Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope

Abstract

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Timely reperfusion with primary percutaneous coronary intervention (PPCI) remains the gold standard in patients presenting with ST-segment elevation myocardial infarction (STEMI), limiting infarct size, preserving left ventricular ejection fraction (LVEF), and improving clinical outcomes. Despite this, a significant proportion of STEMI patients develop post-infarct heart failure. We review the current understanding and up-to-date evidence base for therapeutic intervention of ischaemia-reperfusion injury (IRI), a combination of myocardial ischaemia secondary to acute coronary occlusion and reperfusion injury leading to further myocardial injury and cell death. Multiple treatment modalities have been shown to be cardioprotective and reduce IRI in experimental animal models. Recent phase II/III randomised controlled trials (RCT) have assessed multiple cardioprotective strategies ranging from ischaemic conditioning, therapeutic hypothermia and hyperoxaemia to pharmacological therapies. While several therapies have been shown to reduce infarct size in animal models or proof-of-concept studies, many larger scale trial results have proven inconsistent and disappointing. Hard clinical outcomes remain elusive. We discuss potential reasons for the difficulties in translation to clinical practice.

ST-segment Elevation Myocardial Infarction and Primary Percutaneous Coronary Intervention: Can We Go Beyond the Clock?

“…Furthermore, recognizing 2 distinct patient profiles in terms of development of myocardial necrosis independently of ischemia time may offer an explanation for failure in studies of cardioprotection in acute-phase STEMI, [17][18][19][20] in which case it may be useful to go back to the initial ECGs in these trials and perform a posteriori stratification according to QRS score.…”

Enhancing mitochondrial pyruvate metabolism ameliorates myocardial ischemic reperfusion injury

“…Acute myocardial infarction (AMI) is a major public health problem and a principal cause of heart failure (HF), which is a leading cause of mortality worldwide [1][2][3] . The standard of care for AMI patients is primary percutaneous coronary intervention (PPCI) to reperfuse and restore oxygenated blood flow to the ischemic myocardium 4,5 .…”

“…It is estimated that reperfusion injury accounts for ~50% of the final infarct after an AMI 4,6 . Despite decades of research, there are no pharmacological interventions that have been successfully translated into routine clinical practice to alleviate the detrimental effects of I/R injury [7][8][9] .…”

“…Acute myocardial infarction (AMI) is a major public health problem and a principal cause of heart failure (HF), which is a leading cause of mortality worldwide 1–3 . The standard of care for AMI patients is primary percutaneous coronary intervention (PPCI) to reperfuse and restore oxygenated blood flow to the ischemic myocardium 4, 5 . Paradoxically, PPCI is accompanied by reperfusion injury, which exacerbates tissue injury and increases cardiomyocyte death resulting in a reduction of salvageable myocardium.…”

Editorial: Hyperglycemia and Coronary Artery Diseases: Physio-Pathological Findings and Therapeutic Implications

“…However, treatment with insulin has shown contradictory results. Despite data from monocentric studies, non-randomized clinical trials, and a meta-analysis suggesting the benefits of treatment with insulin, larger randomized control trials have failed to confirm improved survival ( Vergès et al, 2012 ; Singh et al, 2015 ; He et al, 2022 ). Therefore, the hyperglycemia treatment during STEMI remains unclear.…”