Aortic acceleration as a noninvasive index of left ventricular contractility in the mouse

Abstract

The maximum value of the first derivative of the invasively measured left ventricular (LV) pressure (+ dP/dt_max or P') is often used to quantify LV contractility, which in mice is limited to a single terminal study. Thus, determination of P' in mouse longitudinal/serial studies requires a group of mice at each desired time point resulting in "pseudo" serial measurements. Alternatively, a noninvasive surrogate for P' will allow for repeated measurements on the same group of mice, thereby minimizing physiological variability and requiring fewer animals. In this study we evaluated aortic acceleration and other parameters of aortic flow velocity as noninvasive indices of LV contractility in mice. We simultaneously measured LV pressure invasively with an intravascular pressure catheter and aortic flow velocity noninvasively with a pulsed Doppler probe in mice, at baseline and after the administration of the positive inotrope, dobutamine. Regression analysis of P' versus peak aortic velocity (v_p), peak velocity squared/rise time (v_p²/T), peak (+ dv_p/dt or v'_p) and mean (+ dv_m/dt or v'_m) aortic acceleration showed a high degree of association (P' versus: v_p, r² = 0.77; v_p²/T, r² = 0.86; v'_p, r² = 0.80; and v'_m, r² = 0.89). The results suggest that mean or peak aortic acceleration or the other parameters may be used as a noninvasive index of LV contractility.

Figure 1

Experimental setup to simultaneously measure ascending aortic flow velocity using DFVS, left ventricular pressure using Millar catheter, and ECG in group 1 mice. Here the 20 MHz Doppler probe is oriented (angle ≤ 20°) towards the ascending aorta with sample volume placed at aortic root. Shown in the plot are ascending aortic outflow velocity (sampled at the site shown by blue dot), LV pressure (sampled at catheter tip in LV), and ECG signals.

Figure 2

Waveforms of (A) invasively measured left ventricular pressure (P) waveform and its first derivative (P′) and (B) noninvasively measured aortic outflow velocity (v) waveform and its first derivative (v′). (C) Figure showing the invasive parameter left ventricular P′ and the noninvasive parameters peak aortic velocity (v_p), peak aortic velocity squared/rise time (v_p²/T), peak aortic acceleration (v′_p) and mean aortic acceleration (v′_m). Also shown is the ECG waveform and the time in milliseconds.

Figure 3

Experimental setup to simultaneously measure ascending aortic Doppler flow velocity using DFVS, left ventricular dimensions and ascending aortic flow velocity using VEVO770 system with 710B probe. Also, shown in the figure are lines representing the horizontal plane, and the angle of orientation of 20 MHz Doppler probe (≤ 25°) and that of the 710B probe (≈70°).

Figure 4

Linear regression analysis of (A) peak aortic velocity, v_p vs. P′ ( or + dP/dt_max), (B) peak aortic velocity²/T, v_p²/T vs. P′, (C) peak aortic acceleration, v′_p vs. P′, and (D) mean aortic acceleration, v′_m vs. P′. Shown in each plot is the linear fit equation, the coefficient of determination and the correlation coefficient. The p-values of all were p < 0.0001.

Figure 5

(A) Normalized Bland–Altman plot of the agreement between + dP/dt_max (P′) and peak aortic velocity (v_p). Plot of Difference (P′–v_p) versus Mean ½(P′ + v_p) along with the histogram distribution of the differences. (B) Normalized Bland–Altman plot of the agreement between + dP/dt_max (P′) and peak aortic velocity²/T (v_p²/T). Plot of Difference (P′–v_p²/T) versus Mean ½ (P′ + v_p²/T) along with the histogram distribution of the differences.

Figure 6

(A) Normalized Bland–Altman plot of the agreement between + dP/dtmax (P′) and peak aortic acceleration (v′_p). Plot of Difference (P′– v′_p) versus Mean ½ (P′ + v′_p) along with the histogram distribution of the differences. (B) Normalized Bland–Altman plot of the agreement between + dP/dtmax (P′) and mean aortic acceleration (v′_m). Plot of Difference (P′– v′_m) versus Mean ½ (P′ + v′_m) along with the histogram distribution of the differences.

Figure 7

Percent changes in Doppler (DFVS) and Echocardiography (VEVO770) parameters of group 2 mice induced by administration of dobutamine. All dobutamine induced changes were significantly higher regardless of the method used to measure.

Figure 8

Ascending aortic flow velocity at (A) no intravascular pressure catheter, (B) intravascular pressure catheter in the ascending aorta, and (C) intravascular pressure catheter in the left ventricle via aortic valves (presence of aortic regurgitation—see circle).