Reducing myocardial infarct size: challenges and future opportunities

Abstract

Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is ‘myocardial reperfusion injury’, a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies—however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury.

Time to Give Up on Cardioprotection?

“…The translation of cardioprotection by the conditioning phenomena and by drugs that recruit part of their signaling to the clinical arena has been difficult to date. [13][14][15][16][17][18][19] Although there are several positive proof-of-concept studies for each of the conditioning phenomena, no phase III study has yet reported a better clinical outcome as the primary end point. With the neutral results of 2 recent phase III trial in cardiosurgical patients, that is, ERICCA (Effect of Remote Ischemic Preconditioning on Clinical Outcomes in CAGB Surgery) 37 and RIPHeart (Remote Ischemic Preconditioning in Heart Surgery), 38 and also a number of recent neutral trials which used drugs to recruit signaling steps of the conditioning phenomena in patients with AMI, that is, CIRCUS (Does Cyclosporine Improve Clinical Outcome in ST Elevation Myocardial Infarction Patients) 39 and CYCLE (Cyclosporine A in Reperfused Myocardial Infarction), 40 disappointment and frustration prevail.…”

“…[10][11][12] Therefore, additional interventions and treatments on top of timely reperfusion are still needed to reduce infarct size and improve the clinical outcome of patients with AMI. [13][14][15][16][17][18][19][20] Apart from acute STEMI (type 1 myocardial infarction), additional cardioprotection is also sought in elective PCI with the aim to reduce periprocedural myocardial infarction (type 4a) and in surgical coronary revascularization with the aim to reduce perioperative myocardial infarction (type 5) 21 ; in some studies, cardioprotection was also sought in major cardiovascular surgery other than coronary artery bypass grafting (CABG).…”

Qiliqiangxin attenuates hypoxia‐induced injury in primary rat cardiac microvascular endothelial cells via promoting HIF‐1α‐dependent glycolysis

“…It is known that cardiac microvascular endothelial cells (CMECs) directly mediate the exchange of substance and energy between microcirculation and myocardial tissue and thus serve as the essential elements responsible for maintaining the normal myocardial tissue metabolism 2. Hypoxia‐induced CMECs injury is considered as an initiating process and pathological basis of various cardiovascular diseases,3 and protecting CMECs from hypoxia insult might thus be an important therapeutic strategy for treating various cardiovascular diseases 4.…”

Protein Kinase C Epsilon PeptideInhibitor Exerts Cardioprotective Effects in Myocardial Ischemia/Reperfusion Injury

“…Reperfusion is essential to salvage ischemic myocardial tissue from infarction. However, the re-establishment of blood flow to acutely ischemic myocardium leads to rapid cell death and compromised heart function [2]. The size of the infarct that results from the combination of the ischemic and reperfusion injury is the major determinant of the prognosis of patients who survive the acute myocardial infarction incident Page -02…”