No-reflow phenomenon persists long-term after ischemia/reperfusion in the rat and predicts infarct expansion

• Published in: Circulation (New York, N.Y.) Vol. 108; no. 23; pp. 2911 - 2917
• Main Authors: REFFELMANN, Thorsten, HALE, Sharon L, DOW, Joan S, KLONER, Robert A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 09-12-2003; American Heart Association, Inc
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Capillaries - pathology; Cardiology. Vascular system; Cicatrix - pathology; Coloring Agents; Coronary Circulation; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Heart - diagnostic imaging; Medical sciences; Myocardial Infarction - pathology; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Myocardial Ischemia - therapy; Myocardial Reperfusion; Myocardial Reperfusion Injury - physiopathology; Prognosis; Radionuclide Imaging; Rats; Rats, Inbred F344; Time Factors; Nervous system diseases; remodeling; Rat; Rodentia; echocardiography; infarction; Cardiovascular disease; microcirculation; Vascular disease; Vertebrata; Mammalia; Reperfusion; Ischemia; Animal; blood flow
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000101917.80668.E1

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.
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 x min(-1) x g(-1), P<0.003, apical slice, and 1.77+/-0.44 versus 5.34+/-0.38 mL x min(-1) x 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).
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.