Low-Dose Propranolol Prevents Functional Decline in Catecholamine-Induced Acute Heart Failure in Rats

Figures

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  Figure 1. Low-dose propranolol improves overall survival and lung-to-body weight ratio. During catecholamine infusion alone or with additional propranolol over 6 h, the following data were measured. (A) Survival rate, sham, n = 6; E + NE, n = 10; E + NE (pro1), n = 7, E + NE (pro10), n = 8; E + NE (pro15), n = 10. (B,C) Organ-to-body weight ratio of the lungs and heart, respectively, in rats at the end of 6 h post-catecholamine or propranolol treatment. Sham, n = 5; E + NE, n = 6, E + NE (pro1), n = 7; E + NE (pro10), n = 7. (D) Heart rate, sham, n = 5; E + NE, n = 6; E + NE (pro1), n = 6; E + NE (pro10), n = 5. (E) Serum NT-proBNP changes, and (F) serum troponin T changes were measured in rat groups: Sham, n = 4; E + NE, n = 4; E + NE (pro1), n = 6; E + NE (pro10), n = 6. Data are represented as mean ± SD. Mann–Whitney U test was used for statistical analysis of all panels. a p < 0.05 vs. sham group; b p < 0.05 vs. E + NE group; c p <0.05 vs. E + NE (pro1) group; d p < 0.05 vs. respective group at 0 h; e p < 0.05 vs. respective group at 1 h; f p < 0.05 vs. respective group at 3 h. E + NE, epinephrine and norepinephrine; pro1, low-dose propranolol 1 mg/kg; pro10, high-dose propranolol 10…

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  Figure 2. Trend graphs of hemodynamic changes of the left ventricle in rat models with excessive catecholamine infusion alone or with additional propranolol treatment. Measurements of (A) left ventricular systolic pressure, (B) left ventricular end-diastolic pressure, (C) systolic duration, and (D) diastolic durations were recorded. These measurements were assessed in the following rat groups: Sham, n = 5; E + NE, n = 6; E + NE (pro1), n = 7; E + NE (pro10), n = 6. (E) Contractility indexes were measured in the following rat groups: Sham, n = 5; E + NE, n = 6; E + NE (pro1), n = 6; E + NE (pro10), n = 5. Data are represented as median. Mann–Whitney U test was used for statistical analysis of all panels. a p < 0.05 vs. sham group; b p < 0.05 vs. E + NE group; c p < 0.05 vs. E + NE (pro1) group. E + NE, epinephrine and norepinephrine; pro1, low-dose propranolol 1 mg/kg; pro10, high-dose propranolol 10 mg/kg.

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  Figure 3. Trend graphs of the hemodynamic changes of the right ventricle in rat models with excessive catecholamine infusion alone or with additional propranolol treatment. (A) Right ventricular systolic pressure, and (B) right ventricular end-diastolic pressure, were recorded in rat groups of sham, n = 5; E + NE, n = 6; E + NE (pro1), n = 7; E + NE (pro10), n = 6. (C) Systolic durations were measured in groups of sham, n = 5; E + NE, n = 6; E + NE (pro1), n = 7; E + NE (pro10), n = 5. (D) Diastolic durations were measured in groups of sham, n = 5; E + NE, n = 6; E + NE (pro1), n = 7; E + NE (pro10), n = 6. (E) Contractility indexes were measured in groups of n = 5 for all conditions, except for E + NE (pro10), n = 6. Data were presented as median. Mann–Whitney U test was used for statistical analysis of all panels. a p < 0.05 vs. sham group; b p < 0.05 vs. E + NE group; c p < 0.05 vs. E + NE (pro1) group. E + NE, epinephrine and norepinephrine; pro1, low-dose propranolol 1 mg/kg; pro10, high-dose propranolol 10 mg/kg.

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  Figure 4. Changes in connexin 43 distribution reveal lateralization in cardiac tissue with 6 h continuous catecholamine infusion alone or with propranolol treatment. (A) Representative immunohistochemical staining with connexin 43 antibodies in cardiac tissue and (B) quantitative analysis of lateralized Cx43 in LV lateral wall, LV septum, and RV lateral wall of after 6 h in rat groups of: sham, n = 4; E + NE, n = 5; E + NE (pro1), n = 5; E + NE (pro10), n = 5. Data are represented as mean ± SD. Mann–Whitney U test was used for statistical analysis of all panels. a p < 0.05 vs. sham group. Cx43, connexin 43; E + NE, epinephrine and norepinephrine; LV, left ventricle; pro1, low-dose propranolol 1 mg/kg; pro10, high-dose propranolol 10 mg/kg; RV, right ventricle. The scale bars represent 50 μm.

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  Figure 5. Expression of fibroblast growth factor-23 (FGF-23) in cardiac tissue after 6 h infusion of catecholamine alone or with propranolol treatment. (A) Representative immunohistochemical staining with FGF-23 antibodies, and (B) the immunohistochemical scores of FGF-23 in LV lateral wall, LV septum, and RV lateral wall after 6 h in groups of: sham, n = 6; E + NE, n = 6; E + NE (pro1), n = 6; E + NE (pro10), n = 5. Data are expressed as mean ± SD. Mann–Whitney U test was used for statistical analysis of all panels. a p < 0.05 vs. sham group; b p < 0.05 vs. E + NE group; c p < 0.05 vs. E + NE (pro1) group. E + NE, epinephrine and norepinephrine; LV, left ventricle; pro1, low-dose propranolol 1 mg/kg; pro10, high-dose propranolol 10 mg/kg; FGF-23, fibroblast growth factor-23; RV, right ventricle. The scale bars represent 50 μm.

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  Figure 6. Differences in protein expression among groups in lung tissue after catecholamine-induced toxicity alone or with propranolol treatment. Representative immunohistochemical staining and quantitative analysis of RAGE, pro-SpC, Cx43, and HMGB1 in lung tissues after 6 h in sham, E + NE, E + NE (pro1), and E + NE (pro10) groups. n = 4 in all groups except for the sham group in quantitative analysis of Cx43, n = 3. Data are expressed as mean± SD. Mann–Whitney U test was used for statistical analysis of all panels. a p < 0.05 vs. sham group; b p < 0.05 vs. E + NE group; c p < 0.05 vs. E + NE (pro1) group. Cx43, connexin 43; E + NE, epinephrine and norepinephrine; HMGB1, High mobility group box 1; pro1, low-dose propranolol 1 mg/kg; pro10, high-dose propranolol 10 mg/kg; pro-SpC, pro-surfactant protein C; RAGE, receptor for advanced glycation end products. The scale bars represent 50 μm.