Aim of the study: Anesthetic agents can alter microvascular perfusion, affecting tissue oxygenation and delivery of other 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. Since mice are a validated translational model to study anesthetic effects, 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). Materials and Methods: Thirty-two age-matched and sex-paired CD1 mice were allocated to 3 groups undergoing 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 monitored by a rectal probe and adjusted to 36 °C by an infrared lamp. Heart (HR) and breath (BR) rate were recorded. Bilateral hind paws blood flow (Perfusion Units, volt) was recorded by LDPI 10 and 20 minutes after isoflurane induction and at different intervals after treatments. A further scan was recorded after reversing dexmedetomidine by the ?2-antagonist atipamezole. Results: BR decreased in all groups without significant differences to baseline values (P>0.05). Dexmedetomidine sharply reduced over time HR (P<0.001), while atipamezole gradually reported these values close to baseline (P>0.05). Acepromazine+dexmedetomidine significantly decreased HR (P<0.001), reaching steady values after 5 minutes (P>0.05); atipamezole gradually raised this value close to baseline (P>0.05). Peripheral perfusion under isoflurane anesthesia showed an increasing trend after 10 and 20 minutes (4.25 to 4.55 volts), without significant differences among groups (P=0.1). Between 10 and 20 minutes after acepromazine administration, a significant perfusion increase was observed from 4.55 to 4.85 volts (P=0.005). Dexmedetomidine significantly reduced blood perfusion (2.47 volts) after 5 minutes (P=0.0001), followed by an increase to 4.32 volts after 15 minutes (P=0.008). No significant changes (4.34 volts) were seen 5 minutes after atipamezole (P=0.9). Administration of acepromazine+dexmedetomidine resulted in steady perfusion values over time (P=0.44), which after atipamezole increased to 4.4 volt, very close to baseline values (P=0.237). Conclusions: Concurrent administration of acepromazine and dexmedetomidine in mice produced more temperate and steady peripheral perfusion values compared to those following single agent, reducing the entity of the ?2 -agonist biphasic hemodynamic pattern. Our translational approachby LDPI in a new mouse model allows an easy, accurate and non invasive measurement of the effects of anesthetics on peripheral microcirculation. Bibliography 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. Brouns, M. F. Callahan, T. L. Smith, "Effects of anesthetics on systemic hemodynamics in mice," Am J Physiol Heart Circ Physiol, vol. 4, no. 287, pp. 1618-1624, 2004. 3.Z. Turek, R. Sykora, M. Matejovic, V .Cerni, "Anesthesia and microcirculation," Seminars in Cardiothoracic and Vascular Anesthesia, vol. 4, no.13, pp. 249-258, 2009. 4.Adelaide Greco, Monica Ragucci, Raffaele Liuzzi, Sara Gargiulo, Matteo Gramanzini, Anna Rita Daniela Coda, Sandra Albanese, Marcello Mancini, Marco Salvatore and Arturo Brunetti. Reproducibility and Standardization of Laser doppler Imaging technique for the evaluation of normal mice hindlimbs perfusion. Sensor 2013, 13(1):500-515
The effects of some anesthetic agents on microcirculation evaluated by Laser Doppler Perfusion Imaging (LDPI) in mice
Sara Gargiulo;Matteo Gramanzini;
2013
Abstract
Aim of the study: Anesthetic agents can alter microvascular perfusion, affecting tissue oxygenation and delivery of other 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. Since mice are a validated translational model to study anesthetic effects, 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). Materials and Methods: Thirty-two age-matched and sex-paired CD1 mice were allocated to 3 groups undergoing 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 monitored by a rectal probe and adjusted to 36 °C by an infrared lamp. Heart (HR) and breath (BR) rate were recorded. Bilateral hind paws blood flow (Perfusion Units, volt) was recorded by LDPI 10 and 20 minutes after isoflurane induction and at different intervals after treatments. A further scan was recorded after reversing dexmedetomidine by the ?2-antagonist atipamezole. Results: BR decreased in all groups without significant differences to baseline values (P>0.05). Dexmedetomidine sharply reduced over time HR (P<0.001), while atipamezole gradually reported these values close to baseline (P>0.05). Acepromazine+dexmedetomidine significantly decreased HR (P<0.001), reaching steady values after 5 minutes (P>0.05); atipamezole gradually raised this value close to baseline (P>0.05). Peripheral perfusion under isoflurane anesthesia showed an increasing trend after 10 and 20 minutes (4.25 to 4.55 volts), without significant differences among groups (P=0.1). Between 10 and 20 minutes after acepromazine administration, a significant perfusion increase was observed from 4.55 to 4.85 volts (P=0.005). Dexmedetomidine significantly reduced blood perfusion (2.47 volts) after 5 minutes (P=0.0001), followed by an increase to 4.32 volts after 15 minutes (P=0.008). No significant changes (4.34 volts) were seen 5 minutes after atipamezole (P=0.9). Administration of acepromazine+dexmedetomidine resulted in steady perfusion values over time (P=0.44), which after atipamezole increased to 4.4 volt, very close to baseline values (P=0.237). Conclusions: Concurrent administration of acepromazine and dexmedetomidine in mice produced more temperate and steady peripheral perfusion values compared to those following single agent, reducing the entity of the ?2 -agonist biphasic hemodynamic pattern. Our translational approachby LDPI in a new mouse model allows an easy, accurate and non invasive measurement of the effects of anesthetics on peripheral microcirculation. Bibliography 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. Brouns, M. F. Callahan, T. L. Smith, "Effects of anesthetics on systemic hemodynamics in mice," Am J Physiol Heart Circ Physiol, vol. 4, no. 287, pp. 1618-1624, 2004. 3.Z. Turek, R. Sykora, M. Matejovic, V .Cerni, "Anesthesia and microcirculation," Seminars in Cardiothoracic and Vascular Anesthesia, vol. 4, no.13, pp. 249-258, 2009. 4.Adelaide Greco, Monica Ragucci, Raffaele Liuzzi, Sara Gargiulo, Matteo Gramanzini, Anna Rita Daniela Coda, Sandra Albanese, Marcello Mancini, Marco Salvatore and Arturo Brunetti. Reproducibility and Standardization of Laser doppler Imaging technique for the evaluation of normal mice hindlimbs perfusion. Sensor 2013, 13(1):500-515I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
