摘要
目的研究大鼠慢性心衰(HF)急性加重模型方法学。方法 SD大鼠麻醉后,测定术前左室缩短分数(FS),结扎冠状动脉前降支(假手术组只穿线不结扎),8周后,测定术后FS,选取FS较术前下降50%以上的大鼠作为HF模型鼠,按FS心衰程度随机分为3组,每组10只。采用生理盐水作为容量负荷方式,按容量负荷程度分为轻度(1 m L/kg,即HF+轻度负荷组)、中度(2 m L/kg,即HF+中度负荷组)、重度(3 m L/kg,即HF+重度负荷组)3种模式,输注速度1 m L/min。假手术组同重度负荷模式。测定左室压最大上升/下降速率(±LVdp/dtmax)、左室舒张末期压(LVEDP)、中心静脉压(CVP)、呼吸频率(RR)、心率(HR)并对数据进行统计学处理。结果 HF大鼠给予不同容量负荷,+LVdp/dtmax出现不同程度降低,轻、中、重负荷心脏收缩功能恶化百分率分别可达40%、80%、100%;随着负荷加重,RR减低率逐渐增多,重度负荷可达到100%;轻、中、重度负荷HR降低幅度最大可达3.5%、7.5%、8.4%,CVP升高幅度分别最大可达23.7%、31.1%、51.5%;LVEDP升高幅度分别最大可达2.5、5.7、10.3 mm Hg。与假手术组比较,中、重负荷组负荷后一段时间内±LVdp/dtmax、LVEDP、CVP、RR、HR差异显著(P<0.05、0.01、0.001)。结论容量负荷法在一定程度上,可以使大鼠慢性心衰具备部分急性加重的特征。
Objective To study a methodology of acute exacerbation heart failure model in rats. Methods After anesthesia, the preoperative left ventricular FS was detected in SD rats, and the anterior descending coronary artery was ligated（the sham group＇s line was not ligated, normal group）. After 8 weeks, the postoperative FS was detected and the rats whose FS was decreased by more than 50% from the preoperative level were randomly divided into three groups（10 rats in each group） according to the degree of FS heart failure. Using NS as a volume overload, the postoperative rats were divided into three groups according to the degree of volume overload： HF ＋ mild group（1 mL/kg）; HF ＋ moderate group（2 mL/kg）; HF ＋ severe group（3 mL/kg）.The infusion rate was 1 mL/min. The NS load mode was used in the same manner as the heavy load mode in the normal group. ±LVdp/dtmax, left ventricular end-diastolic pressure（VEDP）, central venous pressure（CVP）, respiratory rate（RR）, and heart rate（HR） was detected and the date was performed statistical processing. Results ＋ LVdp/dtmax decreased to various degrees after the rats with heart failure were given series of volume overload. The percentage of systolic dysfunction in light, moderate and heavy capacity was 40%, 80%, and 100%, respectively; The reduced percentage of RR gradually increases as the capacity load increases and the heavy load can be reached at 100%; The maximum reduction of HR in light, medium, and severe load groups can reach 3.5%, 7.5%, and 8.4%, and the maximum increase of CVP can reach 23.7%, 31.1%, and 51.5%, and the maximum increase of LVEDP can be 2.5, 5.7, and 10.3 mmHg, respectively. Compared to sham group, ±LVdp/dtmax, LVEDP, CVP, RR, and HR of moderate and severe groups had significantly difference. Conclusion To a certain extent, volume overload method can cause acute exacerbation heart failure.
作者
张珊
郝春华
张蕊
孙双勇
王维亭
赵专友
汤立达
ZHANG Shan, HAO Chunhua, ZHANG Rui, SUN Shuangyong, WANG Weiting, ZHAO Zhuanyou, TANG Lida Tianjin(Institute of Pharmaceutical Research New Drug Evaluation Co., Ltd., Tianjin 300310, China)
出处
《药物评价研究》
CAS
2018年第8期1380-1385,共6页
Drug Evaluation Research
关键词
慢性心衰
急性加重
容量负荷
心脏收缩功能
chronic heart failure
acute exacerbation heart failure
volume overload
cardiac systolic function
作者简介
张珊（1994-），女，天津医科大学在读硕士生，主要从事心血管药理学研究。Tel：（022）84845240E-mail：15731113356@163．com;通信作者：王维亭（1974-），男，研究员，主要从事心血管药理学研究。Tel：（022）84845240E-mail：wangwt@tijpr.com;汤立达（1963-），男，研究员，主要从事新药药理、新靶点药物分子设计及新药发现研究。Tel：（022）23006908E-mail：langld@tjipr．com
