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 micrograms/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/s2), 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.
Hoit
B D
BD
Division of Cardiology, University of Cincinnati, Ohio 45267-0542, USA.
Khoury
S F
SF
Kranias
E G
EG
Ball
N
N
Walsh
R A
RA
D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D004452:Echocardiography; D005260:Female; D018390:Gene Targeting; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016277:Ventricular Function, Left; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D007545:Isoproterenol; D000099211:Phospholamban