Aims To assess the occurrence of a histologically validated measure of transmural (TM) atrial ablation -pure R unipolar electrogram (UE) morphology change -at first-ablated left atrial posterior wall (LAPW) sites during contact force (CF)-guided pulmonary vein isolation (PVI). significantly greater impedance drop (median 13.5Ω versus 9.9Ω; p=0.003). Importantly, neither the first-site RF duration (14.9 versus 15.0s) nor the maximum ablation catheter tip distance moved (during RF) were significantly different, yet the mean CF was significantly higher at right-sided sites (16.5g versus 11.2g; p=0.002). Concurrent impedance and objectively annotated bipolar electrogram (BE) data demonstrated ~6-8Ω impedance drop and ~30% BE decrease at the time of first pure R UE morphology change. Methods and results ConclusionUsing objective ablation site annotation, TM UE morphology change was typically achieved within 7s at the LAPW, with significantly greater ablative effect evident at left-sided sites. The methodology described in this report represents a novel and scientifically more rigorous foundation towards future research into the biological effects of RF ablation in vivo.. CC-BY-NC-ND4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/234799 doi: bioRxiv preprint first posted online Dec. 15, 2017; 3 KeywordsAtrial fibrillation; contact force catheter ablation; pulmonary vein isolation; unipolar electrogram; VISITAG™ Module . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/234799 doi: bioRxiv preprint first posted online Dec. 15, 2017; 4 Condensed abstractThrough appropriate use of the VISITAG™ Module and CARTOREPLAY™, unipolar electrogram morphology change indicative of histologically confirmed transmural atrial ablation in animal models, was proven to occur typically within 7s, during first-site contact force-guided ablation at the left atrial posterior wall during pulmonary vein isolation.. CC-BY-NC-ND4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/234799 doi: bioRxiv preprint first posted online Dec. 15, 2017; 5What's New?• The VISITAG™ Module provides objective, automated ablation site annotation and may be used to record and identify biophysical parameters at positions of stable radiofrequency (RF) energy delivery in vivo.• CARTOREPLAY™ permits electrogram analyses at annotated sites; together, these modules permit evaluation of histologically validated unipolar electrogram (UE) criteria for transmural (TM) atrial ablation, following pulmonary vein isolation (PVI).• At first-ablated left atrial posterior wall sites, RF-induced UE morphology change from RS to pure R occurred in 98%. The time to pure R UE morphology change w...

Solutions of synthetic fecapentaene 12 (FP-12) intended for carcinogenicity studies were found to decompose extremely rapidly during customary dosage procedures. Apparent half-lives as short as 15 min were observed. While rates and even the qualitative course of decomposition were surprisingly variable in replicate experiments, high concentration and exposure to air were confirmed to be especially important destabilizing influences. The results suggested a primary role for a radical decomposition mechanism in the presence of atmospheric oxygen. Consistent with this hypothesis, FP-12 solutions were significantly stabilized by the radical chain-breaking antioxidant vitamin E. On the other hand, dithiothreitol greatly destabilized FP-12, presumably because of its nucleophilicity. The diacetyl diester of FP-12 was more soluble than the parent diol, but its decomposition rates in the presence and absence of vitamin E were similar to those of unesterified FP-12. Ultraviolet irradiation of an all-trans-FP-12 solution decreased its concentration by 70% in 0.5 min. The mutagenicities of the decomposition/isomerization products of FP-12, as studied in Salmonella typhimurium tester strain TA 100, ranged from negligible to comparable with all-trans-FP-12 itself. It is concluded that unchecked decomposition of fecapentaene preparations can profoundly affect biological tests therewith. While this can be largely controlled through the use of rigorous precautions, including protection from air, light, nucleophiles, and acids as well as selection of the lowest concentration compatible with the application at hand, the data argue strongly for inclusion of appropriate quality control measures in all future dosing operations to prove that the biological activity reported is that of the fecapentaene itself rather than that of a decomposed dosing solution.