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Myocardial ischaemia-reperfusion injury and cardioprotection in perspective
1Institute for Pathophysiology, West German Heart and Vascular Center, University of Duisburg-Essen, Essen, Germany. gerd.heusch@uk-essen.de.
Insights
Cardioprotective strategies aim to reduce heart attack size, but clinical translation lags. Future trials should target specific patient groups and consider broader outcomes beyond infarct size reduction.
Area of Science:
- Cardiology
- Cellular Biology
- Pathophysiology
Background:
- Acute myocardial infarction (AMI) treatment relies on reperfusion, yet morbidity and mortality remain high.
- Myocardial infarct size is a key prognostic factor, driving the search for cardioprotective strategies.
- A significant gap exists between preclinical infarct size reduction findings and clinical outcomes.
Purpose of the Study:
- To review the pathophysiology of myocardial ischemia-reperfusion injury.
- To discuss mechanical and pharmacological cardioprotective strategies and their clinical translation challenges.
- To advocate for additive cardioprotective interventions and refined clinical trial designs.
Main Methods:
- Review of preclinical and clinical research on cardioprotection in myocardial infarction.
- Discussion of the pathophysiology, including autophagy and cell death pathways (necrosis, apoptosis, necroptosis, pyroptosis).
- Analysis of signal transduction pathways involved in cardioprotection and coronary microcirculation.
Main Results:
- Ischemia-reperfusion injury involves complex cellular mechanisms beyond cardiomyocytes.
- Many interventions show promise in preclinical settings but fail to translate to improved clinical outcomes.
- Effective cardioprotection requires considering factors like age, comorbidities, and microvascular obstruction.
Conclusions:
- Translating cardioprotective strategies requires addressing infarct size, microvascular obstruction, and long-term repair.
- Future trials should focus on high-risk patients with severe hemodynamic alterations.
- Additive cardioprotective interventions are crucial for improving patient outcomes in acute myocardial infarction.
Abstract:
Despite the increasing use and success of interventional coronary reperfusion strategies, morbidity and mortality from acute myocardial infarction are still substantial. Myocardial infarct size is a major determinant of prognosis in these patients. Therefore, cardioprotective strategies aim to reduce infarct size. However, a perplexing gap exists between the many preclinical studies reporting infarct size reduction with mechanical and pharmacological interventions and the poor translation into better clinical outcomes in patients. This Review revisits the pathophysiology of myocardial ischaemia-reperfusion injury, including the role of autophagy and forms of cell death such as necrosis, apoptosis, necroptosis and pyroptosis. Other cellular compartments in addition to cardiomyocytes are addressed, notably the coronary microcirculation. Preclinical and clinical research developments in mechanical and pharmacological approaches to induce cardioprotection, and their signal transduction pathways, are discussed. Additive cardioprotective interventions are advocated. For clinical translation into treatments for patients with acute myocardial infarction, who typically are of advanced age, have comorbidities and are receiving several medications, not only infarct size reduction but also attenuation of coronary microvascular obstruction, as well as longer-term targets including infarct repair and reverse remodelling, must be considered to improve patient outcomes. Future clinical trials must focus on patients who really need adjunct cardioprotection, that is, those with severe haemodynamic alterations.
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