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.

Molecular and Integrative Physiological Effects of Isoflurane Anesthesia: The Paradigm of Cardiovascular Studies in Rodents using Magnetic Resonance Imaging

“…In conjunction with anesthesia-induced flow reductions, metabolic downregulation, the extreme bradycardic state, and a possible altered cardiac functional modus operandi , the assessment of optimal induction and anesthetic administration and maintenance over prolonged time periods (e.g., ≥90 min) that match most conventional MRI protocols becomes critical. In our prior study ( 43 , 44 ), we have accomplished a highly reproducible and stable mouse maintenance protocol (beyond 40 min) under ISO at optimal levels of approximately 1.5% [mean HR = 478 ± 11.4 and coefficient of variability (CV) = 11 ± 1%; mean MAP = 92 ± 2 mmHg, CV = 8 ± 2%], following the end of the surgical procedure for sensor placements and the reestablishment of thermal stabilization (Figure 4 ).…”

“…Isoflurane is a potent cerebral ( 46 , 47 ), coronary ( 113 ), and peripheral vasculature vasodilator ( 43 , 44 ). Furthermore, it also likely abolishes (in a dose-dependent manner) sympathetic tone, although published results from Ebert and Stowe ( 49 ) suggest that this effect may be spatially heterogeneous, given evidence for preservation of sympathetic vasomotor activity.…”

“…Correspondingly, the major determinants of myocardial oxygen consumption (MVO 2 ) are myocardial contractility, wall tension, and heart rate. MVO 2 is thus often correlated to the product of HR and MAP and regional contractility ( 48 ), and it is expected to be decreased, but potentially maintained constant over prolonged anesthesia exposure ( 43 , 44 ). This decrease (in association to oxygen extraction), directly reflects contractile changes (to be discussed below) or metabolic changes, manifested by reductions in the efficiency of ATP production by the mitochondria, or both.…”

“…Pacher et al ( 75 ) have published catheterization protocols for various anesthetics (including ISO) and proper hemodynamic ranges of contractile function (Table 1 ). Although these ranges reflect open and closed chest preparations and short-term anesthetic exposure, Constantinides et al ( 43 , 44 ) have extended the study of global functional indices (Figure 4 ) ( 44 ) under optimal and prolonged anesthetic conditions (up to 90 min post-induction) to the study of regional functional indices (Table 1 ). These results are in close agreement or within the ranges reported by Pacher et al ( 75 ) and indicate constancy of contractile and relaxation performance at the regional fiber level, most appropriate for prolonged MRI cardiac imaging studies.…”

Effect of hypertonic saline on hypotension following induction of general anesthesia: A randomized controlled trial

“…[212223242526] The effect of HS on cardiac function is offset by lowering of the peripheral vascular resistance, thus maintaining cardiac pump function. [27] Evidence showing that HSS may be an effective treatment for brain edema and elevated increased intracranial pressure after head trauma, and also the beneficial effects during hemorrhagic shock in the presence of IH associated with systemic hypotension have been noted.…”