thiopental and Disease-Models--Animal

Topics: Animals; Body Temperature; Disease Models, Animal; Hypothermia, Induced; Hypoxia; Mice; Nitrous Oxide; Thiopental; Time Factors

Experimental and clinical studies of the protective effect of barbiturates in cerebral ischaemia are reviewed. Their action in protecting the brain from the effects of ischaemia is related to their action as anaesthetic agents and probably to the depression of neuronal function and metabolism but is incompletely understood. Their effect is dose related. Early administration is likely to be crucial to the success of barbiturate therapy as secondary events following an episode of cerebral ischaemia can lead to irreversible brain damage within 2--3 h. A potential collateral circulation appears to be essential for the protective effect of barbiturates. There may be a possibility of partly overcoming time delays in administration by giving larger doses of barbiturates.

Topics: Animals; Barbiturates; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypothermia, Induced; Pentobarbital; Thiopental; Time Factors

To determine the normal optical nerve sheath (ONS) diameter ultrasonography (ONSUS) and evaluate the possible effects of drugs on ONS diameter during anesthetic induction in healthy pigs.. Healthy piglets were divided into three groups: a control group, that received xylazine and ketamine (X/K); other that received xylazine, ketamine and propofol (X/K/P); and a third group that received xylazine, ketamine, and thiopental (X/K/T). The sheath diameter was assessed by ultrasonography calculating the average of three measurements of each eye from the left and right sides.. 118 animals were anesthetized (49 X/K 33 X/K/P and 39 X/K/T). Mean ONS sizes on both sides in each group were 0.394 ± 0.048 (X/K), 0.407 ± 0.029 (X/K/P) and 0.378 ± 0.042 cm (X/K/T) (medians of 0.400, 0.405 and 0.389, respectively). The ONS diameter varied from 0.287-0.512 cm (mean of 0.302 ± 0.039 cm). For group X/K, the mean diameter was 0.394 ± 0.048 cm. Significant differences in ONS sizes between the groups P and T (X/K/P > X/K/T, p = 0.003) were found. No statistically significant differences were detected when other groups were compared (X/K = X/K/P, p = 0.302; X/K = X/K/T, p = 0.294).. Sedation with thiopental lead to significative ONS diameter reduction in comparison with propofol. ONSUS may be useful to evaluate responses to thiopental administration.

Topics: Anesthesia; Animals; Disease Models, Animal; Ketamine; Optic Nerve; Propofol; Swine; Thiopental; Xylazine

Acute ischemic stroke is associated with pulmonary complications, and often dexmedetomidine and propofol are used to decrease cerebral metabolic rate. However, it is unknown the immunomodulatory actions of dexmedetomidine and propofol on brain and lungs during acute ischemic stroke. The effects of dexmedetomidine and propofol were compared on perilesional brain tissue and lung damage after acute ischemic stroke in rats. Further, the mean amount of both sedatives was directly evaluated on alveolar macrophages and lung endothelial cells primarily extracted 24-h after acute ischemic stroke. In twenty-five Wistar rats, ischemic stroke was induced and after 24-h treated with sodium thiopental (STROKE), dexmedetomidine and propofol. Dexmedetomidine, compared to STROKE, reduced diffuse alveolar damage score [median(interquartile range); 12(7.8-15.3) vs. 19.5(18-24), p = 0.007)], bronchoconstriction index [2.28(2.08-2.36) vs. 2.64(2.53-2.77), p = 0.006], and TNF-α expression (p = 0.0003), while propofol increased VCAM-1 expression compared to STROKE (p = 0.0004). In perilesional brain tissue, dexmedetomidine, compared to STROKE, decreased TNF-α (p = 0.010), while propofol increased VCAM-1 compared to STROKE (p = 0.024). In alveolar macrophages and endothelial cells, dexmedetomidine decreased IL-6 and IL-1β compared to STROKE (p = 0.002, and p = 0.040, respectively), and reduced IL-1β compared to propofol (p = 0.014). Dexmedetomidine, but not propofol, induced brain and lung protection in experimental acute ischemic stroke.

Topics: Animals; Brain; Brain Ischemia; Dexmedetomidine; Disease Models, Animal; Endothelial Cells; Hypnotics and Sedatives; Interleukin-1beta; Interleukin-6; Ischemic Stroke; Lung; Macrophages, Alveolar; Male; Propofol; Rats; Rats, Wistar; Thiopental; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Various issues related to clinical use of medicines remain unclear, and pharmacists are expected to establish evidence for appropriate use of medicines. The present review summarizes our findings from three areas of research regarding the use of medicines in the operating room: 1) We evaluated the extent of extravasation injury due to thiopental (2.5 mg/100 μL) and propofol (1.0 mg/100 μL) at the macroscopic and histopathologic levels in a rat model. Thiopental, which causes tissue necrosis, can be classified as a "vesicant", and propofol can be classified as an "irritant". Moreover, warming strongly exacerbated the degeneration or necrosis induced by extravasation of thiopental. 2) The cytotoxicity of povidone-iodine solution (PVP-I) for ophthalmic use and that of polyvinyl alcohol-iodine solution (PAI) was compared using a human corneal epithelial cell line. Despite exhibiting equivalent antiseptic effects, the cytotoxicity of PVP-I diluted 16-fold was greater than that of PAI diluted 6-fold. After inactivation of iodine, the cytotoxicity of PVP-I persisted; therefore, to avoid corneal damage, antisepsis should be achieved with PAI. 3) The stability of 1 μg/mL adrenaline when used as an intraocular irrigating solution to maintain pupil dilation was evaluated. After mixing for 6 h, the adrenaline concentration was 65.2% (pH 8.0) of the initial concentration. Moreover, the low concentration of sodium bisulfite in the irrigating solution could have caused adrenaline reduction. Our results strongly suggest that intraocular irrigation solution containing adrenaline should be prepared just prior to use in surgery.

Topics: Animals; Anti-Infective Agents, Local; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Stability; Epinephrine; Evidence-Based Practice; Male; Operating Rooms; Povidone-Iodine; Propofol; Rats; Rats, Wistar; Solutions; Sulfites; Therapeutic Irrigation; Thiopental

In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.. In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays.. Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment.. The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.. Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.

