Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.
J Am Soc Echocardiogr. 2014 Feb;27(2):192-9. doi: 10.1016/j.echo.2013.10.011. Epub 2013 Dec 4.
Small animal models of ischemic left ventricular (LV) dysfunction are important for the preclinical optimization of stem cell therapy. The aim of this study was to test the hypothesis that temporal changes in LV function and regional perfusion after cell therapy can be assessed in mice using echocardiographic imaging.
Wild-type mice (n = 25) were studied 7 and 28 days after permanent ligation of the left anterior descending coronary artery. Animals were randomized to receive closed-chest ultrasound-guided intramyocardial delivery of saline (n = 13) or 5 × 10(5) multipotential adult progenitor cells (MAPCs; n = 12) on day 7. LV end-diastolic and end-systolic volumes, LV ejection fraction, and stroke volume were measured using high-frequency echocardiography. Multiplanar assessments of perfusion and defect area size were made using myocardial contrast echocardiography.
Between days 7 and 28, MAPC-treated animals had 40% to 50% reductions in defect size (P < .001) and 20% to 30% increases in total perfusion (P < .01). Perfusion did not change in nontreated controls. Both LV end-diastolic and end-systolic volumes increased between days 7 and 28 in both groups, but LV end-systolic volume increased to a lesser degree in MAPC-treated compared with control mice (+4.2 ± 7.9 vs +19.2 ± 22.0 μL, P < .05). LV ejection fraction increased in the MAPC-treated mice and decreased in control mice (+3.0 ± 4.3% vs -5.6 ± 5.9%, P < .01). There was a significant linear relation between the change in LV ejection fraction and the change in either defect area size or total perfusion.
High-frequency echocardiography and myocardial contrast echocardiography in murine models of ischemic LV dysfunction can be used to assess the response to stem cell therapy and to characterize the relationship among spatial flow, ventricular function, and ventricular remodeling.
缺血性左心室（LV）功能障碍的小动物模型对于干细胞治疗的临床前优化非常重要。本研究旨在验证以下假设：通过超声心动图成像，可以在小鼠中评估细胞治疗后 LV 功能和区域灌注的时间变化。
对 25 只野生型小鼠在左前降支永久性结扎后 7 天和 28 天进行研究。动物随机分为两组，分别于第 7 天接受闭胸超声引导下心肌内注射生理盐水（n=13）或 5×10(5)个多能成体祖细胞（MAPCs；n=12）。使用高频超声心动图测量 LV 舒张末期和收缩末期容积、LV 射血分数和每搏量。使用心肌对比超声心动图进行多平面灌注和缺陷面积大小评估。
在第 7 天至 28 天期间，MAPC 治疗组的缺陷面积减少了 40%至 50%（P<.001），总灌注增加了 20%至 30%（P<.01）。未治疗的对照组灌注没有变化。两组 LV 舒张末期和收缩末期容积均在第 7 天至 28 天之间增加，但 MAPC 治疗组比对照组 LV 收缩末期容积增加程度较小（+4.2±7.9 与+19.2±22.0 μL，P<.05）。MAPC 治疗组的 LV 射血分数增加，而对照组则降低（+3.0±4.3%与-5.6±5.9%，P<.01）。LV 射血分数的变化与缺陷面积大小或总灌注的变化之间存在显著的线性关系。
高频超声心动图和心肌对比超声心动图可用于评估缺血性 LV 功能障碍的小鼠模型对干细胞治疗的反应，并描述空间血流、心室功能和心室重构之间的关系。
