-
Annals of Palliative Medicine Oct 2021γ-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid in the nervous system and has a wide range of physiological functions in the body. Walnut...
BACKGROUND
γ-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid in the nervous system and has a wide range of physiological functions in the body. Walnut peptide (WP) contains high levels of arginine, aspartic acid, and glutamate, and has been shown to improve cognitive deficits and memory impairment in mice, while restoring antioxidant enzyme levels and reducing brain inflammatory mediators.
METHODS
This study investigated the effects of GABA and WP, either alone or in combination, on sleep disturbances in mice. The pentobarbital-prolonged sleep test, pentobarbital-threshold sleep test, and barbital-induced sleep test were conducted to assess the effects of GABA and WP on sleep quality by gavage for 30 days as follows: GABA (102.25 mg/kg), WP (102.25 mg/kg), GABA (33.95, 102.25, 306.75 mg/kg)/WP (102.25 mg/kg) mixture. Furthermore, neurotransmitter tests were performed using mice brain tissue to investigate the possible mechanisms of GABA and WP on sleep status.
RESULTS
The results showed that the combined use of GABA and WP significantly increased sleep duration compared with single administration of either WP or GABA. Increasing doses of GABA in mice treated with combined GABA and WP elevated the sleep rate to 50.00%, 64.28%, and 64.28%, respectively, compared to mice treated with GABA alone (35.71%) or mice treated with WP alone (28.57%). In mice that received a combination of GABA and WP orally, the latency time was significantly decreased after 30 days compared to control mice (P<0.05). Additionally, in mice treated with GABA, WP, or the combination of GABA and WP, the concentrations of GABA and acetylcholine (Ach) in the brain were significantly elevated and the concentration of serotonin (5-HT) was decreased compared to untreated mice.
CONCLUSIONS
These results demonstrated that the combined administration of GABA and WP could prolong the sleep duration, increase sleep rate, and shorten the sleep latency more effectively than the administration of either GABA or WP alone. The mechanisms of action may be related to the regulation of neurotransmitters in the brain tissue by the combination of GABA and WP.
Topics: Animals; Juglans; Mice; Pentobarbital; Peptides; Sleep; gamma-Aminobutyric Acid
PubMed: 34763469
DOI: 10.21037/apm-21-2798 -
Journal of Veterinary Diagnostic... Mar 2022Pentobarbital is used commonly to euthanize animals. Occasionally during a death investigation, it is necessary to determine whether a cat or dog was euthanized via...
Pentobarbital is used commonly to euthanize animals. Occasionally during a death investigation, it is necessary to determine whether a cat or dog was euthanized via pentobarbital overdose. Screening for the detection of barbiturates including pentobarbital can be performed using commercial immunochromatographic tests. We used a commercial immunochromatographic test for barbiturates in humans to screen for barbiturates in urine collected postmortem from 20 dogs and 20 cats to determine whether they had been euthanized with pentobarbital. Additionally, we analyzed the urine for pentobarbital using liquid chromatography-mass spectrometry as a confirmatory test. Screening and confirmation testing revealed 100% agreement between the tests and with the euthanasia status of each animal. Our results support the use of the immunochromatographic test for the screening of urine collected postmortem to assess for the presence of barbiturates, specifically pentobarbital, used for euthanasia.
Topics: Animals; Barbiturates; Cat Diseases; Cats; Dog Diseases; Dogs; Euthanasia, Animal; Humans; Pentobarbital
PubMed: 35012382
DOI: 10.1177/10406387211070539 -
Anesthesiology Feb 1997Anesthesia may represent a considerable bias in experimental medicine, particularly in conditions of stress (such as hemorrhage). Sodium pentobarbital (PB), widely used...
BACKGROUND
Anesthesia may represent a considerable bias in experimental medicine, particularly in conditions of stress (such as hemorrhage). Sodium pentobarbital (PB), widely used for cardiovascular investigations, may impair oxygen delivery by hemodynamic and respiratory depression. The critical issue, however, is whether the microcirculation can still maintain tissue oxygenation during anesthesia. To answer this question, the authors studied the effect of PB anesthesia on subcutaneous microvascular oxygen delivery and interstitial oxygenation in Syrian golden hamsters.
METHODS
Sodium pentobarbital anesthesia was induced by intravenous injection (30 mg/kg body weight) and maintained by a 15-min infusion (2 mg.kg-1.min-1), with animals breathing spontaneously (PB-S) or ventilated with air (PB-V). Systemic parameters evaluated were mean arterial pressure (MAP), heart rate, cardiac index (CI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), base excess, and pH. Microvascular and interstitial oxygen tension (PO2), vessel diameter, red blood cell velocity (vRBC), and blood flow (Qb) were measured in a dorsal skinfold preparation. Microcirculatory PO2 values were determined by phosphorescence decay.
