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PloS One 2012General anesthetics are used during medical and surgical procedures to reversibly induce a state of total unconsciousness in patients. Here, we investigate, from a...
General anesthetics are used during medical and surgical procedures to reversibly induce a state of total unconsciousness in patients. Here, we investigate, from a dynamic network perspective, how the cortical and cardiovascular systems behave during anesthesia by applying nonparametric spectral techniques to cortical electroencephalography, electrocardiogram and respiratory signals recorded from anesthetized rats under two drugs, ketamine-xylazine (KX) and pentobarbital (PB). We find that the patterns of low-frequency cortico-cardio-respiratory network interactions may undergo significant changes in network activity strengths and in number of network links at different depths of anesthesia dependent upon anesthetics used.
Topics: Anesthesia, General; Anesthetics, General; Animals; Cardiovascular System; Electrocardiography; Electroencephalography; Ketamine; Male; Models, Theoretical; Pentobarbital; Rats; Rats, Wistar; Xylazine
PubMed: 23028572
DOI: 10.1371/journal.pone.0044634 -
Epilepsia Sep 2013Refractory status epilepticus (RSE) is a life-threatening emergency, demonstrating, by definition, significant pharmacoresistance. We describe five cases of pediatric...
PURPOSE
Refractory status epilepticus (RSE) is a life-threatening emergency, demonstrating, by definition, significant pharmacoresistance. We describe five cases of pediatric RSE treated with mild hypothermia.
METHODS
Retrospective chart review was performed of records of children who received hypothermia for RSE at two tertiary-care pediatric hospitals between 2009 and 2012.
KEY FINDINGS
Five children with RSE received mild hypothermia (32-35°C). Hypothermia reduced seizure burden during and after treatment in all cases. Prior to initiation of hypothermia, four children (80%) received pentobarbital infusions to treat RSE, but relapsed after pentobarbital discontinuation. No child relapsed after treatment with hypothermia. One child died after redirection of care. Remaining four children were discharged.
SIGNIFICANCE
This is the largest pediatric case series reporting treatment of RSE with mild hypothermia. Hypothermia decreased seizure burden during and after pediatric RSE and may prevent RSE relapse.
Topics: Adolescent; Child; Electroencephalography; Female; Humans; Hypothermia, Induced; Infant; Male; Pentobarbital; Retrospective Studies; Secondary Prevention; Seizures; Status Epilepticus; Treatment Outcome
PubMed: 23906244
DOI: 10.1111/epi.12331 -
Journal of the Experimental Analysis of... Jan 2000Eight rats were trained to discriminate pentobarbital from saline under a concurrent variable-interval (VI) VI schedule, on which responses on the pentobarbital-biased...
Eight rats were trained to discriminate pentobarbital from saline under a concurrent variable-interval (VI) VI schedule, on which responses on the pentobarbital-biased lever after pentobarbital were reinforced under VI 20 s and responses on the saline-biased lever were reinforced under VI 80 s. After saline, the reinforcement contingencies programmed on the two levers were reversed. The rats made 62.3% of their responses on the pentobarbital-biased lever after pentobarbital and 72.2% on the saline-biased lever after saline, both of which are lower than predicted by the matching law. When the schedule was changed to concurrent VI 50 s VI 50 s for test sessions with saline and the training dose of pentobarbital, responding on the pentobarbital-biased lever after the training dose of pentobarbital and on the saline-biased lever after saline became nearly equal, even during the first 2 min of the session, suggesting that the presence or absence of the training drug was exerting minimal control over responding and making the determination of dose-effect relations of drugs difficult to interpret. When the pentobarbital dose-response curve was determined under the concurrent VI 50-s VI 50-s schedule, responding was fairly evenly distributed on both levers for most rats. Therefore, 6 additional rats were trained to respond under a concurrent VI 60-s VI 240-s schedule. Under this schedule, the rats made 62.6% of their responses on the pentobarbital-biased lever after pentobarbital and 73.5% of their responses on the saline-biased lever after saline, which also is lower than the percentages predicted by perfect matching. When the schedule was changed to a concurrent VI 150-s VI 150-s schedule for 5-min test sessions with additional drugs, the presence or absence of pentobarbital continued to control responding in most rats, and it was possible to generate graded dose-response curves for pentobarbital and other drugs using the data from these 5-min sessions. The dose-response curves generated under these conditions were similar to the dose-response curves generated using other reinforcement schedules and other species.
Topics: Animals; Discrimination Learning; Dose-Response Relationship, Drug; Male; Motivation; Pentobarbital; Rats; Rats, Sprague-Dawley; Reinforcement Schedule
PubMed: 10682343
DOI: 10.1901/jeab.2000.73-103 -
American Journal of Veterinary Research Jul 2023To determine the ability of transmucosal euthanasia solution to induce euthanasia in pond slider turtles (Trachemys scripta).
