Changes of Heart Function Caused by Doxorubicin in Rabbits_West China Medical Journal

Authors：

CHE Feifei ^1,2 , XU Juan ¹ , LIU Yu ¹ ,  XU Caigang ¹

1. Department of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P. R. China; 2. Department of Hematology, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, P.R.China;

Corresponding author：

XU Caigang, Email: chefeifei1@126.com

Keywords：

多柔比星; 心脏毒性; 彩色多普勒超声心动图; 脑钠肽; 兔

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【摘要】　目的　采用多柔比星（doxorubicin，DOX）制备心肌损伤动物模型，评价各种检测心功能变化方法的意义。　方法　 14只新西兰大白兔，DOX耳缘静脉注射，每周3 mg/kg，共10周。分别于给药前、第4周末及实验结束时测定血清肌钙蛋白Ⅰ（cTnI）和脑钠肽（BNP）水平，彩色多普勒超声心动图检测心功能变化，并观察心肌组织病理形态学改变及心肌细胞凋亡情况。　结果　使用DOX前后对比，血清cTnI和BNP浓度升高（P lt;0.05）；左室射血分数（LVEF）和左室短轴缩短率（LVFS）下降（P lt;0.05）；心肌组织病理显示心肌细胞出现不同程度的空泡变性与水肿，细胞间隙明显增宽，大量炎性细胞浸润。心肌细胞凋亡明显增加。　结论　结合心脏超声检查和血清cTnI、BNP指标检测可判断心肌损伤程度。
【Abstract】　Objective　 To observe the changes of heart function caused by doxorubicin in rabbits.　Methods　 A total of 14 New-Zealand white rabbits were intravenous-injected with doxorubicin with a dosage of 3 mg/kg intravenously once a week, and the accumulative dose was 30 mg/kg. Before the medication and at the 4th and 10th weekend after the medication, the serum levels of cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) were measured; left ventricular ejection function (LVEF) and left ventricular fractional shortening (LVFS) were performed on the rabbits respectively. At the 10th weekend, the pathological changes of cardiac tissue and the apoptosis of myocardial cell were detected.　Results　 The levels of cTnI and BNP significantly increased (P lt;0.05), and the LVEF and LVFS markedly decreased (P lt;0.05) after the administration of doxorubicin. Uneven vacuolar degeneration and edema of cardiocytes could be observed with a wide cell spaces and inflammatory cell infiltration in the histopathological slices.　Conclusion　 The combined application of heart sonography with the detection of the serum levels of cTnI and BNP can evaluate the degree of myocardial damage of the rabbits models very well.

Citation： CHE Feifei,XU Juan,LIU Yu,XU Caigang. Changes of Heart Function Caused by Doxorubicin in Rabbits. West China Medical Journal, 2010, 25(12): 2167-2170. doi: Copy

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1. 　Lefrak EA, Pitha J, Rosenheim S, et al. A clinicopathologic analysis of adriamycin cardiotoxicity[J]. Cancer, 1973, 32 (2): 302-314.
2. 　Ivona Klimtová. Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits[J]. Hum Exp toxicol, 2002, 21(12): 649-657.
3. 　Dragojevic-Simic VM, Dobric SL, Bokonjic DR, et al. Amifostine protection against doxorubicin cardiotoxicity in rats[J]. Anticancer Drugs, 2004, 15(2): 169-178.
4. 　Aupperle H, Garbade J, Schubert A, et al. Effects of autologous stem cells on immunohistochemical patterns and gene expression of metalloproteinases and their tissue inhibitors in doxorubicin cardiomyopathy in a rabbit model[J]. Vet Pathol, 2007, 44(4): 494-503.
5. 　Kawada T, Yamazaki T, Akiyama T, et al. Chronic adriamycin treatment impairs myocardial interstitial neuronal release of norepinephrine and epinephrine[J]. J Cardiovasc Pharmacol, 2000, 36(Suppl 2): 31-34.
6. 　Barcin C, Kursaklioglu H, Safali M, et al. Effect of octreotide in the prevention of doxorubicin cardiotoxicity[J]. Anadolu Kardiyol Derg, 2005, 5(1): 18-23.
7. 　Aiken MJ, Suhag V, Garcia CA, et al. Doxorubicin-induced cardiac toxicity and cardiac rest gated blood pool imaging[J]. Clin Nucl Med, 2009, 34(11): 762-767.
8. 　Kim SY, Kim SJ, Kim BJ, et al. Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes[J]. Exp Mol Med, 2006, 38(5): 535-545.
9. 　Lipshultz SE, Lipsitz SR, Sallan SE, et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia[J]. J Clin Oncol, 2005, 23(12): 2629-2636.
10. 　Adamcova M, Simunek T, Kaiserova H, et al. In vitro and in vivo examination of cardiac troponins as biochemical markers of drug-induced cardiotoxicity[J]. Toxicology, 2007, 237(1-3): 218-228.
11. 　Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure[J]. N Engl J Med, 2002, 347(3): 161-167.
12. 　Yeh ET, Tong AT, Lenihan DJ, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management[J]. Circulation, 2004, 109(25): 3122-3131.

West China Medical Journal

Changes of Heart Function Caused by Doxorubicin in Rabbits

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