Universidad de Cantabria, Facultad de Medicina, Santander, E-39011, Cantabria, Spain.
Instituto de Investigación Valdecilla (IDIVAL), Cardenal Herrera Oria Av. s/n, Santander, E-39011, Cantabria, Spain.
Sci Rep. 2018 Feb 16;8(1):3167. doi: 10.1038/s41598-018-21548-x.
Pressure overload left ventricular hypertrophy is a known precursor of heart failure with ominous prognosis. The development of experimental models that reproduce this phenomenon is instrumental for the advancement in our understanding of its pathophysiology. The gold standard of these models is the controlled constriction of the mid aortic arch in mice according to Rockman's technique (RT). We developed a modified technique that allows individualized and fully controlled constriction of the aorta, improves efficiency and generates a reproducible stenosis that is technically easy to perform and release. An algorithm calculates, based on the echocardiographic arch diameter, the intended perimeter at the constriction, and a suture is prepared with two knots separated accordingly. The aorta is encircled twice with the suture and the loop is closed with a microclip under both knots. We performed controlled aortic constriction with Rockman's and the double loop-clip (DLC) techniques in mice. DLC proved superiority in efficiency (mortality and invalid experiments) and more homogeneity of the results (transcoarctational gradients, LV mass, cardiomyocyte hypertrophy, gene expression) than RT. DLC technique optimizes animal use and generates a consistent and customized aortic constriction with homogeneous LV pressure overload morphofunctional, structural, and molecular features.
压力超负荷性左心室肥厚是心力衰竭的已知前驱病变,预后凶险。复制这种现象的实验模型的发展对于深入了解其病理生理学至关重要。这些模型的金标准是根据罗克曼(Rockman)技术对小鼠中主动脉弓进行控制性缩窄(RT)。我们开发了一种改良技术,可实现主动脉的个体化和完全控制性缩窄,提高效率并产生可重复的狭窄,操作技术简单,易于进行和释放。一种算法可根据超声心动图弓直径计算缩窄处的预期周长,并准备带有两个相应分开结的缝线。用缝线环绕主动脉两次,并在两个结下用微型夹闭合环。我们在小鼠中进行了罗克曼(Rockman)技术和双环夹(DLC)技术的控制性主动脉缩窄。DLC 在效率(死亡率和无效实验)方面优于 RT,结果的均一性更好(跨缩窄梯度、LV 质量、心肌细胞肥大、基因表达)。DLC 技术优化了动物的使用,并产生了一致的定制性主动脉缩窄,具有均匀的 LV 压力超负荷形态、功能、结构和分子特征。