Gaweda Boguslaw, Iwasieczko Artur, Gaddam Manikantam, Bush Jared D, MacDougal Brian, Timek Tomasz A
Division of Cardiothoracic Surgery, Spectrum Health; Clinical Department of Cardiac Surgery, Clinical District Hospital no 2, Faculty of Medicine, University of Rzeszow.
Research Department, Meijer Heart and Vascular Institute at Spectrum Health; Department of Urology, Stanford University School of Medicine.
J Vis Exp. 2023 Mar 17(193). doi: 10.3791/64529.
The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 ± 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 ± 2 mmHg to 62 ± 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.
与右心室功能障碍相关的重度功能性三尖瓣反流（FTR）的病理生理学机制尚不清楚，导致临床效果欠佳。我们着手建立一种FTR和右心衰竭的慢性绵羊模型，以研究FTR的机制。20只成年雄性绵羊（6至12个月大，体重62±7千克）接受左胸切开术及基线超声心动图检查。放置一条肺动脉束带（PAB）并环绕主肺动脉（PA）收紧，使收缩期肺动脉压（SPAP）至少翻倍，从而诱发右心室（RV）压力过载及RV扩张迹象。PAB使SPAP从21±2 mmHg急性升高至62±2 mmHg。对这些动物进行为期8周的跟踪观察，使用利尿剂治疗心力衰竭症状，并通过监测超声心动图评估胸腔和腹腔积液情况。在随访期间，有3只动物因中风、出血和急性心力衰竭死亡。2个月后，进行正中胸骨切开术及心外膜超声心动图检查。在存活的17只动物中，3只出现轻度三尖瓣反流，3只出现中度三尖瓣反流，11只出现重度三尖瓣反流。8周的肺动脉束带结扎形成了一个稳定的右心室功能障碍和显著FTR的慢性绵羊模型。这个大型动物平台可用于进一步研究RV衰竭和功能性三尖瓣反流的结构及分子基础。
