Arrhythmogenesis in acute myocardial infarction (MI) is associated with depolarization of resting membraine potential (RMP) and decrease of inward rectifier potassium current (IK1) in cardiomyocytes. However, clinical anti-arrhythmic agents that primarily act on RMP by enhancing the IK1 channel are not currently available. We hypothesized that zacopride, a selective and moderate agonist of the IK1/Kir2.1 channels, prevents and cures acute ischemic arrhythmias. To test this viewpoint, adult Sprague-Dawley (SD) rats were subjected to MI by ligating the left main coronary artery. The antiarrhythmic effects of zacopride (i.v. infusion) were observed in the settings of pre-treatment (zacopride given 3 min prior to coronary occlusion), post-treatment (zacopride given 3 min after coronary occlusion) and therapeutic treatment (zacopride given 30 s after the onset of the first sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) post MI). In all the three treatment modes, zacopride (15 μg/kg) inhibited MI-induced ventricular tachyarrhythmias, as shown by significant decreases in the premature ventricular contraction (PVC) and the duration and incidence of VT or VF. In Langendorff perfused rat hearts, the antiarrhythmic effect of 1 μmol/L zacopride were reversed by 1 μmol/L BaCl2, a blocker of IK1 channel. Patch clamp results in freshly isolated rat ventricular myocytes indicated that zacopride activated the IK1 channel and thereby reversed hypoxia-induced RMP depolarization and action potential duration (APD) prolongation. In addition, zacopride (1 μmol/L) suppressed hypoxia- or isoproterenol- induced delayed afterdepolarizations (DADs). In Kir2.x transfected Chinese hamster ovary (CHO) cells, zacopride activated the Kir2.1 homomeric channel but not the Kir2.2 or Kir2.3 channels. These results support our hypothesis that moderately enhancing IK1/Kir2.1 currents as by zacopride rescues ischemia- and hypoxia- induced RMP depolarization, and thereby prevents and cures acute ischemic arrhythmias. This study brings a new viewpoint to antiarrhythmic theories and provides a promising target for the treatment of acute ischemic arrhythmias.

Background: Optical coherence tomography (OCT)-defined suboptimal stent implantation characteristics at the culprit lesion of acute coronary syndrome (ACS) were demonstrated to be associated with adverse outcome. Purpose: This study sought to investigate the impact of pre-PCI culprit lesion morphological features and post-PCI suboptimal stent implantation characteristics obtained by OCT on device-oriented clinical endpoints (DoCE) of patients with ACS. Methods: Retrospective analysis was performed in 216 de novo coronary lesions in 209 patients with ACS who underwent OCT examinations before and after stent implantation. OCT analysis included plaque rupture, thin-capped fibroatheroma, and thrombus in pre-PCI OCT and malapposition, edge dissection, and irregular protrusion >500μm thickness in post-PCI OCT. DoCE were defined as cardiac death, target vessel-related myocardial infarction, target lesion revascularization, and stent thrombosis. Baseline clinical characteristics, angiographic findings, and OCT findings before and after PCI were analysed and compared between DoCE group and non-DoCE group. Follow-up data were collected to determine the predictors of DoCE. Results: Mean follow-up duration was 683±470 days. DoCE occurred in 21 lesions (9.7%) in total. There were no significant differences in baseline clinical characteristics and angiographic findings between the two groups except for the prevalence of bare-metal stent use (12/21, 57% vs 46/195, 24%, P<0.01). The prevalence of OCT-derived thin-cap fibroatheroma and ruptured plaque were similar between the two groups (10/21, 48% vs 79/195, 41%, P=0.53, 9/21, 43% vs 113/195, 58%, P=0.39, respectively). In post-PCI OCT, stent edge dissection was observed more frequently in DoCE group than in non-DoCE group (8/21, 38% vs 27/195, 14%, P<0.01). Intrastent irregular protrusion (protrusion height >500μm) was more frequently observed in DoCE group than in non-DoCE group (11/21, 52% vs 50/195, 26%, P=0.01). Cox-proportional hazard analysis showed that bare-metal stents (hazard ratio [HR] 3.36; 95% confidence interval [CI] 1.41-7.99; P<0.01), post-PCI OCT findings of edge dissection (HR 3.22; 95% CI 1.33-7.77; P<0.01), and intrastent irregular protrusion (HR 3.00; 95% CI 1.27-7.09; P=0.01) were associated with DoCE independent of pre-PCI OCT parameters. Conclusions: Stent type and post-PCI OCT findings more significantly influenced DoCE after ACS stent implantation than clinical characteristics, angiographic findings, and pre-PCT OCT-derived vulnerable plaque features. Background: Despite the well-described association between plaque morphology and acute coronary syndromes, there is limited in vivo evidence regarding the temporal evolution of non-culprit coronary plaque morphology. Purpose: We evaluated changes in non-culprit plaque morphology over time by optical coherence tomography (OCT). Methods: 119 patients had undergone serial OCT of the same vessel between 1/1/2009 and 31/8/2014. Among those, 72 patients with 257 non-culprit segments fitted the inclusion criter...

Data on risk factors and periprocedural complications associated with side branch (SB) occlusion after chronic coronary total occlusion (CTO) recanalization are limited. The aims of this study were to identify independent predictors of side branch (SB) occlusion after chronic total occlusion (CTO) recanalization and assess the relationship between SB occlusion and perioperative complications. 245 patients with CTO bifurcation lesions (BFLs) who underwent successful CTO recanalization were included in the study. In the occlusion group, most of the SB occlusions were observed after the implantation of the stents and lack of SB protection was more common. However, there was no significant between-group difference in the angles between the main vessel (MV) and SB. SB occlusion was associated with a higher risk of periprocedural myocardial infarction and a higher composite periprocedural complication rate. Identified as predictors of SB occlusion were no SB protection, use of a dissection-reentry strategy, ostial SB stenosis, and proximal MV stenosis of 50% or more.