Tone-Evoked Acoustic Change Complex (ACC) Recorded in a Sedated Animal Model.

The acoustic change complex (ACC) is a scalp-recorded cortical evoked potential complex generated in response to changes (e.g., frequency, amplitude) in an auditory stimulus. The ACC has been well studied in humans, but to our knowledge, no animal model has been evaluated. In particular, it was not known whether the ACC could be recorded under the conditions of sedation that likely would be necessary for recordings from animals. For that reason, we tested the feasibility of recording ACC from sedated cats in response to changes of frequency and amplitude of pure-tone stimuli. Cats were sedated with ketamine and acepromazine, and subdermal needle electrodes were used to record electroencephalographic (EEG) activity. Tones were presented from a small loudspeaker located near the right ear. Continuous tones alternated at 500-ms intervals between two frequencies or two levels. Neurometric functions were created by recording neural response amplitudes while systematically varying the magnitude of steps in frequency centered in octave frequency around 2, 4, 8, and 16 kHz, all at 75 dB SPL, or in decibel level around 75 dB SPL tested at 4 and 8 kHz. The ACC could be recorded readily under this ketamine/azepromazine sedation. In contrast, ACC could not be recorded reliably under any level of isoflurane anesthesia that was tested. The minimum frequency (expressed as Weber fractions (df/f)) or level steps (expressed in dB) needed to elicit ACC fell in the range of previous thresholds reported in animal psychophysical tests of discrimination. The success in recording ACC in sedated animals suggests that the ACC will be a useful tool for evaluation of other aspects of auditory acuity in normal hearing and, presumably, in electrical cochlear stimulation, especially for novel stimulation modes that are not yet feasible in humans.

Differential Intraocular Pressure Measurements by Tonometry and Direct Cannulation After Treatment with Soluble Adenylyl Cyclase Inhibitors.

PURPOSE: To validate the increase in intraocular pressure (IOP) caused by soluble adenylyl cyclase (sAC) inhibitors and determine reasons behind variation in IOP measurements performed by tonometry. METHODS: C57BL/6J mice were administered DMSO solubilized sAC inhibitors (KH7 or LRE-1) by intraperitoneal injection. Two hours post-treatment, mice were anesthetized with avertin or ketamine/xylazine/acepromazine (KXA). IOP was measured by a rebound tonometer or direct cannulation of the anterior chamber. Spectral-domain optical coherence tomography was used to measure anterior chamber depth and corneal thickness in live mice. Outflow facility was measured in perfused, enucleated mouse eyes. RESULTS: Compared with DMSO controls, KH7 treatment caused an increased IOP in avertin- and KXA-anesthetized mice when measured by direct cannulation [avertin: 14.4 ± 2.1 mmHg vs. 11.1 ± 1.0 mmHg (P = 0.003); KXA: 14.4 ± 1.0 mmHg vs. 11.3 ± 0.8 mmHg (P < 0.001)] and tonometry [avertin: 10.8 ± 1.4 mmHg vs. 7.4 ± 0.6 mmHg (P < 0.001); KXA: 11.9 ± 0.9 mmHg vs. 10.3 ± 1.7 mmHg (P = 0.283)]. However, treatment with KH7 in nonanesthetized mice showed a significant decrease in IOP measured by tonometry and compared with DMSO-treated animals [13.1 ± 2.6 mmHg vs. 15.6 ± 0.5 mmHg (P = 0.003)]. Both KH7- and DMSO-treated groups anesthetized with avertin showed increased corneal thickness, whereas KH7-treated mice anesthetized with KXA exhibited a shallower anterior chamber compared with untreated mice. KH7 decreased outflow facility by 85.1% in nonanesthetized, enucleated eyes (P < 0.003). CONCLUSIONS: Systemically administered DMSO and anesthesia have significant effects on anterior chamber characteristics, resulting in altered IOP readings measured by tonometry. In the presence of DMSO and anesthesia, tonometry IOP readings should be confirmed with direct cannulation.

[Treatment of surgical stress response by neuroleptics, leu-enkephalin, glycyl-proline dipeptide, and electroanesthesia in experimental animals].

We have studied the effects of chlorpromazine, acepromazine, droperidol, and transcranial electroanesthesia upon evacuation function of the stomach in piglets and the effects of leu-enkephalin and glycyl-proline upon secretory activity of the stomach in dogs and rats during surgical stress to optimize anesthetic dosage. All pharmaceutical and nonpharmaceutical methods of anesthesia used in the experiments were implemented by actiovating stress-limiting systems in post-operational period. Leu-enkephalin, apart from stimulating the stress-limiting factors of neurohumoral systems of the organism, shifted the vector ratio of aggressive and protective factors of gastric mucosa toward strengthening of the latter. The opposite trends of changes in the secretory activity of the stomach of rats in response to surgical stress can be leveled using glycyl-proline as a component of anesthesia.

