The coronary circulation in acute myocardial ischaemia/reperfusion injury: a target for cardioprotection

Abstract

The coronary circulation is both culprit and victim of acute myocardial infarction. The rupture of an epicardial atherosclerotic plaque with superimposed thrombosis causes coronary occlusion, and this occlusion must be removed to induce reperfusion. However, ischaemia and reperfusion cause damage not only in cardiomyocytes but also in the coronary circulation, including microembolization of debris and release of soluble factors from the culprit lesion, impairment of endothelial integrity with subsequently increased permeability and oedema formation, platelet activation and leucocyte adherence, erythrocyte stasis, a shift from vasodilation to vasoconstriction, and ultimately structural damage to the capillaries with eventual no-reflow, microvascular obstruction (MVO), and intramyocardial haemorrhage (IMH). Therefore, the coronary circulation is a valid target for cardioprotection, beyond protection of the cardiomyocyte. Virtually all of the above deleterious endpoints have been demonstrated to be favourably influenced by one or the other mechanical or pharmacological cardioprotective intervention. However, no-reflow is still a serious complication of reperfused myocardial infarction and carries, independently from infarct size, an unfavourable prognosis. MVO and IMH can be diagnosed by modern imaging technologies, but still await an effective therapy. The current review provides an overview of strategies to protect the coronary circulation from acute myocardial ischaemia/reperfusion injury. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

Keywords: Cardioprotection; Coronary circulation; Ischaemia; Microvascular obstruction; Reperfusion.

Graphical Abstract

Figure 1

Potential mechanisms underlying capillary damage following AMI. During thrombotic coronary occlusion and interruption of flow, the endothelium shows morphological and functional changes, including swelling and blebbing and loss of endothelial junctions via release of angiopoietins and VEGF. Instantaneous opening of the coronary vessel by placement of a coronary stent induces additional damage leading to endothelial gaps, extravasation of erythrocytes, and intramyocardial haemorrhage. Figure modified with permission from Betgem et al.

Figure 2

Intramyocardial haemorrhage following AMI on cardiac MRI. (A) On T2-weighted images relaxation times and thus signal strength increase due to myocardial oedema formation after AMI (white arrow heads). In case of IMH, haemoglobin degradation products lead to a relative decrease in relaxation time, and thus a relative signal attenuation within the MI zone (black arrow heads). (B) On T2* images a relatively lower increase is observed with myocardial oedema (white arrow heads), and a relative higher decrease is observed upon IMH (black arrow heads), providing a stronger signal separation when compared with T2. (C) On LGE images the hypointense core indicates that no gadolinium entered the infarct core (yellow arrow heads). Overall infarct area is indicated by the hyperintense signal of the gadolinium that is retained within the tissue (white line). Note the large overlap between MVO as assessed by LGE and IMH as assessed by T2 and T2*. Figure modified with permission from Betgem et al.

Figure 3

Effects of acute myocardial ischaemia/reperfusion injury on the coronary vasculature, and therapeutic vascular targets for cardioprotection. This scheme depicts the diverse consequences of acute myocardial ischaemia/reperfusion injury on the coronary vasculature following acute myocardial infarction, and highlights the vascular targets of endogenous cardioprotective strategies (IPC, ischaemic preconditioning, IPost, ischaemic postconditioning, and RIC, remote ischaemic conditioning) and Pharmacological agents (Pharm). Figure modified with permission from Heusch et al.