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Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative ultra high performance liquid chromatography--tandem mass spectrometry (UHPLC--MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538–17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats.

Objectives Most individuals with spinal cord injury have neurogenic bowel dysfunction, which includes slowed colonic motility and has a significant impact on their health and quality of life. Bowel management typically includes mechanical rectal distension to evoke a recto-colic reflex and promote bowel emptying. Electrical stimulation could replace this mechanical distension. The purpose of this study was to determine the feasibility of evoking colonic activity using electrical stimulation. Materials and methods Acute experiments were conducted in eight neural-intact cats under chloralose anesthesia. Patterned electrical stimulation was administered via electrodes placed on the surface of the distal colon or proximal colon. Distal and proximal colon pressures were measured using saline-filled balloon catheters. Outcome measures included peak colonic pressure; time to onset of response; and time to peak pressure compared to baseline without stimulation. Results Stimulation elicited colonic activity in all animals. Peak colon pressures were 15 ± 28 cmH2 O and were proportional to stimulation amplitudes. Time to onset and time to peak pressure were 13 ± 19 s and 37 ± 49 s, respectively, and were not significantly affected by stimulus parameters. Proximal colon stimulation only resulted in pressure responses from the proximal colon, but distal colon stimulation resulted in both proximal and distal responses in 40% of trials. Adding isoflurane anesthesia removed this proximal response to distal stimulation. Conclusions Distal colon stimulation evoked colonic activity. The dependence of this response on stimulation location and anesthesia suggests that responses were reflex mediated. Colonic stimulation may have the potential to improve colonic motility for individuals with neurogenic bowel dysfunction.

By reducing the cerebral blood flow and thereby increasing the resting deoxyhaemoglobin concentration, many human studies have shown that caffeine has a beneficial effect on enhancing the magnitude of blood-oxygenation-level-dependent (BOLD) responses. However, the effect of caffeine on BOLD responses in animals under anaesthesia has not been demonstrated. In this study, we aimed to determine the effect of systemic caffeine administration on BOLD responses in rats under alpha-chloralose. By applying electric whisker pad stimulation to male Sprague-Dawley rats, we performed fMRI measurements before and after the caffeine injection (40 mg/kg, n = 7) or an equivalent volume of saline (n = 6) at 7T. To understand the potential perturbation of animal physiology during stimulation, arterial blood pressure was measured in a separate group of animals (n = 3) outside the scanner. Caffeine significantly decreased baseline BOLD signals (p = .05) due to the increased deoxyhaemoglobin level. Both BOLD responses and t-values in the primary somatosensory cortex were significantly increased (both p .05). The blood pressure changed insignificantly (p .05). No significant differences in BOLD responses and t-values were observed in the control condition of saline injection (both p .05). These findings suggested that, although the cerebral activity was lower under alpha-chloralose anaesthesia, the higher level of deoxygemoglobin at the baseline under the caffeinated condition can benefit the magnitude of BOLD responses in rats. These findings suggest that animal models might serve as potential platforms for further caffeine-related fMRI research studies.

The aim of this study was to assess the effects of radiofrequency electromagnetic field (RF EMF) on heart rate variability (HRV) in rabbits with intensity slightly exceeding the limits for occupations. Totally 21 New Zealand white rabbits divided into two groups were used in this double-blind study. The first group of animals without general anesthesia was subjected to HRV examination under exposure to a device generated RF EMF source (frequency 1788 MHz, intensity 160 V/m, lasting 150 min.). The second group (premedications + α chloralose mg/kg) underwent the same protocol under the exposure to the real RF EMF signal from the base stations of mobile providers (frequency range 1805 – 1870 MHz - corresponding to the downlink signal of Slovak mobile providers, 160 V/m, 150 min., respectively). Individual 5 min records were used to analyze the HRV parameters: heart rate and root Mean Square of the Successive Differences (rMSSD) for time domain analysis and spectral powers in the low (LF-VFS) and high frequency (HF-VFS) bands for frequency domain analysis. Our study revealed the increased in HRV parameters (HF-HRV, rMSSD) associated with lower heart rate indicating increased cardiac vagal control under the exposure to RF EMF in experimental methods.

Purpose: identification of pathological changes in the liver at early stages of the effect of clozapine and clozapine combined with ethanol to improve the diagnosis of this acute exposure.Materials and methods. The experiments were carried out on outbred male rats (n=15). The animals were split into 3 groups, 5 animals in each: 1) control (intact rats); 2) clozapine, 3) clozapine and ethanol. Clozapine at a dose of 150 mg/kg of the animal’s body weight was administered orally under anesthesia (chloralose), clozapine (150 mg/kg) with ethanol at a dose of 5 ml/kg — orally. Rats were removed from the experiment after 3 hours by decapitation. Samples of liver tissue were studied using light microscopy. During histological examination, the following morphological signs were evaluated: blood circulation disorder (presence of venous, capillary, and arterial congestion, appearance of venous hemorrhage), absence of nuclei staining, cytoplasm lumpiness, cytoplasm vacuolation, presence of necrosis foci, appearance of cellular response (a large quantity of leukocytes per power field). The assessment was done using the F-test. Forensic chemical analysis was carried out using a high-performance liquid chromatograph equipped with a mass detector. The content of clozapine, norclozapine, and clozapine-N-oxide in blood serum and liver homogenate of rats was evaluated.Results. In the control group, no pathological changes in liver tissue were observed. 3 hours after clozapine administration, venous congestion was detected. 3 hours after administration of clozapine and ethanol combination, venous congestion and absence hepatocyte nuclei staining were observed. It was found that after combined administration of clozapine and ethanol, the blood serum clozapine was 1.94-fold and clozapine-N-oxide was 2.3-fold lower than when clozapine was administered as a single drug while the content of norclozapine showed no difference.Conclusion. Changes detected in the liver, together with changes in other organs and findings of the forensic chemical analysis, allow establishing the fact of clozapine poisoning. Understanding of the processes going on in the body during such intoxications helps rendering medical assistance to victims more effectively.

Periaqueductal gray (PAG) is a midbrain region that projects to areas controlling behavioral and autonomic outputs and is involved in the behavioral and physiological components of defense reactions. Since Raphe Pallidus (RPa) is a medial medullary region comprising sympathetic premotor neurons governing heart function, it is worth considering the PAG-RPa path. We assessed: i) whether PAG projects to RPa; ii) the amplitude of cardiac responses evoked from PAG; iii) whether cardiovascular responses evoked from PAG rely on RPa. Experiments conducted in Wistar rats (±300 g) were approved by Ethics Committee CEUA-UFG (092/18). Firstly, (n = 3), monosynaptic retrograde tracer Retrobeads was injected into RPa; PAG slices were analyzed. Other two groups (n = 6 each) were anesthetized with urethane (1.4 g/kg) and chloralose (120 mg/kg) and underwent craniotomy, tracheostomy, catheterization of femoral artery and vein and of cardiac left ventricle. In one group, we injected the GABAA receptor antagonist, bicuculline methiodide (BMI – 40 pmol/100 nL) into lateral/dorsolateral (l/dl) PAG. Another group was injected (100nL) with the GABAA receptor agonist muscimol (20 mM) into RPa, 20 min before BMI into PAG. The results were: i) retrogradely labelled neurons were found in PAG; ii) PAG activation by BMI caused positive chronotropism and inotropism, which were accompanied by afterload increases; iii) RPa inhibition with Muscimol reduced heart rate, arterial and ventricular pressures; iv) the subsequent PAG activation still increased arterial pressure, cardiac chronotropy and inotropy, but these responses were significantly attenuated. In conclusion, PAG activation increases cardiac chronotropy and inotropy, and these responses seem to rely on a direct pathway reaching ventromedial medullary RPa neurons.

