Independence Blue Cross Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
Am J Physiol Heart Circ Physiol. 2021 Feb 1;320(2):H690-H698. doi: 10.1152/ajpheart.00672.2020. Epub 2020 Dec 24.
Despite advances in the diagnosis and treatment of ischemic heart disease (IHD), it remains the leading cause of death globally. Thus, there is a need to investigate the underlying pathophysiology and develop new therapies for the prevention and treatment of IHD. Murine models are widely used in IHD research because they are readily available, relatively inexpensive, and can be genetically modified to explore mechanistic questions. Ischemia-reperfusion (I/R)-induced myocardial infarction in mice is produced by the blockage followed by reperfusion of the left anterior descending branch (LAD) to imitate human IHD disease and its treatment. This I/R model can be widely used to investigate the potential reparative effect of putative treatments in the setting of reperfusion. However, the surgical technique is demanding and can produce an inconsistent amount of damage, which can make identification of treatment effects challenging. Therefore, determining which hearts have been significantly damaged by I/R is an important consideration in studies designed to either explore the mechanisms of disrupted function or test possible therapies. Noninvasive echocardiography (ECHO) is often used to determine structural and functional changes in the mouse heart following injury. In the present study, we determined that ECHO performed 3 days post I/R surgery could predict the permanent injury produced by the ischemic insult. We believe our work is noteworthy due to its creation of standards for early evaluation of the level of myocardial injury in mouse models of ischemia-reperfusion. This improvement to study design could reduce the sample sizes used in evaluating therapeutics and lead to increased confidence in conclusions drawn regarding the therapeutic efficacy of treatments tested in these translational mouse models.
尽管在缺血性心脏病（IHD）的诊断和治疗方面取得了进展，但它仍是全球范围内的主要死亡原因。因此，有必要研究其潜在病理生理学机制，并开发预防和治疗 IHD 的新疗法。由于易于获得、相对便宜且可进行基因修饰以探索机制问题，因此小鼠模型在 IHD 研究中得到广泛应用。在小鼠中，通过阻塞左前降支（LAD）后再灌注来产生缺血再灌注（I/R）诱导的心肌梗死，以模拟人类 IHD 疾病及其治疗。这种 I/R 模型可广泛用于研究在再灌注情况下潜在治疗方法的修复效果。然而，该手术技术要求较高，且可能造成不一致的损伤程度，这使得治疗效果的鉴定变得具有挑战性。因此，确定哪些心脏受到 I/R 的严重损伤是研究探索功能障碍机制或测试可能的治疗方法的重要考虑因素。非侵入性超声心动图（ECHO）常用于确定损伤后小鼠心脏的结构和功能变化。在本研究中，我们发现 I/R 手术后 3 天进行的 ECHO 可以预测缺血损伤引起的永久性损伤。我们认为我们的工作具有重要意义，因为它为早期评估缺血再灌注小鼠模型中心肌损伤程度建立了标准。这种研究设计的改进可以减少评估治疗方法所需的样本量，并提高对这些转化型小鼠模型中测试治疗方法的疗效的结论的可信度。
