Functional and morphologic imaging of coronary atherosclerosis in living mice using high-resolution color Doppler echocardiography and ultrasound biomicroscopy.
OBJECTIVE
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 microg/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 microm and 190 to 370 microm, 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.
Wikström
Johannes
J
Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Sweden.
Grönros
Julia
J
Bergström
Göran
G
Gan
Li-ming
LM
D000241:Adenosine; D000818:Animals; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D018618:Echocardiography, Doppler, Color; D005260:Female; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D033401:Microscopy, Acoustic
D000241:Adenosine