2-s2.0-85051568657, Four novel dinuclear Cu(II) complexes (1a–4a) have been prepared from ONO-tridentate chiral Schiff base derivatives of chloralose (1–4). All the new complexes (1a–4a) have been characterized by Fourier transform infrared spectroscopy, UV–visible spectroscopy and elemental analysis. The complex 2a was further characterized by X-Ray crystallography. And also, the magnetic susceptibility measurement of this complex (2a, ?eff 2.61 BM/dimer) was measured at room temperature. The activities of ONO-tridentate chiral Schiff base derivatives of chloralose (1–4) and their dinuclear Cu(II) complexes (1a–4a) on viability of human cervical cancer cell line (HeLa) were investigated by MTT assay. The obtained results indicated that the Schiff base ligand 1 and its dinuclear Cu(II) complex (1a) have excellent cytotoxic activity. Also, dinuclear Cu(II) complexes of the galactochloralose and ?-chloralose derivative Schiff base ligands were screened for their in vitro antimicrobial activity against eight bacterial species as well as yeast species Candida albicans ATCC 10231 using disc diffusion method. Complex 4a exhibited promising in vitro antimicrobial activity with inhibition zone diameter from 10 to 22 mm against the tested Gram-positive bacterial strains and yeast C. albicans. © 2018 Elsevier B.V., Ege Üniversitesi: 2014 FEN 071, We would like to Ege University for financial support of this work (2014 FEN 071) and Associate Prof. Dr. Serpil Denizaltı for carrying out the magnetic susceptibility measurement.

Summary Introduction The alphachloralose or chloralose is a dangerous rodenticide implied in a significant number of accidental or voluntary poisonings. The acute poisoning by the alphachloralose is frequent, appears at a dose of 1 g for adults and 20 mg/kg for children. The neurological signs dominate the clinical picture usually associating a driving hyperexcitability with myoclonus characteristics and a coma of variable depth according to the ingested dose. Objectives To estimate the demographic, clinical, analytical and therapeutic characteristics of the cases of poisoning by the alphachloralose received in the laboratory of toxicology of the hospital center Hassan II of Fez. Patients and methods It is about a retrospective study led between May 2011 and December 2015, which concerned cases of acute poisoning with alphachloralose. The study was carried out in the toxicology laboratory of the University of Hassan II Hospital Centre in Fez city. We have included all confirmed cases of alphachloralose poisoning regardless of age, sex, provenance and circumstance of intoxication. The confirmation was made by toxicological analysis with Fujiwara-Ross. Results During the study period, one hundred and two cases of suspicion of acute poisoning by alphachloralosis were recorded, accounting for 12.7% (102/798) of all laboratory-testing requests received; of which 39 cases were analyzed. The average age was 20.4 ± 7.1 with extremes of age going from 3 years to 38 years; the sex ratio was 2.9 with a net feminine ascendancy. The circumstances of poisoning were generally suicidal in adults in 69.2% of the cases (27/39); four cases of pediatric poisonings were voluntary. The neurological signs of appeal were the most frequent symptoms (66.8% of the sick), with characteristic myoclonus in 12.5% of cases, pupils were mydriasis to 9.4% of the cases (28/39) and 9.38% of the cases (28/39) presented a bronchial congestion. The symptomatic treatment was realized in 94.1% of the cases. The evolution was favorable in all of the cases. Conclusion In spite of a rich neurological picture with quasi-constant presence of a coma, the forecast of the acute poisoning by the alphachloralose remains favorable under early and adequate symptomatic treatment.

WOS: 000403692800006, Four new chiral Schiff base ligands (3a-4a, 3b-4b) have been prepared using aminoisopropylidene derivatives of glucose and aminochloralose derivatives of mannose. The synthesized compounds 1 and 2 were characterized by nuclear magnetic resonance (H-1 and C-13 NMR), Fourier transform infrared spectroscopy (FTIR), UV/visible spectroscopy, and elemental analysis. A total of eight Schiff base compounds (3a-6a, 3b-6b) were tested for antimicrobial activity against Escherichia coli ATCC 12228, Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae CCM 2318, Pseudomonas aeruginosa ATCC 27853, Salmonella typhimurium CCM 5445, Enterococcus faecalis ATCC 29212, Bacillus subtilis ATCC 6633, and Candida albicans ATCC 10239 and exhibited a range of activities.

In this study, D-glucose and D-galactose were used as starting sugar. Firstly, the experimental works were constituted on the simple synthesis of the 6-amino derivatives of 1,2-O-(R)-trichloroethylidene-α-D-glucofuranose (α-chloralose) and 1,2-O-(S)-trichloroethylidene-α-D-galactofuranose. The trichloroethylidene acetals of D-glucose and D-galactose were prepared from the reaction of sugars and anhydrous chloral. Tosyl derivates of trichloroethylidene acetals of D-glucose and D-galactose were obtained through the reaction of these compounds with p-toluenesulfonylchloride and then, these tosyl derivates were converted to the azide form by following nuclephilic substitution reaction. Obtained azide derivates were reacted with triphenylphosphine as reducing agent in order to get the related amino-sugars derivates. Also the same amino-sugars were synthesized in the C-3 hydroxy groups are methylated to derivatives by the same method. Then, in order to synthesize Schiff bases; the homogeneous mixture aqua form of aldehyde (salicylaldehyde or 3,5-ditbutylsalicylaldehyde) in MeOH was added dropwise into the solution of amino sugar derivative in 5mL of MeOH. Schiff bases were synthesized at the last of reaction. For to perform Henry reaction; to a solution of shiff bases as a ligand and solvent at the given temperature was added Cu(OAc)2.nH2O. Then the aldehyde(4-nitrobenzaldehit) and nitromethane were added into the solution. Subsequential of the completion, to afford the desired Henry product the solvent was evaporated and the residue was purified by column chromatography using hexane:ethyl acetate. HPLC using a Chiralcel OD-H column used to determine the enantiomeric excess values. Spectroscopic analysis, like 1H-NMR, IR and13C-NMR, helped us to learn the structures of all the compounds., Bu çalışmada D-glukoz ve D-galaktoz başlangıç şekerleri olarak kullanılmıştır. Öncelikle deneysel çalışmalar, 1,2-O-(R)-trikloroetiliden-α-D-glukofuranoz (α-kloraloz) ve 1,2-O-(S)-trikloroetiliden-α-D-galaktofuranoz'un 6-amino türevlerinin sentezleri üzerinde oluşturulmuştur. D-glukoz ve D-galaktoz'un trikloroetiliden acetalleri, susuz kloral ve şekerlerle reaksiyonu sonucu hazırlanmıştır. D-glukoz ve D-galaktoz'un trikloroetiliden acetallerinin tosil türevleri p-toluensülfonilklorür ile reaksiyon sonucu elde edimiştir ve daha sonra bu tosil türevleri nükleofilik yerdeğiştirme tepkimesi ile azit formuna dönüştürülmüştür. Elde edilen azit bileşikleri, ilgili amino şeker türevini elde etmek için indirgeyici reaktif olan trifenilfosfin ile reaksiyona sokulmuştur. Ayrıca bu amino şekerlerin C-3 hidroksil grupları metillenmiş olan türevleride benzer yöntemle sentezlenmiştir. Daha sonra Schiff bazı sentezlemek amacı ile, MeOH içinde aldehit (salisilaldehit veya 3,5-ditbutilsalisilaldehit) çözeltisi 5 ml MeOH'deki amino şeker türevi çözeltisi içine damlatılarak ilave edilmiştir. Henry reaksiyonunu gerçekleştirmek amacıyla belirtilen sıcaklıkta ligant olan Schiff bazı ve çözgen, Cu(OAc)2.nH2O üzerine eklenmiştir. Daha sonra aldehit (4-nitrobenzaldehit) ve nitrometan bu çözeltiye ilave edilmiştir. Reaksiyon tamamlandıktan sonra solvent buharlaştırılarak istenen Henry ürünü, hekzan ve etilasetat kullanılarak kolon kromatografisi ile saflaştırılmıştır. Enantiyomerik fazlalık değerleri Chiralcel OD-H kolon kullanılarak HPLC'de belirlenmiştir. Bütün bileşiklerin yapıları 1H-NMR, 13C-NMR ve IR gibi spektroskopik yöntemlerle belirlenmiştir.

