慢性缺血性舒张性心力衰竭动物模型的建立

目的通过反复冠状动脉微球栓塞,模拟缺血性心脏病所诱导的舒张性心力衰竭（Diastolic Heart Failure,DHF）,建立动物模型。方法采用股动脉穿刺方法,对125条比格犬冠状动脉进行反复微球栓塞,直到出现DHF症状,比较栓塞前和最后1次栓塞后血流动力学、超声心动图、血清脑钠肽水平以及组织形态学的差异。结果（1）125条比格犬经反复冠脉微球栓塞,最后成功建立心力衰竭（心衰）模型86条,其中收缩性心衰犬48条、DHF犬38条。（2）DHF犬与术前比较,左室射血分数由术前的58.88%±12.38%降至54.56%±10.47%（P〉0.05）,而左室舒张末压则由8.79±3.24mmHg升至15.27±6.04mmHg（P〈0.01）;等容舒张期松弛时间常数（τ）由36.99±2.91ms升至57.80±9.79ms（P〈0.01）;二尖瓣血流舒张早期峰速度（E）/心肌舒张早期峰速（Em）由10.76±2.40升高至13.47±4.84（P〈0.01）。（3）脑钠肽浓度对数水平由1.86±0.18pg/ml升高至2.37±0.07pg/ml（P〈0.01）。（4）光镜下可见DHF犬心肌出现细胞肥大、坏死和间质纤维化。结论应用反复经皮冠状动脉微球栓塞的方法,可以成功建立稳定的DHF动物模型。

Establishment of diastolic heart failure model in canine with chronic myocardial ischemia

Objective To establish model of diastolic heart failure（DHF）in canine mimicking ischemic cardiomyopathy in humans by coronary microembolization with microspheres repeatedly.Methods One hundred twenty five dogs underwent one to four intracoronary embolizations apart.Embolizations were discontinued until anorexy and depressed had appeared.Haemodynamics,echocardiogram and brain natriuretic peptide were measured.Results（1）DHF were successfully induced in 38 dogs.（2）LV-ejection fraction was 58.88±12.38% at baseline and decreased to 54.56±10.47% after the last embolization（P0.05）.During the same period,LV end-diastolic pressure increased from 8.79±3.24 to 15.27±6.04 mmHg（P0.01）;relax constant increased from 36.99±2.91 to 57.80±9.79 ms（P0.01）;E/Em increased from10.76±2.40 to 13.47±4.84（P0.01）.The common logarithm of Plasma atrial natriuretic factor increased from 1.86±0.18 at baseline to 2.37±0.07 after the last embolization（P0.01）.Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy.Conclusions Multiple intracoronary embolizations with microspheres repeatedly can lead to chronic diastolic heart failure in dogs.The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.