Topics: Acetylcholinesterase; Analgesics, Opioid; Anesthesia, Intravenous; Anesthetics, Intravenous; Animals; Biomarkers; Cholinesterase Inhibitors; Consciousness; Disease Models, Animal; Fentanyl; GPI-Linked Proteins; Male; Organophosphate Poisoning; Propofol; Rats, Wistar; Soman; Thiopental

Intracranial pressure (ICP) is a major neurological parameter in animals and humans. ICP is a function of the relationship between the contents of the cranium (brain parenchyma, cerebrospinal fluid, and blood) and the volume of the skull. Increased ICP can cause serious physiological effects or even death in patients who do not quickly receive proper care, which includes ICP monitoring. Epilepsies are a set of central nervous system disorders resulting from abnormal and excessive neuronal discharges, usually associated with hypersynchronism and/or hyperexcitability. Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy and is also refractory to medication. ICP characteristics of subjects with epilepsy have not been elucidated because there are few studies associating these two important neurological factors. In this work, an invasive (ICPi) and the new minimally invasive (ICPmi) methods were used to evaluate ICP features in rats with chronic epilepsy, induced by the experimental model of pilocarpine, capable of generating the main features of human TLE in these animals.

Topics: Animals; Anticonvulsants; Brain; Chronic Disease; Disease Models, Animal; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Intracranial Pressure; Magnetic Resonance Imaging; Male; Muscarinic Agonists; Organ Size; Pilocarpine; Rats; Rats, Wistar; Thiopental

We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1β expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation.

Topics: Acute Lung Injury; Animals; Cytokines; Dexmedetomidine; Disease Models, Animal; Endotoxins; Female; Hypnotics and Sedatives; Lipopolysaccharides; Lung; NF-E2 Transcription Factor; Nitric Oxide Synthase; Propofol; Rats; Rats, Wistar; RNA, Messenger; Statistics, Nonparametric; Thiopental

The incidence of Alzheimer disease may increase after surgical interventions. Amyloid β-protein (Aβ) fibrillogenesis, which is closely related to Alzheimer disease, is reportedly accelerated by exposure to anesthetics. However, the effects of GM1 ganglioside (GM1) on Αβ fibrillogenesis have not yet been reported. The current study was designed to examine whether the anesthetics propofol and thiopental are associated with Αβ assembly and GM1 expression on the neuronal cell surface.. PC12N cells and cultured neuronal cells were treated with propofol or thiopental, and GM1 expression in treated and untreated cells was determined by the specific binding of horseradish peroxidase-conjugated cholera toxin subunit B (n = 5). The effects of an inhibitor of the γ-aminobutyric acid A receptor was also examined (n= 5). In addition, the effects of the anesthetics on GM1 liposome-induced Αβ assembly were investigated (n = 5). Finally, the neurotoxicity of the assembled Αβ fibrils was studied by the lactate dehydrogenase release assay (n = 6).. Propofol (31.2 ± 4.7%) and thiopental (34.6 ± 10.5%) decreased GM1 expression on the cell surface through the γ-aminobutyric acid A receptor. The anesthetics inhibited Αβ fibril formation from soluble Αβ in cultured neurons. Moreover, propofol and thiopental suppressed GM1-induced fibril formation in a cell-free system (propofol, 75.8 ± 1.9%; thiopental, 83.6 ± 1.9%) and reduced the neurotoxicity of a mixture containing Aβ and GM1 liposomes (propofol, 35.3 ± 16.4%; thiopental, 21.3 ± 11.6%).. Propofol and thiopental have direct and indirect inhibitory effects on Αβ fibrillogenesis.

Topics: Amyloid; Anesthetics, Intravenous; Animals; Cell Membrane; Cell-Free System; Cells, Cultured; Disease Models, Animal; G(M1) Ganglioside; Male; Mice; Neurons; PC12 Cells; Propofol; Receptors, GABA; Thiopental

Glucose homeostasis is maintained under strict physiological control in which the central nervous system is very important. Ketamine/xylazine mixture induces hyperglycemia, although the mechanism involved is unknown. We aimed to study the role of sympathoadrenal axis on glycemia and insulinemia in adult rats.. NInety-day-old male Wistar rats were used. Half of the rats underwent removal of the adrenal gland medullae (adrenodemedullation, ADM). After overnight fasting, all rats were given the intravenous glucose tolerance test (ivGTT), which was performed in six groups: awake, ketamine/xylazine (KX) and thiopental (Thiop) anesthetized intact rats, and the same groups of ADM rats. The intraperitoneal insulin tolerance test (1U/kg BW) was performed in an additional animal group to record the rate constant of plasma glucose disappearance (Kitt). Tissue insulin sensitivity was also evaluated by the homeostasis model assessment (HOMA).. Ketamine/xylazine increased basal glycemia by 110.6% (P<0.001) in intact rats. In the ADM group, KX rats had a reduction of 36.6% (P<0.05) basal glycemia. Thiop caused a decrease of 70.3% (P<0.05) in basal insulinemia in intact rats. ADM reduced fasting insulin in all groups. Insulin sensitivity was elevated in intact Thiop rats, while insulin resistance was observed in intact KX rats. Both anesthetics induced glucose intolerance during ivGTT in the intact group, but not in ADM rats. Insulin secretion was reduced for both anesthetics in intact and ADM rats.. Sympathoadrenal axis activity is not involved with the hyperglycemia induced by thiopental or ketamine/xylazine.

Topics: Adrenal Medulla; Adult; Anesthetics; Animals; Disease Models, Animal; Drug Combinations; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Ketamine; Rats; Rats, Wistar; Sympathetic Nervous System; Thiopental; Xylazine

In this study, we investigated the combined effect of Neurotropin® and pregabalin for L5-spinal nerve ligation (L5-SNL) model in rats and thiopental-induced sleep in mice.. The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. The hindpaw withdrawal threshold was measured by application of von Frey filaments. Thiopental sodium was intravenously administered in mice and sleeping time was measured. In L5-SNL rats, an isobolographic analysis was performed to clarify the combined antiallodynic effect of Neurotropin and pregabalin 14 days after ligation in rats. In isobolographic analysis and thiopental-induced sleep test, Neurotropin and pregabalin were orally administered to coincide with the timing of the peak effect of each drug.. Neurotropin (50-200 NU/kg) and pregabalin (2.5-10mg/kg) showed a dose-dependent antiallodynic action in L5-SNL rats. The antiallodynic effect of pregabalin was reversed by intrathecal injection of yohimbine or ondansetron. Isobolographic analysis suggested that the combined antiallodynic effect of Neurotropin and pregabalin in L5-SNL rats may have been more than a mere additive effect. Neurotropin (50-400 NU/kg) had no effect on thiopental-induced sleeping time whereas pregabalin (30-100mg/kg) significantly prolonged it. When the dose of pregabalin was 30 mg/kg, Neurotropin (50-400 NU/kg) did not further exacerbate the prolongation effect of pregabalin on thiopental-induced sleep.. It was suggested that when Neurotropin was administered in combination with pregabalin, it might provide more effective pain relief than that obtained with each agent alone in neuropathic pain without aggravating adverse effects of pregabalin.

