Effects of tolazoline and yohimbine on xylazine-induced central nervous system depression, bradycardia, and tachypnea in sheep

We compared the ability of tolazoline and yohimbine to antagonize xylazine-induced central nervous system depression, bradycardia, and tachypnea in 9 ewes and 5 rams. Once a week for 3 weeks, each sheep received one IV treatment of 0.4 mg xylazine/kg, 0.4 mg xylazine/kg followed in 10 minutes by 2 mg tolazoline/kg, or 0.4 mg xylazine/kg followed in 10 minutes by 0.2 mg yohimbine/kg. The order of the 3 treatments in each sheep was randomized. Xylazine alone caused recumbency for 41.0 +/- 3.7 minutes (mean +/- SEM). Tolazoline and yohimbine shortened the xylazine-induced recumbency to 12.1 +/- 0.9 minutes and 18.1 +/- 1.5 minutes, respectively. Sheep given xylazine alone had head droop for 34.0 +/- 5.4 minutes after rising. Head drooping of sheep given tolazoline or yohimbine was reduced to 10.1 +/- 1.7 minutes and 14.2 +/- 1.7 minutes, respectively. Both tolazoline and yohimbine reversed the bradycardia and tachypnea that followed xylazine administration. No statistical differences in the rate and magnitude of the reversal were observed between the 2 drugs.     

Effects of idazoxan, tolazoline, and yohimbine on xylazine-induced respiratory changes and central nervous system depression in ewes

We compared the ability of 3 alpha 2-adrenoreceptor antagonists, idazoxan (0.05 mg/kg), tolazoline (2 mg/kg), and yohimbine (0.2 mg/kg) to reverse xylazine (0.3 mg/kg)-induced respiratory changes and CNS depression in 6 ewes. Once weekly, each ewe was given a random IV treatment of xylazine, followed in 5 minutes by either an antagonist or 0.9% NaCl solution. Xylazine alone caused recumbency for 54.2 +/- 5.3 minutes (mean +/- SEM). Xylazine also increased respiratory rate and decreased PaCO2 for at least 45 minutes, but did not significantly change arterial pH or PaCO2. Idazoxan and tolazoline were equally effective in reversing the respiratory actions of xylazine; however, yohimbine was less effective in reducing the respiratory rate and was ineffective in antagonizing the decreased PaO2. Idazoxan and tolazoline decreased the duration of xylazine-induced recumbency to 6.3 +/- 0.6 and 9.5 +/- 2.3 minutes, respectively, whereas yohimbine did not significantly change this effect of xylazine. Thus, at the dosages studied, idazoxan and tolazoline appeared to be more effective than yohimbine in reversing the respiratory and CNS depressant actions of xylazine in sheep.     

Antagonistic effect of atipamezole on xylazine-induced sedation, bradycardia, and ruminal atony in calves.

Three doses of an alpha 2-adrenoreceptor antagonist, atipamezole, were administered to reverse xylazine-induced sedation, bradycardia, and ruminal atony in calves. Once a week for 4 weeks, each of 6 calves was administered IV 1 treatment of: 0.3 mg of xylazine/kg of body weight, followed in 10 minutes by 1 ml of 0.9% NaCl; 0.3 mg of xylazine/kg, followed in 10 minutes by 3 micrograms of atipamezole/kg; 0.3 mg of xylazine/kg, followed in 10 minutes by 10 micrograms of atipamezole/kg; or 0.3 mg of xylazine/kg, followed in 10 minutes by 30 micrograms of atipamezole/kg. The order of the 4 treatments in each calf was selected at random. Xylazine alone caused lateral recumbency for 33.6 +/- 7.1 minutes (mean +/- SEM). Atipamezole administered at dosages of 3, 10, and 30 micrograms/kg shortened xylazine-induced lateral recumbency to 20.5 +/- 3.0, 10.2 +/- 0.2, and 9.3 +/- 0.5 minutes, respectively. Calves given xylazine alone stood at greater than 60 minutes after the onset of recumbency. Atipamezole given at 3, 10, and 30 micrograms/kg shortened the time from onset of lateral recumbency to standing to 40.2 +/- 6.9, 12.8 +/- 1.1, and 10.0 +/- 0.7 minutes, respectively. Drowsiness was found in calves given the lowest dosage of atipamezole (3 micrograms/kg) after the calves stood. Atipamezole given at dosages of 10 and 30 micrograms/kg reversed xylazine-induced ruminal atony in a dose-dependent manner. In addition, 30 micrograms of atipamezole/kg reversed xylazine-induced bradycardia, but the lower dosages of this antagonist did not. Results indicated that 30 micrograms of atipamezole/kg should be a useful antidote for xylazine overdose in cattle.     

