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PubMed2007

Comparison of functional activity in the rat cervical spinal cord during alpha-chloralose and halothane anesthesia.

Alpha-chloralose is commonly used during animal fMRI studies for anesthesia, however, recovery of animals is difficult, limiting experimental design. The use of a less invasive anesthetic would enable chronic experiments. The present study compares functional activity in the spinal cord of the alpha-chloralose and halothane-anesthetized rat. Functional MRI of the rat cervical spinal cord was performed on 6 alpha-chloralose and 6 halothane-anesthetized rats in a Bruker 7 T MR system during electrical stimulation of the right forepaw. Following imaging, four animals from each group were perfused and spinal cords removed for immunohistochemical analysis. Areas of c-fos expression were identified with immunofluorescent labeling to confirm the presence of neuronal activity. Functional activity and c-fos expression were observed predominantly between the fifth and seventh cervical spinal cord segments. Areas of fMRI activation in the spinal cord correspond well with spinal cord physiology. Areas of c-fos expression confirmed that neuronal activity was present in the regions of fMRI activity. The regions and amount of fMRI activity observed were similar for both anesthetics. Functional magnetic resonance imaging of the spinal cord can be achieved using both alpha-chloralose and halothane anesthesia in rats. We therefore suggest that halothane may be used as an anesthetic agent for chronic fMRI studies of the spinal cord.

Anesthetics, Inhalation↗
PubMed1997

A simple method, using 2-hydroxypropyl-beta-cyclodextrin, of administering alpha-chloralose at room temperature.

Effective long term stable anaesthesia is a goal of many drug regimens employed in neuroscience in which procedures carried out are not practical in awake animals. A particular problem is the study of nociceptive mechanisms where good anaesthesia is essential. Similarly studies of cardiovascular or cerebrovascular mechanisms require that normal physiological reflexes be preserved as much as is practical. For non-recovery anaesthesia alpha-chloralose is a good choice since it provides good anaesthesia without excess depression of physiological reflexes. However, alpha-chloralose is sparingly soluble so that its use is not straightforward. We describe the characterisation of a simple procedure to solubilise alpha-chloralose in a solution of 2-hydroxypropyl-beta-cyclodextrin. The resulting solution is stable at room temperature and gives a high concentration of alpha-chloralose making it easier to administer regularly during longer time course experiments.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

Testing for alpha-chloralose by headspace-GC/MS. A case report.

A case is presented involving an acute fatality resulting from self-administered alpha-chloralose, a rodenticide. A 18-year-old man was found dead at home, with several stains of vomit on the carpet. An empty box of three bags of 5 g 100% alpha-chloralose (Corbeaux nuisibles, Rhône Poulenc) was found near the body. The compound was identified and quantified by headspace gas chromatography coupled to mass spectrometry. Alpha-chloralose was converted by concentrated sulphuric acid into chloral, a volatile compound, that was, after chromatography on a HP5-MS capillary column, identified by the following ions, m/z 82, 111 and 148. Peripheral blood concentration was 175.7 mg/l. Alpha-chloralose was quantified in several tissues, indicating kidney sequestration. No other drugs, including ethanol, were detected.

Adolescent↗
PubMed1995

Influence of isoflurane, fentanyl, thiopental, and alpha-chloralose on formation of brain edema resulting from a focal cryogenic lesion.

The objective of this study was to analyze the effects of various anesthetics on the formation of brain edema resulting from a focal cryogenic lesion. Thirty rabbits (six per group) were anesthetized with isoflurane (1 minimum alveolar anesthetic concentration [MAC] 2.1 vol%), fentanyl (bolus 5 micrograms/kg; infusion rate 1.0-0.5 micrograms.kg-1.min-1), thiopental (32.5 mg.kg-1.h-1), or alpha-chloralose (50 mg/kg). Control animals (sham operation, no lesion) received alpha-chloralose (50 mg/kg). Regional cerebral blood flow (rCBF) in perifocal brain tissue was measured by H2-clearance. Animals anesthetized with isoflurane required support of arterial pressure by angiotensin II (0.15 micrograms.kg-1.min-1). Six hours after trauma the animals were killed. Formation of brain edema was studied by specific gravity of cortical gray matter, white matter, hippocampus, caudate nucleus, putamen, and thalamus. Brain tissue samples were collected at multiple sites close to and distant from the lesion. Mean arterial pressure, arterial PCO2 and PO2, hematocrit, body temperature, and blood glucose were not different between groups during the posttraumatic course (except for an increased arterial pressure with alpha-chloralose compared to thiopental 4-6 h after trauma). The specific gravity of cortical gray matter was significantly reduced up to a distance of 6 mm from the center of the lesion in animals anesthetized with isoflurane, thiopental, or alpha-chloralose and up to 9 mm in animals given fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1990

