Experimental Study of Effect of Fontan Circuit on Pulmonary Microcirculation

Abstract

Pulsatile pulmonary blood flow plays an important role in regulating shear-stress-mediated release of endothelium-derived nitric oxide and endothelin-1, and it reduces pulmonary vascular resistance by passive capillary recruitment. The aim of this study was to demonstrate changes in pulmonary capillary structure and endothelial function induced by the chronic nonpulsatile flow of the Fontan circulation. A canine model with nonpulsatile flow in the right lung was established, and sacrificed 3 months later. Compared to the left lung, wall thickness of the pulmonary arterioles was thinner, endothelin-1 expression was weaker, endothelial nitric oxide synthase activity was stronger, and there was a good correlation between the histomorphometric and immunohistochemical findings. These data indicate that long-term nonpulsatile flow can lead to endothelial dysfunction, which may be involved in distention and vascular structure remodeling due to the increase in pulmonary vascular resistance; but it also can lead to increased patency of the arteriovenous shunt, which might be at least partly involved in pulmonary arteriovenous fistula development and exercise limitation after the Fontan operation.

Diverse multi‐organ histopathologic changes in a failed Fontan patient

“…Although repeated catheter examinations indicated only mildly elevated increased pressure of the pulmonary artery, thickened endothelium of pulmonary capillary artery, to some extent, resembles that in pulmonary hypertension. Overexpression of endothelin‐1 and endothelin receptors in the pulmonary arteries has been observed in failed Fontan patients; and subclinical pulmonary pathophysiologic conditions with high plasma levels of endothelin‐1 in Fontan patients may play a role in the histologic finding …”

Acute histological changes of the lung after experimental Fontan circulation in a swine model

“…These data support the process of an endothelial dysfunction, which may be involved in distention and vascular structure remodeling due to the increase in pulmonary vascular resistance. Yin et al observed that the pulmonary arteriolar wall became thinner, endothelin-1 expression was weaker, and eNOS was stronger in the lung with chronic nonpulsatile flow, confirming endothelial dysfunction [9]. In addition, Adachi et al described their immunohistological analysis on main pulmonary artery tissue from a patient who had been palliated with a classic Fontan operation 23 years before.…”

Evolution in Experimental Fontan Circulation: A Review

“…Yin, et al observed that the pulmonary arteriolar wall became thinner, endothelin-1 expression was weaker, and eNOS was stronger in the lung with chronic non-pulsatile flow confirming that endothelial dysfunction. 21) However, further and systematic studies are needed to explain these possible alterations.…”