Adenosine induces dilation of epicardial coronary arteries in mice: relationship between coronary flow velocity reserve and coronary flow reserve in vivo using transthoracic echocardiography.

For an accurate estimate of volumetric coronary flow reserve (CFR) using Doppler-assessed flow velocity measurement, it is important to take into consideration potential diameter change during coronary hyperemia. Using ultrasound techniques, left coronary artery (LCA) flow velocity and LCA lumen diameter (LCA(D)) were measured simultaneously for the first time to measure coronary flow during baseline and adenosine-induced hyperemic condition in isoflurane-anesthetized C57BL/6 (n = 38) and in old apolipoprotein E-gene deficient (ApoE(-/-)) mice (n = 44) mice. LCA(D) increased significantly and to a similar extent during adenosine infusion in both groups (3.7 +/- 1.1 %, p < 0.003 for C57BL/6; 4.2 +/- 0.9 %, p < 0.00003 for ApoE(-/-)). Yet, a positive correlation was still found between velocity-based coronary flow velocity reserve (CFVR) and volumetric CFR in both strains (R(2) = 0.77, p < 0.001 for C57BL/6; R(2) = 0.80, p < 0.001 for ApoE(-/-)). Coronary reserve was higher in C57BL/6 mice than in ApoE(-/-) mice (CFR 1.93 +/- 0.17 vs. 1.47 +/- 0.07, p < 0.05; CFVR 1.73 +/- 0.13 vs. 1.28 +/- 0.07, p < 0.01). Thus, ultrasound techniques can be used to measure volumetric flow in the LCA and flow-based CFR measurements of intact, living mice. The positive correlation between CFR and CFVR, together with the lower method variability of the latter, makes CFVR a more robust protocol for assessing mouse in-vivo coronary artery function. Therefore, the CFVR protocol will probably work well in most settings.