Hocum Stone Laura, Wright Christin, Chappuis Erin, Messer Mia, Ward Herbert B, McFalls Edward O, Kelly Rosemary F
Department of Surgery, University of Minnesota;
Department of Surgery, University of Minnesota.
J Vis Exp. 2018 Mar 27(133):57229. doi: 10.3791/57229.
Chronic cardiac ischemia that impairs cardiac function, but does not result in infarct, is termed hibernating myocardium (HM). A large clinical subset of coronary artery disease (CAD) patients have HM, which in addition to causing impaired function, puts them at higher risk for arrhythmia and future cardiac events. The standard treatment for this condition is revascularization, but this has been shown to be an imperfect therapy. The majority of pre-clinical cardiac research focuses on infarct models of cardiac ischemia, leaving this subset of chronic ischemia patients largely underserved. To address this gap in research, we have developed a well-characterized and highly reproducible model of hibernating myocardium in swine, as swine are ideal translational models for human heart disease. In addition to creating this unique disease model, we have optimized a clinically relevant treatment model of coronary artery bypass surgery in swine. This allows us to accurately study the effects of bypass surgery on heart disease, as well as investigate additional or alternate therapies. This model surgically induces single vessel stenosis by implanting a constrictor on the left anterior descending (LAD) artery in a young pig. As the pig grows, the constrictor creates a gradual stenosis, resulting in chronic ischemia with impaired regional function, but preserving tissue viability. Following the establishment of the hibernating myocardium phenotype, we perform off-pump coronary artery bypass graft surgery to revascularize the ischemic region, mimicking the gold-standard treatment for patients in the clinic.
损害心脏功能但未导致梗死的慢性心脏缺血被称为冬眠心肌（HM）。冠状动脉疾病（CAD）患者中有很大一部分临床亚组存在HM，这不仅会导致功能受损，还会使他们面临更高的心律失常和未来心脏事件风险。针对这种情况的标准治疗方法是血运重建，但已证明这是一种不完善的治疗方法。大多数临床前心脏研究集中在心脏缺血的梗死模型上，使得这一慢性缺血患者亚组在很大程度上未得到充分研究。为了填补这一研究空白，我们开发了一种特征明确且高度可重复的猪冬眠心肌模型，因为猪是人类心脏病理想的转化模型。除了创建这种独特的疾病模型外，我们还优化了猪冠状动脉搭桥手术的临床相关治疗模型。这使我们能够准确研究搭桥手术对心脏病的影响，并研究其他或替代疗法。该模型通过在幼猪的左前降支（LAD）动脉植入一个缩窄器，手术诱导单支血管狭窄。随着猪的生长，缩窄器会造成逐渐狭窄，导致慢性缺血并伴有局部功能受损，但保留组织活力。在建立冬眠心肌表型后，我们进行非体外循环冠状动脉搭桥移植手术，使缺血区域血运重建，模拟临床上对患者的金标准治疗。
