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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (2): 140-144.doi: 10.3736/jcim20090209

• Original Experimental Research • Previous Articles     Next Articles

Effects of salvianolate on cardiomyocytic apoptosis and heart function in a swine model of acute myocardial infarction

 Ming-wei Wang, Dian-fu Zhang , Jian-jin Tang, Bo Chen , Lian-sheng Wang , Zhi-jian Yang, Jun Huang   

  1. Department of Cardiology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China
  • Received:2008-04-30 Accepted:2008-10-29 Online:2009-02-20 Published:2009-02-15

Objective

To observe the effects of salvianolate on cardiomyocytic apoptosis and heart function in a swine model of acute myocardial infarction (AMI).
Methods

A total of 21 young swines were randomly divided into untreated group, low-dose salvianolate (LS) group and high-dose salvianolate (HS) group (7 in each group). AMI was induced by ligaturing left anterior descending coronary artery. After the operation, 400 or 200 mg salvianolate dissolved in 250 mL 5% glucose saline was administered by intravenous drip to swines in the HS group and the LS group respectively for 7 days. The swines in the untreated group were administered with 250 mL 5% glucose saline. The left ventricular ejection fraction (LVEF) and myocardial perfusion were measured by gated myocardial perfusion imaging at the end of the 4th week after operation. And myocardial apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Apoptosis index was calculated under an optical microscope.
Results

Myocardial apoptotic index in the edge of myocardial infarction was decreased in the HS group and the LS group, which in the HS group was lower than that in the untreated group (P<0.05). Radioactive defect regions were found by gated myocardial perfusion imaging in all the three groups, but those in the HS group and the LS group were less than those in the untreated group (P<0.05). And the levels of myocardial perfusion and LVEF in the HS group were significantly higher than those in the untreated group (P<0.05).
Conclusion

Salvianolate administered by intravenous drip can inhibit the cardiomyocytic apoptosis and improve the function of heart after AMI in swines.

Key words: Myocardial infarction, Salvianolate, Apoptosis, Swines

Figure 1

Myocardial apoptosis in swines with AMI detected by TUNEL (Light microscopy, ×400) A: Untreated group; B: Low-dose salvianolate group; C: High-dose salvianolate group."

Figure 2

Myocardial apoptotic index in swines with AMI in different groups 4 weeks after operation A: Untreated group; B: Low-dose salvianolate group; C: High-dose salvianolate group. *P<0.05, vs untreated group. n=6."

Table 1

Myocardial perfusion scores and left ventricular ejection fractions of swines with AIM in different groups 4 weeks after operation (x±s)"

Group n Myocardial
perfusion
Left ventricular
ejection fraction (%)
Untreated 6 14.60±0.55 38.50±4.67
Low-dose salvianolate 6 15.20±0.84 43.16±4.33
High-dose salvianolate 6 16.35±0.22* 60.66±5.81*

Figure 3

Gated myocardial perfusion imaging of swines in different groups 4 weeks after operation A: Untreated group; B: Low-dose salvianolate group; C: High-dose salvianolate group. Red color in the picture refers to the normal myocardial perfusion in myocardium. Yellow color in the picture refers to the sparse myocardial perfusion in myocardium. No color/defects refers to no blood perfusion in myocardium."

