Hemodynamic effects of incremental doses of acepromazine in isoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of incremental doses of acepromazine on hemodynamics in isoflurane-anesthetized dogs.Study designProspective, experimental study.AnimalsHealthy, adult, mixed-breed dogs (two male and four female) weighing 16.8 ± 5.1 kg (mean ± standard deviation).MethodsDogs were anesthetized with propofol (7 mg kg^–1) intravenously (IV) and isoflurane. Thermodilution and arterial catheters were placed for hemodynamic monitoring and arterial blood sampling for blood gas analysis. Baseline measurements were performed with stable expired concentration of isoflurane (Fe′Iso) at 1.8%. Each dog was then administered four incremental acepromazine injections (10, 15, 25 and 50 μg kg^–1) IV, and measurements were repeated 20 minutes after each acepromazine injection with Fe′Iso decreased to 1.2%. The four acepromazine injections resulted in cumulative doses of 10, 25, 50 and 100 μg kg^–1 (time points ACP₁₀, ACP₂₅, ACP₅₀ and ACP₁₀₀, respectively).ResultsCompared with baseline, cardiac index (CI) increased significantly by 34%, whereas systemic vascular resistance index (SVRI) decreased by 25% at ACP₅₀ and ACP₁₀₀. Arterial oxygen content (CaO₂) was significantly lower than baseline after all acepromazine injections (maximum decreases of 11%) and was lower at ACP₅₀ and ACP₁₀₀ than at ACP₁₀. No significant change was found in heart rate, stroke index, oxygen delivery index and systolic, mean and diastolic blood pressures. Hypotension (mean arterial pressure < 60 mmHg) was observed in one dog at baseline, ACP₁₀, ACP₂₅ and ACP₁₀₀, and in two dogs at ACP₅₀.Conclusions and clinical relevanceCompared with isoflurane alone, anesthesia with acepromazine–isoflurane resulted in increased CI and decreased SVRI and CaO₂ values. These effects were dose-related, being more pronounced at ACP₅₀ and ACP₁₀₀. Under the conditions of this study, acepromazine administration did not change blood pressure.     

Haemodynamic changes during sedation in ponies

The cardiovascular changes induced by several sedatives were investigated in five ponies with a subcutaneously transposed carotid artery by means of cardiac output determinations (thermodilution technique), systemic and pulmonary artery pressure measurements (direct intravascular method) and arterial blood analysis (blood gases and packed cell volume). The cardiovascular depression (decrease in systemic blood pressure and cardiac output) was long lasting (greater than 90 min) after administration of propionylpromazine (0.08 mg/kg intravenous (i.v.)) together with promethazine (0.08 mg/kg i.v.). The phenothiazine-induced sedation was not optimal. alpha 2-Agonists (xylazine (0.60 mg/kg i.v.) and detomidine (20 micrograms/kg i.v.)) induced initial but transient cardiovascular effects with an increase in systemic blood pressure and a decrease in cardiac output for about 15 min. Second degree atrioventricular blocks and bradycardia were seen during this period. The cardiovascular depression was more pronounced during detomidine sedation. Atropine (0.01 mg/kg i.v.) induced a tachycardia with a decrease in stroke volume but did not alter the cardiac output or other cardiovascular parameters. It prevented the occurrence of the bradycardia and heart blocks normally induced by xylazine or detomidine. Atropine potentiated the initial hypertension induced by the alpha 2-agonistic sedatives (especially detomidine). The decrease in cardiac output induced by xylazine, and to a lesser extent by detomidine, was partially counteracted when atropine was given in advance. The atropine-xylazine combination seemed the best premedication protocol before general anaesthesia as it only resulted in minor and transient cardiovascular changes.     

N-异辛基吩噻嗪的高效合成与表征

以廉价的吩噻嗪为母体,分别采用一次反应、二次连续反应和二次连续反应加氢化钠三种不同的方法有效地合成了脂溶性异辛基吩噻嗪,并运用傅立叶变换红外光谱、质谱、元素分析、核磁共振谱等手段进行了表征;研究表明采用第三种方法合成产率最高;这为高效合成脂溶性有机中间体进行了有益的探索。     

Administration of acepromazine maleate to 31 dogs with a history of seizures

Objective: To retrospectively evaluate the incidence of seizures in dogs presenting with a history of seizures that were treated with acepromazine (ACE) during hospitalization. Design: Retrospective study. Setting: Privately owned emergency and referral hospital. Animals: Thirty‐one client‐owned dogs. Interventions: Administration of ACE. Measurements and main results: The medical records from dogs with an acute or chronic seizure history that received ACE were reviewed. Factors evaluated included presenting complaint, seizure history, ACE dosage, duration of observation, seizure activity, and other medications used. Thirty‐one dogs qualified for the study: 20 males and 11 females. Age range was 3 months to 14.9 years. Presenting complaint was seizure in 28/31 dogs. There was a prior history of seizures in 22/31 dogs, and 15/22 were currently on antiseizure medication. ACE was given 1–5 times per dog. Mean ACE dose was 0.029 mg/kg IV (range: 0.008–0.057 mg/kg; n=46), 0.036 mg/kg IM (range: 0.017–0.059 mg/kg; n=14), 0.53 mg/kg PO (n=2). Twenty‐seven dogs did not seizure after administration of ACE within the observation period (mean: 16.4 hours, range: 0.25–66 hours). Twenty‐five dogs received antiseizure medication before ACE. Eight seizure episodes occurred in 4 dogs (all of whom presented for seizures) within 0.3–10 hours after ACE administration. Conclusions: There was no observed correlation between ACE administration in dogs with a seizure history and the recurrence of seizure activity during hospitalization. The time from ACE administration to seizure activity was greater than expected for measurable effects to be seen in 1 dog (10 hour). Further studies with a larger group and alternative ACE doses are needed to more thoroughly evaluate the safety of short‐term ACE use in dogs with a seizure history.     

