右美托咪定抑制NOX4缓解急性应激致大鼠肾损伤

本研究拟探索右美托咪定（dexmedetomidine,DEX）对大鼠急性应激致肾损伤的保护作用,并从氧化应激的角度探索DEX对大鼠肾的保护通路。本研究使用了急性束缚应激模型,其中,大鼠被迫游泳15 min,并束缚3 h。本试验采用生化检测、组织病理学切片观察以评估肾功能,然后测定了氧化应激以及氧化应激的相关通路蛋白。旷场试验证实成功建立了急性应激模型。急性应激引起的肾损伤增加了NOX4,降低了Nrf2/HO-1/NQO1表达水平。DEX可降低NOX4表达,同时升高Nrf2/HO-1/NQO1的表达水平。DEX治疗组与急性应激组相比的肾生化结果明显恢复正常,病理切片观察损伤显著降低。试验结果表明,DEX治疗急性应激可影响NOX4/Nrf2/HO-1/NQO1信号通路,并抑制氧化应激。因此,DEX对急性应激引起的肾损伤具有保护作用,并在应激综合征中具有潜在的临床应用。     

Retrospective evaluation of acute hyperkalemia of unknown origin during general anesthesia in dogs

ObjectiveTo report and characterize cases of acute hyperkalemia of unknown origin in dogs under anesthesia.Study designMulticentric retrospective clinical study.AnimalsMedical records of 19 client-owned dogs that developed acute hyperkalemia during anesthesia.MethodsAnesthetic records of dogs developing acute hyperkalemia from January 2015 to December 2022 were evaluated. Data collected included demographics, duration of anesthesia until the episode, electrolytes and blood gas measurements, electrocardiogram (ECG) abnormalities, drugs used as part of the anesthetic protocol, hyperkalemia treatment and outcome.ResultsA total of 13 cases met the inclusion criteria with documented acute hyperkalemia with no apparent underlying cause during anesthesia. Dogs were [mean ± standard deviation (range)] 6.5 ± 5.0 (3–10) years old and weighed 18.0 ± 14.3 (5.1–40.0) kg. All dogs were administered dexmedetomidine and an opioid as part of the premedication. All dogs had inhalation anesthesia of >60 minutes’ duration. The first clinical sign was bradycardia that was minimally responsive to anticholinergic administration and was often accompanied by moderate/severe hypotension. These signs were rapidly followed by ECG changes compatible with hyperkalemia and/or cardiac arrest. Rapid identification and treatment for hyperkalemia, with or without dexmedetomidine reversal, resulted in survival of 12 dogs and one fatality.Conclusions and clinical relevanceUnknown origin hyperkalemia is a life-threatening complication that can occur during general anesthesia. In healthy dogs, preanesthetic administration of dexmedetomidine in association with an opioid and followed by inhalation anesthesia of more than 1 hour duration may predispose to this complication. A sudden decrease in heart rate >90 minutes after dexmedetomidine administration, or ECG changes, may warrant measurement of blood potassium concentrations.     

Comparison of the sedative effects of intranasal or intramuscular dexmedetomidine at low doses in healthy dogs: a randomized clinical trial

ObjectiveTo compare the sedative effects of dexmedetomidine administered either intranasally or intramuscularly to healthy dogs.Study designProspective, randomized, blinded, clinical trial.AnimalsA group of 16 client-owned healthy dogs.MethodsDogs were randomly allocated to one of two groups that were administered dexmedetomidine 5 μg kg^–1 via either the intranasal route (IN_Dex), through a mucosal atomization device in one nostril, or the intramuscular route (IM_Dex), into the epaxial muscles. Ease of intranasal administration, sedation score, onset of sedation, cardiopulmonary variables, mechanical nociceptive thresholds (MNTs) and response to venous catheterization were recorded at 0 (baseline), 5, 10, 15, 20, 25, 30, 35, 40 and 45 minutes, following drug administration. Data were compared with the one-way anova, Mann-Whitney U test, and chi-square test, where appropriate.ResultsGroups were not different for age, sex, weight, body condition score or temperament. Sedation scores, MNTs and response to intravenous catheter placement were not different when dexmedetomidine was administered by either route (p = 0.691; p = 0.630 and p = 0.435, respectively). Onset of sedation was not different between groups IN_Dex and IM_Dex reaching a score of 4.2 ± 0.9 and 5.5 ± 1.2 at 9 ± 5 and 8 ± 4 minutes, respectively (p = 0.467). The highest sedation score was achieved at 30 and 35 minutes and sedation scores were 9.7 ± 2.0 and 9.5 ± 2.3 in groups IN_Dex and IM_Dex, respectively (p = 0.799). Respiratory rate was higher in group IN_Dex (p = 0.014), while there were no differences between routes in heart rate (p = 0.275), systolic (p = 0.957), diastolic (p = 0.837) or mean arterial pressure (p = 0.921).Conclusions and clinical relevanceIntranasal administration of dexmedetomidine at 5 μg kg^–1 provides effective sedation in healthy dogs.     

