A stepwise approach to the induction of idiopathic fascicular ventricular tachycardia.

PURPOSE: Noninducibility of the clinical tachycardia is a major limitation while mapping and ablating idiopathic fascicular ventricular tachycardia (FVT). There is very little data on systematic induction protocols in this entity. Our aim was to study the role of systematic induction protocols in patients with clinically documented ventricular tachycardia (VT). METHODS: Programmed electrical stimulation was performed at baseline from high right atrium, right ventricular apex, right ventricular outflow tract and from left ventricle as per the protocol. Programmed ventricular stimulation was performed at two drive cycle lengths up to three extrastimuli and short-long-short sequence. If FVT remained non inducible at baseline, pharmacological provocation with isoprenaline/atropine/phenylephrine was used based on the baseline atrio-ventricular Wenckebach cycle length. RESULTS: This systematic induction protocol was studied in 68 patients with clinically documented FVT and sustained FVT was inducible in 64 patients (94 %). Of these 64 patients, pharmacological provocation was required in 18 patients (28 %) while in the remaining, sustained VT was induced at baseline. This high induction rate allowed ablation during tachycardia, which resulted in 100 % acute procedural success in the patients where sustained tachycardia could be induced. At a follow up of 29 ± 13 months, two patients (3 %) had recurrence. CONCLUSIONS: Systematic induction protocol along with the appropriate use of pharmacological agents results in a high induction rate of FVT. This may result in more defined and limited ablation during tachycardia with better success rates and lesser recurrence.

Synthetic curcumin analog UBS109 inhibits the growth of head and neck squamous cell carcinoma xenografts.

The natural compound curcumin has been investigated as an anticancer agent in many cellular systems, in animal models and in the clinic. The overriding negative characteristics of curcumin are its low solubility, weak potency and poor bioavailability. We have examined the efficacy and mechanism of action of a synthetic curcumin analog, UBS109, in head and neck squamous cell carcinoma. By nephelometry, this analog exhibits considerably greater solubility than curcumin. Pharmacokinetic studies of a single oral dose of UBS109 in mice revealed that peak plasma concentrations were reached at 0.5 hours post-dose (Tmax) with average plasma concentrations (Cmax) of 131 and 248 ng/mL for oral doses of 50 and 150 mg/kg, respectively. The terminal elimination half-lives (T½) for these doses averaged 3.7 and 4.5 hours, respectively. In both in vitro and in vivo studies, we found that UBS109 decreased the levels of phosphorylated IKKß and phosphorylated p65 and, unexpectedly, increased the levels of phosphorylated IκBα by Western blot analysis. These observations may suggest that UBS109 suppresses tumor growth through, in part, inhibition of NF-κB p65 phosphorylation by PKAc and not through IκBα. Finally, we demonstrate that UBS109 is efficacious in retarding the growth of Tu212 (head and neck) squamous cell carcinoma (SCC) xenograft tumors in mice and may be useful for treating head and neck SCC tumors.