Pharmaceutical Interventions for the Management of No-Reflow

Tim A. Fischell, MD

J Invasive Cardiol. 2008;20(7):374-379. 

In This Article

Etiology of Angiographic No-reflow

The exact pathophysiology underlying the no-reflow phenomenon is unknown, but is likely multifactorial. Potential mechanisms responsible for no-reflow include processes and mediators whose individual contribution to poor reperfusion may depend on the clinical or experimental setting, and ultimately on whether reperfusion is accomplished by thrombolysis or PCI ( Table 1 ).[11,17] "Angiographic" no-reflow, the type most often encountered by interventionalists during angioplasty or stent deployment, is partly an expression of vascular reperfusion injury, one of the major types of reperfusion abnormalities (others include lethal reperfusion injury, myocardial stunning and reperfusion dysrhythmia).[11,12,18,19]

Reperfusion injury is associated with extremely complex and interrelated phenomena, including production of oxygen free radicals, altered membrane permeability, capillary edema, modified calcium metabolism, complement activation, apoptosis and a degraded cellular ultrastructure facilitating progressive microvascular dysfunction despite removal of an upstream occlusion.[9,11,17,19,20,21]

While reperfusion injury per se may contribute to angiographic no-reflow, additional mechanisms are related directly to the introduction of a percutaneous device into a diseased native vessel or degenerated vein graft. Angioplasty causes plaque rupture, which in turn yields particulate and plaque debris to be showered downstream within seconds of balloon deflation.[22] Progressive microvascular impairment results from distal embolization of fragments, cholesterol crystals, microthrombi and other matter from dilated sites.[23,24] Additionally, complex homeostatic interactions between platelets and endothelial cells are disturbed by reperfusion. Stimulated by increased expression of endothelium-secreted cellular adhesion molecules or selectins from exposed postischemic coronary endothelial surfaces, occlusive platelet aggregates and leukocytes have direct involvement in the development of no-reflow in cardiac microvessels.[25]

Finally, vasoconstriction develops in response to soluble, potent vasoactive substances contained in effluent released from target sites during PCI, or elaborated following local activation of platelet- or endothelium-derived factors within the arteriolar bed. This has emerged as a critically important mechanism for no-reflow, with good evidence to suggest that intense microvascular spasm plays a key role in most cases of angiographic no-reflow, particularly in elective SVG PCI.[26,27]


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