Structural and Electroanatomical Characterisation of the Equine Pulmonary Veins: Implications for Atrial Fibrillation

Introduction/objectives: Spontaneous pulmonary vein (PV) activity triggers atrial fibrillation (AF) in humans. Although AF frequently occurs in horses, the origin remains unknown. This study investigated the structural and electro-anatomical properties of equine PVs to determine the potential presence of an arrhythmogenic substrate. Animals, materials and methods: Endocardial three-dimensional electro-anatomical mapping (EnSite Precision) using high-density (HD) catheters was performed in 13 sedated horses in sinus rhythm. Left atrium (LA) access was obtained retrogradely through the carotid artery. Post-mortem, tissue was harvested from the LA, right atrium (RA), and PVs for histological characterization and quantification of ion channel expression using immunohistochemical analysis. Results: Geometry, activation maps, and voltage maps of the PVs were created and a median of four ostia were identified. Areas of reduced conduction were found at the veno-atrial junction. The mean myocardial sleeve length varied from 28 13 to 49 22 mm. The PV voltage was 1.2 1.4 mV and lower than the LA (3.4 0.9 mV, P < 0.001). The fibrosis percentage was higher in PV myocardium (26.1 6.6 %) than LA (14.5 5.0 %, P ¼ 0.003). L-type calcium channel (CaV1.2) expression was higher in PVs than LA (P ¼ 0.001). T-type calcium channels (CaV3.3), connexin-43, ryanodine receptor-2, and small conductance calcium-activated potassium channel-3 was expressed in PVs. Conclusions: The veno-atrial junction had lower voltages, increased structural heterogeneity and areas of slower conduction. Myocardial sleeves had variable lengths, and a different ion channel expression compared to the atria. Heterogeneous properties of the PVs interacting with the adjacent LA likely provide the milieu for re-entry and AF initiation.S.T. Kjeldsen, S.D. Nissen, A. Saljic, E.M. Hesselkilde, H. Carstensen, S.M. Sattler, T. Jespersen, D. Linz, C. Hopster-Iversen, R. Kutieleh, P. Sanders, R. Buh

Characterization of spontaneous air space enlargement in mice lacking microfibrillar-associated protein 4

Microfibrillar-associated protein 4 (MFAP4) is localized to elastic fibers in blood vessels and the interalveolar septa of the lungs and is further present in bronchoalveolar lavage. Mfap4 has been previously suggested to be involved in elastogenesis in the lung. We tested this prediction and aimed to characterize the pulmonary function changes and emphysematous changes that occur in Mfap4 deficient (Mfap4-/-) mice. Significant changes included increases in total lung capacity and compliance, which were evident in Mfap4-/- mice at 6 months and 8 months, but not at 3 months of age. Using in vivo breath-hold gated micro-computed tomography (micro-CT) in 8-month-old Mfap4-/- mice, we found that the mean density of the lung parenchyma was decreased, and the low-attenuation area (LAA) was significantly increased by 14 % compared to Mfap4+/+ mice. Transmission electron microscopy (TEM) did not reveal differences in the organization of elastic fibers, and there was no difference in elastin content, but borderline significant increase in elastin mRNA expression in 3-month-old mice. Stereological analysis showed that alveolar surface density in relation to the lung parenchyma and total alveolar surface area inside of the lung were both significantly decreased in Mfap4-/- mice by 25 % and 15 %, respectively. The data did not support an essential role of MFAP4 in pulmonary elastic fiber organization or content, but indicated increased turnover in young Mfap4-/- mice. However, Mfap4-/- mice developed a spontaneous loss of lung function, which was evident at 6 months of age, and moderate airspace enlargement, with emphysema-like changes