Recurrent episodes of airway obstruction, hypoxemia and pulmonary hypertension (PH) are present during exacerbations of severe equine asthma (SEA). Pulmonary hypoxic vasoconstriction is known to contribute to the development of PH, which may lead to cor pulmonale. However, as PH is only partially reversible by oxygen administration, other etiological factors are likely to be involved. In human chronic obstructive pulmonary disease, pulmonary artery (PA) remodeling contributes to the development of PH. Furthermore, allergic airway inflammation results in remodeling of pulmonary vasculature in mouse models, suggesting that similar findings may be present in asthma. We therefore postulated that PA remodeling is present in SEA and contributes to PH. The project aimed to investigate 1) the presence of PA remodeling in severe equine asthma and its distribution throughout the lungs, 2) the involvement of vascular smooth muscle (VSM) alterations, and 3) their reversibility following long-term antigen avoidance strategies or inhaled corticosteroids administration. Using histomorphometry and tissue bank (ERTB) lung samples, the PA wall was measured on sections stained with hematoxylin-eosin saffron, collected post-mortem from different lung regions of 12 asthmatic horses and 6 age-matched controls. Pulmonary vascular smooth muscle (VSM) mass was also measured on sections stained for α-smooth muscle actin collected with in vivo thoracoscopy or post-mortem peripheral lung biopsy from 5 controls, 6 asthmatic horses in remission, and 11 asthmatic horses while exacerbation and after 1 year of antigen avoidance alone (5 horses) or treatments with fluticasone (6 horses). Data were compared using one tailed unpaired t tests with Welch correction or paired t tests (p<0.05). Increased PA wall surface was detected in apical (p=0.002) and caudodorsal (p=0.03) lung regions of asthmatic horses in both exacerbation and remission, when compared to controls. The VSM mass was similarly increased (p=0.03) when compared to controls. A tendency for a normalization of the VSM mass was observed after treatment with antigen avoidance (p=0.05), but not with fluticasone (p=0.27). Remodeling of the PA develops in SEA and is associated with an increase in VSM. The resulting narrowing of the lumen of the PA could enhance hypoxic vasoconstriction, contributing to PH during exacerbation of SEA. VSM mass normalization is better achieved by antigen avoidance than by corticosteroids.
PULMONARY ARTERY REMODELING IN SEVERE EQUINE ASTHMA / S. Ceriotti ; supervisor: F. Ferrucci ; co-supervisor: J. P. Lavoie. - Milano : Università degli studi di Milano. Università degli Studi di Milano, 2018 Mar 27. ((30. ciclo, Anno Accademico 2017.
|Titolo:||PULMONARY ARTERY REMODELING IN SEVERE EQUINE ASTHMA|
|Supervisori e coordinatori interni:||FERRUCCI, FRANCESCO|
|Data di pubblicazione:||27-mar-2018|
|Parole Chiave:||equine asthma; vascular remodeling; pulmonary hypertension|
|Settore Scientifico Disciplinare:||Settore VET/08 - Clinica Medica Veterinaria|
|Citazione:||PULMONARY ARTERY REMODELING IN SEVERE EQUINE ASTHMA / S. Ceriotti ; supervisor: F. Ferrucci ; co-supervisor: J. P. Lavoie. - Milano : Università degli studi di Milano. Università degli Studi di Milano, 2018 Mar 27. ((30. ciclo, Anno Accademico 2017.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.13130/ceriotti-serena_phd2018-03-27|
|Appare nelle tipologie:||Tesi di dottorato|