Topics: Administration, Oral; Analgesics; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; gamma-Aminobutyric Acid; Hyperalgesia; Ligation; Lumbosacral Region; Male; Neuralgia; Pain Threshold; Polysaccharides; Pregabalin; Rats; Rats, Wistar; Sleep; Spinal Nerves; Thiopental

The aim of this study was to investigate the neuroprotective effects of propofol, thiopental, etomidate, and midazolam as anesthetic drugs in fetal rat brain in the ischemia-reperfusion (IR) model.. Pregnant rats of day 19 were randomly allocated into eight groups. Fetal brain ischemia was induced by clamping the utero-ovarian artery bilaterally for 30 min and reperfusion was achieved by removing the clamps for 60 min. In the control group, fetal rat brains were obtained immediately after laparotomy. In the sham group, fetal rat brains were obtained 90 min after laparotomy. In the IR group, IR procedure was performed. No treatment was given in the IR group. One milliliter intralipid solution, 40 mg/kg propofol, 3 mg/kg thiopental, 0.1 mg/kg etomidate, and 3 mg/kg midazolam was administered intraperitoneally in the vehicle group, propofol group, thiopental group, etomidate group, and midazolam group, respectively, 20 min before IR procedure. At the end of the reperfusion period, the whole brains of the fetal rats were removed for evaluation of thiobarbituric acid reactive substances and for examination by electron microscopy.. According to lipid peroxidation data, all the anesthetic drugs provide neuroprotection; however, ultrastructural findings and mitochondrial scoring confirms that only propofol and midazolam provides a strong neuroprotective effect.. Propofol and midazolam may be used to protect fetal brain in case of acute fetal distress and hypoxic injury as a first choice anesthetic drug in cesarean delivery.

Topics: Animals; Disease Models, Animal; Embryo, Mammalian; Etomidate; Female; Lipid Peroxidation; Male; Microscopy, Electron, Transmission; Midazolam; Neurons; Neuroprotective Agents; Pregnancy; Propofol; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Statistics, Nonparametric; Thiobarbituric Acid Reactive Substances; Thiopental; Time Factors

Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese-enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well-established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE).. To modulate MFS, cycloheximide (CHX), a protein synthesis inhibitor, was coadministered with Pilo in a subgroup of animals. In vivo MEMRI was performed 3 months after induction of SE and compared to the neo-Timm histologic labeling of zinc mossy fiber terminals in the dentate gyrus (DG).. Chronically epileptic rats displaying MFS as detected by neo-Timm histology had a hyperintense MEMRI signal in the DG, whereas chronically epileptic animals that did not display MFS had minimal MEMRI signal enhancement compared to nonepileptic control animals. A strong correlation (r = 0.81, p < 0.001) was found between MEMRI signal enhancement and MFS.. This study shows that MEMRI is an attractive noninvasive method for detection of mossy fiber sprouting in vivo and can be used as an evaluation tool in testing therapeutic approaches to manage chronic epilepsy.

Topics: Animals; Anticonvulsants; Cycloheximide; Disease Models, Animal; Drug Interactions; Epilepsy; Hippocampus; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Manganese; Mossy Fibers, Hippocampal; Muscarinic Agonists; Pilocarpine; Protein Synthesis Inhibitors; Rats; Rats, Wistar; Statistics, Nonparametric; Thiopental

We evaluated the effectiveness of intrathecal antagonists of α1- (WB4101) and α2- (idazoxan) adrenoceptors and serotonergic (methysergide), opioid (naloxone), muscarinic (atropine), GABA(A) (bicuculline) and GABA(B) (phaclofen) receptors in blocking 2- or 100-Hz electroacupuncture (EA)-induced analgesia (EAIA) in the rat tail-flick test. EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints in lightly anesthetized rats. EA increased tail-flick latency, where the effect of 2-Hz EA lasted longer than that produced by 100-Hz EA. The 2-Hz EAIA was inhibited by naloxone or atropine, was less intense and shorter after WB4101 or idazoxan, and was shorter after methysergide, bicuculline, or phaclofen. The 100-Hz EAIA was less intense and shorter after naloxone and atropine, less intense and longer after phaclofen, shorter after methysergide or bicuculline, and remained unchanged after WB4101 or idazoxan. We postulate that the intensity of the effect of 2-Hz EA depends on noradrenergic descending mechanisms and involves spinal opioid and muscarinic mechanisms, whereas the duration of the effect depends on both noradrenergic and serotonergic descending mechanisms, and involves spinal GABAergic modulation. In contrast, the intensity of 100-Hz EAIA involves spinal muscarinic, opioid, and GABA(B) mechanisms, while the duration of the effects depends on spinal serotonergic, muscarinic, opioid, and GABA(A) mechanisms.. The results of this study indicate that 2- and 100-Hz EA induce analgesia in the rat tail-flick test activating different descending mechanisms at the spinal cord level that control the intensity and duration of the effect. The adequate pharmacological manipulation of such mechanisms may improve EA effectiveness for pain management.

Topics: Adjuvants, Anesthesia; Adrenergic alpha-Antagonists; Analgesia; Anesthetics, Intravenous; Animals; Atropine; Baclofen; Bicuculline; Biophysics; Dioxanes; Disease Models, Animal; Electroacupuncture; GABA Agents; Male; Methysergide; Models, Biological; Multivariate Analysis; Naloxone; Narcotic Antagonists; Pain; Pain Management; Pain Measurement; Rats; Rats, Wistar; Reaction Time; Serotonin Antagonists; Tail; Thiopental; Time Factors

Hypocretin receptor-2 (Hcrt-r2)-mutated dogs exhibit all the major symptoms of human narcolepsy and respond to drugs that increase or decrease cataplexy as do narcoleptic humans; yet, unlike narcoleptic humans, the narcoleptic dogs have normal hypocretin levels. We find that drugs that reduce or increase cataplexy in the narcoleptic dogs, greatly increase and decrease, respectively, hypocretin levels in normal dogs. The effects of these drugs on heart rate and blood pressure, which were considerable, were not correlated with their effects on cataplexy. Administration of these drugs to Hcrt-r2-mutated dogs produced indistinguishable changes in heart rate and blood pressure, indicating that neither central nor peripheral Hcrt-r2 is required for these cardiovascular effects. However, in contrast to the marked Hcrt level changes in the normal dogs, these drugs did not alter hypocretin levels in the Hcrt-r2 mutants. We conclude that Hcrt-r2 is a vital element in a feedback loop integrating Hcrt, acetylcholine, and norepinephrine function. In the absence of functional Hcrt-r2, Hcrt levels are not affected by monoaminergic and cholinergic drugs, despite the strong modulation of cataplexy by these drugs. Conversely, strong transient reductions of Hcrt level by these drugs do not produce episodes of cataplexy in normal dogs. The Hcrt-r2 mutation causes drug-induced cataplexy by virtue of its long-term effect on the functioning of other brain systems, rather than by increasing the magnitude of phasic changes in Hcrt level. A similar mechanism may be operative in spontaneous cataplexy in narcoleptic dogs as well as in narcoleptic humans.

