Goats have been used as animal models in research and are increasingly kept as companion animals. However, information about effective anesthetic drugs is scarce in this species. The objective of this study was to evaluate the effect of xylazine premedication on alfaxalone induction. Twelve clinically healthy goats weighing 18.5 ± 2 kg were randomly assigned to two groups. Induction was performed with alfaxalone alone intravenously (ALF group) or with xylazine premedication before alfaxalone administration (XYL-ALF group). The quality of induction was scored, induction doses of alfaxalone were determined, and cardiorespiratory parameters and nociceptive thresholds were measured before any treatment(s) (baseline) and at 5, 15, 25 and 35 min after alfaxalone administration. The mean dose of alfaxalone required for induction in the ALF group was greater than that in the XYL-ALF group (p < 0.001). There were no significant changes in diastolic arterial pressure (DAP), mean arterial pressure (MAP) or systolic arterial pressure (SAP) compared to baseline in either group, while hemoglobin oxygen saturation (SpO2) was lower from 5 to 25 min (p < 0.5) in the XYL-ALF group. The nociceptive threshold was significantly higher at 5 min in the XYL-ALF group than in the ALF group (p = 0.0417). Xylazine premedication reduced the required dose of alfaxalone for anesthetic induction and produced better antinociception than alfaxalone alone. In addition, the combination of xylazine and alfaxalone allowed for successful induction; however, oxygen supplementation is necessary to counteract xylazine-associated hypoxemia.
12 March 2021 in Journal of Veterinary Pharmacology and Therapeutics
Goats have been used as animal models in research, and the need for achieving safer anesthesia for research or surgical intervention is gaining much attention. The objective of this study was to evaluate intraoperative effects and the immediate postoperative analgesia of nalbuphine–ketamine regimen in goats. Twenty clinically healthy adult female crossbred goats weighing 14 ± 2 kg were allocated randomly into each of two equally sized groups. All animals were sedated with intramuscular (IM) xylazine (0.07 mg/kg), then anesthesia was intravenously (IV) induced with ketamine alone (10 mg/kg) (XK group), or a combination of nalbuphine (0.5 mg/kg) and ketamine (5 mg/kg) (XNK group). Following induction, left flank laparotomy was performed and then sutured. The quality of anesthesia and immediate postoperative analgesia was evaluated. Immediate postoperative analgesia was assessed up to 5 h after standing, using a modified Unesp–Botucatu acute composite pain scale (USAPS). Serum cortisol, glucose, insulin, and C-reactive protein (CRP) were measured at ½, 1, 2, 4, 6, 12, and 24 h, postoperatively (PO). The USAPS pain scores were significantly lower in the XNK compared to the XK group (p < 0.05). The XNK group exhibited a statistically significant difference in the level of serum cortisol at ½ and 1 h PO (p = 0.018 and 0.045, respectively) compared to the XK group. At 2, 4, 6 h PO, CRP significantly decreased (p = 0.023, 0.040 and 0.005, respectively) in the XNK compared to the XK group. Nalbuphine–ketamine produced an acceptable induction of anesthesia and recovery compared to ketamine. Recovery with nalbuphine–ketamine was faster and better quality. The USAPS pain scores were lower in nalbuphine–ketamine, indicating that this novel combination produces better postoperative pain control than ketamine alone.