In this research, D-mannose, D-galactose and D-glucose were used as starting sugars. Starting from these monosaccharides, the synthesis and characterization of acrylic and methacrylic polymers were investigated. As a result of anhydrous chloral and D-galactose reaction, 1,2-O-trichloroethylidene-α-D-galactofuranose was obtained. 5,6-O-isopropylidene-1,2-O-trichloroethylidene-α-D-galactofuranose was obtained, 2-O- trichloroethylidene -α-D-galactofuranose and 2,2-dimethoxypropane. In the next stage, 5,6-O-isopropylidene-1,2-O-trichloroethylidene-α-D-galactofuranose and epichlorohydrine were reacted and the result of this reaction epoxy ring was added to number 3 carbon. Epoxy rings may be opened with the base catalyst. The use of this property was performed ring opening reactions with acrylic and methacrylic acid. In this way, sugar-based monomers were obtained and investigated. Likewise D-glucose and D-mannose were used as starting sugar.5,6-O-isopropylidene-1,2-O-trichloroethylidene-α-D-glucofuranose and 5,6-O-isopropylidene-1,2-O-trichloroethylidene-α-D-mannofuranose were obtained. The steps of D-galactose reaction were repeated for other sugars., Bu araştırmada D-mannoz, D-galaktoz ve D-glukoz başlangıç şekerleri olarak kullanıldı. Bu monosakkaritlerden yola çıkılarak yeni akrilik ve metakrilik polimerlerin sentezi ve karakterizasyonu üzerine çalışılmıştır. D-galaktoz'un susuz kloralle tepkimesi sonucu 1,2-O-trikloroetiliden-α-D-galaktofuranoz elde edildi. 1,2-O-trikloroetiliden-α-D-galaktofuranoz ile 2,2-dimetoksipropan tepkimeye sokularak 5,6-O-izopropiliden-1,2-O-trikloroetiliden-α-D-galaktofuranoz oluşturuldu. Bir sonraki basamakta 5,6-O-izopropiliden-1,2-O-trikloroetiliden-α-D-galaktofuranoz'un epiklorohidrin ile tepkimesi sonucu 3 numaralı karbona epoksi halkası bağlandı. Epoksi halkasının bazik ortamdaki açılma tepkimesinin özelliğinden faydalanarak akrilik ve metakrilik asitler ile halka açılma tepkimesi gerçekleştirildi. Benzer şekilde D-glukoz ve D-mannoz' dan başlayarak sırasıyla 5,6-O-izopropiliden-1,2-O-trikloroetiliden-α-D-glukofuranoz ve 5,6-O-izopropiliden-1,2-O-trikloroetiliden-α-D-mannofuranoz oluşturuldu. D-galaktoz'un reaksiyon basamakları bu şekerler için de aynen tekrarlandı.

BACKGROUND Obstructive sleep apnea (OSA) increases susceptibility to atrial fibrillation (AF) by a combined sympatho-vagal hyperactivation. The purpose of this study was to investigate the effect of autonomic nervous system modulation by low-level baroreceptor stimulation (LL-BRS) compared to high-level BRS (HL-BRS) on atrial arrhythmogenic changes in a pig model of OSA. METHODS AND RESULTS Sixteen pigs received tracheotomy under general urethane/chloralose anesthesia. Group 1 pigs (n = 8) received LL-BRS (at 80% of that slowing sinus rate) for 3 hours and group 2 pigs (n = 8) received HL-BRS (slowing sinus rate). Changes in atrial effective refractory period (AERP) and AF-inducibility were determined during applied negative thoracic pressure (NTP) for 2 minutes before and at the end of the 3-hour stimulation protocol. Group 1: LL-BRS prolonged AERP from 150 ± 5 to 172 ± 19 milliseconds (P < 0.001). After 3 hours of LL-BRS, NTP-induced AERP-shortening was diminished from -51 ± 10 milliseconds (-34%) to -22 ± 4 milliseconds (-13%) (P < 0.01). AF-inducibility during NTP maneuvers decreased from 90% at baseline to 15% (P < 0.01). Group 2: HL-BRS shortened AERP from 150 ± 17 to 132 ± 8 milliseconds (P = 0.024). After 3 hours of HL-BRS, NTP-induced AERP-shortening was increased from -55 ± 7 milliseconds (-36%) to -72 ± 11 milliseconds (-54%) (P < 0.05) and AF-inducibility was not affected. NTP-induced changes in blood gases and blood pressure were not different between the groups. CONCLUSION LL-BRS suppressed NTP-induced AERP-shortening and AF-inducibility. By contrast HL-BRS further perpetuated NTP-induced AERP-shortening and increased AF-inducibility. These findings support only the use of LL-BRS as a novel therapeutic modality to treat AF in OSA.

Objective To present, in a murder case, toxicological findings of chloralose in non-biological and biological matrices including hair. Case history A 28-year-old woman was found dead in her bedroom. The same morning her former flatmate, worried because she had had no news from her friend, went to the victim's home where she was met by a male friend of the victim who forced her to drink a paste-like, bitter liquid at knifepoint. After ingestion, she immediately felt very tired and almost incapable of moving. She eventually managed to escape from the flat. The suspect was arrested some days later. He admitted strangling the deceased victim and trying to kill himself with a type of rat poison called Caussade®. To our knowledge, this company only sells two products on the French market: chloralose and brodifacoum. The autopsy confirmed cause of death by strangulation associated with massive bronchial inhalation of vomit. The judge ordered a toxicological investigation of blood, urine and hair (collected 3 months after the murder) from the surviving victim (former flatmate), hair from the perpetrator (taken 6 weeks after his arrest), autopsy samples from the deceased victim and various different materials that were collected at the scene (powder, liquid, a cup and drinking glasses). Method Hair strands were decontaminated twice and then segmented as appropriate to cover the period of interest. Each segment of hair was cut into small pieces ( Results The analyses show the following main results ( Table 1 ). Conclusion Toxicological analysis confirmed that the rodenticide poison used by the perpetrator to try and commit suicide and to poison both victims was composed exclusively of chloralose. In particular, hair analysis for chloralose (for which there is very limited data within the scientific literature), allowed us to unequivocally confirm the perpetrator's statements and provide useful input to the police investigation. The symptoms observed in the surviving victim are in accordance with an oral absorption of chloralose. Concerning the deceased victim, the concentrations of chloralose measured were much lower than those encountered in other non-fatal and fatal poisoning cases, for which postmortem blood concentrations from 5 to over 100 μg/mL have been observed. Despite the probable low exposure to this pesticide and given that the main cause of death is known, the potential contributory role of chloralose, which can cause vomiting and lead to bronchial inhalation, cannot be totally ruled out.

