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Evaluation of two combinations of Domitor, Zoletil 100, and Euthatal to obtain long-term nonrecovery anesthesia in Sprague-Dawley rats.

We sought to evaluate a new protocol designed to maintain long-term, nonrecovery, surgical anesthesia in Sprague-Dawley rats. In the first phase, two groups of rats were anesthetized with two different dose combinations of Domitor (medetomidine) and Zoletil 100 (tiletamine-zolazepam) to investigate their efficacy in induction of anesthesia. One combination comprised Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg, whereas the other comprised Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg. Both combinations effectively induced deep anesthesia and caused no mortality, but the duration of anesthesia differed statistically. In the second phase, we induced anesthesia with both Domitor-Zoletil 100 dose combinations then investigated the possibility of maintaining anesthesia for 5 h by administering Euthatal (pentobarbitone) intra-arterially at 10 mg/kg hourly. Depth of anesthesia, mortality, physiological parameters, blood gas analysis, hematology, clinical chemistry, and postmortem histopathology were recorded. Euthatal provided stable long-term anesthesia with both dose combinations of Domitor-Zoletil 100. Seven of 8 (88%) animals anesthetized with Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg successfully were maintained under deep anesthesia for 5 h. Higher mortality (36% versus 12%) occurred in group of animals treated with Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg. This difference may be linked to dose-related respiratory depression, as alterations of arterial gas levels were noted. Our findings suggest that, when long-term nonrecovery anesthesia is required, doses of 50 microg/kg Domitor and 20 mg/kg Zoletil 100 are preferable when given with Euthatal to maintain physiological conditions in animals.

Anesthesia↗

Evaluation of use of tiletamine/zolazepam for anesthesia of bullfrogs and leopard frogs.

Use of tiletamine hydrochloride and zolazepam hydrochloride (1:1 fixed ratio combination) as an anesthetic agent in 2 anuran species was studied. A dosage of 5 mg/kg of body weight, administered IM, resulted in variable weak tranquilization. Intramuscular administration at dosages of 10 and 20 mg/kg induced variable states of tranquilization or anesthesia in leopard frogs (Rana pipiens) and bullfrogs (R catesbeiana). The dosages of 50 mg/kg induced anesthesia with greater consistency than lower dosages in bullfrogs, but resulted in mortalities. The same dosage was uniformly fatal in leopard frogs. Neither gross nor histologic lesions were identified in the frogs that died. Depth and duration of anesthesia was dosage related. At the 20 and 50 mg/kg dosages, leopard frogs attained a greater depth of anesthesia and remained anesthetized for a significantly greater duration than did bullfrogs; however, at the 5 and 10 mg/kg dosages, bullfrogs developed greater tranquilization for longer periods than did leopard frogs. Results of this study revealed profound intraspecies variation in depth and duration of effect of tiletamine/zolazepam; therefore, the drug does not appear to be a suitable injectable anesthetic in anurans.

Anesthesia, General↗

Efficacy of the intranasal route for administration of anesthetic agents to adult rabbits.

Anesthetic agents were administered to adult rabbits by using the intranasal route. Six sedative or anesthetic protocols were studied as follows: group 1 (n = 12), 2.0 mg midazolam/kg body weight (BW); group 2 (n = 8), 25.0 mg ketamine/kg BW; group 3 (n = 8), 10 mg of combination of tiletamine and zolazepam/kg BW; group 4 (n = 10), 3 mg xylazine/kg BW and 10 mg ketamine/kg BW; group 5 (n = 8), 1.0 mg midazolam/kg BW and 25 mg ketamine/kg BW; and group 6 (n = 6), 0.3 ml of a combination of fentanyl and droperidol/kg BW. All drugs were diluted to a final volume of 0.4 ml/kg BW and an equal volume was administered with a catheter-tipped syringe into each nostril. Time to onset and duration of sedation or anesthesia were recorded. Muscle relaxation was graded as poor, fair, or excellent on the basis of flexibility of limbs. Presence or absence of a toe pinch response was recorded. Heart rate, respiratory rate, and hemoglobin saturation were measured before and at 5-min intervals after drug administration. The mean onset times for groups 1, 2, 3, 4, and 5 were 3.0, 1.2, 2.5, 2.0, and 0.8 min, respectively. The mean duration of action was 24.6, 36.7, 44.4, 35.2, and 52.5 min for midazolam, ketamine, tiletamine/zolazepam, xylazine/ketamine, and midazolam/ketamine, respectively. All protocols resulted in a significant decrease in respiratory rate. Hemoglobin saturation decreased in all groups except group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

CI-744 anesthesia for ophthalmological examination and surgery in monkeys.

