 days post‐MI. (A) representative echocardiographic M‐mode cines obtained at the PM level for the sham, MI+Vehicle and TVP1022 (20 mg/kg) groups (additional groups are depicted in Fig. S2B). (B) EF and FS measured 14 days post‐MI in the different groups: MI+Vehicle (n = 21), MI+TVP1022 (20 mg/kg) (n = 11), MI+TVP1022, (40 mg/kg) (n = 17), MI+TVP1022 (IV‐only) (n = 8), and Sham (n = 8). *P < 0.05 versus MI+Vehicle, # P < 0.05 versus Sham, $ P < 0.05 versus IV‐only, ɛP < 0.05 versus baseline.

Figure 3. TVP1022 preserved LV global CS 14 days post‐MI. (A) Representative CS distribution along the cardiac wall measured at the apical level, obtained from the sham, MI+Vehicle and MI+TVP1022 (20 mg/kg) groups (additional groups are depicted in Fig. S2C). Dark red colors represent strong CS, whereas dark blue colors represent severe stretching; Echocardiographic CS measured at the PM (B) and apical (C) levels 14 days post‐MI from the MI+Vehicle (n = 11), MI+TVP1022 (20 mg/kg) (n = 12), MI+TVP1022, (40 mg/kg) (n = 11), MI+TVP1022 (IV‐only) (n = 8), and Sham (n = 8) groups. *P < 0.05 versus MI+Vehicle, # P < 0.05 versus Sham.

Figure 4. TVP1022 preserved hemodynamics and LV function 14 days post‐MI. (A) Representative P‐V loops obtained from sham, MI+Vehicle and MI+TVP1022 (40 mg/kg) rats (additional groups are depicted in Fig. S3A). Red arrows – SV, brown arrows – EDV. (B) Representatives dP/dt recordings obtained from the sham, vehicle and TVP1022 (40 mg/kg) treated rats (additional groups are depicted in Fig. S3B). Red lines – Sham max and min dP/dt values, blue lines – MI+Vehicle max and min values.

Figure 5. Selected cardiac functional measurements obtained from the different groups: MI+Vehicle (n = 22), MI+TVP1022 (20 mg/kg) (n = 8), MI+TVP1022, (40 mg/kg) (n = 14), MI+TVP1022 (IV‐only) (n = 8) and sham (n = 6). *P < 0.05 versus MI+Vehicle, # P < 0.05 versus sham.

Figure 6. TVP1022 attenuated post‐MI myocardial interstitial fibrosis. (A) Representative sections of the myocardium from the remote viable zone of the different treated rats, stained with Masson's trichrome staining at ×400 magnification. Viable myocardium is stained bright red. Fibrosis is stained bright blue. (B) CVF measurements in the treatment groups: MI+Vehicle (n = 6), MI+TVP1022 (20 mg/kg) (n = 6), MI+TVP1022, (40 mg/kg) (n = 6) and sham (n = 6). *P < 0.05 versus MI+Vehicle, # P < 0.05 versus sham.

Figure 7. TVP1022 attenuated post‐MI myocyte hypertrophy. Representative sections of the myocardium from the scar border tissue of the different treated rats, stained for dystrophin (green), and for nuclei with DAPI (blue), at ×200 magnification (A) (additional group is depicted in Fig. S4A). Myocyte dimensions: at the remote tissue – area (B), diameter (C); at the scar border tissue – area (D), diameter (E) of the treatment groups: MI+Vehicle (n = 5), MI+TVP1022 (40 mg/kg) (n = 5), MI+TVP1022 (IV‐only) (n = 4), and sham (n = 4). *P < 0.05 versus MI+Vehicle, # P < 0.05 versus sham, Ɨ P < 0.05 versus MI+TVP1022 (IV‐only).

Figure 8. TVP1022 attenuated post‐MI myocardial BNP levels. (A) Representative sections of the myocardium obtained from the different treatment groups, stained for BNP (red), and for nuclei with DAPI (blue), at ×400 magnifications (additional groups are depicted in Fig. S4B). (B) Myocardial BNP levels of the treatment groups: MI+Vehicle (n = 5), MI+TVP1022 (40 mg/kg) (n = 5), MI+TVP1022 (IV‐only) (n = 4), and sham (n = 4). *P < 0.05 versus MI+Vehicle, # P < 0.05 versus sham.