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Turning Basic Research into Clinical Success
Cardiology 2010;117:246–252 DOI: 10.1159/000323499
Received: November 11, 2010 Accepted after revision: December 7, 2010 Published online: January 18, 2011

Reappraisal of Functional Importance of Coronary Collateral Circulation
Masatoshi Fujita a Shigetake Sasayama b, c


Human Health Sciences, Kyoto University Graduate School ofMedicine, and b Faculty of Life and Medical Science, Doshisha University, Kyoto, and c Daijukai Hospital, Hirakata, Japan

Key Words Coronary collateral development Coronary collateral regression Myocardial ischemia Myocardial viability Repeated coronary occlusion

Abstract Coronary collateral circulation (CCC) is defined as an alternative blood-conveying circuit to the ischemic myocardiumsupplied by a jeopardized coronary artery. Accumulating evidence on CCC and its functional role has been derived from basic and clinical studies over several decades. Progress in molecular biology and genetic engineering has enabled us to elucidate the mechanisms of collateral growth on the basis of the development of new experimental models and methods for accurate assessment of CCC. Theseachievements in basic research have been promptly translated into the clinical setting. Interaction between basic and clinical sciences in the fascinating field of CCC will contribute to the establishment of innovative collateral-promoting therapy for severe coronary artery disease.
Copyright © 2011 S. Karger AG, Basel

tery [1, 2]. Augmentation of the flow reserve of CCC is an attractive therapeuticapproach for patients who are not suitable for clinically available revascularization procedures [3]. Rapid progress in basic and clinical research has been made by the development of new animal models for coronary collateral functional growth, exploitation of accurate quantitative assessment of CCC and establishment of conceptual frameworks for coronary collateral recruitment and growth. Recentadvances in medical technology, molecular biology and genetic engineering have largely contributed to the aforementioned progress. In this review, we discuss experimental and clinical studies with a focus on the function of CCC from these points of view and provide future perspectives.

Experimental Models for Coronary Collateral Development


Coronary collateral circulation(CCC) is an alternative circuit that conveys blood to the ischemic myocardium perfused by a severely stenosed or occluded coronary ar© 2011 S. Karger AG, Basel 0008–6312/10/1174–0246$26.00/0 Fax +41 61 306 12 34 E-Mail Accessible online at:

Ameroid Constrictors Investigation of CCC involves the use of animal models. Ameroid constrictors have longbeen utilized to develop extensive CCC in response to the gradual occlusion of coronary artery [4–6]. Although implantation of an ameroid constrictor to a coronary artery is relatively easy, the degree of vessel constriction, namely, the extent of coronary stenosis, is uncontrollable. Therefore, the dayto-day change in shear stress at the site of preexistent collateral arterioles, which is the mainstimulus for develMasatoshi Fujita, MD Human Health Sciences, Kyoto University Graduate School of Medicine 53 Kawaharacho, Shogoin, Sakyo-ku Kyoto 606-8507 (Japan) Tel. +81 75 751 3932, Fax +81 75 751 3909, E-Mail mfujita @

opment of CCC, may show a wide variation among animals [7]. Brief Repeated Coronary Occlusion Franklin and his group [8] investigated the hypothesisthat brief repeated coronary occlusion develops a functionally significant CCC in conscious dogs. The hypothesis was inspired by the fact that patients with vasospastic angina have an angiographically demonstrable CCC in the absence of significant coronary stenosis [9, 10]. In Franklin’s model, 2 min of occlusion time and 58 min of interval between consecutive occlusions were determined to be...
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