Topics: Animals; Blood Pressure; Cataplexy; Cholinesterase Inhibitors; Disease Models, Animal; Dogs; Female; Gene Expression Regulation; Heart Rate; Hypnotics and Sedatives; Intracellular Signaling Peptides and Proteins; Male; Mutation; Neuropeptides; Orexin Receptors; Orexins; Phenylephrine; Physostigmine; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Respiration; Sympathomimetics; Thiopental

The fact that a considerable amount of clinical conditions suffering from ischemia-reperfusion injury (IRI) occur under general anesthesia has triggered researchers to focus on the effects of anesthetic drugs on IRI. Hence, the aim of this study was to compare the use of different anesthetic drugs in a skeletal IRI model. Tourniquet IRI method was performed and two experimental groups were established as sham-control and IRI group. Rats in each group were anesthetized either with thiopental, ketamine, propofol or etomidate. Malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were measured in skeletal muscle via a spectrophotometer. Zinc, iron, copper, and selenium were evaluated by atomic absorption spectrophotometer. In rats anesthetized with thiopental (40 mg/kg, i.p.), malondialdehyde values in IRI group were higher and glutathion peroxidase levels were lower compared to sham-control group. However, superoxide dismutase and catalase activities were identical. On the other hand, while the level of zinc in IRI group attenuated, no differences in iron and copper values were determined. Rats anesthetized with ketamine (60 mg/kg), propofol (100 mg/kg), or etomidate (20 mg/kg) did not show increased malondialdehyde levels in comparison with control levels. While the drugs did not cause a distinction in the levels of superoxide dismutase, catalase, glutathion peroxidase, iron, and copper, zinc was in a lower level in IRI group compared to sham-control. In conclusion, ketamine, propofol, and etomidate, with anesthetic doses, denoted efficacious effects on IRI; hence the drugs might be preferred in certain operations with the risk of IRI.

Topics: Anesthetics, Dissociative; Anesthetics, Intravenous; Animals; Disease Models, Animal; Etomidate; Female; Ketamine; Muscle, Skeletal; Propofol; Rats; Rats, Wistar; Reperfusion Injury; Thiopental; Zinc

Despite earlier research studying the influence of anesthetics in arrhythmia models, a lot of controversy remains. The aim was to compare the influence of three anesthetics (60 mg/kg thiopental, 1200 mg/kg urethane, 60 mg/kg pentobarbital intraperitoneally) on ventricular arrhythmias and to combine it with measured hemodynamic parameters to find the most suitable agent for such experiments.. In the model of ischemia- and reperfusion-induced arrhythmias in Sprague-Dawley rats, after left anterior descending coronary artery occlusion (7 minutes) and reperfusion (15 minutes), the following parameters have been measured or calculated: mortality index; ventricular fibrillation and tachycardia incidence and duration; systolic, diastolic, and mean arterial blood pressure; heart rate; myocardial index of oxygen consumption; and plasma creatine kinase concentration.. Evident depressive action of urethane on heart rate, blood pressures, and myocardial index of oxygen consumption should be reason enough to exclude it from use in such studies. Pentobarbital had no effect on arrhythmias, whereas thiopental was antiarrhythmic.. Pentobarbital is the most suitable anesthetic offering stable hemodynamic values during arrhythmia studies. These hemodynamic values, which were similar to physiological values in awake rats, the long arrhythmia duration during reperfusion and approximately 50% mortality index are crucial parameters for evaluating antiarrhythmic drugs.

Topics: Adjuvants, Anesthesia; Anesthetics, Intravenous; Animals; Arrhythmias, Cardiac; Blood Pressure; Disease Models, Animal; Heart Rate; Male; Myocardial Reperfusion Injury; Oxygen Consumption; Pentobarbital; Rats; Rats, Sprague-Dawley; Thiopental; Urethane

Calcium channel blockers (CCBs) are widely used as therapeutic agents, for the treatment of cardiovascular disorders. However, the discovery that CCBs bind to various regions of the brain suggest that they might also offer some beneficial effects in the treatment of neuropsychiatry disorders. This study was carried out to evaluate the anti-psychotic and sedative effects of two notable calcium channel blockers, verapamil and nifedipine in mice. The anti-psychotic effects of the CCBs were studied in the animal model of amphetamine-induced stereotyped behavioral disorders. The sedative effect was assessed utilizing the prolongation of the time of sleep, induced by thiopentone. The ability of CCBs to produce catalepsy in mice was also evaluated in the study. Graded doses of verapamil (5.0-20.0 mg/kg, i.p) significantly (p<0.05) suppressed stereotyped behaviour induced by amphetamine (10.0 mg/kg, i.p). In contrast, nifedipine (5.0-20.0 mg/kg, i.p) did not exhibit anti-psychotic effect, as it could not significantly reduce stereotypy caused by amphetamine. In the test for sedation, both verapamil (5.0-20.0 mg/kg, i.p) and nifedipine (10.0-20.0 mg/kg) significantly (p<0.05) prolonged the sleeping time induced by thiopentone (50.0 mg/kg, i.p). However, neither verapamil (5.0-20.0 mg/kg, i.p.) nor nifedipine (5.0-20.0 mg/kg, i.p.) at the tested doses produced any cataleptic behaviour in the animals. The results of the study suggest that verapamil has both anti-psychotic and sedative effects without inducing the side effect of catalepsy and might be relevant in the treatment of psychosis.

Topics: Amphetamine; Animals; Antipsychotic Agents; Calcium Channel Blockers; Catalepsy; Disease Models, Animal; Hypnotics and Sedatives; Male; Mice; Nifedipine; Psychoses, Substance-Induced; Sleep; Stereotyped Behavior; Thiopental; Verapamil

Thiopental is an anesthetic used for controlling high intracranial pressure (ICP) caused by brain surgery, brain trauma, and severe stroke. However, it remains controversial whether Thiopental is detrimental or beneficial in ischemic stroke. In this study, we used an animal model of ischemic stroke in spontaneously hypertensive rats to determine whether or not Thiopental is neuroprotective in the setting of brain ischemia. We observed that Thiopental caused a prolonged duration of unconsciousness with a high rate of mortality, that Thiopental created exaggerated neurological deficits that were revealed through limb placement tests at 4 days and 4 weeks after brain ischemia, and that infarct volume was increased in Thiopental-anesthetized rats. These data suggest that Thiopental is detrimental in ischemic stroke. Thus, our findings raise a caution about the use of Thiopental in the setting of ischemic stroke.

