Animal model of left atrial thrombus in congestive heart failure in rats.Am J Physiol Heart Circ Physiol 2019; 317(1):H63-H72AJ
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 mm2) that had formed, whereas small LATs (<5 mm2) 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. NEW & NOTEWORTHY 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.