经冠状动脉内注射自体微血栓构建大鼠急性左心衰竭模型

Novel rat model with acute left ventricular heart failure developed by cornary microembolism with homologous microthrombi

目的建立重复性好、相对稳定的大鼠急性左心衰模型。方法36只SD大鼠随机分为模型组(n=24)、假手术组(n=12)。经左心室内注射自体微血栓、同时短暂主动脉夹闭,造成冠状动脉微栓塞及左室微小心肌梗死,构建大鼠实验性左心衰模型。分别采用超声心动图、血液动力学和病理学检测观察大鼠的心功能变化及心肌微小梗死灶面积。结果术后模型组除8只死亡,存活的16只大鼠均出现精神萎靡、呼吸急促、活动及进食减少等表现。术后48h模型组与假手术组比较,左室射血分数及短轴缩短率显著降低,左室收缩压及左室内压最大上升速率、最大下降速率)明显下降,伴左室舒张末压显著升高。HE染色显示模型组斑片状心肌梗死灶,梗死面积(21.00±2.55)%;肺组织显示肺水肿。结论冠状动脉微栓塞是构建小动物急性左心衰竭模型的有效方法。

[Objective] To develop a reproducible and relatively stable model of acute left ventricular heart failure in rats.[Methods] After thoracotomy,24 Sprague Dawley rats underwent injection of homologous microthrombotic particle suspension into left ventricle when clamping the ascending aorta and 12 rats were subjected to sham operation.We evaluated left ventricular ejection fraction（LVEF）,minor axis fractional shortening（LVFS）echocardiographically,left ventricular systolic pressure（LVSP）,＋dP/dtmax and-dP/dtmax of the left ventricle,and left ventricular end-diastolic pressure（LVEDP）hemodynamically,and myocardial and pulmonary pathology by HE-staining.[Results] Eight rats died following the procedure,acute heart failure model was developed successfully in sixteen rats 48 hours after microembolization,as evidenced by depression,tachypnea,inactivity and intaking decrease.Compared with the measurements in the sham group,LVEF and LVFS significantly reduced in model group（88.60±2.12）% vs（60.75±9.09）%,（53.73±2.90）% vs（29.63±4.06）%,P 〈0.01;LVSP significantly decreased（153±18）vs 109±13）mmHg,P 〈0.01 with significant reductions of ＋dP/dt max（5964±663）vs（3032±379）,P 〈0.01 and-dP/dtmax（5181±1124）vs（2669±343）,P 〈0.01,and LVEDP significantly increased（3.70±1.64）vs（16.38±3.39）mmHg,P 〈0.01 in model group.Histological examination showed patchy myocardial necrosis and pulmonary edema,with myocardial microinfarcted area of（21.00±2.55%）.[Conclusions] Coronary microembolism with homologous microthrombi is an effective method to produce acute left ventricular heart failure in small animals.