RESULTS
Sodium pentobarbital anesthesia significantly decreased CI, MAP, vRBC, and Qb. During PB infusion, PaO2 values were 56 +/- 12.8 mmHg (PB-S) and 115.9 +/- 14.6 mmHg (PB-V) compared with 69.4 +/- 18.2 mmHg and 61.4 +/- 12.6 mmHg at baseline. However, microvascular PO2 was reduced by 25-55% in both groups, resulting in an interstitial PO2 decrease from 23.9 +/- 5.6 mmHg (control) to 13.1 +/- 9.1 mmHg (PB-S) and 15.2 +/- 7 mmHg (PB-V). Microcirculatory PO2 values were restored 30 min after PB infusion, even though hemodynamic depression and a light anesthetic plane were maintained.
CONCLUSIONS
Sodium pentobarbital anesthesia caused impairment of microvascular oxygen delivery and interstitial oxygenation, effects that were not prevented by mechanical ventilation. Although these effects were restricted to deep anesthetic planes, prolonged hemodynamic depression suggests that caution is warranted when using PB as an anesthetic in cardiovascular investigations.
Topics: Anesthesia; Animals; Blood Flow Velocity; Cricetinae; Hemodynamics; Male; Mesocricetus; Microcirculation; Oxygen; Pentobarbital
PubMed: 9054255
DOI: 10.1097/00000542-199702000-00012 -
Critical Care (London, England) May 2014Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated...
INTRODUCTION
Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE.
METHODS
We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year.
RESULTS
Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5) severely disabled, and 10% (N = 3) had no or minimal disability. Death or unresponsive wakefulness was associated with catastrophic etiology (p = 0.03), but none of the other collected variables.
CONCLUSIONS
cIV-PTB effectively aborts SRSE and complications are infrequent; outcome in this highly refractory cohort of patients with devastating underlying etiologies remains poor. Phenobarbital may be particularly helpful when weaning cIV-PTB.
Topics: Adult; Aged; Cohort Studies; Electroencephalography; Female; Humans; Hypotension; Infusions, Intravenous; Male; Middle Aged; Pentobarbital; Pneumonia; Retrospective Studies; Status Epilepticus; Treatment Outcome
PubMed: 24886712
DOI: 10.1186/cc13883 -
Journal of the Experimental Analysis of... Mar 1989Similar rates of punished and nonpunished responding, maintained with equated rates of reinforcement, were established in pairs of rats. One subject of each pair was...
Similar rates of punished and nonpunished responding, maintained with equated rates of reinforcement, were established in pairs of rats. One subject of each pair was exposed to a random-ratio schedule of food presentation. The interreinforcement intervals for this subject comprised the intervals of a random-interval schedule of reinforcement for the other (yoked) rat. The random-ratio schedule maintained rates of responding higher than those maintained by the same rate of reinforcement schedule according to the yoked random-interval contingency. A random-ratio schedule of electric foot shock added to the random-ratio schedule of food presentation suppressed rates of responding such that similar rates of responding were observed in rats of both groups. Pentobarbital (3.0 to 17.0 mg/kg) increased punished responding at doses that had little effect on or decreased nonpunished responding, whereas cocaine (5.6 to 30 mg/kg) increased nonpunished responding at doses that decreased or did not alter punished responding. Qualitatively different effects of pharmacological agents on punished and nonpunished responding can be obtained using procedures that generate similar rates and temporal patterns of punished and nonpunished responding. The effects of pentobarbital and cocaine on responding can be determined by factors other than simply the baseline rate of responding.
Topics: Animals; Arousal; Cocaine; Conditioning, Operant; Dose-Response Relationship, Drug; Electroshock; Male; Motivation; Pentobarbital; Punishment; Rats; Rats, Inbred F344; Reinforcement Schedule
PubMed: 2708936
DOI: 10.1901/jeab.1989.51-173 -
Biomolecules Jun 2022GABA receptors are a major contributor to fast inhibitory neurotransmission in the brain. The receptors are activated upon binding the transmitter GABA or allosteric...
GABA receptors are a major contributor to fast inhibitory neurotransmission in the brain. The receptors are activated upon binding the transmitter GABA or allosteric agonists including a number of GABAergic anesthetics and neurosteroids. Functional receptors can be formed by various combinations of the nineteen GABA subunits cloned to date. GABA receptors containing the ε subunit exhibit a significant degree of constitutive activity and have been suggested to be unresponsive to allosteric agents. In this study, we have characterized the functional properties of the rat α1β2ε GABA receptor. We confirm that the α1β2ε receptor exhibits a higher level of constitutive activity than typical of GABA receptors and show that it is inefficaciously activated by the transmitter and the allosteric agonists propofol, pentobarbital, and allopregnanolone. Manipulations intended to alter ε subunit expression and receptor stoichiometry were largely without effect on receptor properties including sensitivity to GABA and allosteric agonists. Surprisingly, amino acid substitutions at the conserved 9' and 6' positions in the second transmembrane (TM2) domain in the ε subunit did not elicit the expected functional effects of increased constitutive activity and resistance to the channel blocker picrotoxin, respectively. We tested the accessibility of TM2 residues mutated to cysteine using the cysteine-modifying reagent 4-(hydroxymercuri)benzoic acid and found a unique pattern of water-accessible residues in the ε subunit.