Electroacupuncture (EA) treatment has proved to significantly decrease nociception in inflammatory nociception model by suppressing the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). However, repeated EA treatment results in gradual attenuation of its analgesic effects, which was defined as “EA tolerance.” Recent studies have shown that let-7b-5p microRNA (miRNA) contributes to the EA tolerance. The present study aimed to explore the function of let-7b-5p in p38MAPK pathway and the development of EA tolerance in the inflammatory nociception. Dual luciferase reporter gene experiments were used in cortical neurons to determine the target gene locus of let-7b-5p. The threshold of nociception was assessed by tail flick latency (TFL) and paw withdrawal threshold (PWT). Western blots were used to measure the expression of mitogen-activated protein kinase phosphatase 1 (MKP-1) and phosphorylation level of p38MAPK after intracerebroventricular (ICV) injections of let-7b-5p agomir, antagomir, and controls. In vitro dual luciferase experiments demonstrated that the MKP-1-3′ untranslated region (UTR) is a target of let-7b-5p. In vivo experiment, rat with repeated EA treatment exhibits gradual decrease in TFL and PWT, which showed formation of EA tolerance. This trend was delayed after IVC injection of let-7b-5p antagomir and facilitated after IVC injection of let-7b-5p agomir. The protein levels of MKP-1 in the EA+let-7b-5p antagomir group were significantly higher than in the EA + let-7b-5p agomir group. However, P-p38MAPK in the EA+let-7b-5p antagomir group was significantly lower than in the EA+let-7b-5p agomir group. By upregulating the p38MAPK pathway through the inactivation of the MKP-1 gene, let-7b-5p contributes to EA tolerance in complete Freund’s adjuvant (CFA)-induced inflammatory nociception rats. Our work revealed the mechanism of EA tolerance and indicated that let-7b-5p could be targeted to improve the long-term effects of EA.
Total intravenous anesthesia (TIVA) is increasingly used in companion animals. The effect of electroacupuncture (EA) on alfaxalone-based TIVA has not been previously reported in goats. Therefore, the objective of this study was to determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to standardized noxious stimulation during its combination with EA in goats. Twelve clinically healthy goats weighing 18.5 ± 2 kg were randomly assigned to two groups (six goats/group). Alfaxalone alone (ALF group) and alfaxalone combined with EA (EA-ALF group). In the EA-ALF, alfaxalone was administered 30 min after EA stimulation. For induction of anesthesia, a bolus of alfaxalone was given at 3 mg/kg IV, and an infusion dose of 9.6 mg/kg/h was initially set for maintenance. The MIR of alfaxalone in both groups was determined by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) at 10-min intervals after induction of anesthesia till the entire period of the experiment. Cardiopulmonary parameters and nociceptive threshold were measured throughout anesthesia. The median alfaxalone MIR was significantly lower in the EA-ALF group than the ALF group [9 (4.8–9.6) and 12 (11.4–18)], respectively; p = 0.0035). In the ALF group, goats anesthetized with MIR showed a significant increase in heart rate and cardiac output (p < 0.0001 and 0.0312, respectively), and decrease in respiratory rate (p < 0.0001), hemoglobin oxygen saturation (p = 0.0081), and rectal temperature (p = 0.0046) compared with those in the EA-ALF. Additionally, goats in the EA-ALF showed a higher nociceptive threshold than those in the ALF group (p < 0.0001). EA provided analgesia, reduced the MIR of alfaxalone-based IV anesthesia and thereby alleviated the adverse cardiorespiratory effects associated with alfaxalone anesthesia in goats.
Adenosine (AD) has been implicated in human healthcare as an endogenous signaling nucleotide in both physiologic and pathologic states. The effects of AD on cardiorespiratory parameters in ruminants has not yet been studied. The objective of this study was to evaluate the cardiac and respiratory changes that resulted from an intravenous AD infusion in goats. Six clinically healthy adult goats weighing 28 ± 2 kg were randomly assigned to one of four treatments in a crossover design with a seven day washout period. The goats received a 0.9 % saline solution (SAL treatment) and three AD treatments (AD 50, 100 and 200) intravenously at a dose rate of 50, 100 and 200 μg/kg/min. Cardiorespiratory and key cardiac parameters were measured before the treatment (baseline), during the infusion (dInf) and at 1, 3, 5 and 10 min after each infusion was discontinued. The AD 100 produced a significant increase in HR (p = 0.001) and the AD 200 resulted in significant rises in HR (p = 0.006) and RR (p = 0.001) compared with the baseline. This study concluded that the AD infusion could trigger an increase in HR and RR in a dose-dependent manner in healthy goats.
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College of Veterinary, Huazhong Agricultural University, Wuhan, Hubei, China
College of Veterinary, Huazhong Agricultural University, Wuhan, Hubei, China