Effects of ketamine on response properties of neurons in the superior paraolivary nucleus of the mouse.

The superior paraolivary nucleus (SPON; alternative abbreviation: SPN for the same nucleus in certain species) is a prominent brainstem structure that provides strong inhibitory input to the auditory midbrain. Previous studies established that SPON neurons encode temporal sound features with high precision. These earlier characterizations of SPON responses were recorded under the influence of ketamine, a dissociative anesthetic agent and known antagonist of N-methyl-d-aspartate glutamate (NMDA) receptors. Because NMDA alters neural responses from the auditory brainstem, single unit extracellular recordings of SPON neurons were performed in the presence and absence of ketamine. In doing so, this study represents the first in vivo examination of the SPON of the mouse. Herein, independent data sets of SPON neurons are characterized that did or did not receive ketamine, as well as neurons that were recorded both prior to and following ketamine administration. In all conditions, SPON neurons exhibited contralaterally driven spikes triggered by the offset of pure tone stimuli. Ketamine lowered both evoked and spontaneous spiking, decreased the sharpness of frequency tuning, and increased auditory thresholds and first-spike latencies. In addition, ketamine limited the range of modulation frequencies to which neurons phase-locked to sinusoidally amplitude-modulated tones.

Effects of anesthesia on DPOAE level and phase in rats.

Many studies of the auditory system are performed on animals under general anesthesia. A concern for researchers is that these agents may significantly alter the underlying neurophysiologic mechanisms being studied. The effects may very across species, and even among individuals within a species. An investigation was undertaken to study whether DPOAE measures differ using three different anesthetic regimens: acetylpromazine-ketamine, xylazine-ketamine, and sodium pentobarbital. The same rat was anesthetized in three consecutive weeks using a different anesthetic regimen each week. DPOAE magnitude and phase temporal responses were recorded from which several measures were taken: DPOAE levels at the onset of the primaries, changes in DPOAE level as a function of time during presentation of the primaries (DeltaLI) and changes in DPOAE level (DeltaLC) and phase (DeltaPC) during presentation of a broad-band noise presented contralateral to the probe. Each week the same measurements were repeated with the rat anesthetized using a different regimen and at the end of the third week, the middle ear muscles were sectioned and the measurements repeated once again. Results showed that the anesthetic regimens did not differentially alter the DPOAE onset levels. When sodium pentobarbital was used as the anesthetic regimen, DeltaLC and DeltaPC were significantly smaller relative to those measured when the rats were anesthetized with acetylpromazine-ketamine and xylazine-ketamine. Based on the assumption that large, positive (DeltaPC) values are related to middle ear muscle activation, the middle ear muscle reflex remained at least partially active in some rats under sodium pentobarbital anesthesia. The DeltaLI measures were significantly smaller when the animals were anesthetized with xylazine-ketamine and sodium pentobarbital than when they were anesthetized with acetylpromazine-ketamine. Recordings taken after sectioning the middle ear muscles suggested that the middle ear muscle reflex substantially contributes to DeltaLC and DeltaPC measures under the anesthetic regimens xylazine-ketamine and acetylpromazine-ketamine. Data indicated that anesthetic agents variably alter neurophysiologic mechanisms involved with the complex control of the auditory signal even among individuals in the same species. Extreme care should be taken when comparing DeltaLI, DeltaLC and DeltaPC across studies when different anesthetic regimens are used within and across species.

Middle-latency auditory-evoked potential in acepromazine-sedated dogs.

The middle-latency auditory-evoked potential (MLAEP) has been investigated as means of monitoring anesthesia in dogs. The goals of this study were to develop a technique to record MLAEPs in awake dogs and to determine the effects of sedation. The MLAEP was recorded in 12 dogs with and without sedation with acepromazine. Three needle electrodes were inserted SC. Click stimuli were delivered biaurally. Signal acquisition, averaging, and analysis were performed by software developed in-house. Signals were recorded for 128 milliseconds, and the responses to 1,024 stimuli were averaged. The waveforms from 10 recordings were averaged, and the amplitudes and latencies of peaks that could be consistently identified were measured. Data measured were compared by means of a paired 2-sided Student's t-test. Interpretable MLAEPs were recorded in 10 of the 12 dogs. Three peaks were consistently identified (Pa, Nb, and Pb). The latencies of these peaks were significantly (P = .032, .035, and .028, respectively) shorter in awake (mean +/- SD milliseconds) (Pa = 18.85 +/- 1.36, Nb = 30.50 +/- 3.55, and Pb = 47.70 +/- 5.53) than in sedated (Pa = 22.40 +/- 3.88, Nb = 35.75 +/- 6.77, and Pb = 55.30 +/- 10.55) dogs. The Pb amplitude was not significantly different (2.51 +/- 1.30 microV awake and 2.19 +/- 1.10 microV sedated). This study demonstrates that acepromazine sedation causes changes in MLAEP.

