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清醒比格犬胸下腔静脉缩窄心衰模型的建立

Model of heart failure for thoracic inferior vena caval constriction in conscious Beagle dogs

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【作者】 王维亭徐向伟赵专友何小云汤立达

【Author】 WANG Wei-ting,XU Xiang-wei,ZHAO Zhuan-you,HE Xiao-yun,TANG Li-da(State Key Laboratory of Pharmacokinetics and Pharmacodynamics,Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China)

【机构】 天津药物研究院药代与药效动力学重点实验室

【摘要】 目的建立清醒比格犬的心衰模型。方法比格犬分为模型组(将下腔静脉直径缩窄50%)和假手术组(仅在下腔静脉处穿线不缩窄)。用清醒比格犬胸下腔静脉缩窄法与遥控检测技术,研究在心衰形成过程中的心脏功能与血流动力学变化。结果模型组动物逐渐出现腹壁静脉曲张、腹壁水肿、腹水等静脉瘀血体征;术后Tau时间常数明显延长,dp/dtmin在4周内增加,6周后开始降低;LVEDP术后1~2周明显降低(P<0.001~0.01),术后5周开始升高,8~9周时升高更为显著(P<0.01~0.05);术后6周E峰开始明显下降,A峰明显升高,E/A比值在术后即开始轻度减小,6~9周减小最明显;手术后1~4周dp/dtmax明显增加,6~9周的dp/dtmax明显降低;术后8~9周HR增加(P<0.05);术后3周内SBP变化不明显,4周后开始明显增加,至9周时增加最为显著;术后1周开始DBP、MABP、LVSP即明显增加,持续至第9周。模型组术后耗氧量开始稍有增加,其中1、7周后与假手术组比较有明显统计学差异(P<0.05~0.01)。结论采用清醒比格犬与遥控实时检测技术建立的心衰模型,能模拟临床心衰病人的部分特征,可用于抗心衰药物研发与心衰疾病机制研究。

【Abstract】 Objective To establish the model of heart failure by thoracic inferior vena caval constriction(TIVCC)in conscious Beagle dogs.Methods Conscious dogs were chosen as experiment animals.Telemetry monitoring technology was applied to measure the hemodynamic parameters,and the peaks of velocity at the tip of opened mitral valve leaflets were measured by echocardiography.Results Signs of varicosis,edema and hydroperitoneum appeared in conscious Beagle dogs with TIVCC.The Tau constant in model group was prolonged,dp/dtmin increased within 4 weeks after operation but declined at 6 weeks after operation,LVEDP reduced at 1 to 2 weeks while increased at 5 weeks.E wave decreased,A wave increased with decline of the ratio of E wave to A wave(E/A ratio)at 6 weeks after TIVCC.dp/dtmax increased from 1 to 4 weeks after operation,but decreased at 6 weeks.Heart rate increased significantly at 8 weeks,while DBP,MABP and LVSP increased at 1 week.The oxygen-consumption was increased,especially at 1 week and 7 weeks.Conclusion The model of heart failure established with real-time remote technology in conscious dogs was in accordance with clinical characteristics of patients with heart failure,and can be used in research and development of new agents for treatment and study on mechanism of pathogenesis in heart failure.

【基金】 国家科技支撑计划项目(2007BAI41B02);系列化、国际化的国家生物医药国际创新园新药研发综合性大平台建设项目(2009ZX09301-008)
  • 【文献出处】 现代药物与临床 ,Drugs & Clinic , 编辑部邮箱 ,2010年05期
  • 【分类号】R-332
  • 【被引频次】4
  • 【下载频次】152
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