OBJECTIVE
To determine the ability of transmucosal euthanasia solution to induce euthanasia in pond slider turtles (Trachemys scripta).
ANIMALS
16 pond slider turtles (T. scripta).
PROCEDURES
Pentobarbital 100 mg/kg was delivered through esophageal gavage (n = 8) or cloacal administration (8). The presence of voluntary movement, heart rate (HR), respiratory rate (RR), palpebral reflex, corneal reflex, and response to noxious stimuli were recorded until death, confirmed via the absence of reflexes, movement, heartbeat, and absence of cardiac electrical activity.
RESULTS
No signs of irritation were observed in any turtles. Leakage after administration occurred in 75% (6/8) of the cloacal group, including 2 turtles with marked leakage or expulsion. Two of eight turtles in the cloacal group regained movement and required euthanasia by a standard method and 1 turtle in the oral group was excluded from further analysis due to a miscalculated dose. The remaining 13 turtles (7/8 oral, 6/8 cloacal) had cessation of a heartbeat at a median of 18 hours (range = 6 to 26 hours) with respiratory arrest occurring within 15 minutes. The median time to loss of corneal reflex was 45 minutes (range = 15 minutes to 4 hours). Time-to-loss of parameters was similar between oral and cloacal routes, respectively.
CLINICAL RELEVANCE
Transmucosally administered pentobarbital via the oral and cloacal routes both result in euthanasia within approximately 24 hours. Given that 25% of the turtles in the cloacal group required a secondary method of euthanasia, the oral route is a preferred route to induce euthanasia in pond turtles.
Topics: Animals; Turtles; Pentobarbital; Euthanasia, Animal; Blinking; Heart Rate
PubMed: 37142234
DOI: 10.2460/ajvr.23.01.0011 -
Journal of Neurophysiology Dec 2002Pentobarbital, a general anesthetic, has received extensive study for its ability to potentiate inhibition at GABA(A) subtype of receptors for GABA. Using whole cell...
Pentobarbital, a general anesthetic, has received extensive study for its ability to potentiate inhibition at GABA(A) subtype of receptors for GABA. Using whole cell current-clamp techniques and bath applications, we determined the effects of pentobarbital and GABA receptor antagonists on the membrane properties and tonic or burst firing of medial geniculate neurons in thalamic slices. Pentobarbital (0.01-200 microM) induced depressant effects in 50 of 66 neurons (76%). Pentobarbital hyperpolarized neurons by a mean of 3 mV and decreased the number of action potentials in tonic firing, evoked by current pulse injection from near the resting potential. Pentobarbital also decreased burst firing or low threshold Ca(2+)-spikes, evoked by current pulse injection into neurons at potentials hyperpolarized from rest. The blockade of tonic and burst firing, as well as low threshold Ca(2+)-spikes, was surmountable by increasing the amplitude of input current. The GABA(A) receptor antagonists, bicuculline (100 microM) and picrotoxinin (50-100 microM), did not block the depressant effects of pentobarbital (10 microM). The GABA(B) receptor antagonist, saclofen (200 microM), and GABA(C) receptor antagonist, (1,2,3,6-tetrahydropyridine-4-yl)methylphosphinate (10-50 microM), did not significantly alter the depressant effects. Pentobarbital produced excitatory effects (0.1-50 microM) on 11 neurons (17%) but had no effects on 5 neurons (7%). The excitation consisted of approximately 3 mV depolarization, increased tonic and burst firing and the rate of rise and amplitude of low threshold Ca(2+) spikes. These effects were associated with a increase in input resistance. In contrast, the depressant effects of pentobarbital correlated to a decreased input resistance measured with hyperpolarizing current pulse injection (IC(50) = 7.8 microM). Pentobarbital reduced Na(+)-dependent rectification on depolarization and lowered the slope resistance over a wide voltage range. Tetrodotoxin eliminated both Na(+)-dependent rectification and the pentobarbital-induced decrease in membrane resistance at depolarized voltages in two-thirds of the neurons. The pentobarbital-induced decrease in membrane resistance at voltages hyperpolarized from rest was not evident during co-application with Cs(+), known to block the hyperpolarization-activated rectifiers. In summary, the pentobarbital acted at low concentrations to depress thalamocortical neurons. The depression resulted from decreased rectification on depolarization, which no longer boosted potentials over threshold, and an increased conductance that shunted spike generation. The depressant effects of pentobarbital did not involve known types of GABA receptor interactions.