Objective: to detect lung morphological changes in acute intoxications with clozapine, ethanol, and their combination 3 and 24 hours after poisoning. Materials and methods. Experiments were carried out in outbred male rats weighing 270—300 g. Clozapine was given in a dose of 250 mg per kg animal body weight under chloralose anesthesia. Following 3 and 24 hours, the animals were withdrawn from the experiment by decapitation. Lung histological sections from 6 rats that had received oral clozapine 250 mg/kg, 6 rats that had oral ethanol 8.6 ml/kg, and 6 rats that had a combination of ethanol and clozapine orally in the above doses were examined 3 hours after intoxication. Those from 18 rats that had been orally given the similar agents in the above doses and withdrawn from the experiment were also investigated 24 hours after drug administration. The sections were compared with those from 6 rats that had not received the above agents. Nonparametric methods (χ2 test) were used for statistical processing. The investigators assessed the following morphological signs: circulatory disorders (plethora, hemorrhages), interstitial and alveolar edema, damage to the bronchial and alveolar epithelium and to the endothelium, and a cell reaction. The differences were considered significant at p

It has previously been proved that sodium nitrite, infused prior to coronary artery occlusion or before reperfusion, results in marked antiarrhythmic effect in anaesthetized dogs. We have now examined whether this protection involves the modulation of gap junction (GJ) function by nitric oxide (NO), derived from nitrite administration under ischaemic conditions. Two groups of chloralose and urethane anaesthetized dogs, each containing 13 animals, were subjected to a 25 min period occlusion of the left anterior descending (LAD) coronary artery, followed by reperfusion. One group was infused with sodium nitrite (0.2 μmol/kg/min, i.v.), the other group with saline 10 min prior to reperfusion. The severities of arrhythmias and of ischaemia (epicardial ST-segment, total activation time), parallel with changes in myocardial tissue impedance, a measure of electrical coupling of gap junctions, were assessed during the experiments. Compared to the controls, nitrite infusion administered prior to reperfusion significantly attenuated the severity of ischaemia, the ischaemia-induced impedance changes and, consequently, the severity of arrhythmias, occurring during the 1B phase of the occlusion, and increase survival following reperfusion (0% vs. 85%). It is concluded that the marked antiarrhythmic effect of sodium nitrite is partly due, to the preservation of the electrical coupling of GJs by NO.

Thiosemicarbazones(7–10)/semicarbazones(11–14) were synthesized in good yields via the condensation of α-gluco-, β-gluco-, galacto-, manno- chloralose derived 1,4-furanodialdoses (1-4) with thiosemicarbazide(5)/semicarbazide(6). The structures of all products were characterized by FTIR, NMR spectroscopic methods and elemental analysis. The compounds have been found to display moderate antimicrobial activity against Gram-positive, Gram-negative bacteria and antifungal activity against a Candida albicans. MIC values of the compounds range from 260 to 1510 μg/mL.

Resume Le chloralose a une action sedative et stimulante sur le systeme nerveux central. Il est actuellement utilise en tant que rodenticide. L’intoxication au chloralose est responsable de crises convulsives et parfois de deces. Objectif Le but de notre etude est d’evaluer l’epidemiologie de ces intoxications aux urgences du centre hospitalo-universitaire (CHU) de Pointe-a-Pitre afin d’optimiser la prise en charge d’une intoxication au chloralose. Patients et methodes Il s’agit d’une etude retrospective entre le 01/01/2009 et le 31/12/2012. Les dossiers ont ete inclus suite a recherche informatique depuis le logiciel des urgences. Resultats Dix-sept dossiers ont ete inclus. Aucun deces n’a ete enregistre. Dix-sept pour cent des intoxications concernaient des mineurs (3/17). Le lieu de l’intoxication etait majoritairement le domicile (16/17). Dans trois quarts des cas l’intoxication etait volontaire (13/17). Aucune intoxication pediatrique n’etait volontaire. Les signes dominant etaient les convulsions et des signes nicotiniques. Le taux d’hospitalisation etait de 65 % (11/17) et parmi eux 27 % (3/11) l’ont ete en reanimation. Conclusion L’intoxication au chloralose reste rare et peu mortelle. Cependant, une meilleure sensibilisation des medecins pour reconnaitre rapidement les signes d’intoxication au chloralose permettrait une prise en charge plus precoce et plus adaptee de ces patients, avec notamment une utilisation plus large et anticipee des benzodiazepines, evitant ainsi les convulsions et le recours a l’intubation. La mise en place d’un registre des intoxications permettrait un meilleur suivi de l’epidemiologie de ces dernieres.

La Presse Medicale - In Press.Proof corrected by the author Available online since jeudi 10 septembre 2015

The frequent accompaniment of hypertension by orthostatic circulatory disorders prompted us to investigate the effect of repeated and sustained head-up and head-down tilt positions on cardiovascular responses in spontaneously hypertensive rats vs. Wistar rats using radiotelemetric implants. Repeated orthostasis caused a transient elevation in blood pressure (7.3±1.7 mmHg) and heart rate (39.7±10.5 BPM), while repeated antiorthostasis led only to reversible tachycardia (85.6±11.7–54.3±16.8 BPM) in spontaneously hypertensive rats. In contrast to the Wistar rats, sustained tilt failed to affect the blood pressure or heart rate in spontaneously hypertensive rats because the environmental stress of being placed in horizontal tilt cages prior to the sustained tilt test induced marked changes in cardiovascular parameters. Non-specific stress responses were eliminated both by the anxiolytic diazepam and a sub-anesthetic dose of chloralose. Unlike diazepam, chloralose amplified the orthostatic pressor responses in the Wistar rats. In contrast to diazepam preventing the pressor response and associated tachycardia in spontaneously hypertensive rats, chloralose elicited this effect during both sustained orthostasis (36.0±7.3 mmHg, 63.7±21.8 BPM) and antiorthostasis (42.9±10.9 mmHg, 82.8±25.4 BPM), with a reduced baroreflex sensitivity. However, during sustained orthostasis, removal of the vestibular input led to a depressor response with bradycardia (12.5±3.2 mmHg, 59.3±17.3 BPM), whereas antiorthostasis only reduced blood pressure (20.5±7.1 mmHg) in the spontaneously hypertensive rats. We conclude that repeated tilts induce a transient pressor response and/or tachycardia in spontaneously hypertensive rats. Cardiovascular parameters are suppressed by diazepam, whereas chloralose evokes both blood pressure and heart rate responses during sustained tilts, which are primarily elicited by baroreflex suppression in hypertension. Vestibular inputs support cardiovascular tolerance to sustained postural changes in a rat model of human ‘essential’ hypertension.