CI-744 is a new agent for chemical restraint and surgical anesthesia in animals, consisting of equal parts by weight of the cataleptoid agent tiletamine-HCl and the tranquilizer zolazepam-HCl. We have used it in the intramuscular dose of five to ten milligrams per kilogram to anesthetize 110 cynomolgus and 10 vervet monkeys a total of 1,500 times for various ophthalmological procedures. At these dosages its characteristics of action were rapid onset, thirty of fifty minutes of surgical depth anesthesia during which there was excellent muscular relaxation and an absence of ocular movements, a very gradual emergence, and no adverse after effects. In these monkey species, we judge CI-744 superior to phencyclidine or methohexital as a short-acting general anesthetic for most ophthalmological procedures.

Anesthesia↗

Comparison of Telazol, Telazol-ketamine, Telazol-xylazine, and Telazol-ketamine-xylazine as chemical restraint and anesthetic induction combination in swine.

The use of Telazol (T, tiletamine and zolazepam, 4.4 mg T/kg) alone, Telazol-ketamine (TK, 4.4 mg T/kg and 2.2 mg K/kg), Telazol-xylazine (TX, 4.4 mg T/kg, 2.2 mg X/kg), and Telazol-ketamine-xylazine (TKX, 4.4 mg T/kg, 2.2 mg K/kg, and 2.2 mg X/kg) as chemical restraint and anesthetic induction combination was compared in pigs. Forty mixed-breed healthy pigs (24.4 +/- 5.6 kg, mean +/- SD) were randomly assigned to the four treatment groups (T, TK, TX, TKX) with 10 pigs in each group. All the anesthetics were premixed by adding sterile water, ketamine, xylazine, or xylazine and ketamine directly into the Telazol vial and given as a single intramuscular injection. All four anesthetic combinations induced a rapid onset of sternal recumbency within 1.76 +/- 1.0 minutes and lateral recumbency within 3.02 +/- 2.2 minutes in pigs after intramuscular injection; there was no significant difference among treatments. The combinations TX and TKX induced analgesia (as evident by a lack of response to needle prick in the middle portion of the pinna and flank regions) duration of 29.0 +/- 11.0 and 36.0 +/- 12.2 minutes, respectively, and ability to tolerate tracheal intubation (as evident by lack of coughing and chewing response to a laryngoscope) for a period of 34.0 +/- 8.4 and 39.0 +/- 9.9 minutes, respectively. The combinations T and TK did not induce analgesia nor conditions suitable for intubation. Duration of lateral recumbency was 29.9 +/- 10, 33.1 +/- 6.9, 52.2 +/- 6.9, and 61.5 +/- 10.7 minutes in T-, TK-, TX-, and TKX-treated pigs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗

Anaesthetics for general anaesthesia in growing pigs.

A comparison was made between different anaesthetics for general anaesthesia in growing pigs, with focus on minor surgery under field conditions and for experiments in clinical research. Healthy cross-breed pigs (Hampshire x Yorkshire x Swedish Landrace) weighing 20-45 kg were used. The anaesthetics combinations compared were 1) azaperone plus metomidate (AM), 2) Zoletil (zolazepam + tiletamine) plus xylazine (ZX), and 3) Zoletil plus xylazine plus ketamine (ZXK). Parameters measured were: heart rate, respiratory rate, blood pressure, body temperature, and depth of analgesia (pin-prick). Minor surgery was performed to test the reliability of the "pin-prick" tests. It was clearly shown that AM produces anaesthesia with good cardiovascular stability and is a drug combination that is suitable for minor surgery. ZX also produces a good anaesthesia characterized by reliable and rapid induction. Good cardiovascular function is maintained, and the laryngeal relaxation makes intubation possible. These characteristics are very useful in a laboratory environment, as easy handling to avoid stress is necessary for research. Although it is difficult to evaluate the quality of analgesia from this study, it is concluded that ZX did not provide a superior anaesthesia and analgesia compared to AM in crossbreed pigs. However, these drugs are too expensive for regular use in ambulatory practice. The effects of ZXK resemble those of ZX, but the ZXK-drug combination has no anaesthetic advantages and is more laborious to work with.

