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Journal articleJones DG, Markides V, Chow AW, et al., 2017,
Characterization and consistency of interactions of triggers and substrate at the onset of paroxysmal atrial fibrillation.
, Europace, Vol: 19, Pages: 1454-1462, ISSN: 1099-5129Aims: Initiating mechanisms of atrial fibrillation (AF) remain poorly understood, involving complex interaction between triggers and the atrial substrate. This study sought to classify the transitional phenomena, hypothesizing that there is consistency within and between patients in trigger-substrate interaction during transition to AF. Methods and results: Non-contact left atrial (LA) mapping was performed in 17 patients undergoing ablation for paroxysmal AF. All had spontaneous ectopy. Left atrial activation from the first ectopic to established AF was examined offline to characterize the initiating and transitional sequence of activation. In 57 fully mapped spontaneous AF initiations in 8 patients, all involved interaction of pulmonary venous/LA triggers with a septopulmonary line of block (SP-LOB) also evident in sinus rhythm, by 4 different transitional mechanisms characterized by (i) continuous focal firing: AF resulted from fragmentation of each ectopic wavefront through gaps in the SP-LOB and persisted only while focal firing continued (n = 18/32%) (ii) transient focal firing, wavefront fragmentation at the SP-LOB produced wavelet re-entry that persisted after cessation of an initiating ectopic source (n = 12/21%), (iii) of two separate interacting ectopic foci (n = 15/26%), or from (iv) transiently stable macroreentry (n = 12/21%), around the SP-LOB extending to the LA roof, resulting in progressive wavefront fragmentation. It was found that 79 ± 22% of each of the initiations in individual patients showed the same triggering mechanism. Conclusion: Onset of paroxysmal AF can be described by discrete mechanistic categories, all involving interaction of ectopic activity with a common SP-LOB. Within/between-patient consistency of initiations suggests constancy of the interacting triggers and substrate, and supports the concept of mechanistically tailored treatment.
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Journal articleBagdadi AV, Safari M, Dubey P, et al., 2016,
Poly(3-hydroxyoctanoate), a promising new material for cardiac tissue engineering.
, Journal of Tissue Engineering and Regenerative Medicine, Vol: 12, Pages: e495-e512, ISSN: 1932-6254Cardiac tissue engineering (CTE) is currently a prime focus of research due to an enormous clinical need. In this work, a novel functional material, Poly(3-hydroxyoctanoate), P(3HO), a medium chain length polyhydroxyalkanoate (PHA), produced using bacterial fermentation, was studied as a new potential material for CTE. Engineered constructs with improved mechanical properties, crucial for supporting the organ during new tissue regeneration, and enhanced surface topography, to allow efficient cell adhesion and proliferation, were fabricated. Our results showed that the mechanical properties of the final patches were close to that of cardiac muscle. Biocompatibility of the P(3HO) neat patches, assessed using Neonatal ventricular rat myocytes (NVRM), showed that the polymer was as good as collagen in terms of cell viability, proliferation and adhesion. Enhanced cell adhesion and proliferation properties were observed when porous and fibrous structures were incorporated to the patches. Also, no deleterious effect was observed on the adults cardiomyocytes' contraction when cardiomyocytes were seeded on the P(3HO) patches. Hence, P(3HO) based multifunctional cardiac patches are promising constructs for efficient CTE. This work will provide a positive impact on the development of P(3HO) and other PHAs as a novel new family of biodegradable functional materials with huge potential in a range of different biomedical applications, particularly CTE, leading to further interest and exploitation of these materials.
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