A five-year-old domestic cat with acute unexplainable neurological signs was presented for postmortem examination. Clinically, the cat showed an acute onset of ataxia, depressed mentation and continuous twitching/ seizure activity in the morning after having been outside overnight. Despite immediate treatment, the cat# progressed within 24 hours to a comatose state, opisthotonus and severe miosis unresponsive to light. Given a poor prognosis, euthanasia was elected. Gross findings were disappointing and consisted of a nonspecific lung oedema and congested lungs and spleen. Surprisingly, within the stomach and intestines, fragments of cockshafers were found. Histological examination confirmed the gross findings and additionally showed evidence of mild brain oedema, but failed to identify a cause for the severe clinical signs. In a final attempt to solve the case, a urine sample was tested for toxic substances and it was found to contain a significant amount of α-chloralose. This finding was unexpected.

Background Mechanosensitive afferents innervating the bladder increase their firing rate as the bladder fills and pressure rises. However, the relationship between afferent firing rates and intravesical pressure is not a simple linear one. Firing rate responses to pressure can differ depending on prior activity, demonstrating hysteresis in the system. Though this hysteresis has been commented on in published literature, it has not been quantified. Results Sixty-six bladder afferents recorded from sacral dorsal root ganglia in five alpha-chloralose anesthetized felines were identified based on their characteristic responses to pressure (correlation coefficient ≥ 0.2) during saline infusion (2 ml/min). For saline infusion trials, we calculated a maximum hysteresis ratio between the firing rate difference at each pressure and the overall firing rate range (or Hmax) of 0.86 ± 0.09 (mean ± standard deviation) and mean hysteresis ratio (or Hmean) of 0.52 ± 0.13 (n = 46 afferents). For isovolumetric trials in two experiments (n = 33 afferents) Hmax was 0.72 ± 0.14 and Hmean was 0.40 ± 0.14. Conclusions A comprehensive state model that integrates these hysteresis parameters to determine the bladder state may improve upon existing neuroprostheses for bladder control.

Anticoagulant rodenticides are the largest group of poisons used to kill harmful rodents. Their fundamental mode of action consists in the inhibition of the vitamin K epoxide reductase, which causes blood-clotting alteration, ultimately leading to hemorrhagic events as the cause of death. In this study, we developed an UHPLC-MS-MS for the simultaneous determination of 10 anticoagulant hydroxycoumarine rodenticides, plus α-chloralose in human hair, with the scope of detecting potential trace of chronological poison exposure in clinical and forensic cases. The method was fully validated and applied to a case of intentional poisoning perpetrated by administration of difenacoum and α-chloralose to a 97-year-old woman, who was hospitalized because of severe symptoms, including drowsiness, convulsions, pallor and hematoma. Hair sample from the victim was segmentally analyzed. Difenacoum was detected in the proximal 3-cm hair segment at the concentration of 2.9 pg/mg. To our knowledge, this is the first study to report that exposure to difenacoum is detectable in real hair samples. The other target analyte found in the hair sample was α-chloralose, which was detected in the 0-3 cm segment at the concentration of 85 pg/mg. The two subsequent and consecutive segments (3-6 cm and 6-9 cm) showed only traces of difenacoum (below LOQ) and low but quantifiable concentrations of α-chloralose (29 and 6 pg/mg, respectively). Therefore, hair segmental analysis allowed us to conclude that the victim was repeatedly exposed to two poisons in the period corresponding to the first segment of hair.

Procedure Male Sprague–Dawley rats weighing 250–400 g are used. At least two animals are necessary for screening of one compound. The rats are anesthetized by intraperitoneal injection of 8 ml/kg of a solution of 8 % urethane and 0.6 % chloralose. The trachea is cannulated to facilitate spontaneous respiration. Body temperature is maintained at 38 C by placing the animal on a heating pad. The left femoral vein is cannulated for drug administration, which is standardized to injections of 0.2 ml/100-g body weight over a period of 1 min. For measurement of hemodynamic parameters and for intra-arterial administration of test compound, a cannula is inserted retrogradely into the right carotid artery. The tip of the catheter is positioned close to the origin of the subclavian artery. This allows most of the injected substances to reach the CNS via the vertebral artery before going into the general circulation. For continuous monitoring of blood pressure (systolic and diastolic pressure) and heart rate, the catheter is connected to a pressure transducer (Statham DB 23). When stable hemodynamic conditions are achieved for at least 20 min (control values), test boli of adrenaline (1 mg/kg) and isoprenaline (0.25 mg/kg) are administered. When baseline values are again established, increasing doses of the test substance (0.01, 0.1, 3.0 mg/kg) are given intra-arterially. In case of no effect, the interval between successive doses is 15 min, otherwise 60 min. To check for aor b-blocking activity, adrenaline and isoprenaline administration is repeated after injection of the highest dose of test compound. If the test compound shows no effect, a standard antihypertensive compound is administered for control purpose. Hemodynamic parameters are recorded continuously during the whole experiment.

Functional magnetic resonance imaging of mice requires that the physiology of the mouse (body temperature, respiration and heart rates, blood pH level) be maintained in order to prevent changes affecting the outcomes of functional scanning, namely blood oxygenation level dependent (BOLD) measures and cerebral blood flow (CBF). The anesthetic used to sedate mice for scanning can have major effects on physiology. While alpha chloralose has been commonly used for functional imaging of rats, its effects on physiology are not well characterized in the literature for any species. In this study, we anesthetized or sedated mice with isoflurane or alpha chloralose for up to two hours, and monitored physiological parameters and arterial blood gasses. We found that, when normal body temperature is maintained, breathing rates for both drugs decrease over the course of two hours. In addition, alpha chloralose causes a substantial drop in heart rate and blood pH with severe hypercapnia (elevated blood CO2) that is not seen in isoflurane-treated animals. We suggest that alpha chloralose does not maintain normal mouse physiology adequately for functional brain imaging outcome measures.

Despite positive metabolic effects, genetic deletion of protein phosphatase 1b (PTP1b) results in sympathetically mediated elevations in arterial pressure (AP) in mice. Because several PTP1b-regulated peptides also impair the baroreflex sensitivity (BRS) for control of heart rate (HR), we hypothesized that PTP1b in the solitary tract nucleus (NTS) participates in the maintenance of resting baroreflex function. To test this hypothesis, we performed acute bilateral microinjection of an allosteric PTP1b inhibitor (100 nM/120 nL) in the NTS of urethane/chloralose anesthetized Sprague-Dawley rats and assessed the BRS, responses to cardiac vagal chemosensitive fiber activation, and resting AP and HR before and after the injection. PTP1b inhibition impaired the BRS for bradycardia (n = 6; 0.93 ± 0.14 baseline vs. 0.48 ± 0.04 at 10 minutes vs. 0.49 ± 0.04 millisecond/mm Hg at 60 minutes; P0.01), with no significant effect on the BRS for tachycardia (0.30 ± 0.16 baseline vs. 0.24 ± 0.08 at 10 minutes vs. 0.24 ± 0.12 millisecond/mm Hg at 60 minutes). The reduced BRS for bradycardia was associated with a significant decrease in alpha-adrenergic responsiveness to phenylephrine at 60 minutes after PTP1b inhibition. Injection of the PTP1b inhibitor in the NTS elicited transient decreases in AP and HR in these animals. However, there was no effect of the inhibitor on depressor or bradycardic responses elicited by activation of cardiac vagal chemosensitive fibers, which converge with baroreceptor afferents in the NTS. These results suggest that PTP1b within the NTS may be a novel molecular mechanism for preservation of resting baroreflex function and provides further evidence for deleterious cardiovascular effects associated with PTP1b inhibition.

