Key result
Future cellular protection research requires improved experimental methodologies to better reflect clinical scenarios.
This workshop report highlights the parallels in cellular injury mechanisms across STEMI, ischaemic stroke, and cardio-oncology, emphasizing the need for improved experimental methodologies and multi-targeted strategies for cytoprotection.
May identify targets to limit cardiomyocyte loss; leaves open whether pathway modulation improves MI or stroke outcomes.
Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury.
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Davidson et al. (2018) conducted a review in Myocardial infarction, ischaemic stroke, and cardio-oncology. Cellular protection strategies (e.g., remote ischaemic conditioning) was evaluated. The 10th Hatter Cardiovascular Institute workshop concluded that future cellular protection research across myocardial infarction, ischaemic stroke, and cardio-oncology must improve experimental methodologies to better reflect clinical scenarios.
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