Coronary flow velocity reserve is reduced in mice with atherosclerosis, pressure overload hypertrophy, and coronary occlusion

Abstract

In man, coronary flow reserve (CFR) is reduced by most forms of heart disease, but it is not known how heart diseases modeled in mice alter CFR. We used Doppler ultrasound to measure left main coronary flow velocity (CFV) noninvasively in: 20 2‐yr old ApoE‐/‐ (atherosclerotic) mice, 10 age‐matched wild‐type (WT) controls, 10 6‐wk old WT mice, and 13 3‐mo old WT mice before and 21 days after transverse aortic banding (TAB) or LAD coronary artery occlusion (OCCL). All mice were C57BL6. We measured CFV and heart rate (HR) at baseline (B) and hyperemia (H) induced by changing the level of isoflurane gas anesthesia from 1 to 2.5%, and estimated CFR as H/B. Baseline HR and CFV in WT mice were 434±20 b/min and 16±3 cm/s (mean±SEM), and CFR was 2.4±0.1 (6‐wk), 3.2±0.3 (3‐mo), and 3.6±0.2 (2‐yr). For the disease models, CFR was: 2.5±0.2 (ApoE‐/‐), 1.1±0.1 (TAB), and 2.0±0.1 (OCCL), all P<0.05 versus control or pre‐intervention. The average change in HR at H versus B was 1.05±0.3. We found that isoflurane gas is a convenient and noninvasive coronary vasodilator with minimal effects on HR in mice, and that CFR increases with age and is reduced significantly in each disease model. Indeed, CFR is nearly abolished 3 wks after TAB. We conclude that the magnitudes of CFV and CFR and the responses to pressure overload hypertrophy and coronary artery disease are similar in mice and man and that global CFR may serve as an index of cardiac function.