Glenn circulation causes early and progressive shunting in a surgical model of pulmonary arteriovenous malformations. bioRxiv 2024 Apr 05
Date
04/15/2024Pubmed ID
38617317Pubmed Central ID
PMC11014550DOI
10.1101/2024.04.03.588015Abstract
BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) universally develop in patients with single ventricle congenital heart disease (CHD). Single ventricle PAVMs have been recognized for over 50 years, yet they are poorly understood, and we lack any medical therapies. To improve our understanding of single ventricle PAVM initiation and progression, we developed a surgical rat model of Glenn circulation and characterized PAVM physiology over multiple time points.
METHODS: Using adult rats, 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 for PAVM physiology in the left lung, we quantified intrapulmonary shunting using two independent methods (bubble echocardiography and fluorescent microsphere injection) at 2 weeks, 2 months, and 6 months. Additionally, we performed arterial blood gas measurements to assess oxygenation and plethysmography to assess ventilation.
RESULTS: We identified pathologic intrapulmonary shunting by bubble echocardiography as early as 2 weeks post-Glenn surgery, and shunting continued chronically at 2- and 6-months post-Glenn. Shunting also progressed over time, demonstrated by increased shunting of 10µm microspheres at 6 months. Shunting was accompanied by mildly decreased arterial oxygenation, but there were no differences in ventilation as quantified by plethysmography.
CONCLUSIONS: Our surgical animal model of unilateral Glenn circulation re-creates 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.
Author List
Wan T, Rousseau H, Mattern C, Tabor M, Hodges MR, Ramchandran R, Spearman ADAuthors
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of WisconsinAndrew Spearman MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