Topics: Anesthetics, Intravenous; Animals; Brain; Brain Ischemia; Chloral Hydrate; Disease Models, Animal; Dyskinesia, Drug-Induced; Magnesium Sulfate; Male; Methohexital; Pentobarbital; Random Allocation; Rats; Rats, Inbred SHR; Stroke; Thiopental; Time Factors; Treatment Outcome; Unconsciousness

In this study, we used a porcine model to investigate whether impaired coagulation and severe arterial or venous bleeding could be normalized by substitution with a prothrombin complex concentrate (PCC), Beriplex P/N, containing coagulation factors II, VII, IX, and X.. Dilutional coagulopathy was induced in anesthetized pigs by fractionated blood withdrawal (approximately 65% of total volume), followed by erythrocyte retransfusion and volume substitution with a total of 1000 mL of hydroxyethyl starch (Infukoll 6%). Animals were randomized to no treatment, treatment with placebo, or treatment with 35 U/kg PCC. Arterial (spleen incision) or venous (bone injury) bleeding was inflicted. Thromboelastometry, hematology, and coagulation tests were performed at baseline, after dilution, and after study treatments had been administered and injury inflicted. The primary end-point was postinjury time to hemostasis.. Hemodilution resulted in a decrease in coagulation factor concentrations to approximately 35% and prolonged prothrombin time. Platelet numbers decreased from approximately 400,000 to approximately 100,000/microL, and aggregation and adhesion were impaired. PCC effectively substituted the deficient prothrombin factors (II, VII, IX, and X) and normalized the prolonged prothrombin time. After spleen injury, PCC significantly reduced time to hemostasis versus dilutional control (median, 35 vs 82.5 min; P < 0.0001), and produced a nonsignificant trend towards reduction in blood loss (mean, 275 vs 589 mL). PCC also significantly reduced time to hemostasis (median, 27 vs 97 min; P < 0.0011) and blood loss (mean, 71 vs 589 mL; P < 0.0017) after bone injury.. Dilutional coagulopathy produced a generalized decrease in coagulation factors and impaired platelet function. Substitution with PCC effectively normalized coagulation and significantly improved hemostasis after venous and arterial bleeding.

Topics: Anesthetics, Intravenous; Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Disease Models, Animal; Hemodilution; Hemorrhage; Platelet Aggregation; Swine; Thiopental

There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 microg/side) or 6-OHDA (10 microg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67%) or severe (~91%) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Anesthetics, Combined; Animals; Biogenic Monoamines; Corpus Striatum; Disease Models, Animal; Immunohistochemistry; Ketamine; Male; Maze Learning; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Rats; Rats, Wistar; Substantia Nigra; Thiopental; Tyrosine 3-Monooxygenase; Xylazine

During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood.. Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests--spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)--were conducted on mice aged 55-70 days.. Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol.. This study shows that both a gamma-aminobutyric acid type A agonist (thiopental or propofol) and an N-methyl-D-aspartate antagonist (ketamine) during a critical stage of brain development potentiated neonatal brain cell death and resulted in functional deficits in adulthood. The use of thiopental, propofol, and ketamine individually elicited no or only minor changes.

Topics: Analgesics; Anesthetics, Combined; Anesthetics, Intravenous; Animals; Animals, Newborn; Anti-Anxiety Agents; Apoptosis; Behavior, Animal; Brain; Diazepam; Disease Models, Animal; Drug Combinations; Drug Synergism; Excitatory Amino Acid Agonists; GABA Antagonists; Ketamine; Male; Maze Learning; Mice; N-Methylaspartate; Neurodegenerative Diseases; Propofol; Receptors, GABA-A; Sodium Chloride; Thiopental; Time Factors

Controversy and speculation exist regarding intracranial pressure (ICP) changes produced by various combinations of rapid sequence intubation (RSI) agents. In this pilot study, we sought to develop a swine model to investigate these changes in classic RSI.. Eight adult swine were instrumented with arterial and intracranial pressure monitors. Four different versions of rapid sequence intubation were then performed sequentially in each animal in a crossover trial design: regimen 1, thiopental; regimen 2, thiopental and succinylcholine; regimen 3, lidocaine, thiopental, and succinylcholine; and regimen 4, pancuronium, lidocaine, thiopental, and succinylcholine. ICP and hemodynamic parameters were recorded and compared. Trials were excluded from analysis if baseline ICP measurements were unstable or if intubation was difficult.. Peak changes in ICP were noted at 2 to 3 minutes after administration of induction agents. Mean values for peak changes in ICP were as follows: regimen 1 (n = 5), 3.6 mm Hg (95% confidence interval [CI], 1.0-6.2 mm Hg); regimen 2 (n = 9), 13.6 mm Hg (95% CI, 9.6-17.6 mm Hg); regimen 3 (n = 2), 16.0 mm Hg (95% CI, -34.8-66.8 mm Hg); and regimen 4 (n = 3), 12.0 mm Hg (95% CI, -8.3-32.3 mm Hg).. The model is effective. It enables investigators to examine the aggregate ICP effects of combinations of RSI medications. RSI regimens with paralysis produced threefold increases in peak ICP change compared with the sedation-only regimen. Pretreatment agents did not affect ICP changes. Future investigations can examine other agents and add experimental manipulation of ICP to simulate head injury physiology. Additional parameters including cerebral metabolism and/or oxygenation may also be explored.

Topics: Animals; Brain Injuries; Cross-Over Studies; Disease Models, Animal; Emergency Treatment; Intracranial Pressure; Intubation, Intratracheal; Lidocaine; Pancuronium; Pilot Projects; Succinylcholine; Swine; Thiopental

Topics: Animals; Disease Models, Animal; Fat Emulsions, Intravenous; Female; Infusions, Intravenous; Pilot Projects; Random Allocation; Rats; Respiratory Insufficiency; Sodium Chloride; Thiopental; Treatment Outcome

Atrial tachyarrhythmias (AT) frequently complicate the perioperative period. Alcohol intoxication is a recognized causative factor for dysrrhythmias. We studied the effects of propofol and thiopental on atrial electrophysiology and vulnerability to AT in a closed-chest porcine model in which AT are facilitated by ethanol.. Thirty-eight pigs were randomly assigned to thiopental (T-group, n=19) or propofol (P-group n=19). All animals were assigned to undergo a right atrial electrical stimulation protocol (RASP) at baseline. Thirty pigs were assigned to undergo additional RASP during ethanol infusion, while the remaining eight were assigned to undergo additional RASP during saline infusion (control group). We analysed effective refractory period (ERP), and intra-atrial conduction interval (ICI) (between atrial sites 4 cm apart), at several cycle lengths (CL).. There were no significant differences at baseline. During ethanol infusion, propofol produced a greater rate-dependent decrease in excitability, manifested by a longer minimum paced CL with 1:1 atrial capture: 145 (11) vs 164 (27) ms in the T- and P-group, respectively (P=0.01). Propofol was associated with a greater rate-related slowing in conduction: difference between ICI at CL of 300 ms and ICI at minimum CL: 30 ms in P-group and 22 ms in T-group (P<0.03). In the P-group we observed a longer duration of induced arrhythmias (145 (131) vs 74 (91) s, P<0.03) and a higher proportion with atrial flutter (AFl) (76 vs 19%, P<0.001).. Propofol in this model was more arrhythmogenic than thiopental, as manifested by a longer duration of induced arrhythmias, particularly AFI.