Topics: Animals; Auditory Pathways; Cesium; Drug Interactions; Electrophysiology; GABA Antagonists; GABA-A Receptor Antagonists; GABA-B Receptor Antagonists; Hypnotics and Sedatives; In Vitro Techniques; Neurons; Pentobarbital; Rats; Rats, Sprague-Dawley; Receptors, GABA; Thalamus
PubMed: 12466430
DOI: 10.1152/jn.00365.2002 -
Anesthesiology Sep 1985Local cerebral glucose utilization was measured in rats during nitrous oxide and pentobarbital anesthesia, using the 2-[14C]-deoxyglucose method. During nitrous oxide...
Local cerebral glucose utilization was measured in rats during nitrous oxide and pentobarbital anesthesia, using the 2-[14C]-deoxyglucose method. During nitrous oxide anesthesia, 67%, marked heterogeneity of glucose utilization was observed. During pentobarbital anesthesia (30 mg/kg), glucose utilization decreased, the decrease being pronounced in the structures where glucose utilization was high during nitrous oxide anesthesia. During combined use of nitrous oxide and pentobarbital (30 mg/kg), with an electroencephalogram (EEG) consisting of 4-6 Hz wave super-imposed by 10-15 Hz wave, glucose utilization was higher in many brain structures, including the midbrain reticular formation, than that observed during pentobarbital (30 mg/kg) anesthesia alone. With pentobarbital, 125 mg/kg, the EEG became nearly flat and a dose-related decrease in glucose utilization was observed in the cerebral cortices and inferior colliculus but not observed in any other structures. During the combined use of nitrous oxide and pentobarbital (125 mg/kg), the EEG was nearly flat, and no statistically significant differences in glucose utilization were observed as compared with those during pentobarbital (125 mg/kg) anesthesia in any of the structures examined. The results suggest that nitrous oxide and pentobarbital affect local cerebral glucose metabolism differently and that nitrous oxide acts as cerebral metabolic stimulant in the presence of cortical function during pentobarbital anesthesia.
Topics: Animals; Blood Glucose; Brain; Deoxyglucose; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Glucose; Male; Nitrous Oxide; Pentobarbital; Rats; Rats, Inbred Strains
PubMed: 4025888
DOI: 10.1097/00000542-198509000-00004 -
European Journal of Vascular and... Dec 2002to evaluate the effects of hypothermia and pentobarbital on spinal cord ischaemia induced in a rabbit model.
OBJECTIVES
to evaluate the effects of hypothermia and pentobarbital on spinal cord ischaemia induced in a rabbit model.
MATERIALS AND METHODS
thirty-two rabbits, allocated into four equal groups, had the infrarenal aorta clamped distal to the left renal artery and above the iliac bifurcation for 40 min. Groups 3 and 4 had infusion of 15 mg/kg of pentobarbital intravenously for 5 min, 15 min before the cross-clamping. Groups 2 and 4 had infusion of 20 ml of Ringer's lactate (LR) solution at 3 degrees C for 3 min during aortic cross clamp into the isolated aortic segment. Group 1 was untreated and served as control. Postoperative functions of spinal cord were assessed.
RESULTS
paraplegia occurred in all rabbits in Group 1, in one in each of Groups 2 and 3, whereas no paraplegia was observed in Group 4. In addition 2 and 3 animals of Groups 2 and 3, respectively revealed varying degree of neurological disturbances, whereas all animals of Group 4 had normal function. This difference between Groups 2, 3, and 4 vs Group 1 was significant (p<0.002). So was the difference between Groups 2 and 4 (p=0.03), whereas the difference between Groups 3 and 4 was not significant.
CONCLUSIONS
hypothermia and pentobarbital was more effective than hypothermia alone for prevention of spinal cord ischaemia in a rabbit model.
Topics: Adjuvants, Anesthesia; Animals; Disease Models, Animal; Hypothermia, Induced; Pentobarbital; Rabbits; Spinal Cord Injuries; Spinal Cord Ischemia; Time Factors; Trauma Severity Indices; Treatment Outcome
PubMed: 12443752
DOI: 10.1053/ejvs.2002.1753 -
Archives of Biochemistry and Biophysics Mar 2007Pentobarbital, a general anesthetic and non-genotoxic carcinogen, can induce gene expression by activating transcription. In the Drosophila glutathione S-transferase D21...