Anesthesia, General↗

[3H]1-[2-(2-thienyl)cyclohexyl]piperidine labels two high-affinity binding sites in human cortex: further evidence for phencyclidine binding sites associated with the biogenic amine reuptake complex.

Previous work demonstrated two high-affinity PCP binding sites in guinea pig brain labeled by [3H]TCP (1-(1-[2-thienyl]cyclohexyl)piperidine): site 1 (N-methyl-D-aspartate [NMDA]-associated) and site 2 (dopamine-reuptake complex associated). The present study examined brain membranes prepared from various species, including human, for the presence of site 2, defined as binding in the presence of (+)-5-methyl-10,11-dihydro-5H-dibenzo [a, d]cyclohepten-5,10-imine maleate ((+)-MK801) minus binding in the presence of 10 microM TCP (nonspecific binding). Studies were conducted in absence of sodium which was found to be inhibitory to [3H]TCP binding. The results demonstrated detectable levels of site 2 in brain membranes of guinea pig, rabbit, pig, mouse, sheep, and human but not in the rat or chicken. Using human cortical membranes, site 2 was the predominant binding site. Detailed studies conducted with human cortical tissue showed that high-affinity dopamine (1-[2- [bis(4-fluorophenyl)-methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR12909)], [1,2]benzo(b)thiophenylcyclo-hexylpiperidine (BTCP), and serotonin (fluoxetine) uptake inhibitors produced a wash-resistant inhibition of [3H]TCP binding to site 2, but not site 1. Preincubation of guinea pig brain membranes with BTCP was shown to produce an increase in the dissociation rate of [3H]TCP from PCP site 2. Structure activity studies with various uptake inhibitors showed that GBR12909, benztropine, fluoxetine, and BTCP have higher affinity for site 2 than for site 1. (+)-MK801, ketamine, and tiletamine were very selective for site 1, whereas dexoxadrol and TCP were moderately selective for site 1. These results suggest that human cortex possesses high-affinity PCP binding sites associated with biogenic reuptake binding sites, and that guinea pig brain, but not rat brain, may be an appropriate animal model for studying PCP site 2 in human brain.

Animals↗

Trans-2-carboxy-3-pyrrolidineacetic acid (CPAA), a novel agonist at NMDA-type receptors.

Although 2-carboxy-3-pyrrolidineacetic acid (CPAA) analogs are associated with activity as agonists at kainate-type receptors, here we report that CPAA is an agonist at N-methyl-D-aspartic acid-type receptors. CPAA evoked the release of [3H]acetylcholine (ACh) from striatal slices with the same efficacy as NMDA, and an EC50 of 20.0 microM, compared to an EC50 of 45.8 microM for NMDA. CPAA-evoked [3H]ACh release was inhibited by CPP (IC50 = 5.1 microM), tiletamine (IC50 = 0.53 microM), MK-801 (IC50 = 0.12 microM), and MgCl2 (IC50 = 26 microM). CPAA produced a tachyphylaxis when applied continuously for 18 min or more, and a cross-tachyphylaxis to NMDA. Similarly, NMDA generated a cross-tachyphylaxis to CPAA. All of these data suggest that CPAA is an agonist at NMDA-type receptors.

Acetylcholine↗

Sustained oxygenation without ventilation in paralyzed pigs with high-flow tracheal oxygen.