[1] Jayasankar V, Woo YJ, Pirolli TJ, Bish LT, Berry MF, Burdick J, Gardner TJ, Sweeney HL . Induction of angiogenesis and inhibition of apoptosis by hepatocyte growth factor effectively treats postischemic heart failure[J]. J Card Surg, 2005,20(1):93-101
doi: 10.1111/jcs.2005.20.issue-1
[2] Xu J, Fan WH . Effect of salvianolate on migration of human vascular endothelial cells[J]. J Chin Integr Med, 2003,1(3):211-214
徐杰, 范维琥 . 丹参多酚酸盐对人血管内皮细胞迁移的影响[J]. 中西医结合学报, 2003,1(3):211-214
[3] Xiong T, Wu XJ, Wang YP . Inhibition of salvianolate on LDL oxidation[J]. Zhong Yao Yao Li Yu Lin Chuang, 2004,20(4):7-10
熊涛, 吴兴军, 王逸平 . 丹参多酚酸盐抑制低密度脂蛋白氧化修饰[J]. 中药药理与临床, 2004,20(4):7-10
[4] Harada K, Grossman W, Friedman M, Edelman ER, Prasad PV, Keiqhley CS, Manning WJ, Sellke FW, Simons M . Basic fibroblast growth factors improves myocardial function in chronically ischemic porcine hearts[J]. J Clin Invest, 1994,94(2):623-630
doi: 10.1172/JCI117378
[5] Gwon HC, Jeong JO, Kim HJ, Park SW, Lee SH, Park SJ, Huh JE, Lee Y, Kim S, Kim DK . The feasi-bility and safety of fluoroscopy-guided percutaneous intramyocardial gene injection in porcine heart[J]. Int J Cardiol, 2001,79(1):77-88
doi: 10.1016/S0167-5273(01)00410-7
[6] Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S . Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function[J]. Nat Med, 2001,7(4):430-436
doi: 10.1038/86498
[7] Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J , McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P.Bone marrow cells regenerate infarcted myocardium[J]. Nature, 2001,410(6829):701-705
doi: 10.1038/35070587
[8] Wang JS, Shum-Tim D, Chedrawy E, Chiu RC . The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic impli-cations[J]. J Thorac Cardiovasc Surg, 2001,122(4):699-705
doi: 10.1067/mtc.2001.116317
[9] Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS; American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging.Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association[J]. Circulation, 2002,105(4):539-542
doi: 10.1161/hc0402.102975
[10] Li Y, Takemura G, Kosai K, Yuge K, Nagano S, Esaki M, Goto K, Takahashi T, Hayakawa K, Koda M, Kawase Y, Maruyama R, Okada H, Minatoguchi S, Mizuguchi H, Fujiwara T, Fujiwara H . Postinfarction treatment with an adenoviral vector expressing hepa-tocyte growth factor relieves chronic left ventricular remodeling and dysfunction in mice[J]. Circulation, 2003,107(19):2499-2506
doi: 10.1161/01.CIR.0000065579.19126.B8
[11] Salam AM . Selective aldosterone blockade with eplere-none in patients with congestive heart failure[J]. Expert Opin Investig Drugs, 2003,12(8):1423-1427
doi: 10.1517/13543784.12.8.1423
[12] Moolman JA, Hartley S, Van Wyk J, Marais E, Lochner A . Inhibition of myocardial apoptosis by ischaemic and beta-adrenergic preconditioning is dependent on p38 MAPK[J]. Cardiovasc Drugs Ther, 2006,20(1):13-25
doi: 10.1007/s10557-006-6257-7
[13] Wiggers H, Nielsen SS, Holdgaard P, FlΦ C, NΦrrelund H, Halbirk M, Nielsen TT, Egeblad H, Rehling M, BΦtker HE . Adaptation of nonrevascularized human hibernating and chronically stunned myocardium to long-term chronic myocardial ischemia[J]. Am J Cardiol, 2006,98(12):1574-1580
doi: 10.1016/j.amjcard.2006.07.035
[14] Bromme HJ, Holtz J . Apoptosis in the heart: when and why?[J]. Mol Cell Biochem, 1996,( 163-164):261-275
[15] Sinagra G, Bussani R, Abbate A, Piro M, Biondi-Zoccai GG, Kontos MC, Sabbadini G, Barresi E, Crea F, Biasucci LM, Aleksova A, Pinamonti B, Silvestri F, Vetrovec GW, Baldi A . Left ventricular diastolic filling pattern at Doppler echocardiography and apoptotic rate in fatal acute myocardial infarction[J]. Am J Cardiol, 2007,99(3):307-309
doi: 10.1016/j.amjcard.2006.08.025
[16] Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P . Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats[J]. Lab Invest, 1996,74(1):86-107
[17] Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM, Tikkanen I . Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats[J]. Am J Physiol Heart Circ Physiol, 2001,280(6):H2726-H2731
doi: 10.1152/ajpheart.2001.280.6.H2726
[18] Haunstetter A, Izumo S . Toward antiapoptosis as a new treatment modality[J]. Circ Res, 2000,86(4):371-376
doi: 10.1161/01.RES.86.4.371
[19] Gao H, Li XH, Li CY, Lu JM . Effect of salvianolate on the platelet aggregation and adhesiveness in healthy volunteers[J]. Bangbu Yi Xue Yuan Xue Bao, 2007,32(5):514-516
高辉, 李先辉, 李春艳, 吕江明 . 丹参多酚酸对健康人血小板聚集与黏附的影响[J]. 蚌埠医学院学报, 2007,32(5):514-516
[20] Zhang ZX, Gao FY, Li KM, Pan L, Dong X, Chen YW, Sun RJ . Effect of magnesium lithospermate B on endothelial cells in human aorta after free radical injury[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2004,24(6):521-524
张知新, 高福云, 李克明, 潘琳, 董晞, 陈玉武, 孙瑞娟 . 丹参酚酸B镁对自由基损伤人主动脉内皮细胞的影响[J]. 中国中西医结合杂志, 2004,24(6):521-524
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