Topics: Alcoholic Intoxication; Anesthetics, Intravenous; Animals; Arrhythmias, Cardiac; Atrial Flutter; Atrial Function, Right; Disease Models, Animal; Electrophysiology; Ethanol; Propofol; Random Allocation; Swine; Thiopental

Many anesthetic agents are known to have cardiac effects. The effects of pentobarbital, thiopental and isoflurane on dogs with electrical remodeling are lacking.. We studied 12 dogs that underwent two anesthesias. First, anesthesia was induced (N=12) with intravenous thiopental (17 mg/kg) induction followed by isoflurane inhalation (1.5%-3% via endotracheal tube). For electrical remodeling, we created complete atrioventricular block (CAVB) and myocardial infarction (MI). In 6 of the 12 dogs we also infused nerve growth factor (NGF) to the right stellate ganglion. All dogs had an implantable cardioverter-defibrillator (ICD) implanted. A second anesthesia was done 66 +/- 20 days later. In 8 of the 12 dogs (6 without NGF), pentobarbital was used as the only anesthetic. In the remaining 4 dogs (all with NGF), 3 received thiopental and 1 received isoflurane.. During the first anesthesia, none of 12 dogs had cardiac arrhythmia. During the second anesthesia, none of the 8 dogs that received pentobarbital developed ventricular fibrillation (VF). In contrast, all the dogs receiving either thiopental or isoflurane died of VF within 2 to 3 minutes. QT and P-P intervals before VF were 440 +/- 36 milliseconds and 298 +/- 28 milliseconds, longer and shorter (respectively) than those obtained the day prior to surgery (315 +/- 25 milliseconds, P < 0.001; 330 +/- 22 milliseconds, P < 0.01, respectively).. Thiopental and isoflurane are not arrhythmogenic in normal dogs and dogs with acute MI and CAVB, but are extremely proarrhythmic in dogs with chronic MI and CAVB. Consistent with the results of in vitro studies, pentobarbital did not induce ventricular arrhythmia in dogs with cardiac electrical remodeling.

Topics: Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Death, Sudden, Cardiac; Disease Models, Animal; Dog Diseases; Dogs; Heart Block; Isoflurane; Myocardial Infarction; Thiopental; Torsades de Pointes

Topics: Animals; Barbiturates; Brain; Brain Ischemia; Coronary Circulation; Cryotherapy; Disease Models, Animal; Evaluation Studies as Topic; Hypothermia; Male; Norepinephrine; Oxygen Consumption; Rats; Rats, Wistar; Thiopental

We examined the effects of intravenous anesthetics (thiopental, fentanyl and morphine) on the ventricular activation in a canine myocardial infarction model. Thiopental at 5 and 10 mg/kg delayed or abolished the delayed activation in the infarcted zones with slight delay of activation of the normal zones. Fentanyl at 30 micrograms/kg slightly but significantly prolonged the activation time in both normal and infarcted zones. Morphine at 1 mg/kg did not produce any significant effect. Thiopental, but neither fentanyl nor morphine, inhibited ventricular stimulation-induced arrhythmias. Thus, thiopental, but not fentanyl nor morphine, markedly depressed the delayed activation in myocardial infarction, which may affect and probably inhibits the ventricular arrhythmias in myocardial infarction. It also should be kept in mind that thiopental may have arrhythmogenic effects in myocardial infarction.

Topics: Action Potentials; Animals; Blood Pressure; Disease Models, Animal; Dogs; Electrocardiography; Fentanyl; Heart Rate; Heart Ventricles; Infusions, Intravenous; Morphine; Myocardial Infarction; Thiopental

This study was designed to investigate the changes in regional distensibility of the ischemic segment and of a remote nonischemic segment brought about by graded myocardial ischemia.. Ventricular distensibility is a major determinant of left ventricular end-diastolic pressure. The effects of graded myocardial ischemia on the regional distensibility of the ischemic area have not been studied. Moreover, there are few data on the effects of myocardial ischemia on the regional distensibility of the nonischemic myocardium.. Nine anesthetized open chest mongrel dogs were fitted with instruments to measure left ventricular pressure and circumferential length (sonomicrometry) in the ischemic segment and in a nonischemic segment. The pressure-length relation was modified by stepwise infusion and withdrawal of 200 ml of each dog's own blood over 30 min in five consecutive stages of regional ischemia. Unstressed dimensions were obtained by repeated inferior vena cava occlusions. In both segments, regional distensibility was assessed at end-diastole by means of the constants of the pressure-length (chamber stiffness), the pressure-strain and the force-strain (myocardial stiffness) relations.. In the ischemic segment, partial and complete coronary occlusions were associated with a twofold increase in the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant, whereas in the nonischemic segment the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant increased by 50%.. Regional myocardial ischemia is associated with a decrease in distensibility of both the ischemic and the remote nonischemic myocardium.

Topics: Analysis of Variance; Anesthesia; Animals; Diastole; Disease Models, Animal; Dogs; Female; Halothane; Hemodynamics; Male; Myocardial Contraction; Myocardial Ischemia; Systole; Thiopental

This study was designed to test whether previous work, which showed that the angiotensin converting enzyme (ACE) inhibitor enalaprilat potentiated the alpha 1-adrenoceptor antagonist activity of doxazosin in isolated rat tail arteries, could be extended to demonstrate a synergistic hypotensive effect of these two drugs.. Groups of untreated or chronically deoxycorticosterone acetate (DOCA)-salt-treated female Sprague-Dawley rats were used. Rats were anaesthetized with Inactin (barbiturate); drugs were administered via a jugular venous catheter; blood pressure was monitored via a carotid arterial catheter.. In previously untreated rats, pretreatment with enalaprilat shifted the dose-response curve for the hypotensive effect of doxazosin to the left, indicating synergism. In rats dosed with DOCA-salt (which suppresses renin and angiotensin II production): (1) there was no synergism between the hypotensive actions of enalaprilat and doxazosin; (2) doxazosin was more potent than in untreated rats; and (3) enalaprilat lowered blood pressure, suggesting a hypotensive mechanism separate from ACE inhibition.. In the absence of angiotensin II (resulting from enalaprilat administration or from chronic DOCA-salt), doxazosin had a greater hypotensive action than in the presence of angiotensin II. This is consistent with the concept that angiotensin II modulates alpha 1-adrenoceptor activity.

