Murine cardiac hemodynamics following manganese administration under isoflurane anesthesia.

Abstract

This study examines (a) the temporal stability of hemodynamic indices of systolic and diastolic function in C57BL/6 mice under 1.5% isoflurane (ISO) (v/v) anesthesia conditions in 50:50 O(2)/N(2)O (v/v) within 90 min post-induction, and (b) the effects of Mn(2+) on the mouse hemodynamic response in male C57BL/6 mice (n = 16). Left ventricular catheterizations allowed estimation of the hemodynamic indices. Hypertonic saline infusion (10%) allowed absolute volume quantification in conjunction with a separate series of aortic flow experiments (n = 3). In a separate cohort of mice (n = 6), MnCl(2) (190 nmoles/g/bw) was infused via the left jugular for 29-39 min, following 11 min of baseline recording, to assess temporal responses. Stable temporal hemodynamic responses were achieved in control mice under ISO anesthesia. Hemodynamic indices during control, time-matched-control, baseline-Mn, and Mn-infused periods, were within normal expected ranges. No chronotropic changes were observed. Significant differences in systolic and diastolic cardiac indices of function (HR, EF, ESP, dP/dt (max), dP/dt (min), PAMP, τ(glantz), and τ(weiss)) resulted between baseline-Mn and Mn-infused time periods in Mn-treated mice at the 1% significance (p < 0.001). Transient positive, or negative, or positive followed by negative evoked pressure-volume loop shifts were observed (exemplified through changes in the end-systolic pressure-volume relationship and dP/dt (max)) in Mn-infusion studies. It is concluded that Mn(2+) can be used safely for prolonged mouse imaging studies, however, the significant variations elicited in cardiovascular hemodynamics post-manganese infusion, necessitate further investigations for its suitability and appropriateness for quantification of global cardiac function in image-based phenotyping.