Catheter-tissue contact optimizes pulsed electric field ablation with a large area focal catheter.

INTRODUCTION: Pulsed electric field (PEF) ablation relies on the intersection of a critical voltage gradient with tissue to cause cell death. Field-based lesion formation with PEF technologies may still depend on catheter-tissue contact (CTC). The purpose of this study was to assess the impact of CTC on PEF lesion formation with an investigational large area focal (LAF) catheter in a preclinical model. METHODS: PEF ablation via a 10-spline LAF catheter was used to create discrete right ventricle (RV) lesions and atrial lesion sets in 10 swine (eight acute, two chronic). Local impedance (LI) was used to assess CTC. Lesions were assigned to three cohorts using LI above baseline: no tissue contact (NTC: ≤∆10 Ω, close proximity to tissue), low tissue contact (LTC: ∆11-29 Ω), and high tissue contact (HTC: ≥∆30 Ω). Acute animals were infused with triphenyl tetrazolium chloride (TTC) and killed ≥2 h post-treatment. Chronic animals were remapped 30 days post-index procedure and stained with infused TTC. RESULTS: Mean (± SD) RV treatment sizes between LTC (n = 14) and HTC (n = 17) lesions were not significantly different (depth: 5.65 ± 1.96 vs. 5.68 ± 2.05 mm, p = .999; width: 15.68 ± 5.22 vs. 16.98 ± 4.45 mm, p = .737), while mean treatment size for NTC lesions (n = 6) was significantly smaller (1.67 ± 1.16 mm depth, 5.97 ± 4.48 mm width, p < .05). For atrial lesion sets, acute and chronic conduction block were achieved with both LTC (N = 7) and HTC (N = 6), and NTC resulted in gaps. CONCLUSIONS: PEF ablation with a specialized LAF catheter in a swine model is dependent on CTC. LI as an indicator of CTC may aid in the creation of consistent transmural lesions in PEF ablation.

Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation In Vitro.

Corneal opacification due to fibrosis is a leading cause of blindness worldwide. Fibrosis occurs from many causes including trauma, photorefractive surgery, microbial keratitis (infection of the cornea), and chemical burns, yet there is a paucity of therapeutics to prevent or treat corneal fibrosis. This study aimed to determine if andrographolide, a labdane diterpenoid found in Andrographis paniculate, has anti-fibrotic properties. Furthermore, we evaluated if andrographolide could prevent the differentiation of fibroblasts to myofibroblasts in vitro, given that the transforming growth factor beta-1(TGF-ß1) stimulated persistence of myofibroblasts in the cornea is a primary component of fibrosis. We demonstrated that andrographolide inhibited the upregulation of alpha smooth muscle actin (αSMA) mRNA and protein in rabbit corneal fibroblasts (RCFs), thus, demonstrating a reduction in the transdifferentiation of myofibroblasts. Immunofluorescent staining of TGF-ß1-stimulated RCFs confirmed a dose-dependent decrease in αSMA expression when treated with andrographolide. Additionally, andrographolide was well tolerated in vivo and had no impact on corneal epithelialization in a rat debridement model. These data support future studies investigating the use of andrographolide as an anti-fibrotic in corneal wound healing.