Tina C. Wan, Henry Rousseau, Carol Mattern, Madeline Tabor, Matthew R. Hodges, Ramani Ramchandran, Andrew D. Spearman
Medical College of Wisconsin and Children’s Wisconsin.
United States
Physiological Reports
Physiol Rep 2024; 12:
DOI: 10.14814/phy2.70123
Abstract
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.
Category
Pulmonary Arteriovenous Malformations
Animal Models of Pulmonary Vascular Disease and Therapy
Diagnostic Testing for Pulmonary Vascular Disease. Non-invasive Testing
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes