This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2005.04.053v1 46/4/720    most recent 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wikström, J. Articles by Gan, L.-m. Search for Related Content PubMed PubMed Citation Articles by Wikström, J. Articles by Gan, L.-m.

CLINICAL RESEARCH

Functional and Morphologic Imaging of Coronary Atherosclerosis in Living Mice Using High-Resolution Color Doppler Echocardiography and Ultrasound Biomicroscopy

Johannes Wikström, MSc^_*, Julia Grönros, MSc^_*, Göran Bergström, MD, PhD and Li-ming Gan, MD, PhD^_*,,_*

^_* Department of Physiology, Institute of Physiology and Pharmacology
Department of Clinical Physiology, Cardiovascular Institute, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden

Manuscript received December 20, 2004; revised manuscript received April 14, 2005, accepted April 25, 2005.

^_* Reprint requests and correspondence: Dr. Li-ming Gan, Göteborg University, Institute of Physiology and Pharmacology, Department of Physiology, Box 432, 405 30 Göteborg, Sweden (Email: li-ming.gan{at}hjl.gu.se).

OBJECTIVES: This study aimed to establish non-invasive methods of assessing coronary artery morphology in normal and atherosclerotic mice in vivo.

BACKGROUND: Coronary flow velocity reserve (CFVR) has been shown to correlate with coronary minimal lumen diameter (MLD) in patients with coronary artery stenosis. In mice, there are no existing non-invasive imaging techniques allowing quantitative measurement of the coronary artery morphology and function.

METHODS: Systemic hemodynamic effects of adenosine were studied in seven C57BL/6 mice. In 17 C57BL/6 mice, CFVR was measured in the mid left coronary artery (LCA) using either hypoxia- or adenosine-induced coronary hyperemia. Further, in another 10 atherosclerotic low-density lipoprotein receptor (LDLR)^–/– mice, the hypoxia-induced CFVR was performed and proximal LCA MLD was measured using ultrasound biomicroscopy (UBM). Histologic sections of the LCA were collected.

RESULTS: The adenosine dose of 160 µg/kg/min induced maximal coronary hyperemia without any systemic hemodynamic effects. Adenosine and hypoxia-induced CFVR values averaged at 2.0 ± 0.1 and 1.9 ± 0.3, respectively, in C57BL/6 mice (p = NS). In LDLR^–/– mice, CFVR and MLD ranged between 1.4 to 2.9 µm and 190 to 370 µm, respectively. Histology revealed proximal lumen-narrowing plaques in the LCA. Significant correlation was found between hypoxia-induced CFVR and the MLD (p < 0.005, R² = 0.8707).

CONCLUSIONS: The CDE and UBM technique can be used to measure atherosclerosis-related lumen narrowing of the LCA in living mice. These non-invasive techniques may provide us with novel tools for following up disease status in mouse coronary arteries in a quantitative manner.

Abbreviations and Acronyms   BP = blood pressure   CDE = color Doppler echocardiography   CFR = coronary flow reserve   CFVR = coronary flow velocity reserve   HR = heart rate   LCA = left coronary artery   LDLR = low-density lipoprotein receptor   MLD = minimal lumen diameter   UBM = ultrasound biomicroscope

This article has been cited by other articles:

				J. Gronros, J. Wikstrom, U. Brandt-Eliasson, G. B. Forsberg, M. Behrendt, G. I. Hansson, and L. M. Gan Effects of rosuvastatin on cardiovascular morphology and function in an ApoE-knockout mouse model of atherosclerosis Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2046 - H2053. [Abstract] [Full Text] [PDF]

				M. J. Raher, H. Thibault, K. K. Poh, R. Liu, E. F. Halpern, G. Derumeaux, F. Ichinose, W. M. Zapol, K. D. Bloch, M. H. Picard, et al. In Vivo Characterization of Murine Myocardial Perfusion With Myocardial Contrast Echocardiography: Validation and Application in Nitric Oxide Synthase 3 Deficient Mice Circulation, September 11, 2007; 116(11): 1250 - 1257. [Abstract] [Full Text] [PDF]

				W. Osika, F. Dangardt, J. Gronros, U. Lundstam, A. Myredal, M. Johansson, R. Volkmann, T. Gustavsson, L. Ming Gan, and P. Friberg Increasing Peripheral Artery Intima Thickness From Childhood to Seniority Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 671 - 676. [Abstract] [Full Text] [PDF]

				A. Saraste, V. Kyto, M. Saraste, T. Vuorinen, J. Hartiala, and P. Saukko Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H871 - H875. [Abstract] [Full Text] [PDF]

				J. Gronros, J. Wikstrom, U. Hagg, B. Wandt, and L.-m. Gan Proximal to Middle Left Coronary Artery Flow Velocity Ratio, As Assessed Using Color Doppler Echocardiography, Predicts Coronary Artery Atherosclerosis in Mice Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1126 - 1131. [Abstract] [Full Text] [PDF]