Krackhardt Florian, Harnoss Jonathan M, Waliszewski Matthias W, Ritter Zully, Granzow Susanne, Felsenberg Dieter, Neumann Konrad, Lerman Lilian O, Hillmeister Philipp, Gebker Rolf, Paetsch Ingo, Riediger Fabian, Bramlage Peter, Buschmann Ivo R
Department of Internal Medicine and Cardiology.
Department for Angiology, Brandenburg Medical School, MHB Medizinische Hochschule Brandenburg, Campus Brandenburg Havel, Germany.
Coron Artery Dis. 2018 Mar;29(2):127-137. doi: 10.1097/MCA.0000000000000569.
For patients with severe ischemic heart disease, complete revascularization by a percutaneous coronary intervention or coronary artery bypass grafting is often not achieved and may still cause residual angina. In case of progressive coronary artery occlusions, therapeutic arteriogenesis constitutes a promising strategy for increasing blood supply to the ischemic myocardium. Whether the formation of collaterals in the hypofused myocardium is angiogenetic in nature or based on preformed coronary artery anastomoses remains debatable. The objectives of this research were (i) the development of an appropriate research methodology to study a humanoid animal semiacute infarction model with low mortality and (ii) to answer the question of whether collateral revascularization follows a pre-existing 'blueprint'.
A porcine model was chosen in which a step-wise vessel occlusion was performed by implantation of a copper stent into the distal left anterior descending artery. Vessel occlusion and collateral development were confirmed in vivo every 14 days up to day 56 by repeated coronary angiography and myocardial perfusion measurement using cardiac MRI. After the completion of the in-vivo imaging studies, animals were euthanized and collateral growth was evaluated using microcomputer tomography.
Our porcine model of semiacute noninvasive coronary artery occlusion confirmed the existence of preformed coronary anastomoses and the proliferation of functional vessels in hypoperfused myocardium. Repetitive intra-animal MRIs showed the functional impact of these growing collaterals.
The confirmation of preformed coronary anastomoses during the process of collateralization (natural bypasses) offers a preclinical avenue to carry out arteriogenetic pharmaceutical research in patients with ischemic heart disease.
对于严重缺血性心脏病患者，经皮冠状动脉介入治疗或冠状动脉旁路移植术往往无法实现完全血运重建，且仍可能导致残余心绞痛。在冠状动脉逐渐闭塞的情况下，治疗性动脉生成是增加缺血心肌血供的一种有前景的策略。低灌注心肌中侧支血管的形成是血管生成性的还是基于预先存在的冠状动脉吻合，仍存在争议。本研究的目的是：（i）开发一种合适的研究方法，以研究低死亡率的类人动物半急性梗死模型；（ii）回答侧支循环血运重建是否遵循预先存在的“蓝图”这一问题。
选择猪模型，通过在左前降支远端植入铜支架进行逐步血管闭塞。在第56天之前，每14天通过重复冠状动脉造影和使用心脏MRI进行心肌灌注测量，在体内确认血管闭塞和侧支血管发育情况。在完成体内成像研究后，对动物实施安乐死，并使用微型计算机断层扫描评估侧支血管生长情况。
我们的半急性非侵入性冠状动脉闭塞猪模型证实了预先存在的冠状动脉吻合的存在以及低灌注心肌中功能性血管的增殖。动物体内重复MRI显示了这些生长中的侧支血管的功能影响。
在侧支循环形成过程中（自然旁路）对预先存在的冠状动脉吻合的确认，为在缺血性心脏病患者中开展动脉生成药物研究提供了一条临床前途径。