Effects of two different anesthetic protocols on 64‐MDCT coronary angiography in dogs

Heart rate is a major factor influencing diagnostic image quality in computed tomographic coronary artery angiography (MDCT‐CA), with an ideal heart rate of 60–65 beats/min in humans. The purpose of this prospective study was to compare effects of two different clinically applicable anesthetic protocols on cardiovascular parameters and 64‐MDCT‐CA quality in 10 healthy dogs. Scan protocols and bolus volumes were standardized. Image evaluations were performed in random order by a board‐certified veterinary radiologist who was unaware of anesthetic protocols used. Heart rate during image acquisition did not differ between protocols (P = 1), with 80.6 ± 7.5 bpm for protocol A and 79.2 ± 14.2 bpm for protocol B. Mean blood pressure was significantly higher (P > 0.05) using protocol B (protocol A 62.9 ± 9.1 vs. protocol B 72.4 ± 15.9 mmHg). The R‐R intervals allowing for best depiction of individual coronary artery segments were found in the end diastolic period and varied between the 70% and 95% interval. Diagnostic quality was rated excellent, good, and moderate in the majority of the segments evaluated, with higher scores given for more proximal segments and lower for more distal segments, respectively. Blur was the most commonly observed artifact and mainly affected the distal segments. No significant differences were identified between the two protocols for optimal reconstruction interval, diagnostic quality and measured length individual segments, or proximal diameter of the coronary arteries (P = 1). Findings indicated that, when used with a standardized bolus volume, both of these anesthetic protocols yielded diagnostic quality coronary 64‐MDCT‐CA exams in healthy dogs.     

A preliminary trial of the sedation induced by intranasal administration of midazolam alone or in combination with dexmedetomidine and reversal by atipamezole for a short‐term immobilization in pigeons

ObjectiveTo assess the sedative and immobilization effect of intranasal administration (INS) of midazolam (MID) without or with INS dexmedetomidine (DXM), and some physiological changes induced by the drugs. The ability of INS atipamezole to reverse the DXM component was also assessed.Study designProspective ‘blinded’ experimental study.AnimalsIn total, 15 pigeons.MethodsPigeons were sedated by INS MID alone at a dose of 5 mg kg⁻¹ (group MID, n = 6) or in combination with INS DXM at a dose 80 μg kg⁻¹ (group MID-DXM, n = 6). Measurements were made of heart rate (HR), respiratory rate (f_R) and cloacal temperature (CT). The degree of sedation was assessed at 15 minutes prior to, immediately after, and at intervals until 100 minutes after drug administrations. Following MID-DXM, INS atipamezole (250 μg kg⁻¹) was administered and the same indices measured 5 and 10 minutes later.ResultsMID had no effect on HR and f_R, and although CT decreased, it remained within physiological range. MID-DXM caused significant falls in HR, f_R and CT that persisted until the end of sedation. Atipamezole antagonized sedation and cardiorespiratory side effects of MID-DXM within 10 minutes of application. In addition, for MID compared to MID-DXM, the lowest sedation scores [10 (7–14) and 10.5 (5–14) versus 2 (1–4) and 2 (1–5)] were achieved in the 10th and 20th minute versus the 20th and 30th minute of the sedation, respectively.Conclusions and clinical relevanceMID alone, given INS had minimal side effects on vital functions but caused inadequate immobilization of pigeons for restraint in dorsal recumbency. MID-DXM caused an effective degree of immobilization from 20 to 30 minutes after administration, at which time birds tolerated postural changes without resistance. Atipamezole antagonized both side effects and sedation, but complete recovery had not occurred within 10 minutes after its application.     

Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats

ObjectiveTo compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats.Study designRandomized, ‘blinded’ crossover study, with 1 month washout between treatments.AnimalsSix healthy neutered female cats, weighing 5.3–7.5 kg.MethodsA combination of dexmedetomidine (40 μg kg^?1) and buprenorphine (20 μg kg^?1) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat’s response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range.ResultsThere were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing.Conclusions and clinical relevanceIn healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats.     

右美托咪定复合舒芬太尼用于老年患者术后自控静脉镇痛的效果观察

目的观察盐酸右美托咪定复合舒芬太尼用于老年患者术后自控静脉镇痛（PCIA）的有效性和安全性．方法所有患者手术均采用咪达唑仑、顺式阿曲库铵、丙泊酚、芬太尼行麻醉诱导,顺式阿曲库铵、芬太尼与丙泊酚维持麻醉,术后患者随机分为A,B,C3组,使用PCA泵镇痛;分别记录苏醒后（T0）,术后4h（T1）,8h（T2）,12h（T3）,24h（T4）VAS评分;Ramsay镇静评分;术后不同时点PCA按压次数;24h舒芬太尼累计用量;镇痛期间低血压等不良反应的发生情况．结果术后24h内VAS评分A,B组高于C组（P〈0．05）;Ramsay镇静评分：A,B组低于C组（P〈0．05）;24h镇痛泵的总按压次数A组高于B组（P〈0．05）,B组高于c组（P〈0．05）;与术前相比,A组术后血压、心率变化不明显,而B,C两组术后血压、心率下降（P〈0．05）;3组患者术后均无呼吸抑制和镇静过度等不良反应（P〉0．05）,恶心的不良反应发生率B,C组明显少于A组（P〈0．05）．结论盐酸右美托咪定复合舒芬太尼用于老年患者术后自控静脉镇痛安全、有效．     

Assessment of dexmedetomidine/ketamine anesthesia in golden-headed lion tamarins (Leontopithecus chrysomelas)

OBJECTIVE: To compare the anesthetic and cardiovascular effects of dexmedetomidine/ketamine combinations in golden-headed lion tamarins. STUDY DESIGN: Prospective blinded randomized study. ANIMALS: Six healthy golden-headed lion tamarins, three males and three females were studied (mean body weight +/- SD = 0.498 +/- 0.054 kg). METHODS: The animals were given one of the dexmedetomidine/ketamine combinations (0.005/10, 0.01/10, and 0.01/5 mg kg(-1) IM; treatments 5D/10K, 10D/10K, and 10D/5K, respectively) on three successive occasions. Time to sedation and recumbency, as well as anesthesia, standing, and walking times were recorded. Heart and respiratory rate, arterial blood pressure, hemoglobin saturation, and rectal temperature were recorded during anesthesia. Sedation, muscle relaxation, and auditory response were evaluated after drug administration. RESULTS: Heart rate decreased after two combinations (10D/5K and 10D/10K). Respiratory rate and rectal temperature progressively decreased in all the treatments. Arterial blood pressures were maintained in 5D/10K and 10D/5K treatments and decreased after 10D/10K administration. There were no differences in sedation and recumbency time between the treatments, but anesthesia time was significantly longer in treatment 10D/10K (67.80 +/- 13.30 minutes) compared to treatments 10D/5K (44.54 +/- 8.25 minutes) and 5D/10K (30.60 +/- 6.80 minutes). Standing time was shorter in treatment 10D/10K (11.13 +/- 10.01 minutes) than in treatments 5D/10K (18.20 +/- 10.03 minutes) and 10D/5K (19.12 +/- 14.55 minutes), and walking time was longer in treatment 5D/10K (20.00 +/- 12.46 minutes) compared with treatments 10D/10K (16.00 +/- 3.43 minutes) and 10D/5K (12.40 +/- 5.02 minutes). Anesthetic quality was significantly better 5 and 15 minutes after treatments 10D/10K and 10D/5K than after treatment 5D/10K. Analgesia scores were higher after administration of 10D/10K than after the 5D/10K treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine/ketamine is useful for chemical immobilization of golden-headed lion tamarins, but bradycardia and hypotension warrant close monitoring.