TY - JOUR
T1 - Doppler Estimation of Reduced Coronary Flow Reserve in Mice with Pressure Overload Cardiac Hypertrophy
AU - Hartley, Craig J.
AU - Reddy, Anilkumar K.
AU - Madala, Sridhar
AU - Michael, Lloyd H.
AU - Entman, Mark L.
AU - Taffet, George
N1 - Funding Information:
We acknowledge the contributions of Thuy Pham, Jennifer Pocius and James Brooks for technical, surgical and editorial assistance. This work was supported in part by National Institutes of Health Grants R01-HL22512, P01-HL42550, R01-AG17899, R41-HL76928, and K25-HL73041.
PY - 2008/6
Y1 - 2008/6
N2 - Aortic banding produces pressure overload cardiac hypertrophy in mice, leading to decompensated heart failure in four to eight weeks, but the effects on coronary blood flow velocity and reserve are unknown. To determine whether coronary flow reserve (CFR) was reduced, we used noninvasive 20-MHz Doppler ultrasound to measure left main coronary flow velocity at baseline (B) and at hyperemia (H) induced by low (1%) and high (2.5%) concentrations of isoflurane gas anesthesia. Ten mice were studied before (Pre) and at 1 d, 7 d, 14 d and 21 d after constricting the aortic arch to 0.4 mm diameter distal to the innominate artery. We also measured cardiac inflow and outflow velocities at the mitral and aortic valves and velocity at the jet distal to the aortic constriction. The pressure drop as estimated by 4V2 at the jet was 51 ± 5.1 (mean ± SE) mm Hg at 1 d, increasing progressively to 74 ± 5.2 mm Hg at 21 d. Aortic and mitral blood velocities were not significantly different after banding (p = NS), but CFR, as estimated by H/B, dropped progressively from 3.2 ± 0.3 before banding to 2.2 ± 0.4, 1.7 ± 0.3, 1.4 ± 0.2 and 1.1 ± 0.1 at 1 d, 7 d, 14 d and 21 d, respectively (all p < 0.01 vs. Pre). There was also a significant and progressive increase the systolic/diastolic velocity ratio (0.17 Pre to 0.92 at 21 d, all p < 0.01 vs. Pre) suggesting a redistribution of perfusion from subendocardium to subepicardium. We show for the first time that CFR, as estimated by the hyperemic response to isoflurane and measured by Doppler ultrasound, can be measured serially in mice and conclude that CFR is virtually eliminated in banded mice after 21 d of remodeling and hypertrophy. These results demonstrate that CFR is reduced in mice as in humans with cardiac disease but before the onset of decompensated heart failure. (E-mail: [email protected]).
AB - Aortic banding produces pressure overload cardiac hypertrophy in mice, leading to decompensated heart failure in four to eight weeks, but the effects on coronary blood flow velocity and reserve are unknown. To determine whether coronary flow reserve (CFR) was reduced, we used noninvasive 20-MHz Doppler ultrasound to measure left main coronary flow velocity at baseline (B) and at hyperemia (H) induced by low (1%) and high (2.5%) concentrations of isoflurane gas anesthesia. Ten mice were studied before (Pre) and at 1 d, 7 d, 14 d and 21 d after constricting the aortic arch to 0.4 mm diameter distal to the innominate artery. We also measured cardiac inflow and outflow velocities at the mitral and aortic valves and velocity at the jet distal to the aortic constriction. The pressure drop as estimated by 4V2 at the jet was 51 ± 5.1 (mean ± SE) mm Hg at 1 d, increasing progressively to 74 ± 5.2 mm Hg at 21 d. Aortic and mitral blood velocities were not significantly different after banding (p = NS), but CFR, as estimated by H/B, dropped progressively from 3.2 ± 0.3 before banding to 2.2 ± 0.4, 1.7 ± 0.3, 1.4 ± 0.2 and 1.1 ± 0.1 at 1 d, 7 d, 14 d and 21 d, respectively (all p < 0.01 vs. Pre). There was also a significant and progressive increase the systolic/diastolic velocity ratio (0.17 Pre to 0.92 at 21 d, all p < 0.01 vs. Pre) suggesting a redistribution of perfusion from subendocardium to subepicardium. We show for the first time that CFR, as estimated by the hyperemic response to isoflurane and measured by Doppler ultrasound, can be measured serially in mice and conclude that CFR is virtually eliminated in banded mice after 21 d of remodeling and hypertrophy. These results demonstrate that CFR is reduced in mice as in humans with cardiac disease but before the onset of decompensated heart failure. (E-mail: [email protected]).
KW - Blood flow
KW - Coronary circulation
KW - Hypertrophy
KW - Ultrasound
KW - Ventricular function
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UR - http://www.scopus.com/inward/citedby.url?scp=43849099195&partnerID=8YFLogxK
U2 - 10.1016/j.ultrasmedbio.2007.11.019
DO - 10.1016/j.ultrasmedbio.2007.11.019
M3 - Article
C2 - 18255218
AN - SCOPUS:43849099195
SN - 0301-5629
VL - 34
SP - 892
EP - 901
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 6
ER -