OBJECTIVES: It is generally assumed that ventilation is necessary for oxygenation. This study tested if paralyzed animals without respirations can maintain arterial oxygenation when administered high-flow oxygen delivered by a catheter in the trachea. METHODS DESIGN: Prospective observational study. SETTING: University research laboratory. PARTICIPANTS: 3 anesthetized/paralyzed swine weighing 29.5 +/- 4.2 kg. INTERVENTIONS/OBSERVATIONS: Pigs were intubated, anesthetized with intravenous tiletamine and a pentobarbital drip. A femoral arterial line was placed to record arterial blood gases and vital signs every 5 minutes. Respiratory paralysis was obtained with vecuronium 150 microg/kg and repeated at any sign of movement. A catheter was placed in the trachea to deliver oxygen at 15 L/min. Outflow gas from the endotracheal tube was analyzed for O2 and CO2. O2 was discontinued at 75 minutes. The institutional animal care and use committee approved the protocol. RESULTS: All pigs survived to 75 minutes. PaO2 was more than 100 mm Hg throughout the study period. Mean PaCO2 was 37.4 +/- 2.8 mm Hg at baseline, 146 +/- 59 at 30 minutes, then rose above 200 mm Hg in all pigs by 45 minutes. Mean arterial pH fell from 7.47 +/- 0.04 at onset to 6.75 +/- 0.06 at 75 minutes. When oxygen was terminated at 75 minutes, PaO2 fell to 16.5 +/- 7.6 mm Hg within 5 minutes, and all pigs were sacrificed within 10 minutes. For outflow gas, O2 was more than 98% and expired CO2 less than 1% throughout the study period. CONCLUSIONS: Paralyzed, unventilated pigs receiving high-flow oxygen via a tracheal catheter remained alive after 75 minutes, although a profound respiratory acidosis developed.

Animals↗

Moxonidine and rilmenidine injected into the medial septal area reduces the salivation induced by pilocarpine.

We determined the effects of moxonidine and rilmenidine 20 nmol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250-300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12+/-3 mg min(-1)) vs. control (99+/-9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20+/-5 mg min(-1)) vs. control (94+/-7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60+/-8 and 95+/-10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70+/-6 and 24+/-6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially. These receptors of the medial septal area have an inhibitory mechanism on salivary secretion.

Adrenergic alpha-Agonists↗

Nitric oxide of the supraoptic nucleus influences the salivary secretion, sodium renal excretion, urinary volume and arterial blood pressure induced by pilocarpine.

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle and stainless steel cannulas were implanted into their supraoptic nucleus (SON). We investigated the effects of the injection into the supraoptic nucleus (SON) of FK 409, a nitric oxide donor, and NW-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (NOS), on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine, which was injected into SON. The drugs were injected in 0.5 microl volume over 30-60 s. Controls was injected with a similar volume of 0.15 M NaCl. FK 409 and L-NAME were injected at doses of 20 microg/0.5 microl and 40 microg/0.5 microl respectively. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into SON. Injection of pilocarpine (10, 20, 40, 80, 160 microg/microl) into SON produced a dose-dependent increase in salivary secretion. L-NAME was injected into SON prior to the injection of pilocarpine into SON, producing an increase in salivary secretion due to the effect of pilocarpine. FK 409 injected into SON attenuating the increase in salivary secretion induced by pilocarpine. Mean arterial pressure (MAP) increase after injections of pilocarpine into the SON. L-NAME injected into the SON prior to injection of pilocarpine into SON increased the MAP. FK 409 injected into the SON prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (0.5 micromol/0.5 microl) injected into the SON induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the SON increased the urinary sodium excretion and urinary volume induced by pilocarpine. FK 409 injected prior to pilocarpine into the SON decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the SON. In summary the present results show: a) SON is involved in pilocarpine-induced salivation; b) that mechanism involves increase in MAP, sodium excretion and urinary volume.

Animals↗

Lateral hypothalamus lesions influences water and salt intake, and sodium and urine excretion, and arterial blood pressure induced by L-NAME and FK 409 injections into median preoptic nucleus in conscious rats.

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125,0 mg and zolazepan chloridrate 125,0 mg) into quadriceps muscle and submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 microg/0.5 microl), a nitric oxide (NO) donor, and N(W)-nitro-L-arginine methyl ester (L-NAME) 40 microg/0.5 microl, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested.

Animals↗

SLO angiography: arterio-venous filling times in monkey and minipig.

