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. 2018 Dec 11;9:1445. doi: 10.3389/fphar.2018.01445

Table 2.

Characteristics of the 27 included animal studies.

Study (years) Species (Sex,
n = experimental/
control group)
Weight Model (method) Anesthetic Treatment group (Method to astragal sides) Control group (Negative/positive) Outcome index (time) Intergroup differences
Jiang et al., 1982 ? canines (male, 11/14) 12–26 kg Block LAD Nembutal DSS (8 mg/kg, i.v) After ischemia No treatment 1. Myocardial infarct size 1. P < 0.01
Tang et al., 1989 Wistar rats (male, 6/6) 200–250 g Langendorff Model 10 min stabilization I/R (60 min/20 min) Nembutal (0.6%) DSS (4*10−8 g/ml) during stabilization No treatment 1. SOD
2. GSH-Px
1. P < 0.001
2. P < 0.005
Li et al., 1996 Wistar rats (male, 7/7) 250–280 g Langendorff Model 10 min stabilization I/R (40 min/20 min) Nembutal (0.6%) DSS (0.4 mg/mL) during stabilization and reperfusion No treatment 1. ATP
2. TAN
3. EC
1. P < 0.001
2. P < 0.001
3. P < 0.004
Zhang et al., 2010 SD rats (male, 6/6) 280–320 g Langendorff Model 30 min stabilization I/R (30 min/30 min) Chloral hydrate (10%) DSS (200 um) at the beginning of ischemia No treatment 1. ATP
2. EC
1. P < 0.01
2. P < 0.01
Lu et al., 2010 SD rats (male, 10/10) 200–220 g Block LAD Urethane (20%) DSS (24 mg/kg/day, i.p) for 7 days before ischemia 0.9% normal saline (10 ml/kg/day, i.p) for 7 days before ischemia 1. Myocardial infarct size
2. CK
3. LDH
1. P < 0.01

2. P < 0.01
3. P < 0.01
Li et al., 2012 SD rats (male, 8/8) 200–240 g ISO (85mg/kg/day, i.h) for 2 consecutive days Nembutal (35 mg/kg) DSS (160 mg/kg/day, i.g) for 21 days and ISO on 20th and 21st day Isosteric 0.3% CMC-Na solution (i.g) for 21 days and ISO on 20th and 21st day 1. Myocardial infarct size
2. ΔST
3. Heart weight/body weight ratio
4. CK-MB
5. LDH
6. SOD
7. TBARS
8. GSH
9. GST
10. Nrf2
11. Bax
12. Bcl-2
13. Caspase3
1. P < 0.01

2. P < 0.001
3. p < 0.001

4. P < 0.001
5. p < 0.001
6. p < 0.001
7. P < 0.001
8. p < 0.001
9. p < 0.001
10. P < 0.05
11. p < 0.001
12. p < 0.001
13. p < 0.001
Yin et al., 2013 SD rats (male, 8/8) 230–270 g Block LAD for 30 min then reflow for 180 min Nembutal (40mg/kg) DSS (60 mg/kg, i.v) Within 5 min at the beginning of reperfusion Isasteric normal saline (i.v) Within 5 min at the beginning of reperfusion 1. Myocardial infarct size
2. CK-MB
1. P < 0.05

2. P < 0.01
Yu J. et al., 2015 SD rats (male, 8/8) 280–320 g Langendorff Model 30 min stabilization I/R (30 min/30 min) Nembutal (30 mg/kg) DSS (10 um) 10 min before ischemia No treatment 1. Myocardial infarct size
2. CK
3. LDH
4. ROS
5. MDA
6. SOD
7. GSH-Px
8. SOD mRNA
9. HO-1 mRNA
10. Nrf2 mRNA
11. P-AKT
12. P-ERK
13. Nrf2
1. P < 0.01

2. P < 0.01
3. P < 0.05
4. P < 0.01
5. P < 0.01
6. P < 0.01
7. P < 0.05
8. P < 0.01
9. P < 0.01
10. P < 0.01
11. P < 0.01
12. P < 0.01
13. P < 0.01
Wei et al., 2016 SD rats (male, 12/12) 220–260 g Block LAD Chloral hydrate (10%, 0.4 ml/kg) DSS (2 mg/kg/day, i.v) for 7 days after ischemia Isasteric normal saline (i.v) for 7 days afterischemia 1. Myocardial infarct size
2. MVD
3. VEGF
4. SDF-1
5. CXCR4
1. P < 0.01