Topics: Animals; Cysteine; Pentobarbital; Propofol; Rats; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 35883422
DOI: 10.3390/biom12070868 -
The Journal of Pediatrics Sep 2011To determine the pharmacokinetics of pentobarbital in neonates, infants, and young children with congenital heart disease after open-heart surgery. (Comparative Study)
Comparative Study
OBJECTIVES
To determine the pharmacokinetics of pentobarbital in neonates, infants, and young children with congenital heart disease after open-heart surgery.
STUDY DESIGN
Thirty-five subjects (3.0 days-4.4 years) after open-heart surgery who received pentobarbital as standard of care were enrolled. Serial pharmacokinetic blood samples were obtained. A population-based, nonlinear mixed-effects modeling approach was used to characterize pentobarbital pharmacokinetics.
RESULTS
A two-compartment model with weight as a co-variate allometrically expressed on clearance (CL), inter-compartmental clearance, central (V1) and peripheral volume of distributions, bypass grafting time as a co-variate on CL and V1, and age and ventricular physiology as co-variates on CL best described the pharmacokinetics. A typical infant (two-ventricle physiology, 6.9 kg, 5.2 months, and bypass grafting time of 60 minutes) had a CL of 0.12 L/hr/kg, V1 of 0.45 L/kg, and peripheral volume of distributions of 0.98 L/kg. The bypass grafting effect was poorly estimated. For subjects <12 months age, an age effect on CL remained after accounting for weight and was precisely estimated.
CONCLUSIONS
Pentobarbital pharmacokinetics is influenced by age and weight. Subjects with single-ventricle physiology demonstrated a 15% decrease in clearance when compared with subjects with two-ventricle physiology.
Topics: Age Factors; Body Weight; Child, Preschool; Heart Defects, Congenital; Humans; Hypnotics and Sedatives; Infant; Infant, Newborn; Pentobarbital; Time Factors
PubMed: 21665222
DOI: 10.1016/j.jpeds.2011.04.021 -
Turkish Journal of Medical Sciences Jun 2022Anesthetics are often used in animal experiments to achieve immobilization and relieve pain. However, many anesthetics can alter the dynamics of cardiovascular systems.... (Observational Study)
Observational Study
BACKGROUND
Anesthetics are often used in animal experiments to achieve immobilization and relieve pain. However, many anesthetics can alter the dynamics of cardiovascular systems. We aimed to compare the effects of two frequently used anesthetics agents on heart rate variability (HRV) parameters in mice.
METHODS
This observational study was performed between May and June 2014 in 21 male BALB/c mice aged 16-20 weeks. The animals were divided into three groups: pentobarbital (P), (n = 7); pentobarbital+fentanyl (P+F), (n = 7); and ketamine+xylazine (K+X), (n = 7). Surface electrocardiography (ECG) electrodes were placed in lead II configuration. The tachogram of RR intervals was obtained after R waves were detected using the Pan-Tompkins real-time QRS recognition algorithm. Frequency-domain, time-domain, and nonlinear HRV analyses were performed.
RESULTS
The bradycardia effect was higher in the K+X group (p < 0.01). Time-domain indices were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). Very low frequency (VLF) power was significantly lower in group K+X compared to group P and group P+F (p < 0.01). Low frequency (LF) power, low frequency/high frequency (LF/HF) ratio, and total power (TP) were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). The detrended fluctuation analysis short-term parameter (DFAα1 ) was significantly higher in group K+X compared to group P+F (p < 0.05) and the long-term parameter (DFAα2 ) was lower in group K+X compared to group P (p < 0.05). Standard deviations SD1 and SD2 were higher in group K+X compared to group P (p < 0.001) and group P+F (p < 0.001), SD2/SD1 ratio was lower in group K+X compared to group P (p < 0.05) and group P+F (p < 0.05). Entropy measures did not differ between groups.
DISCUSSION
HRV analyses, including nonlinear methods, indicated that a K+X combination reduces imbalance and disorder in the regulation of the autonomic nervous system (ANS) in comparison to both P and the P+F combination.
