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(Circulation. 2003;108:2911.)
© 2003 American Heart Association, Inc.

Basic Science Reports

No-Reflow Phenomenon Persists Long-Term After Ischemia/Reperfusion in the Rat and Predicts Infarct Expansion

From the Heart Institute, Good Samaritan Hospital, Division of Cardiovascular Medicine, University of Southern California, Los Angeles.

Correspondence to Robert A. Kloner, The Heart Institute, Good Samaritan Hospital, University of Southern California, 1225 Wilshire Blvd, Los Angeles, CA 90017. E-mail rkloner{at}goodsam.org

Received June 18, 2002; de novo received May 27, 2003; revision received August 8, 2003; accepted August 8, 2003.

Background— No-reflow after reperfusion therapy for myocardial infarction is a strong predictor of clinical outcome. But its fate on a long-term basis and potential significance for infarct healing are not yet known.

Methods and Results— Twenty-nine female Fisher rats were subjected to 60 minutes of coronary occlusion followed by reperfusion. At 4 weeks, 15 survivors were euthanized after measurement of regional myocardial blood flow (radioactive microspheres) and in vivo staining of perfused tissue (0.5 mL 50% Uniperse blue IV). Infarct size (34.3±3.4%), scar thickness (1.19±0.10 mm), and infarct expansion index (0.51±0.04) were assessed from histological sections (2 additional exclusions because of failed occlusion). Regional myocardial blood flow in the reperfused infarct was reduced significantly compared with noninfarcted tissue (1.98±0.47 versus 4.55±0.86 mL · min^-1 · g^-1, P<0.003, apical slice, and 1.77±0.44 versus 5.34±0.38 mL · min^-1 · g^-1, P<0.0001, second slice), accompanied by a striking reduction of perfused capillaries within the infarct (n=23±4 versus 163±8 in the noninfarcted tissue, P<0.0001, microscopically assessed as capillaries containing blue particles per high-power field). Macroscopically, no-reflow areas were visible in 9 of 13 hearts. The number of perfused capillaries within the infarct correlated significantly with infarct expansion index (r=-0.76, P<0.003), infarct thickness (r=0.60, P<0.03), and the ratio of infarct to septum thickness (r=0.74, P<0.004).

Conclusions— The no-reflow phenomenon persists for 1 month after reperfusion and predicts worse scar thinning and infarct expansion. Thus, one might shift the "open-artery" hypothesis downstream to an "open-microvessel" hypothesis, relating infarct healing, infarct expansion, and outcome to the completeness of microvascular reperfusion above and beyond epicardial artery patency.

Key Words: blood flow • infarction • microcirculation • remodeling • echocardiography

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