Influence of pentobarbital and chloralose on metabolic and hemodynamic changes in liver ischemia.

Hemodynamic and metabolic consequences of a 90-minute period of liver ischemia followed by 120 minutes of reperfusion were studied in rats that were awake during most of the experiment and in rats anesthetized with either pentobarbital (40 mg/kg body weight) or chloralose (30 mg/kg X hour) during the complete length of the experiment. Ischemia was induced by occluding the blood vessels to the left and median liver lobes with a small vascular clamp, which was removed after 90 minutes. Protein synthesis rate was determined by measuring incorporation rate of 14C-leucine into protein in incubated liver slices. At the end of the ischemic period, adenosine triphosphate levels in liver tissue and protein synthesis rate were reduced by 80% to 90%, with no significant differences among groups. During reperfusion, energy levels and protein synthesis rate remained depressed in the anesthetized animals, but improved, although not to normal values, in the awake rats. Hepatic tissue water increased during ischemia, probably reflecting hepatocellular membrane injury. The increase in hepatic tissue water was more pronounced in the chloralose group than in the other groups of rats. During reperfusion hepatic tissue water remained increased in the anesthetized rats but was normalized in the awake group. Mean arterial blood pressure was stable during ischemia and reperfusion in the pentobarbital anesthetized rats, while a progressive decrease in blood pressure during the experiment was noted in the chloralose group. The results suggest that hemodynamic and metabolic responses to liver ischemia and reperfusion can be influenced by anesthetics. Chloralose may be less suitable than pentobarbital for anesthesia when liver ischemia is inflicted.

Adenine Nucleotides↗
PubMed1991

Influence of pentobarbital and chloralose anesthesia on quinidine-induced effects on atrial refractoriness and heart rate in the dog.

The effects of pentobarbital and chloralose on the atrial effective refractory period (AERP), atrial and ventricular rates, and mean blood pressure and also on the effects of quinidine on the same parameters were investigated in dogs with chronic atrioventricular block and implanted atrial pacing electrodes. Pentobarbital (30 mg/kg) increased the AERP by up to 12%, atrial and ventricular rates by 39 and 40%, respectively, and after initial lowering (48%) it increased the mean blood pressure (46%). Chloralose (100 mg/kg) increased the AERP (less than 30 min) by up to 7%, the atrial rate by 49%, the ventricular rate (less than 5 min) by 18%, and the mean blood pressure by 47%. In conscious dogs, quinidine at cumulative doses of 2, 4, and 8 mg/kg, i.e., at plasma levels between 2.7 +/- 0.6 and 6.3 +/- 1.3 micrograms/ml, increased the AERP by up to 21, 28, and 46%, the atrial rate by 49, 65, and 72%, and the ventricular rate (less than or equal to 5 min) by 17, 14, and 14%, and lowered the mean blood pressure by 19, 33, and 43%, respectively. Pentobarbital increased the quinidine-induced lengthening of the AERP by up to 10, 21, and 25 ms, respectively, and reduced the corresponding atrial (38, 53, and 67 beats/min) and ventricular (4, 4, and 5 beats/min) chronotropic effects. In contrast, chloralose reduced the quinidine-induced lengthening of the AERP (5, 12, and 22 ms, respectively), but did not modify the corresponding atrial and ventricular chronotropic effects. Neither pentobarbital nor chloralose altered quinidine plasma levels or the hypotensive effects of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1980

Observations on chloralose-induced myoclonus in guinea-pigs.

