Department of Pediatrics, Division of Cardiology, Medical College of Wisconsin, Children's Wisconsin, Herma Heart Institute, Milwaukee, Wisconsin, USA.
Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Physiol Rep. 2024 Nov;12(22):e70123. doi: 10.14814/phy2.70123.
Pulmonary arteriovenous malformations (PAVMs) universally develop in patients with single ventricle congenital heart disease. Single ventricle PAVMs have been recognized for over 50 years but remain poorly understood. To improve our understanding, we developed a surgical rat model of Glenn circulation and characterized PAVM physiology over multiple time points. We performed a left thoracotomy and end-to-end anastomosis of the left superior vena cava to the left pulmonary artery (unilateral Glenn), or sham surgical control. To assess PAVM physiology, we quantified intrapulmonary shunting using two independent methods (bubble echocardiography and fluorescent microsphere injection). Additionally, we performed arterial blood gas measurements to assess oxygenation and plethysmography to assess ventilation. We identified pathologic intrapulmonary shunting by bubble echocardiography as early as 2 weeks post-Glenn, and shunting continued at 2- and 6-months post-Glenn. Shunting also progressed over time, demonstrated by increased shunting of 10 μm microspheres at 6 months. Shunting was accompanied by mildly decreased oxygenation but no differences in ventilation. Our surgical animal model of unilateral Glenn circulation recreates the clinical condition of single ventricle PAVMs with early and progressive intrapulmonary shunting. This model is poised to characterize single ventricle PAVM pathophysiology and lead to mechanistic and therapeutic discovery.
肺动静脉畸形（PAVMs）普遍存在于单心室先天性心脏病患者中。单心室 PAVMs 已被认识超过 50 年，但仍未被充分理解。为了增进我们的认识，我们开发了一种 Glenn 循环的大鼠手术模型，并在多个时间点上对 PAVM 生理学进行了特征描述。我们进行了左开胸手术，将左上腔静脉与左肺动脉端端吻合（单侧 Glenn），或进行假手术对照。为了评估 PAVM 生理学，我们使用两种独立的方法（气泡超声心动图和荧光微球注射）来量化肺内分流。此外，我们进行了动脉血气测量以评估氧合，进行体积描记法以评估通气。我们通过气泡超声心动图早在 Glenn 后 2 周就发现了病理性肺内分流，并且分流在 Glenn 后 2 个月和 6 个月持续存在。分流也随着时间的推移而进展，在 6 个月时 10μm 微球的分流增加证明了这一点。分流伴随着轻度的氧合降低，但通气没有差异。我们的单侧 Glenn 循环手术动物模型再现了单心室 PAVMs 的临床情况，具有早期和进行性的肺内分流。该模型有望对单心室 PAVM 病理生理学进行特征描述，并为机制和治疗发现提供依据。