Topics: Anesthesia; Animals; Antihypertensive Agents; Desoxycorticosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Doxazosin; Drug Evaluation, Preclinical; Drug Interactions; Enalaprilat; Female; Hypertension; Prazosin; Rats; Rats, Inbred Strains; Thiopental

A possible cerebroprotective effect of halothane was investigated in a canine model of 5-min global cerebral ischemia. In pentobarbital-anesthetized dogs, additional inhalation of 0.5 to 1% halothane prior to ischemia prevented the post-ischemic dysfunction of the vagal component of reflex bradycardia. In contrast, pretreatment with thiopental at 10 mg/kg, i.v. failed to prevent it. The influence of ischemia in the absence of anesthetics was similar to that under barbiturate anesthesia. The results suggest that halothane, but not barbiturate, may actively protect the vagal baroreflex system from ischemia.

Topics: Administration, Inhalation; Animals; Blood Pressure; Disease Models, Animal; Dogs; Electroencephalography; Female; Halothane; Heart Rate; Ischemic Attack, Transient; Male; Pressoreceptors; Reflex; Thiopental; Vagus Nerve

The effects of intravenous almitrine under normoxic, hyperoxic, and hypoxic conditions were studied in 5 male beagle dogs (mean weight 15.2 +/- 5 kg) anaesthetized with thiopentone. Plasma concentrations of thiopentone were maintained constant at 27-29 mg.1(-1). Each animal underwent twice the three different experiments, with a lapse of a fortnight between each experiment: a) breathing room air, with intravenous administration of 1 mg.kg-1 almitrine over 30 s, b) breathing room air, then pure oxygen for 15 min, followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing pure oxygen, and c) breathing room air, then progressively less oxygen (FIO2 0.18, 0.16, 0.14, 0.12 for 5 min each), followed by an intravenous administration of 1 mg.kg-1 almitrine over 30 s with the dog still breathing a mixture with 12% oxygen. Tidal volume, respiratory rate, minute ventilation, inspiratory and expiratory duration, arterial pH, PaO2 and PaCO2 were measured respectively in room air, after 100% oxygen, in hypoxia (FIO2 = 0.12), before, 5 and 10 min after the injection of almitrine. Hyperoxia depressed ventilation (-21%), whilst hypoxia stimulated it (+126%), although significantly less than in the awake animal. Almitrine restored the respiratory response to hypoxia, but hyperoxia did not suppress respiratory stimulation due to the drug. It would therefore seem likely that almitrine acts on peripheral arterial chemoreceptors, but also on other structures. The results of this study suggest that almitrine may be useful in restoring the respiratory response to hypoxia during recovery from anaesthesia.

Topics: Almitrine; Anesthesia, General; Animals; Carbon Dioxide; Chemoreceptor Cells; Disease Models, Animal; Dogs; Hypoxia; Male; Oxygen; Oxygen Inhalation Therapy; Respiration; Thiopental

Inadvertent arterial injections, both in cases of drug addiction and in iatrogenic situations, often result in significant loss of tissue and, eventually, loss of function distal to the injection site. Previous experimental studies regarding the effectiveness of agents to reverse vasospasm have been inconclusive. A recent clinical report, however, suggested that intraarterial injection of reserpine was affective in limiting tissue necrosis. This experiment was designed to study the affect of intraarterially injected reserpine and tolazoline hydrochloride in a rabbit ear model of necrosis following intraarterial injection of pentothal. Six groups of 5 rabbits each were studied. Animals in Group 1 received intraarterial saline injections. Animals in Group 2 received intraarterial pentothal. Animals in Group 3 received intraarterially injected pentothal plus intraarterial reserpine 30 minutes later. Animals in Group 4 received intraarterially injected pentothal plus intraarterial tolazoline 30 minutes later. Animals in Group 5 received intraarterially injected pentothal plus intraarterially injected reserpine and intraarterially injected tolazoline both administered immediately. Animals in Group 6 received intraarterially injected pentothal plus intraarterially injected reserpine and intraarterially injected tolazoline, both administered 30 minutes later. Results showed no significant difference in the amount of tissue necrosis between treated and untreated animals. We conclude that the use of intraarterial spasmolytic agents has no effect on the course of tissue necrosis after inadvertent intraarterial injections.

Topics: Animals; Arteries; Disease Models, Animal; Ear, External; Injections, Intra-Arterial; Necrosis; Rabbits; Reserpine; Thiopental; Tolazoline

Inadvertent intra-arterial injection of drugs produces a well-defined clinical syndrome whose pathophysiology remains unclear. This study was designed to determine the role of the inflammatory mediator, thromboxane, in intra-arterial drug injections. The rabbit ear model, as described by Kinmonth and Sheppard, was used. Five of the experimental groups were treated with specific or nonspecific thromboxane blocking agents and two groups served as controls. Immunohistochemical staining of the control ears showed elevated levels of thromboxane within the first 6 hours postinjury. The specific thromboxane blocking agents, methimazole and Aloe vera, showed almost complete blockade of thromboxane production. The percentage of ear survival was significantly greater in the group treated with topical Aloe vera (p less than 0.05) and even greater survival was achieved in the combined Aloe vera/methimazole group (p less than 0.01). On the basis of these results, we have begun treatment of such injuries with specific and nonspecific thromboxane blocking agents.

Topics: Animals; Disease Models, Animal; Drug-Related Side Effects and Adverse Reactions; Ear; Injections, Intra-Arterial; Pharmaceutical Preparations; Rabbits; Thiopental; Thromboxanes

Spinal cord ischemia was produced in male mongrel dogs by permanent occlusion of the infrarenal aorta. All animals were anesthetized with a mixture of nitrous oxide and 1.5% halothane. Group 1 animals were the controls. Group 2 animals were pretreated, 30 minutes prior to aortic occlusion, with sodium thiopental, 20 mg per kilogram of body weight, over 5 minutes, followed by an infusion of 10 mg/kg/hr for 2 1/2 hours. Groups 3 animals received the identical dose of sodium thiopental and, in addition, received mannitol, 1 gm/kg, and methylprednisolone 1 mg/kg. There were no differences in hemodynamic data or arterial blood gases among the groups, except that the thiopental bolus caused a transient reduction in mean arterial pressure. Ninety percent of Group 1 animals were paraplegic, while only 30% of Group 2 and 40% of Group 2 animals were paraplegic. The difference in the incidence of paraplegia in Groups 2 and 3 compared with Group 1 was statistically significant (p less than 0.05). Therefore, thiopental significantly decreased the incidence of paraplegia, while methylprednisolone and mannitol did not enhance its protective effect.

