目的应用选择性冠状动脉前降支(LAD)球囊闭塞结合微血栓微球混悬液灌注方法造成心肌缺血坏死,探索建立稳定存活的小型猪急性心肌梗死(AMI)后心力衰竭(HF)动物模型。方法选择中国五指山小型猪18头,行冠脉造影后沿血管送球囊至LAD中段,依次扩张球囊阻断前向血流1、2、5 min,每次间隔60 s,然后扩张球囊堵闭血流120 min。再以4F导管超选LAD,行微血栓微球混悬液分次注入,间隔10 min重复注射,TIMI心肌灌注分级(TMPG)〈2级和左室舒张末压(LVEDP)〉15 mm Hg时停止注射,同时监测心电图及应用漂浮导管监测有创血流动力学参数。并行pigtail导管测量(LVEDP)的变化,待LVEDP稳定在15~18 mm Hg之间后结扎血管,并加压包扎。监测心肌坏死标志物(cTnI和CK-MB)变化。分别于制模前,制模后第1天、7天、14天行心脏超声检查,制模第14天复查有创血流动力学检查,并行心脏病理检查,认定和评价模型的成功率、稳定性和可重复性。结果制模14 d后共有15头小型猪成活,心电图、心肌坏死标记物、病理检查均符合AMI病理生理过程。其中14头小型猪达到动物模型标准【肺毛细血管楔压(PCWP)〉18 mmHg和心输出量(CO)下降30%以上】,模型成功率为77.78%。制模后第14天PCWP明显升高(P〈0.01),CO平均下降50.76%;左室射血分数(LVEF)明显降低(P〈0.01)。病理检查显示心肌梗死面积占左心室面积的25.4%~34.9%。结论球囊闭塞结合微血栓微球混悬液灌注构建小型猪急性心肌梗死后心力衰竭模型具有闭胸、高成功率、稳定和重复性好等优点,较药物、冠状动脉结扎和起搏诱导的心力衰竭模型更接近临床病理生理学特点。
Objective To evaluate the method of establishment of a minipig model of ischemic heart failure(HF) with acute myocardial infarction(AMI) by coronary balloon occlusion and coadministration of injecting of microthrombi and plastic microspheres.Methods A total of eighteen minipigs were selected.After coronary angiography,angioplasty balloons were placed in the mid-distal of left anterior descending(LAD).The balloon was inflated intermittently to occlude the LAD 3 times and then to occlude it continuously for 120 minutes.After the balloon was taken out,4F Judkins-type angiogrphic catheter was superelectively engaged in LAD and 3 mL intermixture of microthrombi and plastic microspheres were injected at 10 minites interval until TIMI myocardial perfusion was grade 〈2 and left ventricular end-diastolic pressure was maintained from 15 to 18 mmHg.Electrocardiogram (ECG),hemodynamic perameters,ultrasonic cardiogram,cTnI and CK-MB were measured.Myocardial infarction area was evaluated by histopathology.Results Fourteen days later,fifteen minipigs survived and fourteen satisfied the criteria(pulmonary capillary wedge pressure,PCWP 〉18 mmHg and cardio output(CO) decreased beyond 30%).The changes of ECG,hemodynamic perameters,CKMB,cTnI and cardiac pathologic examination were in accordance with AMI.Conclusion A stable experimental method of establishment of minipig model of ischemic heart failure(HF) with acute myocardial infarction(AMI) by coronary balloon occlusion and coadministration of injecting of microthrombi and plastic microspheres is succeded.This method has advantages such as closed chest,higher success rate and stability compared with the drug induced,tachycardia-pacing induced,coronary artery ligation induced or microsphere injection alone methods.