Faculty Collaboration Database

Glenn circulation causes early and progressive shunting in a surgical model of pulmonary arteriovenous malformations. Physiol Rep 2024 Nov;12(22):e70123

Date

11/23/2024

Pubmed ID

39578098

Pubmed Central ID

PMC11584281

DOI

10.14814/phy2.70123

Scopus ID

2-s2.0-85210087220 (requires institutional sign-in at Scopus site)   3 Citations

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.

Author List

Wan TC, Rousseau H, Mattern C, Tabor M, Hodges MR, Ramchandran R, Spearman AD

Authors

Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
Andrew Spearman MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tina C. Wan Research Scientist II in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arteriovenous Fistula
Arteriovenous Malformations
Disease Models, Animal
Fontan Procedure
Heart Defects, Congenital
Male
Pulmonary Artery
Pulmonary Circulation
Pulmonary Veins
Rats
Rats, Sprague-Dawley
Vena Cava, Superior