{
  "abstract": "Myocardial injury is a major global health issue, affecting 10-15% of community populations and over 50% of critically ill hospitalised patients. It involves damage to the myocardium and irreversible loss of cardiomyocytes (CMs). Elevated cardiac troponin levels reflect injury to the contractile machinery of CMs, leading to impaired force generation. Despite extensive research, no curative treatment exists—largely due to limitations in current experimental models.Animal models are costly, raise ethical concerns, and often lack translational relevance due to physiological differences from the human heart. In vitro models, though promising, also fall short. HiPSC-derived CMs remain structurally and electrophysiologically immature, while even mature human CMs quickly lose function in culture. Engineered heart tissues and single-cell systems cannot recapitulate the heart’s multicellular, metabolic complexity. Culture duration is often limited, restricting their ability to model myocardial injury progression.To address these gaps, we developed a human living myocardial slice (LMS) system that models injury and mechanical load in vitro. Cryoinjury was induced using a 3 mm dry ice-cooled probe, and isometric load was applied during culture using mechanical stretchers to mimic physiological condition. Contractile performance, measured by force transducer, was reduced in cryoinjured LMS on day 0 (p=0.01). After two days of isometric loading, cryoinjured LMS showed improved force (p=0.01), faster contraction (p=0.003), quicker relaxation (p=0.005), and increased arrhythmias (p=0.0002) (all N=3, n=11).This platform enables human-relevant investigation of early myocardial injury, remodelling, and progression, with potential to identify therapeutic targets for early intervention and recovery.References Chapman AR, Adamson PD, Mills NL. Assessment and classification of patients with myocardial injury and infarction in clinical practice. Heart 2017 Jan 1;103(1):10–18. doi: 10.1136/heartjnl-2016- 309530. Epub 2016 Nov 2. PMID: 27806987; PMCID: PMC5299097. Thygesen K, Alpert JS, JaUe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction (2018). Circulation. 2018 Nov 13;138(20):e618-e651. doi: 10.1161/CIR.0000000000000617. PMID: 30571511. Pitoulis FG, Watson SA, Perbellini F, Terracciano CM. Myocardial slices come to age: an intermediate complexity in vitro cardiac model for translational research. Cardiovasc Res. 2020 Jun 1;116(7):1275–1287. doi: 10.1093/cvr/cvz341. PMID: 31868875; PMCID: PMC7243278.",
  "authors": [
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "Parisa Keshtkar"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "Danika Heyman"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "Cesare Terracciano"
    }
  ],
  "title": "P31  In vitro study of myocardial injury using living human myocardial slices",
  "uid": "63c43b24-705f-50c5-994d-78d48fc76646"
}