2. P < 0.01
3. P < 0.05
4. P < 0.01
5. P < 0.01
Song et al., 2016 SD rats (male, 8/8) 180–220 g ISO (85 mg/kg/day, i.h) for 2 consecutive days Urethane (4 mg/kg) DSS (10 mg/kg/day, i.p) for 7 days before ischemia Equivalent distilled water
for 7 days before ischemia
1. CK
2. LDH
1. P < 0.01
2. P < 0.01
Fan et al., 2016 SD rats (male, 8/8) 280–320 g Langendorff Model 30 min stabilization I/R (30 min/60 min) Nembutal (50 mg/kg) DSS (10 um) during reperfusion No treatment 1. CK
2. LDH
3. Bcl-2
4. Bax
5. Caspase-3
6. P-mTOR mRNA
7. P-62 mRNA
8. Beclin-1 mRNA
9. LC3 mRNA
10. P-mTOR
11. P-s6k1
12. P-s6
13. P-62
14. Beclin-1
15. LC3-II
16. Bcl-2 mRNA
17.BaxmRNA
18.Caspase-3mRNA
1. P < 0.05
2. P < 0.05
3. P < 0.01
4. P < 0.01
5. P < 0.01
6. P < 0.05
7. P < 0.01
8. P < 0.01
9. P < 0.01
10. P < 0.05
11. P > 0.05
12. P > 0.05
13. P < 0.01
14. P < 0.01
15. P > 0.05
16. P < 0.01
17. P < 0.01
18. P < 0.01
Li et al., 2016 SD rats (male, 8/8) 200–240 g ISO (85 mg/kg/day, i.h) for 2 consecutive days Nembutal (35mg/kg) DSS (160 mg/kg/day, i.g) for 21 days and ISO on 20th and 21st day Isosteric 0.3% CMC-Na solution (i.g) for 21 days and ISO on 20th and 21st day 1. CK-MB
2. cTnT
3. ROS
4. TBARS
5. GSH/GSSH
6. Nrf2
7. Keap1
8. HO-1
9. GST
10. Cytochrome C
11. TNF-α
12. Bcl-2
13. Bax
14. Caspase-3
15. P-PI3K/PI3K
16. P-Akt/Akt
1. P < 0.001
2. P < 0.001
3. P < 0.001
4. p < 0.001
5. p < 0.001
6. P < 0.001
7. P < 0.001
8. P < 0.001
9. P < 0.001
10. P < 0.001
11. P < 0.01
12. P < 0.01
13. P < 0.001
14. p < 0.001
15. P < 0.001
16. P < 0.001
Hu et al., 2016 SD rats (male,9/9) 230–270 g Block LAD for 30 min then reflow for 180 min Nembutal (40 mg/kg) DSS (60 mg/kg, i.v) at the time of reperfusion No treatment 1. Myocardial infarct size
2. CK-MB
3. MDA
4. SOD
1. P < 0.05

2. P < 0.01
3. P < 0.05
4. P < 0.05
Yin et al., 2017 SD rats (male, 17/17) 230–270 g Block LAD Nembutal (30mg/kg) DSS (60 mg/kg/day, i.v) for 14 days after 24 h of ischemia Isasteric normal saline (i.v) for 14 days after 24 h of ischemia 1. Myocardial infarct size
2. MVD
3. VEGF
4. bFGF
5. SDF-1
6. CXCR-4
7. LVEF
8. LVFS
1. P < 0.01

2. P < 0.01
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.01
7. P < 0.05
8. P < 0.05
Gao et al., 2017 SD rats (male, 15/15) 220–280 g Langendorff Model 30 min stabilization I/R (30 min/60 min) Chloral hydrate (300 mg/kg) DSS (10 um) during reperfusion No treatment 1. Cardiac apoptosis
2. Caspase-3
3. MMP
4. MPTP
5. ATP 5G1 mRNA
6. ATP 5G1
1. P < 0.01
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.01
6. P < 0.01
Dong et al., 2009 SD rats (male, 6/6) 200–250 g Block LAD Chloral hydrate (10%, 60mg/kg) DSS (60 mg/kg/day, i.p) for 7 days beforeischemia and 2 days afterischemia No treatment 1. Myocardial infarct size
2. CK
3. LDH
4. MDA
5. SOD
1. P < 0.05

2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
Xiang et al., 2009 SD rats (male, 7/8) 200–250 g Block LAD for 30 min then reflow for 180 min Nembutal (40 mg/kg) DSS (9.47 mg/kg, ?) 2 h before ischemia No treatment 1. Myocardial infarct size
2. CK
3. LDH
4. NO
5. MDA
1. P < 0.01

2. P < 0.01
3. P < 0.05
4. P < 0.01
5. P < 0.01
Cheng et al., 2010 Wistar rats (male,
female, 7/7)
290–320 g Langendorff Model 10 min stabilization I/R (40 min/20 min) Nembutal (1%) DSS (0.4 mg/L) during reperfusion No treatment 1. ATP
2. TAN
1. P < 0.05
2. P < 0.01
Zhao et al., 2012 SD rats (male, 10/10) 180–220 g Block LAD Chloral hydrate (10%, 3.5 ml/kg) DSS (20 mg/kg, i.v) 15 min after ischemia Isasteric normal saline (i.v) 15 min after ischemia 1. Bcl2/Bax
2. Caspase-3
1. P < 0.01
2. P < 0.01
Quan et al., 2012 SD rats (male, 7/7) 230–270 g Block LAD for 30 min then reflow for 180 min Nembutal (3%) DSS (60 mg/kg, i.v) at the time of reperfusion Isasteric normal saline (i.v) at the time of reperfusion 1. Myocardial infarct size
2. CK-MB
3. IL-1
4. IL-6
5. TNF-α
1. P < 0.05

