{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:13:04Z","timestamp":1790885584370,"version":"4.1.0"},"reference-count":248,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008993","name":"University of Zagreb, Zagreb, Croatia","doi-asserted-by":"publisher","award":["10106-22-3071"],"award-info":[{"award-number":["10106-22-3071"]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>This review examines and hypothesizes cytoprotection as a conceptual therapeutic criterion for antiarrhythmic drugs, referring to the possibility of suppressing arrhythmias while avoiding adverse electrophysiological or systemic effects. Toward a theoretically complete cytoprotective profile\u2014preserving benefits and eliminating toxicity\u2014the criterion was the degree of counteraction of arrhythmias (i.e., bradycardia, tachycardia, atrioventricular (AV) block, ventricular tachycardia (VT), ST-segment changes, prolonged P, PR, QRS, and QT\/QTc intervals, and repolarization). Conventional and new antiarrhythmics share class I\u2013IV \u2248 partial cytoprotection\/narrow range; late INa inhibitors, IKs enhancers, RyR2 stabilizers, gap junction modulators, and atrial-selective antiarrhythmics \u2248 partial cytoprotection\/more extended range. Still predominantly in preclinical models, stable gastric pentadecapeptide BPC 157, in the clinic, has not demonstrated adverse effects in available human trials (non-cardiac) to date. As a prominent cytoprotection mediator (LD1 not achieved in toxicology studies), it demonstrates well-matched cytoprotective\u2013antiarrhythmic effects, BPC 157 \u2248 full cytoprotection\/wide-range homeostasis. In vivo, this was across models of hypo-\/hyperkalemia, hypermagnesemia, ischemia\u2013reperfusion, myocardial infarction, drug-induced arrhythmias (including local anesthetics), and vascular occlusion. BPC 157 restores sinus rhythm, normalizes P\/QRS\/QT intervals, prevents AV block, suppresses VT, attenuates ST-segment changes, and stabilizes heart rate, even when insults are advanced. In vitro, HEK293 studies confirm direct membrane-stabilizing actions: BPC 157 prevents hypokalemia-induced hyperpolarization, reduces hyperkalemia- and hypermagnesemia-induced depolarization, and mitigates local anesthetic-induced Na+\/Ca2+ dysregulation, reflecting bidirectional homeostatic modulation of membrane potential. Thus, to confirm the hypothesis, these BPC 157 conditional, not constitutive effects, in rodent models or in vitro systems (HEK293 cells), mandate expansion of now limited clinical data and mechanisms in human investigated as a translational cytoprotective strategy for complex arrhythmias.<\/jats:p>","DOI":"10.3390\/ph19020235","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:29:03Z","timestamp":1769693343000},"page":"235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Conventional Antiarrhythmics Class I\u2013IV, Late INa Inhibitors, IKs Enhancers, RyR2 Stabilizers, Gap Junction Modulators, Atrial-Selective Antiarrhythmics, and Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Therapy in Arrhythmias"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-2252","authenticated-orcid":false,"given":"Predrag","family":"Sikiric","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Barisic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Udovicic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8446-6120","authenticated-orcid":false,"given":"Martina","family":"Lovric 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