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Abstract

Introduction: Echocardiography allows for sensitive, 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 applicability of animal models to the clinical setting, especially in models of shock. We sought to determine whether light level of anesthesia using isoflurane affected cardiac function in mice. The objective of this study was to evaluate the effects of isoflurane dose on myocardial function in a murine model, and to attempt to compare very low doses of isoflurane to a state in which the mice were off anesthesia Methods: 12 healthy male C57BL/6 mice were studied with 3 different isoflurane anesthesia regimens: deep anesthesia with an objective of heart rate (HR) between 350 and 400 beat per minute (bpm), light anesthesia with an objective of HR between 475 and 525 bpm and just before the mice woke up (>575bpm). 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 between the awake group and the light anesthesia group (49 ± 5% in awake mice vs. 48 ± 5%; p=0.62) whereas it was significantly lower in the deep anesthesia group (31 ± 5%, p<0.0001 compared to both groups). Similar results were found for stroke volume (41.35 ± 5.79 μL vs. 41.61 ± 6.86 μL; p=0.81 and 35.01 ± 8,27 μL; p<0.05 compared to both groups). Cardiac output was slightly lower in the light anesthesia group compared to the awake group (21.90 ± 3.56 mL/min vs. 25.61 ± 3.31; p=0.02) attributable entirely to a difference in HR difference (522 ± 17 beats/min vs. 608 ± 23 beats/min; p<0.0001). Conclusions: Doppler echocardiography can be performed under very light anesthesia using small doses of isoflurane without influencing cardiac inotropic function compared to awake imaging after anesthesia. This technique allows for accurate and reproducible assessment of cardiac function while minimizing hemodynamic perturbations.