Abstract 17396: Elevated Pulmonary Vascular Resistance Severely Limits Cardiac Output in Fontan Physiology: Implications for Novel Treatment Strategies
Background: Pulmonary vascular resistance (PVR) has been hypothesized to be a key regulator of cardiac output (CO) in patients who have undergone Fontan type repair of congenital heart lesions via its role in facilitating a gradient to venous return. We sought to test this hypothesis and to better understand the extent to which PVR affects CO in Fontan physiology compared with normal biventricular circulation.
Methods: We used two computational models of circulation (MATLAB v7.8.0) based on differential equations of flow to describe changes in blood volume across body compartments: one incorporating a “normal” biventricular system and the other an atriopulmonary connection. We modeled the relative contribution of PVR, systemic vascular resistance (SVR), stressed vascular volume, and heart rate (HR) on CO in these two systems.
Results: Over the range of normal and pathologic physiology, PVR severely limited CO in the Fontan circulation: For a five-fold increase in PVR (from 1 Woods Unit, WU, to 5 WU), CO fell by 10.1% (5.16 to 4.64 L/min) in the “normal” circulation, and by 52.5% (3.81 to 1.81 L/min; Figure) in the Fontan circulation. Increasing SVR decreased CO similarly in both systems: Raising SVR from 10 to 30 WU decreased CO by 25.1% (4.23 to 3.17 L/min) in the Fontan circulation versus 25.4% (6.03 to 4.56 L/min) in then normal circulation. HR caused a sharp increase in CO up to a range which depended on other physiologic parameters, before causing a gradual deline in CO in both circulations. Increases in preload/stressed vascular volume had a more significant impact on the relative increase in CO at higher PVRs in both the Fontan and normal circulations.
Conclusions: Unlike a normal biventricular circulation, PVR is a critical factor in regulating CO in Fontan physiology. Modulation of PVR is an attractive target for therapeutic interventions, including phosphodiesterase inhibitors, which could improve resting CO and exercise tolerance in these patients.
- © 2010 by American Heart Association, Inc.