Pentobarbital, a general anesthetic and non-genotoxic carcinogen, can induce gene expression by activating transcription. In the Drosophila glutathione S-transferase D21 (gstD21) gene, pentobarbital's regulatory influence extends to the level of mRNA turnover. Transcribed from an intronless gene, gstD21 mRNA is intrinsically very labile. But exposure to pentobarbital renders it stabilized beyond what can be attributed to transcriptional activation. We aim here to identify cis-acting element(s) of gstD21 mRNA as contributors to the molecule's pentobarbital-mediated stabilization. In the context of hsp70 5'UTR and the 3'UTR of act5C, gstD21 mRNA, minus its native UTRs, is stable. Maintaining the same context of heterologous UTRs, we can reconstitute using the full-length gstD21 sequence the inherent instability of gstD21 mRNA and its stabilization by pentobarbital. Transgenic flies that express these chimeric gstD21 mRNA exhibit decay intermediates lacking 3'UTR, which are not stabilized by PB treatment. The 3'UTR sequence, when inserted downstream from a reporter transcript, stabilizes it 1.6-fold under PB treatment. The analysis of the decay intermediates suggests a polysome-associated decay pattern. We propose a regulatory model that features a 59-nucleotide pentobarbital-responsive element (PBRE) in the 3'UTR of gstD21 mRNA.
Topics: Animals; Animals, Genetically Modified; Drosophila; Gene Expression Regulation; Glutathione Transferase; Pentobarbital; RNA Stability; RNA, Messenger; Response Elements
PubMed: 17234150
DOI: 10.1016/j.abb.2006.10.026 -
Behavioural Pharmacology Dec 2008Although cross tolerance can develop among positive gamma-aminobutyric acidA (GABAA) modulators acting at the same modulatory site, cross tolerance does not always...
Although cross tolerance can develop among positive gamma-aminobutyric acidA (GABAA) modulators acting at the same modulatory site, cross tolerance does not always develop to drugs acting at sites that are different from the site of action of the drug administered chronically. To examine the relationship between cross tolerance and site of action, four rhesus monkeys discriminated midazolam and, on separate occasions, received 32 mg/kg of chlordiazepoxide 24 h before dose-effect determinations for drugs acting at different sites. Midazolam, pentobarbital, and pregnanolone produced >80% midazolam-lever responding. Although monkeys responded on the midazolam lever 2-4 h after 32 mg/kg of chlordiazepoxide, they responded on the saline lever 24 h later. Twenty-four hours after an acute injection of 32 mg/kg of chlordiazepoxide, midazolam dose-effect curves were shifted 4.6-fold to the right, whereas pregnanolone dose-effect curves were shifted three-fold to the left. Sensitivity to pentobarbital increased in one monkey and decreased in others 24 h after chlordiazepoxide administration. Decreased sensitivity to midazolam shows that acute cross tolerance develops after chlordiazepoxide administration, although it does not develop to drugs acting at other sites on GABAA receptors. These differences among positive GABAA modulators suggest that even short-term benzodiazepine administration changes GABAA receptors, and those changes impact modulatory sites differently.
Topics: Animals; Behavior, Animal; Chlordiazepoxide; Conditioning, Operant; Discrimination Learning; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Female; GABA Modulators; Macaca mulatta; Male; Midazolam; Pentobarbital; Time Factors
PubMed: 19020414
DOI: 10.1097/FBP.0b013e32831c3b40 -
Anesthesiology May 1990Contractile mechanisms of endothelin, a newly isolated vasoactive substance from endothelium, were evaluated in anterior cerebral arteries (ACA). Furthermore, the...
Contractile mechanisms of endothelin, a newly isolated vasoactive substance from endothelium, were evaluated in anterior cerebral arteries (ACA). Furthermore, the effects of thiopental, pentobarbital, ketamine, and diltiazem on the endothelin-induced cerebral vasoconstriction were also studied. Endothelin induced cerebral arterial contractions in concentrations above 3 X 10(-10) M. The median effective concentration (ED50: X10(-9) M) of endothelin was 2.1 +/- 0.7 (n = 6). Endothelin did not elicit contractions in preparations soaked in Ca2(+)-free solution, but addition of 2.5 mM Ca2+ to the baths induced marked contractions. Thiopental and pentobarbital attenuated endothelin-induced contractions at concentrations above 3 X 10(4) M, while ketamine was effective above 10(-3) M. In contrast, diltiazem decreased endothelin-induced vasoconstriction at 10(-6) M. The findings suggest that endothelin may cause contractions of porcine cerebral arteries by influx of Ca2+ through Ca2+ channels. The cerebral vasomotion induced by endothelin, however, does not seem to be influenced by clinical doses of barbiturates and ketamine.
Topics: Animals; Cerebral Arteries; Endothelins; In Vitro Techniques; Ketamine; Pentobarbital; Peptides; Swine; Thiopental; Vasoconstriction
PubMed: 2187378
DOI: 10.1097/00000542-199005000-00025