Confocal scanning laser ophthalmoscope (cSLO) is a new technique which enables ocular fundus image recording and dynamic retinal angiography to be performed. The ocular fundus image is acquired sequentially, point by point, and is reconstructed on a video monitor at the rate of 25 images per second. The aim of this paper is to evaluate the feasibility of measuring retinal arterio-venous filling times (AVFT) with a I + Tech cSLO. Three young adult cynomolgus monkeys and three young adult Göttingen minipigs were used as experimental models. All animals were anesthetized using a zolazepam + tiletamine mixture injected intramuscularly; heart rate and rectal temperature were monitored and corneal irrigation was regularly performed. For all subjects, prior to examination, hematocrit and globe axial length were measured. The images were recorded, stabilized and analyzed. The retinal examination consisted of retinal images with 40 degrees field cSLO, retinal fluorescein angiography and arterio-venous 50% filling time measurements. For each subject all images were easily recorded while keeping the animals in a normally lighted room without having to use any additional optical device. AVFT using an I + Tech cSLO is easily performed in monkeys and minipigs. AVFT measurements in minipigs and monkeys are similar. These results suggest that minipigs can replace monkeys as an experimental species for AVFT investigations.

Angiography↗

Sedation and chemical restraint of deer.

This review examines the properties of chemical immobilising agents of use or potential use in deer for velvet antler removal. The alpha-2-adrenergic agonist, xylazine, is the most commonly used agent for chemical restraint of stags for this purpose in New Zealand. This compound is often combined with an opioid or ketamine to enhance its effectiveness. Concerns about the carcinogenic potential of a xylazine metabolite have led to a call by the deer industry to limit the use of this drug and stimulated enquiry into alternatives. The potent pure opioid agonists, fentanyl, carfentanil and etorphine, are less effective than xylazine when used alone, and their use presents greater risk to operators and animals and is subject to more stringent legal restrictions. Newer alpha-2-adrenergic agonists, detomidine and medetomidine, are more potent than xylazine and unlikely to result in carcinogenic metabolites. Availability of specific alpha-2-adrenergic antagonists further enhances the usefulness of these drugs. The dissociative agent, ketamine, has proven useful for immobilisation of various domestic and wildlife species and captive species of deer but undesirable side effects and the low concentration, relative to the effective dose, of currently available formulations limit its usefulness. Combination of a dissociative agent with an alpha-2-adrenergic agent reduces the required dose of both and enhances their efficacy. A commercially available combination of the dissociative anaesthetic agent, tiletamine, and the benzodiazepine, zolazepam, is more potent than ketamine and induction times are faster. This combination can be manipulated to varying concentrations by dissolution with alpha-2-adrenergic agents. A long-acting neuroleptic agent, zuclopenthixol, has recently been investigated for calming deer and may be an alternative to classical sedative-immobilising agents. Most chemical immobilisation agents used alone or in combination produce respiratory depression and supplemental oxygen has been recommended. All would likely result in some form of chemical residues in velvet antler.

Journal Article↗

Removal of the OptEase retrievable vena cava filter is not feasible after extended time periods because of filter protrusion through the vena cava.