Topics: Male; Mice; Animals; Heart Rate; Xylazine; Ketamine; Pentobarbital; Electrocardiography; Anesthesia; Anesthetics; Fentanyl
PubMed: 36326322
DOI: 10.55730/1300-0144.5383 -
American Journal of Veterinary Research Aug 2017OBJECTIVE To compare intraosseous pentobarbital treatment (IPT) and thoracic compression (TC) on time to circulatory arrest and an isoelectric electroencephalogram (EEG)... (Clinical Trial)
Clinical Trial Comparative Study
Comparison of intraosseous pentobarbital administration and thoracic compression for euthanasia of anesthetized sparrows (Passer domesticus) and starlings (Sturnus vulgaris).
OBJECTIVE To compare intraosseous pentobarbital treatment (IPT) and thoracic compression (TC) on time to circulatory arrest and an isoelectric electroencephalogram (EEG) in anesthetized passerine birds. ANIMALS 30 wild-caught adult birds (17 house sparrows [Passer domesticus] and 13 European starlings [Sturnus vulgaris]). PROCEDURES Birds were assigned to receive IPT or TC (n = 6/species/group). Birds were anesthetized, and carotid arterial pulses were monitored by Doppler methodology. Five subdermal braided-wire electrodes were used for EEG. Anesthetic depth was adjusted until a continuous EEG pattern was maintained, then euthanasia was performed. Times from initiation of euthanasia to cessation of carotid pulse and irreversible isoelectric EEG (indicators of death) were measured. Data (medians and first to third quartiles) were summarized and compared between groups within species. Necropsies were performed for all birds included in experiments and for another 6 birds euthanized under anesthesia by TC (4 sparrows and 1 starling) or IPT (1 sparrow). RESULTS Median time to isoelectric EEG did not differ significantly between treatment groups for sparrows (19.0 and 6.0 seconds for TC and IPT, respectively) or starlings (88.5 and 77.5 seconds for TC and IPT, respectively). Median times to cessation of pulse were significantly shorter for TC than for IPT in sparrows (0.0 vs 18.5 seconds) and starlings (9.5 vs 151.0 seconds). On necropsy, most (14/17) birds that underwent TC had grossly visible coelomic, pericardial, or perihepatic hemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that TC might be an efficient euthanasia method for small birds. Digital pressure directly over the heart during TC obstructed venous return, causing rapid circulatory arrest, with rupture of the atria or vena cava in several birds. The authors propose that cardiac compression is a more accurate description than TC for this procedure.
Topics: Anesthesia; Animals; Animals, Wild; Electroencephalography; Euthanasia, Animal; Hypnotics and Sedatives; Pentobarbital; Pressure; Sparrows; Starlings; Thorax
PubMed: 28738007
DOI: 10.2460/ajvr.78.8.887 -
American Journal of Veterinary Research Jun 2024To assess the efficacy of transmucosal euthanasia solution to induce euthanasia.
OBJECTIVE
To assess the efficacy of transmucosal euthanasia solution to induce euthanasia.
ANIMALS
6 bearded dragons (Pogona vitticeps).
METHODS
An initial dose of euthanasia solution containing pentobarbital and phenytoin sodium was administered transmucosally in conscious lizards (100 mg/kg pentobarbital dose), followed by a second dose 20 minutes later (400 mg/kg pentobarbital dose). The presence of movement, leakage of euthanasia solution, behaviors consistent with oral irritation, respiratory rate, heart rate, palpebral and corneal reflex, and response to noxious stimuli were recorded until death, confirmed by the absence of Doppler cardiac flow and cardiac electrical activity. The time to loss of all parameters was calculated. Postmortem evaluation allowed for histopathologic evaluation of the oral cavity and gastrointestinal tract to detect potential mucosal damage from the alkaline euthanasia solution.
RESULTS
The median time to death was 300 minutes (range, 300 to 360 minutes), median time to respiratory arrest was 30 minutes (range, 30 to 50 minutes), and median time to loss of deep pain response was 30 minutes (range, 20 to 50 minutes). Signs consistent with oral irritation occurred in 4 of 6 (66.7%) lizards, including 2 lizards that exhibited whole-body spasms after euthanasia solution administration. Histopathologic changes indicating peracute mucosal ulceration, suspected to be from caustic causes, were identified in 1 (1/6 [16.7%]) lizard.
CLINICAL RELEVANCE
Transmucosal euthanasia solution administration resulted in clinical euthanasia within 6 hours. This method should be utilized only after premedication with analgesic and/or anesthetic medications due to the potential for acute mucosal ulceration and behaviors that may be distressing in client-owned animals.
Topics: Animals; Phenytoin; Lizards; Pentobarbital; Euthanasia, Animal; Male; Female; Administration, Mucosal; Hypnotics and Sedatives
PubMed: 38569538
DOI: 10.2460/ajvr.24.02.0026