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Impaired cardiac diastolic function occurs with aging in many species and may be difficult to measure noninvasively. In humans, left atrial (LA) volume is a robust measure of chronic diastolic function as the LA is exposed to increased left ventricular filling pressures. We hypothesized that LA volume would be a useful indicator of diastolic function in aging mice. Further, we asked whether pressures were propagated backwards affecting pulmonary arteries (PAs) and right ventricle (RV). We measured LA, PA, and RV infundibulum dimensions with echocardiography and used mouse-specific Doppler systems and pressure catheters for noninvasive and invasive measures. As C57BL/6 mice aged from 3 to 29–31 months, LA volume almost tripled. LA volume increases correlated with traditional diastolic function measures. Within groups of 14- and 31-month-old mice, LA volume correlated with diastolic function measured invasively. In serial studies, mice evaluated at 20 and 24 months showed monotonic increases in LA volume; other parameters changed less predictably. PA diameters, larger in 30-month-old mice than 6-month-old mice, correlated with LA volumes. Noninvasive LA volume and PA diameter assessments are useful and state independent measures of diastolic function in mice, correlating with other measures of diastolic dysfunction in aging. Furthermore, serial measurements over 4 months demonstrated consistent increases in LA volume suitable for longitudinal cardiac aging studies.

The placement of a ligature to constrict the transverse aorta has become a standard procedure to induce cardiac hypertrophy in mice. Apart from cardiac response, there are adaptive changes in the proximal and distal arterial system that function to maintain adequate peripheral perfusion. The purpose of this study was to characterize the peripheral vascular response by measuring the carotid blood flow using noninvasive Doppler methods, and to investigate the effect of aging on the adequacy and timing of the response after aortic banding in mice. Five 16-month-old and 9 4-month-old male B6D2F1 mice underwent transverse aortic banding. Blood flow velocity was measured with Doppler in the right and left carotid arteries (RCA and LCA) before, 1 day after, and 7 days after, banding. Pulsatility index defined as (peak - minimum)/mean velocity was used to estimate local compliance and distal arterial resistance. The RCA/LCA mean velocity ratio was lower and pulsatility index ratio was higher at 1 day after banding in older mice. However, at 7 days, the RCA/LCA mean velocity ratio and pulsatility index ratio were similar between the 2 age groups. Our data indicate that there is an age-related delay in the development of vascular adaptations in carotid arteries after aortic banding. Older mice take a longer time for adaptation to establish adequate and equal mean flow velocity in the carotid arteries.

With the growth of genetic engineering, mice have become common as models of human diseases, which in turn has stimulated the development of techniques to monitor and image the murine cardiovascular system. Invasive methods are often more quantitative, but noninvasive methods are preferred when measurements must be repeated serially on living animals during development or in response to pharmacological or surgical interventions. Because of the small size and high heart rates in mice, high spatial and temporal resolutions are required to preserve signal fidelity. Monitoring of body temperature and the electrocardiogram is essential when animals must be anesthetized for a measurement or other procedure. Several other groups have developed cardiovascular imaging modalities suitable for murine applications, and ultrasound is the most widely used. Our group has developed and applied high-resolution Doppler probes and signal processing for measuring blood velocity in the heart and peripheral vessels of anesthetized mice noninvasively. We can measure cardiac filling and ejection velocities as indices of systolic and diastolic ventricular function and for timing of cardiac events; velocity pulse arrival times for determining pulse-wave velocity and arterial stiffness; peripheral velocity waveforms as indices of arterial resistance, compliance, and wave reflections; stenotic velocities for estimation of pressure drop and detection of vorticity; and tail artery velocity for determining systolic and diastolic blood pressure using a pressure cuff. These noninvasive methods are convenient and easy to apply and have been used to detect and evaluate numerous cardiovascular phenotypes in mutant mice.