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BACKGROUND AND PURPOSE: Inhibition of the G-protein gated acetylcholine-activated inward rectifier potassium (K+ ) current, IK,ACh , may be an effective atrial selective treatment strategy for atrial fibrillation. Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in an in vivo equine, atrial-tachypacing-induced model of persistent AF in the following.EXPERIMENTAL APPROACH: The in vitro ion channel pharmacological profile of XAF-1407, was investigated using cell lines stably expressing Kir 3.1/3.4, Kir 3.4/3.4, Kir 2.1, Kir 6.2/SUR2A, hERG, Kv 1.5, Kv 4.3 and Nav 1.5. A tachypacing induced model of persistent AF in the horse, a large animal model suited to pre-clinical investigations of longer duration AF, was employed to study the in vivo electrophysiological and anti-arrhythmic profile of XAF-1407. Eleven horses were implanted with implantable cardioverter defibrillators (ICD) enabling atrial-tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated at different time points over a period of one month. Cardioversion success, drug induced changes of atrial tissue refractoriness and ventricular electrophysiology were assessed at baseline (day 0) and at day 3, 5, 11, 17 and 29 after AF induction.KEY RESULTS: XAF-1407 potently and selectively inhibited Kir 3.1/3.4 hetero- and Kir 3.4 homotetramers, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period (aERP) as well as decreased atrial fibrillatory rate (AFR) significantly by approximately 20% and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened AV-nodal refractoriness, without effect on the QRS dura

Background Paranasal sinus cysts (PSC) are a common cause of equine secondary sinusitis. The outcome and associated complications have not been frequently reported. Objectives To review the associated clinical signs, associated morbidities and outcomes of horses treated for PSC. Study design Retrospective multicentre case series. Methods Retrospective analysis of case records and telephone follow up survey. Results Subjects were 37 horses 1–24 years old that were presented with nasal discharge (n = 31), facial swelling (n = 25) and epiphora (n = 19). Radiography and computed tomography allowed identification of the cyst‐induced changes including concomitant tissue destruction (n = 31), leading among other things to local nerve damage causing headshaking (n = 6) and unilateral blindness (n = 1). Radiographic changes to adjacent dental apices were present in 10 horses. Horses over 10 years old showed more of the named associated problems. Post‐operative complications included surgical site infection (SSI) (n = 11), nasofrontal suture periostitis (n = 6) and sequestration (n = 1) following removal of the PSC via osteotomy. The long‐term response to treatment was available for 28 cases with 22 horses (78.6%) fully cured, 4 (14.3%) partially cured and 2 (7.1%) not responding to treatment. In 7 horses (18.9%) there was recurrence of the cyst post‐operatively. Main limitations Due to the study being a multicentre retrospective case series with collection of data over an extended period, there may be inconsistency in data recording and absence of reporting of some findings. Conclusions Overall, the diagnosis and treatment of sinus cysts is relatively straightforward and carries a good prognosis. In long‐standing cases complications secondary to the expansive growth of cysts will dramatically affect the prognosis for full recovery due to pressure‐induced changes to facial bones, cheek