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 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). 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.
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 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). 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.
Authors: Joanna M S Davies; Josiane Cillard; Bertrand Friguet; Enrique Cadenas; Jean Cadet; Rachael Cayce; Andrew Fishmann; David Liao; Anne-Laure Bulteau; Frédéric Derbré; Amélie Rébillard; Steven Burstein; Etienne Hirsch; Robert A Kloner; Michael Jakowec; Giselle Petzinger; Delphine Sauce; Florian Sennlaub; Isabelle Limon; Fulvio Ursini; Matilde Maiorino; Christina Economides; Christian J Pike; Pinchas Cohen; Anne Negre Salvayre; Matthew R Halliday; Adam J Lundquist; Nicolaus A Jakowec; Fatima Mechta-Grigoriou; Mathias Mericskay; Jean Mariani; Zhenlin Li; David Huang; Ellsworth Grant; Henry J Forman; Caleb E Finch; Patrick Y Sun; Laura C D Pomatto; Onnik Agbulut; David Warburton; Christian Neri; Mustapha Rouis; Pierre Cillard; Jacqueline Capeau; Jean Rosenbaum; Kelvin J A Davies Journal: Geroscience Date: 2017-12-21 Impact factor: 7.713
Authors: Darlene L Hunt; Patrick H Campbell; Alexander C Zambon; Karen Vranizan; Sylvia M Evans; Hai-Chien Kuo; Ken D Yamaguchi; Jeffrey H Omens; Andrew D McCulloch Journal: Exp Physiol Date: 2011-10-03 Impact factor: 2.969