BACKGROUND: Therapeutic and prophylactic vena cava filters (VCFs) are used to prevent pulmonary embolism. Concerns exist over placing a permanent filter in a young trauma patient. Recently, retrievable VCFs have become available. One such filter is the OptEase, which has a recommended time of removal of up to 23 days after insertion. Data supporting this recommendation are sparse. Many trauma patients will need filters for more than 2 weeks, and there are no data evaluating the safety of removal after extended time periods. The purpose of this study was to determine the safety, feasibility, and reaction of the vena cava when removing the OptEase retrievable VCF at different time intervals. METHODS: Twenty Yorkshire cross pigs (80-113 kg) underwent general anesthesia with tiletamine and zolazepam. Filters were placed in the infrarenal vena cava (VC) through the femoral vein under fluoroscopic guidance. Animals were then divided into four groups. In group 1, filters were removed at 14 days; in group 2, at 30 days; in group 3, at 60 days; and in group 4, at 90 days. Removal was attempted using a snare-and-sheath technique through the femoral vein. Animals with successful filter removal were allowed to recover; then, the animals underwent autopsy (gross and microscopic VC examination) 2 months later. Animals with unsuccessful filter removal underwent autopsy immediately after attempted removal. Venacavograms were taken at filter insertion, at removal, and before autopsy to evaluate any VC abnormalities. RESULTS: Successful removal of the filter in all five pigs (100%) was reliably performed only in the 14-day group. In this group, the initial VC transverse diameter was 19.4 +/- 0.8 mm and was significantly reduced to 9.8 +/- 1.1 mm (p < 0.05) immediately after removal. Sixty days later, before autopsy, VC diameter had increased to 15.3 +/- 1.9 mm, which was significantly larger than at removal (p < 0.05) but not different from the initial value. In the 30-day group, removal was successful in only one of five animals. Although removal was successful in the one pig, autopsy at 2 months postremoval revealed total occlusion of the VC. Filters could not be removed from 60- and 90-day groups. At autopsy, the VCF struts were embedded or protruded through the VC wall. Microscopic examination of the VC revealed significant scarring underneath and between the struts. CONCLUSION: Removal of the retrievable OptEase VCF may be successfully performed up to 14 days after insertion. Strut protrusion through the VC wall prohibited successful and safe removal at extended time intervals.

Animals↗

High inspired oxygen concentrations increase intrapulmonary shunt in anaesthetized horses.

OBJECTIVES: To compare pulmonary function and gas exchange in anaesthetized horses during and after breathing either O2-rich gas mixtures or air. ANIMALS: Six healthy standard bred trotters (age range 3-12 years; mass range 423-520 kg), four geldings and two mares. Study design Randomized, cross-over experimental study. METHODS: Horses were anaesthetized on two occasions with tiletamine-zolazepam after pre-anaesthetic medication with acepromazine, romifidine and butorphanol. After endotracheal intubation and positioning in left lateral recumbency, animals were allowed to breathe spontaneously. One of two, randomly allocated inspired gas treatments was provided: either i) room air (fractional concentration of inspired O2 [FIO2] = 0.21) provided throughout anaesthesia; or ii) an O2-rich gas mixture (FIO2 = >0.95) for 15 minutes, followed by room air. The alternative treatment was delivered at the second anaesthetic. Respiratory and haemodynamic variables and the distribution of ventilation-perfusion (VA/Q) ratios (using the multiple inert gas elimination technique) were determined in the standing conscious horse (baseline) after sedation and during anaesthesia. RESULTS: Breathing O2-rich gas was associated with a decreased respiratory rate (p = 0.015) increased PaCO2 (p < 0.001) and increased PaO2 (p = 0.004) compared with breathing air. All horses developed intrapulmonary shunt during anaesthesia, but shunt was significantly greater (13 +/- 5%) when O2-rich gas was delivered compared with air breathing (5 +/- 2%; p = 0.013). Ten minutes after O2-rich gas was replaced by air, shunt remained larger in horses that had initially received oxygen compared with those breathing air (p = 0.042). Mixed venous oxygen tensions were significantly lower during sedation than at baseline (p < 0.001) and during anaesthesia (p < 0.001). CONCLUSIONS: During dissociative anaesthesia, arterial oxygenation was greater when horses breathed gas containing more than 95% oxygen, compared with when they breathed air. However, breathing O2-rich gas increased intrapulmonary shunt and caused hypoventilation. The intrapulmonary shunt created during anaesthesia by high inspired O2 concentrations remained larger when FIO2 was reduced to 0.21, indicating that absorption atelectasis produced during O2-rich gas breathing persisted throughout anaesthesia. CLINICAL RELEVANCE: In healthy horses undergoing short-term dissociative anaesthesia, air breathing ensures a level of oxygen delivery that meets tissue demand. There is no benefit to horses in breathing O2-rich gas after the gas supply is discontinued. On the contrary, the degree of shunt induced by breathing O2-rich gas persists. The clinical relevance of this during recovery requires investigation.

Anesthesia↗

Effects of extradural morphine on end-tidal isoflurane concentration and physiological variables in pigs undergoing abdominal surgery: a clinical study.

