Pathophysiology and Treatment of the No-Reflow Phenomenon in ST-Segment Elevation Myocardial Infarction: Focus on Low-Dose Fibrinolysis during Primary Percutaneous Intervention

Abstract

Primary percutaneous coronary intervention (PCI) is the current class I therapeutic approach to treat acute ST-elevation myocardial infarction (STEMI). While primary PCI can restore adequate flow in the infarcted artery in the majority of cases, some patients experience the 'no-reflow' phenomenon, i.e., an abnormal myocardial reperfusion occurring even after the occluded coronary artery has been opened. No-reflow occurs when microvascular obstruction arises from embolization of thrombus or components of the atheromatous plaques. These embolic materials travel downstream within the infarct-related artery at time of primary PCI, leading to compromised blood flow. Currently, no expert consensus documents exist to outline an optimal strategy to prevent or treat no-reflow. Interventional cardiologists frequently employ intracoronary adenosine, calcium channel blockers, nicorandil, nitroprusside or glycoprotein IIb/IIIa inhibitors. However, evidence suggests that these interventions consistently enhance myocardial blood flow in only a specific subset of patients experiencing no-reflow. A recent and innovative therapeutic approach gaining attention is low-dose fibrinolysis during primary PCI, which offers the potential to augment coronary flow post-myocardial revascularization.

Keywords: ST-elevation myocardial infarction; infarct-related artery; microvascular obstruction; no reflow; percutaneous coronary intervention.

Fig. 1.

Interacting mechanisms involved in the pathogenesis of coronary microvascular obstruction in humans (Reproduced with permission by Niccoli et al. [10] European Heart Journal (2016) 37, 1024–1033). ET-1, endothelin-1; TAX2, thromboxane A2.

Fig. 2.

Histological spectrum of thrombus characteristics at time of primary percutaneous coronary intervention. (A) The image displays a fresh thrombus with leukocytes, platelets, erythrocytes, and fibrin. (B) Here a stabilized thrombus is visible with lytic and organized areas, indicating that the thrombus is 1 to 2 days old. (C) In this picture, an organized thrombus is shown, demonstrating collagen deposition in the homogenized thrombus, indicating an older thrombus. Hematoxylin and eosin stains were used for tissue visualization. Bars = 150 µm (Reproduced with permission by Kramer et al. [21] Circulation. 2008;118:1810–1816).