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

Abstract

Developmental changes in left and right ventricular diastolic filling patterns were determined noninvasively in isoflurane-anesthetized outbred ICR mice. Blood velocities in the mitral and tricuspid orifices were recorded in 16 embryos at days 14.5 (E14.5) and 17.5 of gestation (E17.5) using an ultrasound biomicroscope and also serially in three groups of postnatal mice aged 1–7 days ( n = 23), 1–4 wk ( n = 18), and 4–12 wk ( n = 27) using 20-MHz pulsed Doppler. Postnatal body weight increased rapidly to 8 wk. Heart rate increased rapidly from ∼180 beats/min at E14.5 to ∼380 beats/min at 1 wk after birth and then more gradually to plateau at ∼450 beats/min after 4 wk. Ventricular filling was quantified using the 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) (peak E/A ratio) and the ratio of the peak E velocity to total time-velocity integral of E and A waves (peak E/total TVI ratio). 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 third and fifth day, continued to increase to 2.25 ± 0.25 at ∼3 wk, and then remained stable. The tricuspid peak E/A ratio increased much less but stabilized at the same age (increased to 0.79 ± 0.03 at 3 wk). The peak E/total TVI ratio showed similar left-right differences and changes with development. Age-related changes were largely due to increases in peak E velocity. The results suggest that diastolic function matures ∼3 wk postnatally, presumably in association with maturation of ventricular recoil and relaxation mechanisms.