1 The physiological, biochemical and pharmacological features of alpha-chloralose-induced myoclonus in the guinea-pig have been studied. 2 EMG bursts in muscles jerking in chloralose-induced myoclonus are long, and are not time-locked to any cortical event recorded in the EEG, although they are evoked by auditory or peripheral nerve stimuli. 3 The efferent conduction velocity down the spinal cord of the signals generating the EMG bursts is fast but the afferent conduction velocity up the cord for stimulus-evoked jerks is slow, in distinction to the reverse characteristics of the spino-bulbo-spinal relfex arc. 4 alpha-Choralose did not cause any consistent change in 5-hydroxytryptamine (5-HT) or 5-hydroxyindoleacetic acid levels in any brain area, nor did it alter 5-HT turnover as judged by the depletion of 5-HT after p-chlorophenylalanine pretreatment. 5 Pretreatment of animals with drugs that increase brain 5-HT action (L-tryptophan with a monoamine oxidase inhibitor, or 5-hydroxytryptophan), or antagonize the action of 5-HT (cyproheptadine) did not abolish or obviously increase chloralose-induced myoclonus. 6 Chloralose-induced myoclonus is not similar to 5-HT-sensitive reticular reflex myoclonus in man.

Animals↗
PubMed1982

Analysis of adrenergic effects of the anesthetics Inactin and alpha-chloralose.

Renal and systemic adrenergic system responses were examined and compared under conditions of Inactin, a barbiturate, and alpha-chloralose anesthesia in hydropenic Munich-Wistar rats. Base-line plasma norepinephrine and other catecholamine levels were higher in Inactin-anesthetized rats. Norepinephrine was infused to raise blood pressure 15-20 mmHg above base line and plasma norepinephrine was again significantly higher with Inactin. In another group, angiotensin II was infused into the cerebral lateral ventricle in both Inactin- and alpha-chloralose-anesthetized rats, a method of stimulating centrally activated adrenergic output. After central stimulation, mean arterial pressure increased only in alpha-chloralose-anesthetized rats. Micropuncture studies examining systemic and glomerular hemodynamics were performed in alpha-chloralose- and Inactin-anesthetized rats before and after the infusion of phentolamine, an alpha-adrenergic antagonist. Infusion of phentolamine decreased mean arterial pressure to a significantly greater extent in the Inactin-anesthetized rats, suggesting a greater base-line systemic alpha-adrenergic activity with Inactin anesthesia. However, renal afferent and efferent arteriolar resistances were not significantly different after phentolamine, and any trend for resistances to decrease could be explained by autoregulation. Inactin increases systemic adrenergic activity, but renal vascular resistances are not significantly affected by this increased activity.

Anesthetics↗
PubMed1997

Electrophysiological properties of lumbar motoneurons in the alpha-chloralose-anesthetized cat during carbachol-induced motor inhibition.

The present study was undertaken 1) to examine the neuronal mechanisms responsible for the inhibition of spinal cord motoneurons that occurs in alpha-chloralose-anesthetized cats following the microinjection of carbachol into the nucleus pontis oralis (NPO), and 2) to determine whether the inhibitory mechanisms are the same as those that are responsible for the postsynaptic inhibition of motoneurons that is present during naturally occurring active sleep. Accordingly, the basic electrophysiological properties of lumbar motoneurons were examined, with the use of intracellular recording techniques, in cats anesthetized with alpha-chloralose and compared with those present during naturally occurring active sleep. The intrapontine administration of carbachol resulted in a sustained reduction in the amplitude of the spinal cord Ia monosynaptic reflex. Discrete large-amplitude inhibitory postsynaptic potentials (IPSPs), which are only present during the state of active sleep in the chronic cat, were also observed in high-gain recordings from lumbar motoneurons after the injection of carbachol. During carbachol-induced motor inhibition, lumbar motoneurons exhibited a statistically significant decrease in input resistance, membrane time constant and a reduction in the amplitude of the action potential's afterhyperpolarization. In addition, there was a statistically significant increase in rheobase and in the delay between the initial-segment (IS) and somadendritic (SD) portions of the action potential (IS-SD delay). There was a significant increase in the mean motoneuron resting membrane potential (i.e., hyperpolarization). The preceding changes in the electrophysiological properties of motoneurons, as well as the development of discrete IPSPs, indicate that lumbar motoneurons are postsynaptically inhibited after the intrapontine administration of carbachol in cats that are anesthetized with alpha-chloralose. These changes in the electrophysiological properties of lumbar motoneurons were found to be comparable with those that take place during the atonia of active (rapid-eye-movement) sleep in chronic cats. The present results support the conclusion that the neural system that is responsible for motor inhibition during naturally occurring active sleep can also be activated in alpha-chloralose-anesthetized cats following the injection of carbachol into the NPO.

