Published Online
on December 1, 2003

A more recent version of this article appeared on December 9, 2003

This Article Full Text (PDF) All Versions of this Article: 108/23/2911    most recent 01.CIR.0000101917.80668.E1v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reffelmann, T. Articles by Kloner, R. A. Search for Related Content PubMed PubMed Citation Articles by Reffelmann, T. Articles by Kloner, R. A. Related Collections Other Vascular biology

Submitted on June 18, 2002
Revised on August 8, 2003
Accepted on August 8, 2003

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

Thorsten Reffelmann MD, Sharon L. Hale BS, Joan S. Dow BS, and Robert A. Kloner MD, PhD^*

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

^* To whom correspondence should be addressed. E-mail: rkloner{at}goodsam.org.

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

This article has been cited by other articles:

				C. Rempf, T. Standl, K. Schenke, K. Chammas, A. Gottschalk, M.-A. Burmeister, and A. Gottschalk Administration of bovine polymerized haemoglobin before and during coronary occlusion reduces infarct size in rabbits Br. J. Anaesth., October 1, 2009; 103(4): 496 - 504. [Abstract] [Full Text] [PDF]

				V. Dor, F. Civaia, C. Alexandrescu, and F. Montiglio The post-myocardial infarction scarred ventricle and congestive heart failure: the preeminence of magnetic resonance imaging for preoperative, intraoperative, and postoperative assessment. J. Thorac. Cardiovasc. Surg., December 1, 2008; 136(6): 1405 - 1412. [Full Text] [PDF]

				R. A. Kloner and H. Hwang New Insights Into the Open Artery Hypothesis Circ. Res., July 3, 2008; 103(1): 1 - 3. [Full Text] [PDF]

				M. Salio, S. Chimenti, N. De Angelis, F. Molla, V. Maina, M. Nebuloni, F. Pasqualini, R. Latini, C. Garlanda, and A. Mantovani Cardioprotective Function of the Long Pentraxin PTX3 in Acute Myocardial Infarction Circulation, February 26, 2008; 117(8): 1055 - 1064. [Abstract] [Full Text] [PDF]

				T. Freyman, G. Polin, H. Osman, J. Crary, M. Lu, L. Cheng, M. Palasis, and R. L. Wilensky A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction Eur. Heart J., May 1, 2006; 27(9): 1114 - 1122. [Abstract] [Full Text] [PDF]

				E. J. van den Bos, B. M. E. Mees, M. C. de Waard, R. de Crom, and D. J. Duncker A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1291 - H1300. [Abstract] [Full Text] [PDF]

				V. Bodi, J. Sanchis, A. Losada, M. P. Lopez-Lereu, D. Garcia, M. Pellicer, F. J. Chorro, and A. Llacer Usefulness of quantitative intravenous myocardial contrast echocardiography to analyze microvasculature perfusion in patients with a recent myocardial infarction and an open infarct-related artery: comparison with intracoronary myocardial contrast echocardiography Eur J Echocardiogr, June 1, 2005; 6(3): 164 - 174. [Abstract] [Full Text] [PDF]

				H. K. Eltzschig and C. D. Collard Vascular ischaemia and reperfusion injury Br. Med. Bull., October 19, 2004; 70(1): 71 - 86. [Abstract] [Full Text] [PDF]

				T. Reffemann and R. A. Kloner Microvascular Alterations After Temporary Coronary Artery Occlusion: The No-Reflow Phenomenon Journal of Cardiovascular Pharmacology and Therapeutics, July 1, 2004; 9(3): 163 - 172. [Abstract] [PDF]