Preclinical model could aid future research of NSTEMI therapies


Researchers have detailed a new preclinical model for non-ST elevation myocardial infarction (NSTEMI), which they hope will aid in the development of future strategies for the treatment of NSTEMI patients.

Published in Nature Communications in February, the preclinical model is the output of a research collaboration between CÚRAM SFI Research Centre for Medical Devices at the National University of Ireland Galway (Galway, Ireland) alongside University of Milano-Bicocca (Milan, Italy), University of Paris Est Créteil (Paris, France), University of Gothenburg (Gothenburg, Sweden) and the Lithuanian University of Health Sciences (Kaunas, Lithuania).

Patients who survive a heart attack have variable degrees of damage to their cardiac tissue, which can lead to heart failure. In the last two decades, NSTEMIs have markedly risen in hospitalised patients. NSTEMI results in a smaller amount of tissue damage compared to ST segment elevation myocardial infarction (STEMI), though recent clinical registry data shows that NSTEMIs are associated with higher long-term mortality than STEMIs.

Currently, preclinical models of heart attack mimic only full-thickness STEMI and hence cater only for an investigation into therapeutics and interventions directed at the NSTEMI subset of heart attack.

In this new study, researchers have developed a preclinical model of NSTEMI by adopting a novel surgical procedure in an ovine model that closely resembles the complexity of clinical cases in humans. Researchers validated the presented model by comparing it with an established method to achieve STEMIs. They performed a detailed analysis at the main acute and late time points after the induction of NSTEMI, at seven and 28 days, respectively.

Paolo Contessotto and Renza Spelat (both National University of Ireland Galway, Galway, Ireland), who were co-authors on the study, comment: “Advanced analyses on the affected heart tissue highlighted a distinctive pattern of alterations in the tissue, especially in the sugar moieties (glycans) which compose cardiac cell membranes and extracellular matrix (the network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body). Identifying such changes in molecular elements that can be accessed and treated with injectable drugs sheds light on how we can develop targeted pharmacological solutions to correct these changes.”

Adds Abhay Pandit, CÚRAM Scientific Director and senior author of the study: “There is a need in the field to adopt clinically relevant models to study NSTEMI pathophysiology and reveal its functional differences with STEMI induction. This new model will facilitate the translation of future research in the field, enabling the discovery of new clinically relevant treatments for patients.”

Mark Da Costa, Clinical Investigator at CÚRAM and senior author of the study, said: “Currently, NSTEMI is the most common presentation of acute heart attack. The concern is that NSTEMI patients have lower in-patient (during their admission for the primary NSTEMI) and short-term mortality rates but significantly higher long-term mortality than those of STEMI patients. A Danish registry study of 8,889 patients showed that the 5-year mortality after NSTEMI was 16%, and another registry study highlighted a 10-year survival rate of only around 50%. To the best of our knowledge, there are currently no models that can reproduce both the functional and histological characteristics of NSTEMIs. This novel model may specifically serve as a preclinical foundation to study interventions that could combat the short and long-term effects of NSTEMI.”


Please enter your comment!
Please enter your name here