Action Potentials↗
PubMed1995

Sodium pentobarbital versus alpha-chloralose anesthesia. Experimental production of substantially different slopes in the transmural CP/ATP ratios within the left ventricle of the canine myocardium.

BACKGROUND: Transmural analyses of the creatine phosphate (CP)/ATP ratio in various lamina of the canine myocardium have previously revealed significant variations in the CP/ATP ratio, with the subendocardial layer displaying a decreased ratio relative to the subepicardial layer. Without exception, these results were obtained under sodium pentobarbital anesthesia. These findings have been interpreted to imply that the normal endocardium may be operating in the oxygen-limited domain or that there are transmurally varying set points for the regulation of oxidative phosphorylation. METHODS AND RESULTS: In this work, we examine the effect of the anesthetic regimen on the transmural CP/ATP ratio within the left ventricular wall of the canine myocardium using spatially localized 31P-nuclear magnetic resonance (NMR) and an open-chest model. Two anesthetics were compared, alpha-chloralose and sodium pentobarbital. Under sodium pentobarbital, the CP/ATP ratio ranged from 1.92 +/- 0.06 to 2.51 +/- 0.08 from endocardium to epicardium, resulting in a transmural slope in the CP/ATP ratio of 0.149 +/- 0.047 (n = 22). Under alpha-chloralose, CP/ATP ratios ranged from 2.18 +/- 0.05 to 2.32 +/- 0.06, with a transmural slope of 0.035 +/- 0.018 (n = 38). Thus, the transmural slope in CP/ATP ratio was nearly four times greater with sodium pentobarbital than with alpha-chloralose, and the difference in these slopes was statistically significant (P = .029). No difference was observed in average CP/ATP obtained from the entire wall with either anesthetic. CONCLUSIONS: These results demonstrate that the transmural trend in CP/ATP ratio previously reported in the myocardium is likely to be a direct reflection of the sodium pentobarbital anesthetic regimen, not truly reflecting the trend in the normal unanesthetized animal. Moreover, since the transmural variation in CP/ATP ratio was greatly reduced with alpha-chloralose, it appears unlikely that the endocardium in the normal unanesthetized heart is operating in the oxygen-limited domain. These results also point to the importance of the anesthetic regimen in biochemical analysis, indicate the necessity of increased caution in directly translating results obtained under anesthesia, and demonstrate the unique power of in vivo NMR to extract such subtle biochemical information.

Adenosine Triphosphate↗
PubMed1994

Crossed and uncrossed segmental synaptic effects on obliquus externus abdominis motoneurons from cutaneous and cutaneous-muscle nerve in spinal cats and alpha-chloralose-anesthetized cats.

Segmental synaptic responses in the obliquus externus abdominis (OEA) for stimulation of the dorsal cutaneous and cutaneous-muscle (CD) nerve and the ventral cutaneous and cutaneous-muscle (CV) nerve were investigated in 49 spinal cats and 28 cats under alpha-chloralose anesthesia (chloralose cats) with an intracellular recording method. The result that there was no monosynaptic PSP in OEA motoneurons for stimulation of the CD or CV nerves (containing the cutaneous-muscle nerve) indicates that the cutaneous muscle of the dorsal or ventral area does not connect monosynaptically to the OEA motoneuron. The OEA motoneurons in chloralose cats received few effects from descending pathways coming from the upper spinal cord and the brain. Almost all OEA neurons had polysynaptic EPSP responses for stimulation of the ipsilateral or contralateral CD or CV nerves at 5-10T stimulus intensity in spinal or chloralose cats, which indicates that the OEA muscle can contract bilaterally when strong impulses of superficial afferents from the left or right skin or cutaneous muscle enter in the spinal cord.