Influence of yohimbine on xylazine-induced depression of central nervous, gastrointestinal and cardiovascular function in the calf

The antagonistic effect of yohimbine HCl (0.25 mg/kg IV), and alpha 2-adrenergic antagonist, on xylazine (0.05 mg/kg IV)-induced depression of central nervous and cardiovascular activity and rumen motility was studied in post-weaning calves. Yohimbine, administered 3 min post-xylazine, significantly decreased the duration of rumen amotility (38.3 +/- 4.2 min versus 14.0 +/- 2.2 min). Sedation, however, as monitored by the duration of fetlock knuckling in calves suspended in a body sling, was not shortened by yohimbine treatment. Yohimbine alone produced a significant tachycardia and led to a reduction of the duration of xylazine-induced bradycardia. Our data indicate that yohimbine produces a significant reversal of xylazine-induced rumen hypomotility at dosage levels that are without effect on sedation induced by this drug.     

Antagonistic effects of intravenous or epidural atipamezole on xylazine-induced dorsolumbar epidural analgesia in cattle

This study was performed to clarify the antagonistic actions of intravenous or epidural atipamezole on the sedative and analgesic effects of xylazine administered between the epidural fat and dura mater through the first interlumbar space in cattle.Cattle received 5 mL of a solution containing 0.05 mg x kg(-1) xylazine in 0.9% saline. Thirty minutes later, 5 mL of 0.9% saline was administered through the same needle (treatment 1) (XSE). In treatments 2 (XAE) and 3 (XAV), 5 mL of a solution containing 0.025 mg x kg(-1) atipamezole in 0.9% saline was administered epidurally or intravenously, respectively.Sedation and analgesia were similar in all three treatment groups and could be reversed by atipamezole given by either route. In the XAV treatment, the flank area relapsed into analgesia 25+/-5.8 min following reversal of the analgesic effect, and was maintained for 112.5+/-63.8 min.The present study confirmed that the sedative and analgesic effects of xylazine are completely reversed by atipamezole and can be influenced by the epidural fat in cattle. Furthermore, it seems probable that analgesia following epidural administration of xylazine is mediated by alpha(2)-adrenergic receptors, not by a local anaesthetic effect.     

Antagonistic effects of atipamezole,yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α₂-adrenoceptors but not α₁-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.     

Antagonism of xylazine induced sedation by idazoxan in calves.

Idazoxan was studied at three dose rates to assess its potential as an antagonist to xylazine. Calves in the study group were initially given xylazine at a dose rate of 0.2 mg/kg intravenously followed 12 minutes later by idazoxan at a dose rate of either 0.05, 0.075 or 0.10 mg/kg intravenously. A control group received a saline injection instead of idazoxan. All three dose levels of idazoxan successfully reversed the xylazine induced central nervous depression and all animals stood within two minutes of injection. No residual signs of sedation were noticed and relapse did not occur. In addition idazoxan was successful in reversing respiratory and cardiovascular depression produced by xylazine. The results indicated that idazoxan may be used for rapid reversal of xylazine induced sedation in calves.     

