Koudstaal Stefan, Jansen of Lorkeers Sanne, Gho Johannes M I H, van Hout Gerardus P J, Jansen Marlijn S, Gründeman Paul F, Pasterkamp Gerard, Doevendans Pieter A, Hoefer Imo E, Chamuleau Steven A J
Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht; Interuniversity Cardiology Institute of the Netherlands;
Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht.
J Vis Exp. 2014 Apr 25(86):51269. doi: 10.3791/51269.
Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.
将新发现的心血管治疗方法引入人体首次试验依赖于严格规范的伦理和法律路线图。一个重要的前提是充分了解在大型动物模型中获得的所有安全和有效性方面的情况，这些模型要能有效反映心肌梗死（MI）的人类情况。猪在这方面被广泛使用，因为它们的心脏大小、血流动力学和冠状动脉解剖结构与人类接近。在此，我们提出一种使用猪MI模型的有效方案，即通过左前降支（LAD）的闭胸冠状动脉球囊闭塞，随后进行再灌注。这种方法基于90分钟的心肌缺血，可诱导左心室前壁、室间隔和下间隔壁发生大面积梗死。此外，我们还提出了各种结果测量方案，这些方案可提供有关心脏的广泛信息，如心脏收缩和舒张功能、血流动力学、冠状动脉流速、微血管阻力和梗死面积。该方案可轻松调整，以满足在不同阶段（即急性缺血损伤后立即、亚急性情况下或甚至在慢性MI中瘢痕形成完成后）验证新型心脏再生生物制剂的研究特定要求。因此，该模型为研究MI、随后的不良重塑以及新型心脏再生药物的潜力提供了一个有用的转化工具。
