{"doi":"10.1016/j.jacep.2024.03.027","title":"Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions","abstract":"BACKGROUND: Ventricular tachycardia (VT)/ventricular fibrillation (VF) rearrest after successful resuscitation is common, and survival is poor. A mechanism of VT/VF, as demonstrated in ex vivo studies, is when repolarization alternans becomes spatially discordant (DIS ALT), which can be enhanced by impaired gap junctions (GJs). However, in vivo spontaneous DIS ALT-induced VT/VF has never been demonstrated, and the effects of GJ on DIS ALT and VT/VF rearrest are unknown. OBJECTIVES: This study aimed to determine whether spontaneous VT/VF rearrest induced by DIS ALT occurs in vivo, and if it can be suppressed by preserving Cx43-mediated GJ coupling and/or connectivity. METHODS: We used an in vivo porcine model of resuscitation from ischemia-induced cardiac arrest combined with ex vivo optical mapping in porcine left ventricular wedge preparations. RESULTS: In vivo, DIS ALT frequently preceded VT/VF and paralleled its incidence at normal (37°C, n = 9) and mild hypothermia (33°C, n = 8) temperatures. Maintaining GJs in vivo with rotigaptide (n = 10) reduced DIS ALT and VT/VF incidence, especially during mild hypothermia, by 90% and 60%, respectively (P < 0.001; P < 0.013). Ex vivo, both rotigaptide (n = 5) and αCT11 (n = 7), a Cx43 mimetic peptide that promotes GJ connectivity, significantly reduced DIS ALT by 60% and 100%, respectively (P < 0.05; P < 0.005), and this reduction was associated with reduced intrinsic heterogeneities of action potential duration rather than changes in conduction velocity restitution. CONCLUSIONS: These results provide the strongest in vivo evidence to date suggesting a causal relationship between spontaneous DIS ALT and VT/VF in a clinically realistic scenario. Furthermore, our results suggest that preserving GJs during resuscitation can suppress VT/VF rearrest.","journal":"JACC. Clinical electrophysiology","year":2024,"id":455846,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1236957,"name":"Joseph S. Piktel","orcid":"0000-0003-0362-7100","position":1,"is_corresponding":false},{"id":1264548,"name":"Laken Irish","orcid":null,"position":2,"is_corresponding":false},{"id":1271358,"name":"Michelle Nassal","orcid":"0000-0003-2123-2452","position":3,"is_corresponding":false},{"id":1280313,"name":"Aurelia Cheng","orcid":null,"position":4,"is_corresponding":false},{"id":1280314,"name":"Matthew McCauley","orcid":null,"position":5,"is_corresponding":false},{"id":1280315,"name":"G Pawłowski","orcid":null,"position":6,"is_corresponding":false},{"id":759092,"name":"Adrienne T. Dennis","orcid":null,"position":7,"is_corresponding":false},{"id":1280316,"name":"Yi Suen","orcid":null,"position":8,"is_corresponding":false},{"id":1264136,"name":"Soufian Almahameed","orcid":"0000-0003-1603-2886","position":9,"is_corresponding":false},{"id":728349,"name":"Ohad Ziv","orcid":"0000-0001-7515-9970","position":10,"is_corresponding":false},{"id":467137,"name":"Robert G. Gourdie","orcid":"0000-0001-6021-0796","position":11,"is_corresponding":false},{"id":1237407,"name":"Lance D. Wilson","orcid":null,"position":12,"is_corresponding":false},{"id":728353,"name":"Kenneth R. Laurita","orcid":"0000-0002-6341-9656","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:22.974789Z","pmid":"38752959","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}