No-reflow phenomenon in the heart and brain

Am J Physiol Heart Circ Physiol. 2018 Sep 1;315(3):H550-H562. doi: 10.1152/ajpheart.00183.2018. Epub 2018 Jun 8.


The no-reflow phenomenon refers to the observation that when an organ is made ischemic by occlusion of a large artery supplying it, restoration of patency in that artery does not restore perfusion to the microvasculature supplying the parenchyma of that organ. This has been observed after prolonged arterial occlusions in the heart (30-90 min), brain, skin, and kidney. In experimental models, zones of no reflow in the heart are characterized by ultrastructural microvascular damage, including focal endothelial swelling obstructing the lumen of small vessels. Blood elements such as neutrophil plugs, platelets, and stacking of erythrocytes have also been implicated. No reflow is associated with poor healing of the myocardial infarction. In patients, no reflow is associated with a poor clinical outcome independent of infarct size, suggesting that therapy for no reflow may be an important approach to improving outcome for ST elevation myocardial infarction. No reflow occurs after reperfusion of experimental cerebral ischemia and may be observed after only 5-min episodes of ischemia. Aggregation of blood elements may play a greater role than in cardiac no reflow. No reflow in the brain may involve cortical spreading depression with disturbed local vascular control and high, vasculotonic levels of extracellular K+ concentration, postischemic swelling in endothelial cells and abutting end feet of pericytes, pericyte contraction and death, interstitial edema with collapse of cerebral capillaries, and inflammatory reaction. New guidelines suggesting that reperfusion for stroke may be considered as late as 24 h after the onset of symptoms suggest that clinicians may be seeing more no reflow in the future.

Keywords: acute myocardial infarction; cerebrovascular accident; ischemia-reperfusion injury; no-reflow phenomenon; reperfusion; stroke.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / blood supply
  • Brain / physiopathology*
  • Coronary Vessels / physiopathology
  • Heart / physiopathology*
  • Humans
  • No-Reflow Phenomenon / physiopathology*
  • No-Reflow Phenomenon / therapy