Hemodynamic effects of anesthetics in a mouse model assessed by Laser Doppler Perfusion and echocardiographic imaging

Anesthetics can alter microvascular perfusion, affecting tissue oxygenation and delivery of vital substrates. The ??2???adrenergic agonist dexmedetomidine and the ?????blocker acepromazine are powerful sedatives with remarkable hemodynamic effects. Some authors reported an attenuation of the ??2???adrenergic agonist pressor response by an acepromazine???xylazine combination in dogs. We investigated non???invasively the microcirculatory effects of dexmedetomidine, of acepromazine and of their combination in isoflurane anesthetized mice by Laser Doppler Perfusion Imaging (LDPI). Thirty???two age???matched and sex???paired CD1 mice underwent 1.5% isoflurane anesthesia, followed by intraperitoneal injection of either 5 mg/kg acepromazine, or 1 mg/kg dexmedetomidine, or by their combination. Body temperature was adjusted to 36 °C. Heart (HR) and breath (BR) rate were recorded. Hind paws blood flow (Perfusion Units, volt) was recorded by LDPI 10 and 20 minutes after isoflurane induction, at different intervals after treatments, and after reversing dexmedetomidine by the ??2??? antagonist atipamezole. BR decreased in all groups without significant differences to baseline (P>0.05). Dexmedetomidine sharply reduced over time HR (P<0.001), while atipamezole gradually reported HR close to baseline (P>0.05). Acepromazine+dexmedetomidine decreased HR (P<0.001), reaching steady values after 5 minutes (P>0.05); atipamezole gradually raised HR close to baseline (P>0.05). Peripheral perfusion under isoflurane anesthesia showed an increasing trend after 10 and 20 minutes, without differences among groups (P=0.1). Acepromazine increased perfusion between 10 and 20 minutes (P=0.005). Dexmedetomidine reduced blood perfusion after 5 minutes (P=0.0001), followed by an increase after 15 minutes (P=0.008). No significant changes were seen 5 minutes after atipamezole (P=0.9). Acepromazine+dexmedetomidine resulted in steady perfusion values over time (P=0.44), which after atipamezole increased very close to baseline (P=0.237). Acepromazine+dexmedetomidine in mice produced more temperate, steady peripheral perfusion values compared to those following single agent, reducing the entity of the ??2 ???agonist biphasic hemodynamic pattern. Our translational approach by LDPI in a mouse model allows an easy, accurate and non invasive measurement of the effects of anesthetics on peripheral microcirculation. 1. Alvaides RK, Neto FJ, Aguiar AJ, et al. Sedative and cardiorespiratory effects of acepromazine or atropine given before Dexmedetomidine in dogs. Vet Rec 2008; 26: 852???856. 2. B. J. A. Janssen, T. De Celle, J. J. M. Debets, A. E. et al, ???Effects of anesthetics on systemic hemodynamics in mice,??? Am J Physiol Heart Circ Physiol, vol. 4, no. 287, pp. 1618???1624, 2004. 3. Adelaide Greco, Monica Ragucci, Raffaele Liuzzi, Sara Gargiulo, Matteo Gramanzini, e al. Reproducibility and Standardization of Laser doppler Imaging technique for the evaluation of normal mice hindlimbs