IN-VIVO ECHOCARDIOGRAPHIC DETECTION OF ENHANCED LEFT-VENTRICULAR FUNCTION IN GENE-TARGETED MICE WITH PHOSPHOLAMBAN DEFICIENCY

We evaluated the ability of M-mode and Doppler echocardiography to assess left ventricular (LV) function reliably and repeatedly in mice and tested whether these techniques could detect physiological alterations in phospholamban (PLB)-deficient mice. Anesthetized wild-type mice (n=7) and mice deficient in PLB (n=8) were studied with two-dimensional guided M-mode and Doppler echocardiography using a 9-MHz imaging and 5- to 7.5-MHz Doppler transducer. Data were acquired in the baseline state and after intraperitoneal isoproterenol administration (2.0 mu g/g IP). Interobserver and intraobserver variability and reproducibility were excellent. PLB-deficient mice were associated with significant (P<.05) increases in several physiological parameters (mean+/-SD) compared with wild-type: control mice: normalized mean velocity of circumferential shortening (7.7+/-2.1 versus 5.5+/-1.0 circ/sec), peak aortic velocity (105+/-13 versus 75+/-9.2 cm/s), mean aortic acceleration (57+/-16 versus 31+/-4 m/s(2)), and peak early-diastolic transmitral velocity (80.0+/-7.2 versus 66.9+/-7.7 cm/s). LV dimensions, shortening fractions, heart rates, late diastolic transmitral (A) velocities, and early to late (E/A) diastolic velocity ratios were similar in both groups. Isoproterenol administration resulted in significant increases in Doppler indices of ventricular function in control but not PLB-deficient mice. These findings indicate that assessment of LV function can be performed noninvasively in mice under varying physiological conditions and that PLB regulates basal LV function in vivo.