ABSTRACT
Zoletil is an anesthetic and immobilizing drug that has been used in the veterinary field for over 50â¯years; however, the effect of Zoletil, or its constituents, on brain cystathionine ß-synthase (CBS) remains unknown. Here, we aimed to determine the effect of Zoletil on rat brain CBS by administering a single intraperitoneal injection of the drug and examining hydrogen sulfide (H2S) and CBS levels in the cerebral cortex, hippocampus, and thalamus following three distinct behavioral phenotypes associated with the sedation procedure (e.g., loss of the righting reflex, return of the righting reflex, and return of walking). Zoletil administration resulted in significant decreases of endogenous H2S in the cerebral cortex, hippocampus, and thalamus, and H2S was observed to increase in these brain regions when rats recovered from the anesthesia. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry revealed that CBS expression in the cerebral cortex and hippocampus exhibited the same trend as endogenous H2S following Zoletil administration. In summary, our results demonstrated that Zoletil induced the expression of CBS which could exert region-specific regulation of H2S in the cerebral cortex and hippocampus.
Subject(s)
Anesthetics/pharmacology , Brain/drug effects , Brain/metabolism , Cystathionine beta-Synthase/genetics , Gene Expression Regulation/drug effects , Tiletamine/pharmacology , Zolazepam/pharmacology , Anesthetics/administration & dosage , Animals , Cystathionine beta-Synthase/metabolism , Drug Combinations , Female , Hydrogen Sulfide/metabolism , Immunohistochemistry , Injections, Intraperitoneal , Male , Organ Specificity , Rats , Tiletamine/administration & dosage , Zolazepam/administration & dosageABSTRACT
OBJECTIVE: To evaluate the antagonistic effects of atipamezole (ATI), flumazenil (FLU) and naloxone (NAL) alone and in various combinations following administration of tiletamine-zolazepam-xylazine-tramadol. STUDY DESIGN: Prospective, experimental, randomized cross-over study. ANIMALS: Eight Chinese miniature pigs (three females and five males) mean age 8 (range 7-10) months and bodyweight 57.5 (52.4-62.1) kg. METHODS: All animals were anaesthetized with tiletamine/zolazepam (3.0 mg kg(-1)), xylazine (1.2 mg kg(-1)) and tramadol (1.6 mg kg(-1)) given intramuscularly (IM). Thirty minutes later, one of eight treatments was administered IM: saline control, ATI (0.12 mg kg(-1)), FLU (0.1 mg kg(-1)), NAL (0.03 mg kg(-1)), ATI-FLU, FLU-NAL, ATI-NAL or ATI-FLU-NAL. After injection of antagonists the following times were recorded: to recovery of the palpebral, pedal and tail clamp reflexes, to head movement, sternal recumbency, standing and walking. Posture, sedation, analgesia, jaw relaxation and auditory response were scored at set times until 120 minutes after injection of antagonists. Heart rates, respiratory rates and rectal temperature were measured at those times. Data were analyzed by anova for repeated measures, followed by the Tukey's test to compare differences between means, or by Kruskal-Wallis test as appropriate. RESULTS: FLU, NAL alone, or FLU-NAL did not effectively antagonize anaesthesia induced by tiletamine/zolazepam-xylazine-tramadol. ATI, ATI-FLU, ATI-NAL and ATI-FLU-NAL produced an immediate and effective recovery from anaesthesia. The combination of ATI-FLU-NAL was the most effective combination in antagonizing the anaesthetic effect. Adverse effects such as tachycardia, tachypnoea, excitement and muscle tremors were not observed during this study. CONCLUSION AND CLINICAL RELEVANCE: ATI-FLU-NAL is the most effective combination for antagonizing tiletamine/zolazepam-xylazine-tramadol anaesthesia in pigs. However, ATI alone or in various combinations also provides effective antagonism.