Modulating effects of acepromazine on the reactive oxygen species production by stimulated equine neutrophils

ObjectiveTo investigate the effect of acepromazine (ACP) on reactive oxygen species (ROS) production by stimulated equine neutrophils.Study designEx vivo biochemical experiments.AnimalsIsolated neutrophils from healthy untreated horses.MethodsNeutrophils were incubated with ACP at concentrations of 10^?4, 10^?5 or 10^?6 m and then stimulated with phorbol-myristate-acetate (PMA) before measurement of lucigenin-enhanced chemiluminescence (CL). In a second experiment neutrophils were incubated in the presence of α-keto-γ methylthiobutyric acid (KMB) and treated with ACP at concentrations of 10^?4, 10^?5 or 10^?6 m. Subsequent PMA stimulation lead to neutrophilic ROS production and decomposition of KMB to ethylene, which is measured by gas chromatography. Electron paramagnetic resonance-spin trapping (EPR) analysis was performed with PMA-stimulated neutrophils in the presence of ACP (10^?4, 10^?5 or 10^?6 m) directly added to the cell suspension. In the second experiment, the same concentrations of ACP were pre-incubated with neutrophils, then centrifuged to eliminate the excess of ACP and re-suspended in phosphate buffer before stimulation with PMA. In all experiments, the results of ACP-treated and ACP-untreated stimulated neutrophils were compared.ResultsOverall, results obtained with lucigenin-enhanced CL and KMB oxidation were in agreement with those seen in electron paramagnetic resonance spectroscopy. Acepromazine induced a dose-dependent inhibitory effect on neutrophilic ROS production. Electron paramagnetic resonance also showed, at high ACP concentration, the appearance of a cation radical derived from ACP. In contrast, electron paramagnetic resonance study performed with pre-incubated neutrophils showed an important dose-dependent inhibitory effect of ACP.ConclusionThe results indicate that ACP can neutralize O^˙?₂ or its by-products during the stimulation of neutrophils.Clinical relevanceThese findings may have a therapeutic relevance when phenothiazines are used in horses suffering from inflammatory diseases in which neutrophil activation and ROS production are implicated.     

Hemodynamic,respiratory and sedative effects of progressively increasing doses of acepromazine in conscious dogs

ObjectiveTo evaluate the effects of progressively increasing doses of acepromazine on cardiopulmonary variables and sedation in conscious dogs.Study designProspective, experimental study.AnimalsA group of six healthy, adult, mixed-breed dogs weighing 16.5 ± 5.0 kg (mean ± standard deviation).MethodsDogs were instrumented with thermodilution and arterial catheters for evaluation of hemodynamics and arterial blood gases. On a single occasion, acepromazine was administered intravenously to each dog at 10, 15, 25 and 50 μg kg^–1 at 20 minute intervals, resulting in cumulative acepromazine doses of 10 μg kg^–1 (ACP₁₀), 25 μg kg^–1 (ACP₂₅), 50 μg kg^–1 (ACP₅₀) and 100 μg kg^–1 (ACP₁₀₀). Hemodynamic data and sedation scores were recorded before (baseline) and 20 minutes after each acepromazine dose.ResultsCompared with baseline, all acepromazine doses significantly decreased stroke index (SI), mean arterial pressure (MAP) and arterial oxygen content (CaO₂) with maximum decreases of 16%, 17% and 21%, respectively. Cardiac index (CI) decreased by up to 19% but not significantly. Decreases of 26–38% were recorded for oxygen delivery index (DO₂I), with significant differences for ACP₅₀ and ACP₁₀₀. Systemic vascular resistance index (SVRI) and heart rate did not change significantly. No significant difference was found among acepromazine doses for hemodynamic data. After ACP₁₀, mild sedation was observed in five/six dogs and moderate sedation in one/six dogs, whereas after ACP₂₅, ACP₅₀ and ACP₁₀₀, moderate sedation was observed in five/six or six/six dogs.Conclusions and clinical relevanceIn conscious dogs, acepromazine decreased MAP, SI, CaO₂ and DO₂I, but no significant dose effect was detected. SVRI was not significantly changed, suggesting that the reduction in MAP resulted from decreased CI. The ACP₂₅, ACP₅₀ and ACP₁₀₀ doses resulted in moderate sedation in most dogs; ACP₁₀ resulted in only mild sedation.