Developmental changes in left and right ventricular diastolic filling patterns in mice

Developmental changes in left and right ventricular diastolic filling patterns were determined non-invasively in isoflurane-anesthetized outbred ICR mice. Blood velocities in the mitral and tricuspid orifices were recorded in 16 embryos at day 14.5 (E14.5) and 17.5 (E17.5) of gestation using an ultrasound biomicroscope, and also serially in three groups of postnatal mice aged from 1 to 7 days (N=23), 1 to 4 weeks (N=18), and 4 to 12 weeks (N=27), using 20 MHz pulsed Doppler. Postnatal body weight increased rapidly to 8 weeks. Heart rate increased rapidly from ~180 beats/min at E14.5 to ~380 beats/min at 1 week after birth, then more gradually to plateau at ~450 beats/min after 4 weeks. Ventricular filling was quantified using peak E/A (ratio of peak velocity of early ventricular filling due to active relaxation (E wave) to that of the late ventricular filling caused by atrial contraction (A wave)), and peak E/total TVI (the ratio of peak E velocity to total time-velocity integral of E and A waves). Both ventricles had similar diastolic filling patterns in embryos (peak E/A ratio of 0.28 ? 0.02 for mitral flow and 0.27 ? 0.02 for tricuspid flow at E14.5). After birth, mitral peak E/A increased to >1 between the 3rd and 5th day and continued to increase to 2.25 ? 0.25 at ~3 weeks then remained stable. Tricuspid peak E/A ratio increased much less but stabilized at the same age (increased to 0.79 ? 0.03 at 3 weeks). Peak E/total TVI showed similar left-right differences, and changes with development. Age- related changes were largely due to increases in peak E velocity. Results suggest diastolic function matures ~3 weeks postnatally presumably in association with maturation of ventricular recoil and relaxation mechanisms.