Nitric oxide (NO), a potent vasodilator and nontraditional neurotransmitter, is an important mediator of the changes in cerebral blood flow (CBF) associated with increased neuronal activity (neurovascular coupling). In the present work, we investigated the role of NO and of its newly recognized precursor, nitrite, in neurovascular coupling using a well-established rat model of somatosensory stimulation. Biological synthesis of NO of neuronal origin was inhibited pharmacologically. Following the initial uncoupling of neuronal and hemodynamic responses to somatosensory stimulation, the NO donor sodium nitroprusside, added within the range of physiological concentrations, significantly increased, but did not fully restore the functional CBF response. In contrast, nitrite at its physiological concentration fully recovered neurovascular coupling to its original magnitude. The magnitude of the effect is, however, dose-dependent. Sub-physiological concentrations of nitrite were not enough to entirely restore neurovascular coupling and supra-physiological concentrations acted more as a local vasodilator that changed resting CBF and interfered with the functional CBF response. These results suggest that nitrite can be efficiently converted into NO and utilized to support normal cerebrovascular physiology.

The effects of α-chloralose on presynaptic GABA(A) receptors were investigated with respect to spontaneous and evoked GABAergic transmission (sIPSCs and eIPSCs) in rat hippocampal CA1 pyramidal neurons. sIPSCs were recorded in mechanically dissociated CA1 neurons with intact GABAergic terminals, namely the "synaptic bouton preparation." eIPSCs were elicited by focal electrical stimuli of a single GABAergic bouton on an isolated CA1 neuron using the whole-cell patch recording configurations under voltage-clamp condition. We found that α-chloralose potentiated the exogenous GABA-induced Cl(-) response in a concentration dependent manner, and the drug itself induced Cl(-) response at high concentrations (>100 μM). α-Chloralose at low concentrations (3-10 μM) increased sIPSC frequency without affecting the current amplitude and kinetics, but prolonged the slow current decay time constant (τ(s)) at concentrations greater than 30 μM without changing either current amplitude or frequency. α-Chloralose at 10 μM enhanced amplitude of eIPSCs and decreased the failure rate (Rf), but at 30 μM decreased the amplitude and increased the Rf. Pretreatment with bumetanide, a blocker of NKCC-1, completely prevented the 30 μM α-chloralose-induced inhibition on eIPSC amplitude and Rf. These results suggest that α-chloralose activates GABA(A) receptors on GABAergic presynaptic nerve terminals and depolarizes the terminals, mediating presynaptic inhibition or autoregulation, in a concentration-dependent manner. In addition, α-chloralose at high concentrations activates not only extrasynaptic GABA(A) receptors on the postsynaptic soma membrane but also synaptic GABA(A) receptors resulting in prolongation of current decay phase. Thus α-chloralose induces complex and differential modulation of sIPSCs and eIPSCs in a concentration dependent manner.

Our previous studies showed that electrical stimulation of the nuclei ambiguous (NA) or dorsomotor nuclei of the vagus (DMV) complex in the brain stem of spontaneously breathing pond turtles (Cyclemys fiavomarginata), anesthetized with chloralose (4 mg/100 g) and urethane (40 mg/100 g), produced a marked slowing or even cessation of the heart rate, and resulted in an immediate fall of blood pressure. Results of the present study further demonstrated that the cardioinhibitory responses could also be elicited by microinjection of monosodium glutamate (0.2-20 nl, 50 mM) into the NA/DMV complex in turtles. A two-barrel glass micropipette held in a manipulator was connected to a pneumatic pressure pump for microinjection. The glutamate-induced cardioinhibitory responses could be significantly reduced in a dose-dependent manner by pretreatment with AP-5 (a NMDA receptor antagonist, at 1-8 nmole) or CNQX (a non-NMDA receptor antagonist; at 0.1-0.8 nmole) 20 min before glutamate administration. Histochemical verification by injecting horseradish peroxidase into the cervical vagus nerves revealed that retrogradely labeled glutamatergic neurons in the NA/DMV complex were observed. These results suggest that glutamatergic receptors in the caudal medulla may mediate vagal cardioinhibitory responses in the turtle.

Resume L’intoxication aigue par le chloralose est frequente en Tunisie. Les signes neurologiques dominent le tableau clinique, associant habituellement une hyperexcitabilite motrice et un coma de profondeur variable en fonction de la dose ingeree. Les signes respiratoires et hemodynamiques ne sont pas specifiques. Le traitement est essentiellement symptomatique et a comme objectif le maintien de l’integrite des fonctions vitales et la lutte contre l’agitation. Quant au traitement evacuateur, l’administration d’une dose unique de charbon active est conseillee dans les deux heures suivant l’ingestion et apres protection des voies aeriennes si besoin. Le coma est de courte duree, le plus souvent, avec une evolution rapidement favorable et sans sequelles. Le pronostic est directement lie au delai de prise en charge et aux complications de la reanimation.

Background and purpose: Both ischaemia preconditioning (PC) and the intracoronary infusion of peroxynitrite (PN) suppress ischaemia and reperfusion (I/R)-induced arrhythmias and the generation of nitrotyrosine (NT, a marker of PN). However, it is still unclear whether this latter effect is due to a reduction in nitric oxide (NO) or superoxide (O2-) production. Experimental approach: Dogs anaesthetized with chloralose and urethane were infused, twice for 5 min, with either saline (control) or 100 nM PN, or subjected to similar periods of occlusion (PC), 5 min prior to a 25 min occlusion and reperfusion of the left anterior descending coronary artery. Severities of ischaemia and ventricular arrhythmias, as well as changes in the coronary sinus nitrate/nitrite (NOx) levels were assessed throughout the experiment. The production of myocardial NOx, O2- and NT was determined following reperfusion. Key results: Both PC and PN markedly suppressed the I/R-induced ventricular arrhythmias, compared to the controls, and increased NOx levels during coronary artery occlusion. Reperfusion induced almost the same increases in NOx levels in all groups, but superoxide production and, consequently, the generation of NT were significantly less in PC- and PN-treated dogs than in controls. Conclusions and implications: Since both PC and the administration of PN enhanced NOx levels during I/R, the attenuation of endogenous PN formation in these dogs is primarily due to a reduction in the amount of O2 produced. Thus, the anti-arrhythmic effect of PC and PN can almost certainly be attributed to the preservation of NO availability during myocardial ischaemia.

