UMC Utrecht, Experimental Cardiology, G02.523, Heidelberglaan 100, NL-3584 CX Utrecht, The Netherlands.
Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H408-14. doi: 10.1152/ajpheart.00070.2010. Epub 2010 Oct 15.
Therapeutic stimulation of collateral artery growth is a promising approach for treatment of cardiovascular diseases. Unfortunately, translation into clinical practice yet remains cumbersome. Cardiovascular physiology and anatomy are major determinants of vascular growth processes. Hence, large-animal models are needed to improve clinical translatability of preclinical research. Furthermore, acute complete occlusions are mostly applied in experimental research, whereas stepwise occlusions are more often observed in human disease. We developed a model of coronary collateral artery growth in which 1) the artery is occluded in a step wise approach, and 2) effects of local treatment can be measured individually for each supplying coronary vessel. A hemodynamically relevant stenosis was created by implantation of a tapered stent at day 0 (d0) in the left circumflex artery (LCX), followed by complete arterial occlusion at day 14 (d14). Fluorescent microspheres were injected for demarcation of perfusion territories at each time point. Three and four weeks after induction of stenosis, collateral conductance measurements were performed for each coronary artery separately using differently labeled fluorescent microspheres. Postmortem angiography after acute LCX occlusion confirmed the presence of preexistent coronary anastomoses in the pig. The tapered stent created a hemodynamically significant stenosis immediately postplacement (fractional flow reserve, 0.70 ± 0.03). Between day 21 and 28, collateral conductance significantly increased in both the left anterior descending (LAD) and the right coronary artery (RCA)-supplied, collateral-dependent territories (LAD d21, 0.77 ± 0.14; LAD d28, 1.35 ± 0.12; RCA d21, 0.88 ± 0.29; RCA d28, 1.70 ± 0.16 ml · min(-1) · g(-1) · 100 mmHg(-1)), indicating collateral artery growth. We here describe a new translational minimally invasive model of coronary collateral artery growth in pigs, according to a defined protocol of LCX-stenosis and subsequent occlusion, allowing preclinical evaluation of arteriogenic therapies.
治疗性刺激侧支动脉生长是治疗心血管疾病的一种很有前途的方法。不幸的是，将其转化为临床实践仍然很麻烦。心血管生理学和解剖结构是血管生长过程的主要决定因素。因此，需要大型动物模型来提高临床前研究的临床转化能力。此外，急性完全闭塞在实验研究中更为常见，而在人类疾病中则更为常见。我们开发了一种冠状动脉侧支动脉生长模型，该模型 1）动脉呈逐步闭塞方式，2）可以单独测量每个供血冠状动脉的局部治疗效果。在第 0 天（d0）将锥形支架植入左回旋支（LCX）中，创建一个血流动力学相关的狭窄，然后在第 14 天（d14）完全闭塞动脉。在每个时间点注射荧光微球以划定灌注区。在狭窄诱导后 3 周和 4 周，分别使用不同标记的荧光微球对每条冠状动脉进行侧支传导测量。LCX 急性闭塞后的死后血管造影证实猪存在预先存在的冠状动脉吻合。锥形支架放置后即刻形成血流动力学显著狭窄（血流储备分数，0.70 ± 0.03）。在第 21 天至第 28 天之间，左前降支（LAD）和右冠状动脉（RCA）供血的侧支依赖性区域的侧支传导明显增加（LAD d21，0.77 ± 0.14；LAD d28，1.35 ± 0.12；RCA d21，0.88 ± 0.29；RCA d28，1.70 ± 0.16 ml · min(-1) · g(-1) · 100 mmHg(-1)），表明侧支动脉生长。根据 LCX 狭窄和随后闭塞的既定方案，我们在此描述了一种新的转化微创猪冠状动脉侧支动脉生长模型，允许对动脉生成疗法进行临床前评估。