Nogo与中枢神经再生

哺乳动物体内大部分组织如肌肉、皮肤、肝脏和外周神经，损伤后均有很强的再生能力，而中枢神经系统(CNS)却很难再生，损伤后的轴突及神经元几乎不能再生，导致损伤后功能迟迟不能恢复。1981年，David和Aguayo报道了成年动物的轴突能够在外周神经移植物中再生，提示在CNS内环境中可能含有某种抑制性物质，从而导致其再生能力受限。     

Reversal of xylazine-induced sedation in dairy calves with atipamezole: A field trial

Dairy calves immobilized with xylazine (XYL) were given atipamezole-HCl (ATI) at different XYL:ATI dose ratios (w/w) for reversal and the antagonistic effect of xylazine was evaluated. Control animals received saline for comparison. Intramuscular administration of xylazine (0.139–0.357 mg/kg) induced sedation with complete immobilization in all animals (n=195) and there were no spontaneous recoveries before injection of atipamezole or saline. Atipamezole was given 10–81 min and saline 25 min after xylazine administration. Intramuscular administration of atipamezole at XYL:ATI dose ratios of 5:2 (n=11), 10:3 (n=21), 4:1 (n=21) and 5:1 (n=25) effectively antagonized the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 6.09 (3.12), 5.15 (2.87), 6.35 (2.54) and 7.86 (3.11) min, respectively. The mean time to standing for control animals (n=11) was 94.1 (3.0) min. Intravenous administration of atipamezole at XYL:ATI dose ratios of 10:3 (n=7), 4:1 (n=33), 5:1 (n=16), 8:1 (n=27) and 10:1 (n=9) rapidly reversed the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 0.98 (0.22), 1.32 (0.48), 1.09 (0.34), 1.39 (0.52) and 1.60 (0.69) min, respectively. The mean time to standing for control animals (n=14) was 88.1 (13.1) min.Animals given high doses of atipamezole (dose ratio groups 5:2 intramuscularly, 10:3 intravenously and 4:1 intravenously) showed signs of excitement while in animals given low doses of atipamezole (dose ratio groups 5:1 intramuscularly and 10:1 intravenously) resedation and relapse into recumbency occurred. Medium doses of atipamezole (dose ratio groups 10:3 intramuscularly, 4:1 intramuscularly, 5:1 intravenously and 8:1 intravenously) did not cause any undesirable side-effects or resedation, and can be recommended for reversal of xylazine-induced sedation in dairy calvesAbbreviations ATI atipamezole-HCl - BW body weight - IM intramuscular - IV intravenous - SD standard deviation - XYL xylazine     

叶酸对铅中毒幼年大鼠中枢神经系统的保护作用

通过研究铅对大鼠中枢神经元的损伤以及应用叶酸后的影响,探讨了叶酸对铅中毒条件下中枢神经元的保护作用。将健康清洁级初断乳3周龄SD大鼠随机分为铅染毒组,叶酸给药组及生理盐水组。各组于处理后第2、3、4周取材。铅染毒组、叶酸给药组每组各30只,生理盐水组12只,共72只。测量血铅,分别进行海马和小脑组织的H—E染色及凋亡抑制基因Bcl—2、凋亡基因Bax的蛋白免疫电泳,并作光密度分析。结果,通过对各个时间段各组血铅测定,可得叶酸给药组血铅含量低于铅染毒组。铅染毒组Bcl-2蛋白表达量少于给药组,而Bax多于给药组,H—E染色结果铅染毒组神经细胞数量明显少于叶酸给药组。结果表明,叶酸可降低铅中毒大鼠的血铅浓度,并具有一定抗细胞损伤作用,对铅中毒大鼠的中枢神经元具有一定的保护作用。     

高氟对中枢神经系统的影响

综述了氟对智商影响的流行病学调查结果,并通过总结氟对中枢神经系统的直接损伤和氟与其他元素互作对中枢神经的影响,多角度阐释了高氟对中枢神经系统机能影响的机理.     