Autoregulation, an important feature of the cerebral circulation, is affected in many diseases. Since genetically modified mice are a fundamental tool in biomedical research, including neuro(bio)logy also in this specie measurements of cerebral autoregulation (CA) are mandatory. However, this requires anesthesia that unfortunately significantly impacts cerebral perfusion and consequently might distort CA measurements directly or by altering arterial pCO(2). The latter can be avoided by artificial ventilation but requires several control measurements of blood gases, each consuming at least 100 μl of blood or 5% of a mouse's blood volume. To avoid such diagnostic hemorrhage, we systematically analyzed the effect of different common anesthetic protocols used for rodents in spontaneously breathing mice on CA measured with Laser speckle perfusion imaging. Halothane, Isoflurane and Pentobarbital abrogated CA and Ketamin/Xylazine as well as Chloralose had a moderate reproducibility. In contrast, the rather rarely used anesthetic Ethomidate applied in low doses combined with local anesthetics had the best reproducibility. Although with this anesthesia the lower CA limit was lower than with Ketamin/Xylazine and Chloralose as reported in the handful of papers so far dealing with CA in mice, we suggest Ethomidate as the anesthetic of choice for CA measurements in spontaneously breathing mice.

The regulation of blood pressure and sympathetic outflow by the brain renin–angiotensin system in animals subjected to raised or lowered dietary Na+ intake is unclear. This study compared the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to intracerebroventricular (i.c.v.) infusion of angiotensin II (AngII) and III (AngIII) before and after peripheral V1 receptor blockade (V1B) in α-chloralose–urethane-anaesthetized rats fed a low (0.03%, LNa+), normal (0.3%, NNa+) or high Na+ diet (3.0%, HNa+) from 4 to 11 weeks of age. The rise in MAP 2 min post AngII i.c.v. was greater in HNa+ (14 ± 3 mmHg) versus LNa+ (8 ± 1 mmHg, P < 0.05) and after AngIII i.c.v. in HNa+ (14 ± 3 mmHg) versus NNa+ (6 ± 1 mmHg, P < 0.05) and LNa+ (7 ± 1 mmHg, P < 0.05). The MAP responses to AngII and AngIII i.c.v. were abolished after V1B in LNa+, but were only attenuated in HNa+. In NNa+, V1B blunted the MAP responses to AngII and abolished those to AngIII. The MAP remained elevated 30 min after AngII in all groups, but returned to baseline levels 15 min after AngIII in NNa+ and HNa+ (P < 0.01). Twenty minutes after i.c.v. AngII, RSNA rose above baseline in HNa+ (112 ± 1%), a response not observed in the LNa+ and NNa+ groups. Twenty minutes post AngIII i.c.v., RSNA was elevated in both HNa (109 ± 2%) and NNa+ (109 ± 2%). After V1B, RSNA rose only in the HNa+ group 15 min post AngIII infusion (109 ± 1%). Together, these findings: (1) suggest that HNa+ intake augments the MAP and RSNA responses to i.c.v. AngII and AngIII; (2) highlight an important role for peripheral V1 receptors during these responses; and (3) differentiate the effects of AngII and AngIII on blood pressure and RSNA.

Most studies of the effect of cocaine on brain activity in laboratory animals are preformed under anesthesia, which could potentially affect the physiological responses to cocaine. Here we assessed the effects of two commonly used anesthetics [alpha-chloralose (alpha-CHLOR) and isofluorane (ISO)] on the effects of acute cocaine (1 mg/kg i.v.) on cerebral blood flow (CBF), cerebral blood volume (CBV), and tissue hemoglobin oxygenation (S(t)O(2)) using optical techniques and cocaine's pharmacokinetics (PK) and binding in the rat brain using (PET) and [(11)C]cocaine. We showed that acute cocaine at a dose abused by cocaine abusers decreased CBF, CBV and S(t)O(2) in rats anesthetized with ISO, whereas it increased these parameters in rats anesthetized with alpha-CHLOR. Importantly, in ISO-anesthetized animals cocaine-induced changes in CBF and S(t)O(2) were coupled, whereas for alpha-CHLOR these measures were uncoupled. Moreover, the clearance of [(11)C]cocaine from the brain was faster for ISO (peak half-clearance 15.8 +/- 2.8 min) than for alpha-CHLOR (27.5 +/- 0.6 min), and the ratio of specific to non-specific binding of [(11)C]cocaine in the brain was higher for ISO- (3.37 +/- 0.32) than for alpha-CHLOR-anesthetized rats (2.24 +/- 0.4). For both anesthetics, cocaine-induced changes in CBF followed the fast uptake of [(11)C]cocaine in the brain (peaking at approximately 2.5-4 min), but only for ISO did the duration of the CBV and S(t)O(2) changes correspond to the rate of [(11)C]cocaine's clearance from the brain. These results demonstrate that anesthetics influence cocaine's hemodynamic and metabolic changes in the brain, and its binding and PK, which highlights the need to better understand the interactions between anesthetics and pharmacological challenges in brain functional imaging studies.

The ability of intravenous cocaine to induce Fos protein expression in anesthetized rats was tested. Two anesthetic regimens commonly used for in vivo FMRI of animals, i.v. alpha-chloralose and gaseous isoflurane, were studied in separate cohorts. The first experiment included three groups that received the following treatments: saline i.v. and no anesthetic; 2 mg/kg cocaine i.v. and no anesthetic; and 2mg/kg cocaine i.v. under 36 mg/kg/h alpha-chloralose anesthesia. The second experiment had a factorial design of four groups that were either nonanesthetized or isoflurane-treated and were either given saline or cocaine (2 mg/kg, i.v.). Anesthetized rats were maintained for 2 h under 2.5-3.5% isoflurane anesthesia, while nonanesthetized rats were kept in an alternative environment for the same time period. Rats were given 2 mg/kg cocaine or saline i.v., 30 min into the test session. Rats were perfused and their brains were processed for Fos immunohistochemistry 90 min after the i.v. treatment. In both experiments, the frontal cortex and striatum of the cocaine-treated nonanesthetized rats expressed Fos in greater amounts than the saline-treated nonanesthetized rats, as expected. The alpha-chloralose treatment prevented cocaine-induced Fos expression across all eight subregions of the striatum and frontal cortex that were examined. In contrast, isoflurane only partially attenuated Fos expression in the orbital and Cg2 subregions of frontal cortex. These results suggest a strong advantage for using isoflurane, as opposed to alpha-chloralose, when studying anesthetized rats for in vivo effects of psychostimulants.

Focal ventricular tachycardia (VT) in acute myocardial ischemia is closely related to triggered activity (TA), which may be blocked by scavenging reactive oxygen species (ROS).This study analyzed effects of acutely administered ROS scavenger-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) on VT in vivo and TA in vitro.Forty-three alpha chloralose anesthetized dogs with coronary artery occlusion were studied. Three-dimensional activation mapping helped to locate the origin of focal or reentrant VT. TEMPO (30 mg/kg intravenously) or vehicle was given. Endocardium excised from the site of origin of VT was studied using standard microelectrode techniques and measures of ROS.Reentry and focal VT induction were both highly reproducible. TEMPO blocked focal VT in 6 of 11 dogs (P.05), but 9 of 9 dogs with reentrant VT continued to have VT re-induced after TEMPO. TEMPO did not alter effective refractory period (168 +/- 3 to 171 +/- 3 ms), mean blood pressure (88 +/- 3 to 81 +/- 3 mm Hg), and size of ischemia (42% +/- 3% vs 40% +/- 4%). In vitro, TEMPO (10(-3) M, n = 14) produced no change in action potentials. Nevertheless, TA was reversibly attenuated from 5.3 +/- 1.1 to 0.4 +/- 0.4 complexes with TEMPO (n = 15, P.05). Lucigenin-enhanced chemiluminescence and dihydroethidium staining showed increased ROS in ischemic endocardium; TEMPO dramatically reduced ROS in ischemic sites.TEMPO, a scavenger of ROS, prevented triggered activity associated with focal VT during myocardial ischemia in areas of increased ROS. Antioxidant therapy may play an important role in blockade of focal VT under the conditions of myocardial ischemia.

