Immunohistochemical markers for dating cardiac conduction system injury: current knowledge and forensic implications

Abstract The postmortem timing of myocardial injury remains a major challenge in forensic pathology, particularly when conventional histological methods are insufficient during the early hours after an ischemic insult. We conducted a critical narrative review of immunohistochemical markers for myocardial injury dating, focusing on their biological applicability to the cardiac conduction system (CCS). The search was performed using PubMed and Scopus; no date restriction was applied. Over the past three decades, markers including complement components (C5b-9), cardiac troponins, fibronectin, and connexin 43 have been investigated, with varying degrees of validation, for injury dating in working ventricular myocardium. However, the CCS — comprising the sinoatrial node, atrioventricular node, bundle of His, and Purkinje fibers — is a histologically and molecularly distinct tissue that has received remarkably little attention in this context. We highlight fundamental differences in cellular composition, connexin expression profiles, extracellular matrix content, and baseline protein abundance between conduction and ventricular tissue that are likely to significantly alter marker behavior and temporal kinetics. The direct application of ventricular-based immunohistochemical timelines to the CCS lacks empirical support and may lead to forensic misinterpretation. The medico-legal implications are potentially significant, as accurate timing of conduction system injury is relevant to cases of sudden unexplained death, drug-induced arrhythmias, blunt cardiac trauma, and medical negligence litigation. Systematic, tissue-specific validation studies are urgently needed.