Effects of dipyrone on endotoxininduced fever, central nervous depression and hypoglycaemia in sheep

Sixteen sheep were divided into four groups and were given saline, Escherichia coli endotoxin at 35 micrograms/kg0.75, dipyrone at 88 mg/kg0.75, or endotoxin and dipyrone intravenously. Plasma glucose concentrations, rectal temperature and depression of central nervous function were assessed at hourly intervals for 10 h and again at 24 h. Dipyrone had no effect on normal sheep but in sheep given endotoxin, it blocked the febrile response and partially blocked the depression effect upon the central nervous system without affecting the hypoglycaemic response.     

Clinical use of yohimbine as an antagonist of xylazine depression of the central nervous system in cats

Antagonizing effects of various doses of yohimbine on a xylazine depression of the cerebroneural system (CNS) were studied in cats. Administration of various doses of yohimbine was investigated with respect to its antagonizing effects on various doses of xylazine. The time of CNS depression induced by commonly recommended doses of xylazine (2-4 mg/kg live weight) was shortened statistically significantly by intramuscular injections of yohimbine at a dose of 3 mg per kg live weight. After this yohimbine dose, the animals recovered consciousness already 10-15 minutes from application, with the complete resumption of reflexes. Preventive administration of the same dose of yohimbine hindered reliably the full development of CNS depression after the two xylazine doses (2 and 4 mg/kg live weight).     

Toll-like receptor expression in the nervous system of bovine alpha-herpesvirus-infected calves

In this study, the expression levels of viral Toll-like receptors (TLRs) in the nervous system of bovine herpesvirus type 5 (BoHV-5)-infected calves were investigated. A significant increase in the expression of TLRs 3 and 7–9 was found in the anterior cerebral cortex during acute infection and viral reactivation. In the trigeminal ganglia, only TLR9 expression was significantly affected. The magnitude of the increase was lower in BoHV-1-infected calves, suggesting that a restricted immune response might protect against exacerbated inflammatory responses in the brain. This work describes, for the first time, the involvement of TLRs 3 and 7–9 in the recognition of BoHV in the bovine nervous system, indicating that the expression of these receptors might be associated with the development of neurological disease. Modulation of the signalling pathways mediated by TLRs might provide an effective approach to control the neuro-immune response to BoHV-5, which may be responsible for neurological lesions.     

Evaluation of the bispectral index as an indicator of degree of central nervous system depression in isoflurane-anesthetized horses

OBJECTIVE: To determine whether the bispectral index (BIS) can be used as an indicator of degree of CNS depression in isoflurane-anesthetized horses. ANIMALS: 10 Standardbred and 6 Norwegian cold-blooded trotter stallions admitted for routine castration. PROCEDURE: A 2-channel referential electrode configuration was used to record EEG for calculation of BIS by the EEG monitor. The BIS was calculated before (awake) and after (sedated) administration of detomidine (0.01 mg/kg of body weight, IV) and butorphanol (0.01 mg/kg, IV). Anesthesia was induced with ketamine hydrochloride (2.5 mg/kg, IV) and diazepam (0.04 mg/kg, IV) and maintained with isoflurane delivered in oxygen. The BIS was calculated after 30 minutes of equilibration at an end-tidal isoflurane concentration of 1.4% (n = 8) or 1.9% (8) and recorded continuously during surgery. RESULTS: Bispectral index was significantly less in sedated and anesthetized horses, compared with awake horses. However, BIS was not significantly different between sedated and anesthetized horses. Mean BIS in horses anesthetized at 1.9% isoflurane was significantly greater, compared with horses anesthetized at an end-tidal concentration of 1.4%. Four horses in the 1.4% group moved during surgery, and BIS increased immediately prior to movement in 2 of these horses. CONCLUSIONS AND CLINICAL RELEVANCE: BIS is not a precise indicator of degree of CNS depression in isoflurane-anesthetized horses. Thus, determination of BIS may not be a useful technique for monitoring anesthetic depth in isoflurane-anesthetized horses.