The effect of thioridazine on sinusal automaticity, myocardial excitability and auriculoventricular conduction have been studied in dogs by measuring the spontaneous heart rate, the effective refractory period of the atrial contractile tissue, the time of auriculonodal and infrahisian conduction. Chloralose anaesthetized dogs were administered 10 mg/kg thioridazine hydrochloride via intravenous route. While sinusal automaticity was not altered, conduction times were prolonged in the suprahisian and mainly the infrahisian part and the atrial refractory period increased. These effects are related to quinidine-like properties and consistent with cardiotoxic effects previously reported in clinical practice.

Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; alpha-chloralose, alphaCS; and isoflurane, IF) with alphaCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO(2) in 40% O(2) and 55% N(2)). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under alphaCS anesthesia (ca. 2 degrees C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials--alphaCS anesthesia resulted in the largest brain temperature increase (0.32 +/- 0.08 degrees C), while CH and IF anesthesia lead to smaller increases (0.12 +/- 0.03 and 0.16 +/- 0.05 degrees C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2-3 min under CH and IF anesthesia and approximately 4 min under alphaCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures.

Zusammenfassung Gegenstand und Ziel: Darstellung einer Vergiftung mit Alpha-Chloralose anhand von zwei Fällen sowie Zusammenstellung der diesbezüglichen Literatur. Patienten: Zwei Chihuahua-Hündinnen (3- bzw. 12-jährig) wurden nach Aufnahme von mit Alpha-Chloralose präparierten Fleischwürstchen vorgestellt. Ergebnisse: Beide Tiere zeigten Hypoventilation und neurologische Symptome, wobei sich eine Hündin mit Koma und Hypothermie präsentierte, die andere mit Koma, Krämpfen und normaler Temperatur. Initial stand die Aufrechterhaltung und Überwachung der Vitalfunktionen sowie die Dekontamination im Vordergrund. Beide Hunde wurden symptomatisch behandelt und konnten das Tierspital nach 3 Tagen verlassen. Aufgrund der neurologischen Symptome sind bei solchen Patienten andere ZNS-depressive Toxine ebenfalls in Betracht zu ziehen. In diesem Fall wurde das Toxin Alpha-Chloralose nachgewiesen. Schlussfolgerung und klinische Relevanz: Alpha-Chloralose-Intoxikationen sind bisher selten beschrieben. Zu den Symptomen zählen Hypothermie, Hypoventilation, Krämpfe, Koma, Narkose, Miosis, Hypersalivation, bronchiale Hyper-sekretion und Bradykardie. Eine Intoxikation mit Alpha-Chloralose sollte daher sowohl bei komatösen als auch krampfenden Tieren als Differenzialdiagnose in Betracht gezogen werden.

Summary. 1. Experiments have been performed with usnic acid on eats anaesthetized with nembutal or, in a few cases, with chloralose. 2. 10 mg sodium usnate/kg body weight caused a prompt and heavy rise in oxygen consumption accompanied by a pronounced increase in rate and amplitude of respiration and by a gradual rise in body temperature, lasting for about 5 hours and then dowly falling. 3. Larger doses are as a rule lethal. 4. Lethal doses cause an intense rigor mortis. This effect is opposite to the effect of vulpinic acid but similar to the Well known action of the dinitrophenols. 5. In normal anaesthetized cats there is a steep rise in arterial blood sugar to a level of 300–400 mg% lasting for about the same time as the increased respiratory volume. In fasted cats the rise is much slower and somewhat smaller. 6. It is concluded that the major part of the rise in arterial blood sugar is due to an increased breakdown of glycogen to glucose, but there may be increased gluconeogenesis. 7. The actions of usnic acid in the cat are, in the whole, very similar to those of the dinitrophenols.

Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura. It negatively impacts tissue injury during stroke, cerebral contusion and intracranial hemorrhage. Susceptibility to CSD has been assessed in several experimental animal models in vivo, such as after topical KCl application or cathodal stimulation. Various combinations of anesthetics and ambient conditions have been used by different laboratories making comparisons problematic and differences in data difficult to reconcile. We systematically studied CSD susceptibility comparing commonly used experimental anesthetics (isoflurane, alpha-chloralose, and urethane) with or without N(2)O or normobaric hyperoxia (100% O(2) inhalation). The frequency of evoked CSDs, and their propagation speed, duration, and amplitude were recorded during 2 h topical KCl (1 M) application. We found that N(2)O reduced CSD frequency when combined with isoflurane or urethane, but not alpha-chloralose; N(2)O also decreased CSD propagation speed and duration. Urethane anesthesia was associated with the highest CSD frequency that was comparable to pentobarbital. Inhalation of 100% O(2) did not alter CSD frequency, propagation speed or duration in combination with any of the anesthetics tested. Our data show anesthetic modulation of CSD susceptibility in an experimental model of human disease, underscoring the importance of proper study design for hypothesis testing as well as for comparing results between studies.

Blood oxygenation level dependent functional magnetic resonance imaging technique was used to explore the antinociceptive effect of morphine in the rat brain under α-chloralose and isoflurane anesthesia. Formalin was used as a pain-testing model which could produce significant activation in various brain areas. The results also showed that morphine pretreatment modulate neurovascular activities evoked by formalin stimulation, especially in cingulate cortex, somatosensory cortex, caudate putamen, visual cortex, and hippocampus. The present study identified the brain areas involved in modulating nociception.

To investigate postnatal developmental changes in functional characteristics of the afferent pathway of the aortic baroreceptor reflex, the responses of aortic nerve activity (ANA) to blood pressure (BP) changes elicited by phenylephrine and sodium nitroprusside administration were tested in 3-, 8- and 20-week-old male rats under chloralose (60 mg kg −1 I.P.) and urethane (600 mg kg −1 I.P.) anaesthesia. The function curve of ANA in response to BP changes showed a sigmoid shape that shifted to the right from 3 to 8 weeks of age. The maximal activity and maximal gain of the aortic nerve, which were calculated by a logistic function analysis, were significantly higher in 20-week-old rats (maximal activity, 532 ± 47% of baseline; maximal gain, 7.9 ± 0.8% of baseline mmHg −1 ; n = 9) than in 3-week-old rats (maximal ANA, 268 ± 25% of baseline, P < 0.001; maximal gain, 4.9 ± 0.5% of baseline mmHg −1 , P < 0.01, n = 9) and 8-week-old rats (maximal ANA, 309 ± 18% of baseline, P < 0.001; maximal gain, 4.9 ± 0.3% of baseline mmHg −1 , P < 0.01, n = 11). These results suggest that the operating point of aortic baroreceptor afferents is reset to the higher pressure level during development from 3 to 8 weeks of age and, thereafter, the afferent gain increases from 8 to 20 weeks of age. This functional change may be an important factor to prevent an excess increase of BP, which would result in pathophysiological problems.