Accumulation of intracellular lipid may contribute to defective insulin secretion in type 2 diabetes. Although Zucker diabetic fatty (ZDF; fa/fa) rat islets are fat-laden and overexpress the lipogenic master gene, sterol regulatory element binding protein 1c (SREBP-1c), the contribution of SREBP-1c to the secretory defects observed in this model remains unclear. Here we compare the gene expression profile of lean control ( fa/+) and ZDF rat islets in the absence or presence of dominant-negative SREBP-1c (SREBP-1c DN). ZDF islets displayed elevated basal insulin secretion at 3 mmol/l glucose but a severely depressed response to 17 mmol/l glucose. While SREBP-1c DN reduced basal insulin secretion from ZDF islets, glucose-stimulated insulin secretion was not improved. Of 57 genes differentially regulated in ZDF islets and implicated in glucose metabolism, vesicle trafficking, ion fluxes, and/or exocytosis, 21 were upregulated and 5 were suppressed by SREBP-1c DN. Genes underrepresented in ZDF islets were either unaffected ( Glut-2, Kir6.2, Rab3), stimulated (voltage-dependent Ca2+ channel subunit α1D, CPT2, SUR2, rab9, syt13), or inhibited ( syntaxin 7, secretogranin-2) by SREBP-1c inhibition. Correspondingly, SREBP-1c DN largely corrected decreases in the expression of the transcription factors Pdx-1 and MafA but did not affect the abnormalities in Pax6, Arx, hepatic nuclear factor-1α (HNF1α), HNF3β/Forkhead box-a2 (Foxa2), inducible cyclic AMP early repressor (ICER), or transcription factor 7-like 2 (TCF7L2) expression observed in ZDF islets. We conclude that upregulation of SREBP-1c and mild increases in triglyceride content do not explain defective glucose-stimulated insulin secretion from ZDF rats. However, overexpression of SREBP-1c may contribute to enhanced basal insulin secretion in this model.
ABSTRACT. This was a retrospective, single-center, single-operator study examining the safety, feasibility, and short-term efficacy of treating patients with predominantly persistent atrial fibrillation (AF) undergoing pulmonary vein isolation (PVI) with or without cavo-tricuspid isthmus (CTI) ablation by a first-year electrophysiologist (EP) with and without fluoroscopy. The study included 72 consecutive patients undergoing PVI for symptomatic drug refractory paroxysmal (30%) and persistent (70%) AF from August 1, 2015 to August 1, 2016. Fifty-two patients who underwent traditional PVI (30 with radiofrequency (RF) and 22 with cryoablation) with fluoroscopy were compared to 20 patients who underwent RF PVI without fluoroscopy. RF PVI utilized the CARTO s 3-D mapping system (Biosense Webster Inc, Diamond Bar, CA) with a contact force-sensing catheter. All transseptal access was achieved with intracardiac ultrasound (ICE). More patients in the NO fluoroscopy group had coronary artery disease (CAD), but there were no significant differences for other clinical variables. Overall, procedure time was less in the NO fluoroscopy group despite similar ablation times. There was no significant difference in complication rates including vascular complications, tamponade, stroke, and death. Maintenance of sinus rhythm was the same in both groups (70% in the Fluoro group and 68% in the NO Fluoro group). AF ablation with PVI in predominantly persistent patients using RF with NO fluoroscopy in a new operator is feasible and safe with similar short-term efficacy with 3-D electroanatomic mapping in conjunction with contact force-sensing catheters.
Regular atrial tachycardia (AT) is one of the most important proarrhythmic complications that may occur following left atrial pulmonary vein isolation (PVI). These tachycardias that develop after atrial fibrillation ablation may lead to worse symptoms than those from the original arrhythmia existing prior to the index ablation procedure. Ablation of various types of supraventricular tachycardias without the use of fluoroscopy has been shown to be feasible in both children and adults using three-dimensional mapping systems. We describe the case of a 71-yearold woman who developed a focal AT after a successful PVI procedure. The initial ablation failed with one mapping system. Repeat electrophysiologic study despite antiarrhythmic medications revealed the same focal AT, which was successfully ablated with a different mapping system. Both ablations were performed without fluoroscopy.
We present the first ever reported case of a super morbidly obese patient (BMI > 70) with drug refractory, symptomatic atrial flutter who underwent a successful, uncomplicated ablation procedure using a zero fluoroscopy technique. This case demonstrates the following two critical points: (1) difficulties in the treatment of massively obese patients with arrhythmias; (2) increased use of fluoroless ablation techniques.
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