Effect of anesthesia level on murine cardiac function

Fabien Picard,Francois Depret,Sergio Zanotti-Cavazzoni,Steven Hollenberg

doi:10.12688/f1000research.3873.1

Fabien Picard, Francois Depret + Show 2 more

Open Access

https://doi.org/10.12688/f1000research.3873.1

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Abstract

Background: Echocardiography allows for sensitive and non-invasive assessment of cardiac function in mice, but requires sedation and immobility, which influences cardiac performance. Minimizing the hemodynamic effects of anesthesia is extremely important for improving the applicability of animal models to the clinical setting. We sought to evaluate the effects of isoflurane dose on myocardial function in a murine model.Methods: Twelve healthy C57BL/6 mice were studied with three different isoflurane anesthesia regimens: deep anesthesia with an objective of heart rate (HR) between 350 and 400 beats per minute (bpm), light anesthesia with an objective of HR between 475 and 525 bpm and just before the mice woke up (>575 bpm). Using a high-resolution ultrasound system, stroke volume, cardiac output, left ventricle dimension and fractional shortening were recorded.Results: Fractional shortening was not statistically different in the awake group and the light anesthesia group (49±5% in awake mice vs. 48±5%; p=0.62), whereas it was different compared to the deep anesthesia group (31±5%, p<0.0001 compared to both groups). Similar results were found for stroke volume (41.4±5.8 ml vs. 41.6±6.9 ml; p=0.81 and 35±8.3 ml; p<0.05 compared to both groups). Cardiac output was slightly lower in the light anesthesia group compared to the awake group (21.9±3.6 ml/min vs. 25.6±3.3; p=0.02) due to HR significant difference (522±17 bpm vs. 608±23 bpm; p<0.0001).Conclusions: Doppler echocardiography can be performed under very light anesthesia using small doses of isoflurane without influencing cardiac inotropic function. This technique allows for accurate and reproducible assessment of cardiac function while minimizing hemodynamic perturbations.

Highlights

Animal models of disease can provide important insights into pathophysiological mechanisms and allow for evaluation of novel therapies
ejection fraction (EF) was lower in the deep anesthesia group, as compared to the light and to the awake group (59±7% in the deep anesthesia group and 80±5% and 81±5% in the light group and the awake group respectively; p
LV end-diastolic diameter (LVEDD) was slightly higher on the deep anesthesia group (3.74±0.39 mm) but no statistically significant difference could be found between the light anesthesia group (3.0±0.33 mm; p=0.0827) and the awake group (3.37±0.41, p=0.0864) (Table 1)

Summary

Introduction

Animal models of disease can provide important insights into pathophysiological mechanisms and allow for evaluation of novel therapies. Murine models have been widely used for these purposes: cardiac and vascular morphologic differences between mice, rats, and humans are fairly subtle, and many physiological characteristics are comparable[1]. For hemodynamic assessments in murine models, it is critical to develop approaches for accurate and reproducible measurements of cardiac morphology and function in intact animals. Minimizing the hemodynamic effects of anesthesia is extremely important for improving the applicability of animal models to the clinical setting. Conclusions: Doppler echocardiography can be performed under very light anesthesia using small doses of isoflurane without influencing cardiac inotropic function. This technique allows for accurate and reproducible assessment of cardiac function while minimizing hemodynamic perturbations

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