Anesthesia, General↗
PubMed1975

[Possible chloralose poisoning in buzzards (author's transl)].

The use of alpha-chloralose in poisoned eggs is conditionally permitted in the control of Corvidae. Chloralose does not have a selective action. Poisoning occurs in other egg-eating animals (hedgehogs) and, indirectly, in carrion-eating predators which prey on these unintended victims. A tentative diagnosis of alpha-chloralose poisoning in three buzzards (Buteo buteo) was based on the history, the clinical picture (identical with that in magpies with known chloralose poisoning), the complete recovery and the exclusion of other diseases. Other methods for the control of Corvidae are advocated.

Animals↗
PubMed1987

Alpha-chloralose as a canine anesthetic.

Since its initial description in 1893, alpha-chloralose has undergone extensive pharmacologic evaluation. It has been characterized as a compound possessing potent CNS activity and has been evaluated in humans and animal models for its therapeutic properties. Though the toxicity of the compound prohibits its use as a human therapeutic agent, it has been employed widely as an animal anesthetic in the laboratory setting. A thorough search of the literature reveals that alpha-chloralose is second only to sodium pentobarbital as the primary anesthetic agent in acute cardiovascular studies where the preservation of myocardial function is a primary consideration. The literature also shows that alpha-chloralose is the subject of much controversy. The question as to whether alpha-chloralose is a true anesthetic or an immobilizing agent with sedative-hypnotic properties has important implications in light of the current emphasis on ethics in animal research.

Anesthesia, General↗
PubMed1993

Effects of blood pressure changes on the catecholamine release in the locus coeruleus of cats anaesthetized with pentobarbital or chloralose.

Effects of carotid occlusion and drugs applied intravenously on the release of endogenous catecholamines in the locus coeruleus of cats anaesthetized with pentobarbital or chloralose were investigated. The locus coeruleus was superfused bilaterally with artificial cerebrospinal fluid through push-pull cannulae inserted stereotaxically. Dopamine, noradrenaline and in some experiments also adrenaline were determined radioenzymatically in the superfusate. Under pentobarbital anaesthesia, a bilateral carotid occlusion increased the release rate of noradrenaline in the locus coeruleus, while the release of dopamine was decreased. These changes were due to the fall of blood pressure in the carotid sinus caused by the occlusion. Loading of baroreceptors by elevating blood pressure with phenylephrine (10 micrograms.kg-1 x min-1, i.v. infusion) was accompanied by a decreased release of noradrenaline in the locus coeruleus. This decrease in noradrenaline release was not detected in the caudal aspect of the locus coeruleus. Under chloralose anaesthesia, phenylephrine diminished the release rate of noradrenaline to about the same extent as under pentobarbital anaesthesia. The release rate of adrenaline was also decreased. A prolonged infusion of phenylephrine led to a prolonged pressor response associated with a sustained decrease in the noradrenaline release rate. Intravenous injection of chlorisondamine (3 mg.kg-1) did not change the release of noradrenaline, while dopamine release was reduced. It is concluded that the release of catecholamines in the locus coeruleus is influenced by signals originating from peripheral baroreceptors. The influences are similar under pentobarbital and chloralose anaesthesia. Noradrenergic neurons responding to haemodynamic signals are not uniformly distributed within the locus coeruleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1978

Pulmonary and systemic hemodynamic effects of delta9-tetrahydrocannabinol in conscious and morphine--chloralose-anesthetized dogs: anesthetic influence on drug action.

