Time Course of Isoflurane-Induced Vasodilation: A Doppler Ultrasound Study of the Left Coronary Artery in Mice

Isoflurane is widely used as vasodilator in studies of coronary flow reserve (CFR) in small animals, but the protocols have not been standardized. This study assessed the time course of the increase in isoflurane-induced flow in the mouse coronary artery by pulsed-wave Doppler measurements at 1% isoflurane concentration maintained for 6 min and then increased to 2.5% for 30 min. Velocity-time integral and velocity peak values were best fitted by the sigmoid model, which allowed derivation of the mean time (Tt90 = 14 min) of high-isoflurane needed to reach 90% of the hyperemic plateau value. In subsequent experiments, CFR was measured at 4 min (mean time of literature data) and 14 min of hyperemic response. The 4-min CFR was significantly lower than the 14 -min CFR, and the Bland-Altman plot revealed significant bias of the 4-min CFR against the 14-min CFR. This result suggests that measurements of flow velocity at times shorter than 14 min may be inappropriate for expressing the effective value of CFR.