Topics: Animals; Aorta, Abdominal; Disease Models, Animal; Dogs; Ischemia; Ligation; Male; Mannitol; Methylprednisolone; Paraplegia; Postoperative Complications; Spinal Cord; Thiopental

Topics: Analgesia; Animals; Blood Pressure; Brain Damage, Chronic; Brain Ischemia; Disease Models, Animal; Dogs; Hemodilution; Immobilization; Macaca mulatta; Macaca nemestrina; Respiration, Artificial; Resuscitation; Thiopental

To define the utility of high-dose barbiturate therapy following an episode of complete global cerebral ischemia, we investigate the effects of 60 mg/kg of thiopental given to cats five minutes after resuscitation from 12, 14, or 16 min of electrically induced ventricular fibrillation (VF). All aspects of the arrest, resuscitation, with post-arrest care were carefully controlled, with the EEG becoming isoelectric 20-25 s after the onset mean resuscitation time of 2.5 +/- 0.2 (SEM) min. For any given duration of VF, there were no differences (control vs thiopental) in any pre- or post-arrest parameters (blood pressure, blood gases, electrolytes, etc.) A total of 68 resuscitated cats were entered into various treatment and control groups, and all but one group received 20-24 h of post-resuscitation paralysis, mechanical ventilation, and ICU support before being extubated. Cats received an additional six days of aggressive nursing care, and daily examinations were performed with the assignment of a neurologic deficit score (NDS) between 0 (normal) and (brain dead). Autopsies were performed to determine the cause of death in animals which died before the end of the seven-day observation period. The early post-arrest period was marked by the occurrence of repetitive, rhythmic bursts of high-frequency electroencephalographic (EEG) activity (? seizures) in 38 per cent of control animals (16/42, all arrest times combined). Ten of these animals died as a result of severe neurologic injuries. By contrast, only 12 per cent of treated cats (3/26) developed similar EEG patterns (P less than 0.05) and there were no neurologic deaths in the thiopental groups. The differences in the incidence of neurologic deaths (control vs. thiopental) was significant (P less than 0.02). The change in overall mortality did not quite reach significance (36 per cent vs. 21 per cent), and treatment had no effect on the incidence of deaths due to cardiovascular causes (e.g., myocardial infarctions). In spite of the effects on mortality, treatment had no effect on the neurologic function of survivors (assessed by NDS). These findings suggest that thiopental improved survival rates by suppressing an unusual post-arrest EEG pattern (? anticonvulsant effect), but had no additional cerebral protective effects.

Topics: Animals; Brain Diseases; Brain Ischemia; Cats; Disease Models, Animal; Electroencephalography; Heart Arrest; Resuscitation; Thiopental; Ventricular Fibrillation

Myocardial infarction was produced in dogs and cats by occlusion of the left anterior descending coronary artery. Arrhythmia was present in dogs but not in cats 6 to 48 h after occlusion. The absence of arrhythmia in cats was not due to persistent myocardial depressant effects of anaesthesia administered during surgery. Studies in cats with surgically-induced heart block revealed multiple ventricular pacemakers but no change in average ventricular rate following coronary occlusion. These results suggest that sinus overdrive, although not elevated compared with the dog, is sufficient to suppress arrhythmia in the cat. Further, since small dogs developed significantly less arrhythmia than large dogs, heart size may be an additional factor in explaining the absence of arrhythmia in the cat.

Topics: Animals; Arrhythmias, Cardiac; Atrioventricular Node; Body Weight; Cats; Disease Models, Animal; Dogs; Female; Heart; Heart Conduction System; Heart Ventricles; Male; Myocardial Infarction; Organ Size; Thiopental; Vagus Nerve

Experimental asthma was induced in dogs previously sensitized to ascaris antigen by ventilation with ascaris antigen, in an aerosol, for 10 min. Before the administration of antigen, there was no significant difference in pulmonary airways resistance (RL) during thiopentone and ketamine anaesthesia. In dogs anaesthetized with thiopentone, RL increased significantly from a pre-antigen control of 0.36 +/- 0.13 (mean +/- SEM) kPa litre-1 s to 1.56 +/- 0.38 at 5 min after administration of antigen. In dogs anaesthetized with ketamine, RL before (0.30 +/- 0.10) and 5 min after antigen (0.47 +/- 0.18) was not significantly different. Beta adrenergic blockade with propranolol abolished the protective effect of ketamine so that there was no significant difference in the maximal increase (5 min after antigen) in RL in dogs anaesthetized with ketamine (2.92 +/- 0.74) or thiopentone (3.28 +/- 1.16). Beta adrenergic blockade also increased pre-antigen RL in both groups (ketamine 0.87 +/- 0.24; thiopentone 0.77 +/- 0.32).

Topics: Airway Resistance; Anesthesia, Intravenous; Animals; Antigens; Ascaris; Asthma; Bronchial Spasm; Disease Models, Animal; Dogs; Ketamine; Lung Compliance; Propranolol; Thiopental

Topics: Anesthesia, Intravenous; Animals; Brain; Disease Models, Animal; Female; Haplorhini; Hypoxia, Brain; Ischemic Attack, Transient; Macaca mulatta; Thiopental; Time Factors

Topics: Animals; Brain; Disease Models, Animal; Haplorhini; Ischemia; Macaca mulatta; Thiopental

Topics: Animals; Blood Vessels; Chiroptera; Disease Models, Animal; Dosage Forms; Gangrene; Injections, Intra-Arterial; Ischemia; Secobarbital; Thiopental

Hydrochloric acid was instilled into the bronchial tree in anaesthetized dogs. A severe respiratory acidosis resulted. The metabolic component of acid-base balance was little affected.

Topics: Acidosis, Respiratory; Anesthesia, General; Animals; Carbon Dioxide; Disease Models, Animal; Dogs; Female; Halothane; Hematocrit; Hydrochloric Acid; Hydrogen-Ion Concentration; Lung; Male; Nitrous Oxide; Organ Size; Oxygen; Pneumonia, Aspiration; Respiration; Thiopental

Topics: Anesthetics; Angiotensin II; Animals; Autoradiography; Blood Flow Velocity; Blood Pressure; Blood-Brain Barrier; Brain; Carbon Radioisotopes; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Models, Animal; Hypertension; Methoxyflurane; Rabbits; Thiopental; Vasomotor System