Pulmonary and systemic hemodynamic effects of delta 9-tetrahydrocannabinol (delta 9-THC) in conscious dogs and in those anesthetized with morphine (3 mg/kg, i.m.) plus alpha-chloralose (100 mg/kg i.v.) were evaluated in this study. A decrease in the heart rate, cardiac output (PBF) and a concomitant increase in the pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) observed in conscious animals following the administration of delta 9-THC were qualitatively similar to the effects reported in dogs anesthetized with sodium pentobarbital; however, unlike in the pentobarbital group, hypotensive effects to THC were not evident in the consious animals. In contrast, the effect of delta 9-THC in morphine--chloralose dogs were different; in this group delta 9-THC administration resulted in increases in the heart rate the PBF, and significant reductions in PAR, PVR and RVSW. Further, a decrease in the arterial blood pressure noted following THC administration was closely associated with a reduction in the total peripheral resistance in the morphine--chloralose group. The results of this study indicated that the pulmonary effects of THC in dogs may be related to its actions on the heart rate and differ qualitatively as well as quantitatively depending on the anesthetic used.

Anesthetics↗
PubMed1983

Alpha-chloralose suppression of neuronal activity.

Alpha-chloralose, an anesthetic agent widely used in neurophysiologic studies, caused a significant and long-lasting suppression of single neuron activity recorded from two areas of the central nervous system in decerebrate cats. A 50 mg/kg dose (an average anesthetic dose used in many neurophysiologic studies) caused suppression of spontaneous and evoked activity of neurons in the dorsal horn of the spinal cord and greater suppression of neurons in the nucleus reticularis gigantocellularis (NRGC) of the medial medullary reticular formation. Many researchers are of the opinion that alpha-chloralose causes less suppression of the central nervous system (CNS) than other commonly used anesthetic agents. The neuronal suppression recorded in this study appears similar in many ways to suppression caused by other anesthetic agents in the same two areas of the CNS. The results of the present study suggest that alpha-chloralose may be capable of producing significant suppression of neurons in the dorsal horn of the spinal cord and NRGC. Its ability to influence other areas of the CNS should not be inferred from these results, but the data do indicate the importance of evaluating the effects of anesthetics upon neurophysiologic systems under study.

Animals↗
PubMed1981

Functional changes in ventrobasal thalamic neurones responsive to noxious and non-noxious cutaneous stimuli after chloralose treatment: new evidence for the presence of pre-existing "silent connections" in the adult nervous system?

Twenty-five neurones of the thalamic VB complex of the rat, first characterized under moderate volatile anaesthesia (1/3 oxygen - 2/3 nitrous oxide, 0.5% halothane) were subsequently studied under deep chloralose anaesthesia. As described in a previous study, neurones were classified during the control period as "noxious" (N) "non-noxious" (Nn), or "convergent" (NnN) according to their responsiveness to cutaneous mechanical stimulations. For all the N (n = 15) and NnN (n = 4) neurones, the responses induced by noxious stimuli (mechanical electrical or thermal) progressively disappeared after chloralose administration. Simultaneous with disappearance of the responses elicited by noxious stimuli, responses to non-noxious stimuli appeared for 12 N neurones: 5 responded to a brisk tap applied to any part of the body, and 7 to brushing of light touch from a new receptive field (RF), at a variable distance from the initial RF, but always contralateral to the recording site. The Nn neurones (n = 6) continued to be activated by light touch or brushing but there was a consistent concentric enlargement of their RF. The NnN neurones also presented an enlarged RF to the non-noxious stimuli. The depressive an "unmasking" effects of chloralose are discussed and compared to the various indications of pre-existing connections in the CNS.

Animals↗
PubMed1989

Responses of the three-toed sloth, Bradypus tridactylus, to some commonly used pharmacologic agents. II. Chloralose and reserpine.

1. Chloralose, 50 mg/kg i.v., is a safe effective anesthetic for sloths and reduces incidence of cardiac arrhythmias. 2. However, chloralose blocks baroreflexes and may reduce the sensitivity of beta 1 cardiac receptors. 3. Reserpine, 0.70 mg/kg given i.v. in divided doses, blocks the hypertensive effect of 100 micrograms/kg of tyramine in sloths. 4. Reserpine in this dosage materially reduces arterial pressure and heart rate; these effects last at least 7 days. 5. Reserpine potentiates the hypertensive effects of epinephrine and norepinephrine materially. 6. In sloths reserpine increases cardiac irritability but does not block baroreflexes. 7. As is true with most other drugs sloths are more sensitive to chloralose and reserpine than most common laboratory animals.

Animals↗