OBJECTIVE: To evaluate the effects of preoperative extradural morphine on the end-tidal isoflurane (Fe'ISO) concentration and on physiological variables in pigs undergoing abdominal surgery. STUDY DESIGN: Prospective, randomized, blinded study. ANIMALS: Fourteen healthy pigs (20 +/- 4 kg) undergoing intestinal cannulation. MATERIALS AND METHODS: Anaesthesia was induced with a combination of medetomidine (50 microg kg(-1)) and tiletamine-zolazepam (2.5 mg kg(-1)) injected intramuscularly, and was maintained with isoflurane in air and oxygen (FiO(2) = 50% O(2)). In the first group, morphine (0.1 mg kg(-1)) was administered extradurally before surgery. The second group received an equivalent volume of extradural saline as control. During the experiment, heart and respiratory rates, mean arterial blood pressure, tidal volume and minute ventilation were recorded every 10 minutes. The concentration of Fe'ISO was adjusted, according to the depth of anaesthesia, by an experienced animal nurse. Within treatment groups, time-related changes in Fe'ISO and physiological variables were analysed using a repeated measurement anova. Differences in data between treatment groups were analysed at specific time points using a Mann-Whitney U-test. Results are presented as mean +/- SD; p < 0.05 was considered as significant. RESULTS: After the onset of action of the morphine, the Fe'ISO required to maintain anaesthesia was significantly lower in the extradural morphine group compared with control. During the expected maximal effect of the drug, Fe'ISO was significantly lower in the morphine group (0.6 +/- 0.2%) than in the control group (0.9 +/- 0.2%). The decrease in Fe'ISO indicated that the onset of action of morphine was approximately 30 minutes after injection. No significant differences in other clinical variables were found between the groups. CONCLUSION: Pigs that received extradural morphine before abdominal surgery achieved surgical anaesthetic depth at a lower Fe'ISO concentration. CLINICAL RELEVANCE: Extradural morphine allows abdominal surgery to be performed at a lower Fe'ISO concentrations.

Abdomen↗

Characterization of the binding of [3H]-CGS 19755: a novel N-methyl-D-aspartate antagonist with nanomolar affinity in rat brain.

1. CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid), a rigid analogue of 2-amino-5-phosphonopentanoic acid (AP5), is one of the most potent competitive N-methyl-D-aspartate (NMDA) antagonists described. Using Triton-treated crude synaptic membranes from rat brain, binding studies indicated that [3H]-CGS 19755 bound with high affinity and selectivity to the NMDA-type excitatory amino acid receptor. 2. [3H]-CGS 19755 binding was saturable, reversible, heat-labile, pH-dependent and linear with protein concentration. Specific binding represented 80-85% of the total amount bound. 3. Using a centrifugation assay, saturation experiments revealed two distinct binding components with Kd values of 9 and 200 nM, and corresponding Bmax values of 0.55 and 1.00 pmol mg-1 protein. In contrast, a single binding component with a Kd value of 24 nM and an apparent Bmax value of 0.74 pmol mg-1 protein was observed with a filtration assay. 4. Competition experiments in which both assay techniques were used, showed that [3H]-CGS 19755 selectively labels the NMDA receptor. The most active inhibitors of [3H]-CGS 19755 binding were L-glutamate and CGS 19755 (IC50 values = 100 nM). 5. In the centrifugation assay, a number of excitatory amino acids were found to generate shallow inhibition curves, and computer analysis indicated the presence of two binding components. The quisqualate receptor ligand AMPA (D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate), kainic acid and the non-competitive NMDA antagonists, such as phencyclidine, tiletamine and MK-801, were without activity. 6. The high affinity binding obtained with [3H]-CGS 19755 by use of filtration techniques thus permits the more rapid evaluation of compounds as potential NMDA antagonists and agonists. Therefore, this rigid analogue of AP5 is a more suitable radioligand for NMDA receptors than [3H]-CPP (34-+/-)2-carboxypiperazin-4-yl)propyl-1-phosphonic acid), the corresponding analogue of 2-amino-7-phosphonoheptanoic acid (AP7).

Animals↗