Histomorphometric analysis of the pulmonary vasculature in the Fontan circulation. ‘Chronic non-pulsatile pulmonary flow, present in the Fontan circulation is associated with adverse pulmonary vascular remodeling’.

Ridderbos, F.J.S. (2013) Histomorphometric analysis of the pulmonary vasculature in the Fontan circulation. ‘Chronic non-pulsatile pulmonary flow, present in the Fontan circulation is associated with adverse pulmonary vascular remodeling’. thesis, Medicine.

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Abstract

Objective: The Fontan operation is a definitive surgical palliative intervention for patients with a univentricular heart disease for whom a biventricular repair is not possible. In the Fontan circulation the whole systemic venous return flows directly into the pulmonary circulation without the use of a subpulmonary ventricle. Over time there is attrition of the Fontan circulation, the exact mechanisms behind this attrition are not yet discovered. A gradual increase of the pulmonary vascular resistance could be a key factor in the long-term failure of the Fontan circulation. We hypothesized that in the Fontan circulation in which chronic non-pulsatile flow is present adverse pulmonary vascular remodeling occurs in the small pulmonary vessels in the form of media involution and intimal thickening. Methods: Histomorphometric analysis and (immuno) histochemistry were performed on the pulmonary vasculature of lung tissue obtained at autopsy from 12 Fontan patients and 24 age-matched controls. The Fontan patients were divided in 2 subgroups: death < 15 days (N = 5) and death > 5 years (N = 7) after the Fontan operation. Two age-matched sub-groups (N = 10 and N = 14) of controls were also created. Statistical analysis on the differences and correlations between groups, histomorphometric variables and demographic variables was performed. Results: The intima thickness (p = 0.002) is significant increased and the media (p = 0.028) is significant smaller in intra-acinar pulmonary vessels of the older Fontan patients (N = 7) compared with age-matched controls (N = 14). The age at death (r = 0.964; p = 0.000) and the duration of the Fontan circulation (r = 0.714; p = 0.036) are both significant positive correlated with intima thickness in the older Fontan group (N = 7). (Immuno) histochemistry showed severe intimal thickening of the intra-acinar pulmonary vessel wall, the composition of this intimal thickening is acellular fibrosis with collagen deposition. Conclusion: This study shows significant adverse pulmonary vascular remodeling of the intra-acinar pulmonary vessels in the Fontan circulation in which chronic non-pulsatile flow is present. The adverse pulmonary vascular remodeling consists out of media involution combined with accelerated age-associated intimal fibrosis with collagen deposition.

Item Type:	Thesis (Thesis)
Supervisor name:	Berger, Prof. dr. R.M.F.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:03
Last Modified:	25 Jun 2020 11:03
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2324

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