Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai , New York, New York.
Am J Physiol Heart Circ Physiol. 2019 Jul 1;317(1):H63-H72. doi: 10.1152/ajpheart.00086.2019. Epub 2019 May 10.
The aim of the present study was to develop and study a new model of left atrial thrombus (LAT) in rat with congestive heart failure (CHF). CHF was induced by aortic banding for 2 mo, followed by ischemia-reperfusion (I/R) and subsequent aortic debanding for 1 mo. Cardiac function and the presence of LAT were assessed by echocardiography. Masson's staining was performed for histological analysis. All CHF rats presented with significantly decreased cardiac function, fibrosis in remote myocardium, and pulmonary edema. The incidence rate of LAT was 18.8% in the rats. LAT was associated with severity of aortic constriction, aortic pressure gradient, aortic blood flow velocity, and pulmonary edema but not myocardial infarction or a degree of left ventricular depression. The progressive process of thrombogenesis was characterized by myocyte hypertrophy, fibrosis, and inflammation in the left atrial wall. Fibrin adhesion and clot formation were observed, whereas most LAT presented as a relatively hard "mass," likely attributable to significant fibrosis in the middle and outer layers. Some LAT mass showed focal necrosis as well as fibrin bulging. Most LAT occurred at the upper anterior wall of the left atrial appendage. Aortic debanding had no significant impact on large LATs (>5 mm) that had formed, whereas small LATs (<5 mm) regressed 1 mo after aortic release. LAT is found in a rat model of aortic banding plus I/R followed by aortic debanding. The model provides a platform to study molecular mechanisms and potential new pathways for LAT treatment. It is critically important to have a rodent model to study the molecular mechanism of thrombogenesis in the left atrium. Left atrial thrombus (LAT) is not a simple fibrin clot like those seen in peripheral veins or arteries. Rather, LAT is a cellular mass that likely develops in conjunction with blood clotting. Studying this phenomenon will help us understand congestive heart failure and promote new therapies for LAT.
本研究旨在建立并研究一种新的大鼠左心房血栓(LAT)模型,该模型伴充血性心力衰竭(CHF)。CHF 通过主动脉缩窄 2 个月,随后缺血再灌注(I/R)和随后的主动脉去缩窄 1 个月来诱导。通过超声心动图评估心功能和 LAT 的存在。进行 Masson 染色进行组织学分析。所有 CHF 大鼠的心脏功能明显降低,远程心肌纤维化和肺水肿。LAT 的发生率为大鼠的 18.8%。LAT 与主动脉缩窄的严重程度、主动脉压力梯度、主动脉血流速度和肺水肿有关,但与心肌梗死或左心室抑制程度无关。血栓形成的进展过程表现为左心房壁的心肌细胞肥大、纤维化和炎症。观察到纤维蛋白黏附和血栓形成,而大多数 LAT 表现为相对较硬的“肿块”,可能归因于中层和外层的显著纤维化。一些 LAT 肿块显示出局灶性坏死以及纤维蛋白膨出。大多数 LAT 发生在左心房附壁的上前壁。主动脉去缩窄对已形成的大 LAT(>5mm)没有明显影响,而小 LAT(<5mm)在主动脉释放后 1 个月消退。在主动脉缩窄加 I/R 后再行主动脉去缩窄的大鼠模型中发现 LAT。该模型为研究 LAT 治疗的分子机制和潜在新途径提供了一个平台。拥有一种研究左心房血栓形成分子机制的啮齿动物模型非常重要。左心房血栓(LAT)不是像外周静脉或动脉中那样的简单纤维蛋白凝块。相反,LAT 是一种细胞团块,可能与血液凝固一起发展。研究这一现象将有助于我们了解充血性心力衰竭并促进 LAT 的新疗法。