Effects of treatment with oxytocin, xylazine butorphanol, guaifenesin, acepromazine, and detomidine on esophageal manometric pressure in conscious horses.

OBJECTIVE: To compare effects of oxytocin, acepromazine maleate, xylazine hydrochloride-butorphanol tartrate, guaifenesin, and detomidine hydrochloride on esophageal manometric pressure in horses. ANIMALS: 8 healthy adult horses. PROCEDURE: A nasogastric tube, modified with 3 polyethylene tubes that exited at the postpharyngeal area, thoracic inlet, and distal portion of the esophagus, was fitted for each horse. Amplitude, duration, and rate of propagation of pressure waveforms induced by swallows were measured at 5, 10, 20, 30, and 40 minutes after administration of oxytocin, detomidine, acepromazine, xylazine-butorphanol, guaifenesin, or saline (0.9% NaCI) solution. Number of spontaneous swallows, spontaneous events (contractions that occurred in the absence of a swallow stimulus), and high-pressure events (sustained increases in baseline pressure of > 10 mm Hg) were compared before and after drug adminision. RESULTS: At 5 minutes after administration, detomidine increased waveform amplitude and decreased waveform duration at the thoracic inlet. At 10 minutes after administration, detomidine increased waveform duration at the thoracic inlet. Acepromazine administration increased the number of spontaneous events at the thoracic inlet and distal portion of the esophagus. Acepromazine and detomidine administration increased the number of high-pressure events at the thoracic inlet. Guaifenesin administration increased the number of spontaneous events at the thoracic inlet. Xylazine-butorphanol, detomidine, acepromazine, and guaifenesin administration decreased the number of spontaneous swallows. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine, acepromazine, and a combination of xylazine butorphanol had the greatest effect on esophageal motility when evaluated manometrically. Reduction in spontaneous swallowing and changes in normal, coordinated peristaltic activity are the most clinically relevant effects.

Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep premedicated with acepromazine and papaveretum.

The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg-1 intravenously (group 1) or with a mixture of propofol at 3 mg kg-1 and ketamine at 1 mg kg-1 intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean (SD) duration of anaesthesia was 64.8 (3.1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56.6 (13.1) minutes in group 1 and 50.3 (21.4) minutes in group 2; the mean volume of distribution at steady state was 1.037 (0.480) litre kg-1 in group 1 and 1.515 (0.939) litre kg-1 in group 2; the mean body clearance was 85.4 (28.0) ml kg-1 min-1 in group 1 and 128.0 (35.0) ml kg-1 min-1 in group 2; the mean residence time corrected for a bolus injection was 12.1 (4.2) minutes in group 1 and 11.9 (6.6) minutes in group 2; for the infusion, the mean residence time was 72.1 (4.2) minutes in group 1 and 69.9 (7.9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2.8 (0.4), 6.3 (1.2) and 10.9 (1.6) minutes from the end of the infusion, and the times for group 2 were 5.3 (0.9), 11.2 (1.7) and 15.1 (2.2) minutes.

Investigations into the effect of two sedatives on the stress response in cattle.

The effects of the sedatives acepromazine (an alpha-adrenergic antagonist) and xylazine (an alpha 2-adrenergic agonist) on plasma indicators of stress in cows were assessed after intramuscular injection and transport. After blood samples had been taken for baseline values, nine cows were given an intramuscular injection of saline (2.5 ml), acepromazine (0.05 mg/kg in 2.5 ml) or xylazine (0.05 mg/kg in 2.5 ml) on different occasions at least 1 week apart. The animals were then transported for 5 min by truck to a different environment and blood sampled for a further 1-3 h. There was a significant increase in plasma cortisol concentration (3.29 +/- 1.59 x baseline) after the injection of saline and transport. The injection of acepromazine also resulted in a significant increase in cortisol concentration (2.84 +/- 0.84 x baseline). There was no similar increase after injection of xylazine. This suggests that alpha 2-adrenergic receptors are involved in the response of plasma cortisol concentrations to stressors. An hyperglycaemic response occurred after xylazine (1.66 +/- 0.49 x baseline) and saline (1.20 +/- 0.1 x baseline) but not after acepromazine. Both sedatives produced a metabolic alkalosis (1.13 +/- 0.01 x baseline pH after xylazine and 1.034 +/- 0.02 x baseline pH after acepromazine). A greater decrease in haematocrit was seen after both sedatives (0.88 +/- 0.04 x baseline after xylazine, 0.81 +/- 0.08 x baseline after acepromazine) than after the injection of saline (0.97 +/- 0.06 x baseline).