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 equals 7) and mice deficient in PLB (n equals 8) were studied with two-dimensional guided M-mode and Doppler echocardiography using a 9-MHz imagining 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 less than .05) increases in several physiological parameters (mean plus minus SD) compared with wild-type control micenormalized mean velocity of circumferential shortening (7.7 plus minus 2.1 versus 5.5 plus minus 1.0 circ/sec), peak aortic velocity (105 plus minus 13 versus 75 plus minus 9.2 cm/s), mean aortic acceleration (57 plus minus 16 versus 31 plus minus 4 m/s), and peak early-diastolic transmitral velocity (80.0 plus minus 7.2 versus 66.9 plus minus 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.(Circ Res. 1995;77:632-637.)Key Words, echocardiography, gene targeting, phospholamban, sarcoplasmic reticulum, left ventricular function