2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
Cui G. et al., 2013 SD rats (male, 8/8) 220–250 g Block LAD for 30 min then reflow for 120 min Chloral hydrate (10%) DSS (20 mg/kg, i.v) 15 min after ischemia Isasteric normal saline (i.v) 15 min after ischemia 1. Myocardial infarct size
2. P-PI3K/PI3K
3. P-Akt/Akt
4. Nrf2
5. HO-1
1. P < 0.05

2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
Chen et al., 2014 SD rats (male, 10/10) 220–300 g Block LAD for 10 min, reflow for 24 min, then block for 20 min, reflow for 80 min Nembutal (45 mg/kg) DSS patch (0.1 g/kg) for 3 days before r ischemia Normal patch for 3 days before modeling 1. Myocardial infarct size 1. P < 0.05
Cui et al., 2014 SD rats (male, 15/18) 220–250 g Block LAD Chloral hydrate (10%) DSS (30 mg/kg, i.p) 15 min after ischemia Isasteric normal saline (i.p) 15 min after ischemia 1. Myocardial infarct size
2. CK
3. LDH
4. MDA
5. SOD
1. P < 0.01

2. P < 0.05
3. P < 0.05
4. P < 0.01
5. P < 0.01
Wang et al., 2016 Zebrafish embryos (–, 3/3) Treated with Dox (1 μM) DSS (30 μM) for 32 h No treatment 1. Stroke volume
2. Cardiac output
3. Fractional shortening
1. P < 0.01
2. P < 0.01
3. P < 0.01
Zhang X. et al., 2017 SD rats (male, 9/9) 250–270 g Block LAD for 30 min then reflow for 180 min Nembutal (5%) DSS (90 mg/kg, ?) 30 min before ischemia and at the time of reperfusion No treatment 1. Myocardial infarct size 1. P < 0.001
Wang et al., 2017 SD rats (male, 7/7) 250–270 g Block LAD Nembutal (5%) DSS (30 mg/kg, i.v) 10 min after ischemia Isasteric normal saline (i.v) 10 min after ischemia 1. Myocardial infarct size 1. P < 0.01
Tang et al., 2018 Zebrafish embryos (–, 3/3) Treated with Dox (35 μM) DSS (30 μM) for 24 h No treatment 1. Stroke volume
2. Cardiac output
3. Fractional shortening
1. P < 0.01
2. P < 0.01
3. P < 0.01

SD rats, Sprague-Dawley; LAD, the left anterior descending coronary artery; DSS, Danshensu; LVEF, left ventricular ejection fraction; LVFS, left ventricular shortening fraction; ΔST, level of ST-segment depression; CK, creatine kinase; LDH, lactate dehydrogenase; CK-MB, creatine kinase-MB; cTnT, cardiac troponin T; P-Akt, phosphothreonine kinase; P-PI3K, phosphatidylinositol 3-kinase; P-ERK, phosphorylated extracellular signal-regulated kinases; ROS, reactive oxygen species; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, heme oxygenase-1; KEAP1, Kelch-like ECH-associated protein 1; GST, glutathione-S-transferase; GSH-Px, glutathione peroxidase; GSH, glutathione synthetase; MDA, malondialdehyde; SOD, superoxide dismutase; TBARS, thiobarbituric acid reactive substances; Bcl-2, B-cell lymphoma-2; Bax, BCL2-associated X protein; TNF-α, tumor necrosis factor-α; IL-1, Interleukin-1; IL-6, Interleukin-6; SDF-1α, stromal cell-derived factor-1 α; CXCR4, C-X-C chemokine receptor type 4; VEGF, vascular endothelial growth factor; MVD, microvesseldensity; bFGF, basic fibroblast growth factor; NO, nitric oxide; P-mTOR, phosphorylated mammalian target of rapamycin; P-S6k1, phosphorylated ribosomal protein S6 kinase beta-1; P-S6, phosphorylated ribosomal protein s6; p62, sequestosome-1; LC3, microtubule-associated protein light chain 3; P-JNK, phosphorylated c-Jun N-terminal kinase; NF-KB, nuclear factor-κB; TRPC6, transient receptor potential cation channel, subfamily C, member 6; ATP, adenosine triphosphate; TAN, total adenine nucleotides; EC, energy charge; MPTP, mitochondrial permeability transition pore; i.v, intravenous injection; i.p, intraperitoneal injection; i.g, intragastric administration; i.h, hypodermic injection.