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


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.
Reffelmann
Thorsten
T
The Heart Institute, Good Samaritan Hospital, University of Southern California, 1225 Wilshire Blvd, Los Angeles, CA 90017, USA.
Hale
Sharon L
SL
Dow
Joan S
JS
Kloner
Robert A
RA
D000818:Animals; D002196:Capillaries / Q000473:pathology; D002921:Cicatrix / Q000473:pathology; D004396:Coloring Agents; D003326:Coronary Circulation; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011379:Prognosis; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D004396:Coloring Agents