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PubMed1988

Chloralose alters circulatory response to alpha-receptor stimulation and blockade.

Chloralose anesthesia is commonly used in animals for cardiovascular research despite limited data on possible receptor-drug interactions. To investigate potential interactions with alpha-adrenergic receptors, we studied the response of chronically instrumented, spontaneously breathing young lambs to alpha-receptor stimulation (by methoxamine) and blockade (by phentolamine) after infusion of 30 mg/kg of chloralose or an equal volume of vehicle. Both experiments were performed in each animal on different days and in alternate order. Chloralose altered the systemic arterial pressure and heart rate response to both alpha-agonist challenge and to alpha-blockade when compared with control. Despite potentiating the systemic arterial pressor response to methoxamine, chloralose attenuated the reflex decrease in heart rate after alpha-agonist-induced hypertension. This observation suggests that the baroreceptor reflex was blunted. Chloralose, commonly considered an ideal anesthetic for cardiovascular studies, may have important effects on the cardiovascular response to alpha-adrenergic test agents. The potential for interactive effects should be considered in experimental designs that couple the use of chloralose and alpha-adrenergic agents.

Animals↗
PubMed1994

Hemodynamic interaction of chloralose pretreatment with subsequent beta-adrenergic receptor antagonism in lambs.

alpha-Chloralose is a commonly used anesthetic agent in cardiovascular research despite a paucity of information whether it may have important pharmacologic interaction with subsequently given adrenergic drugs. To assess any potential pharmacologic interaction, we studied the cardiovascular response to beta-adrenergic receptor antagonism (propranolol, 1 mg/kg i.v.) after either chloralose (30 mg/kg i.v.) or saline control in paired studies in 10 chronically instrumented neonatal lambs. Chloralose increased heart rate by 46% as compared to control (283 +/- 37 vs. 194 +/- 48 beats/min, p = 0.0002) and had no significant effect on cardiac output; chloralose also increased mean pulmonary arterial pressure by 45% (27 +/- 13 vs. 19 +/- 6 mm Hg, p = 0.050) and pulmonary vascular resistance by 79% (0.211 +/- 0.13 vs. 0.118 +/- 0.04 mm Hg/ml/kg/min, p = 0.050). The group pretreated with chloralose had significantly elevated heart rate (186 +/- 23 vs. 157 +/- 31 beats/min, p = 0.03), mean pulmonary arterial pressure (29 +/- 9 vs. 22 +/- 6 mm Hg, p = 0.03) and pulmonary vascular resistance (0.228 +/- 0.13 vs. 0.130 +/- 0.05 mm Hg/ml/kg/min, p = 0.05) after propranolol as compared to the conscious saline-treated group. We conclude that pretreatment with chloralose as an anesthetic agent may produce important pharmacologic interaction with subsequent adrenergic drugs in neonatal lambs. While anesthesia may be necessary in animal research, investigators should be aware that the anesthetic agent may also qualitatively and quantitatively influence measured outcome variables.

Adrenergic beta-Antagonists↗
PubMed1991

Effect of alpha-chloralose on disposition and pharmacological action of orally administered chlorzoxazone in rats.

The pharmacodynamic behavior of orally administered chlorzoxazone (CZX) was studied in rats. From the time course of CZX plasma concentration data under alpha-chloralose (80 mg/kg, i.p.) anesthesia, it was found that CZX obeyed a one-compartment model with first-order absorption. The pharmacological response intensity of CZX on the crossed extensor reflex was closely related to the plasma concentration data via Hill's equation under alpha-chloralose (80 mg/kg) anesthesia, but not at a 150 mg/kg dose. The influence of alpha-chloralose at the latter dose on CZX pharmacokinetics and pharmacodynamics appeared to be due to the pharmacodynamic interaction of alpha-chloralose and CZX, thus suggesting that the pharmacokinetic and pharmacodynamic concept proposed by Smolen was not applicable to CZX's behavior at such a dose in rats. Under alpha-chloralose (80 mg/kg) anesthesia, the biophase compartment was determined to be identical to the central compartment using our proposed model. On the basis of the effect of anesthetics on drug behavior, one may select an appropriate anesthetic dose to evaluate the relationship between the plasma levels and the onset and duration of the drug action. At the higher dose of alpha-chloralose (150 mg/kg), the free fraction of CZX was increased and a possible enhancement in CZX action was suggested.

Administration, Oral↗
PubMed1992

Oxygen metabolism and catecholamine secretion during chloralose anesthesia in lambs.

Anesthetic agents are required when restraining animals in most forms of animal research. In particular, alpha-chloralose is a widely used anesthetic for respiratory and cardiovascular research despite limited controlled studies investigating whether chloralose could represent a variable influencing cardiorespiratory reflexes in acute animal studies. We previously used a chronically-instrumented neonatal lamb model to determine that chloralose had important effects on oxygen delivery and on basal hemodynamics. To investigate the influence of chloralose on oxygen metabolism and catecholamine secretion in relation to these hemodynamic changes, we studied 12 lambs before and after infusion of chloralose (30 mg/kg, i.v.) or control saline vehicle. Chloralose caused no differences in arterial or mixed venous oxygen contents, arterio-venous oxygen difference, or oxygen delivery, consumption, or extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1988

Intravenous chloralose is a safe anesthetic for longitudinal use in beagle puppies.

Chloralose is an intravenous anesthetic which preserves vagal and central baroreceptor reflexes, thus rendering it useful for physiologic research. However, chloralose is recommended for terminal experiments only, due to concerns relating to long-term toxicity. We investigated the safety of chloralose in longitudinal pulmonary function studies in beagle puppies. Twelve puppies received chloralose anesthesia repeatedly (8-12 times per dog) between the ages of 80 and 300 days. Constant anesthetic depth was maintained reliably throughout the course of the experiments. Recovery lasted approximately 4 hours in each experiment and occurred in four definable stages. Following recovery, the puppies exhibited normal health and growth as compared with other colony animals. There was no biochemical evidence of acute renal, hepatic, pancreatic or cardiac toxicity prior to and immediately after anesthesia, and no evidence of chronic toxicity following completion of the study protocol, after a total cumulative dose of 1.18 g/kg chloralose. These studies demonstrate that intravenous chloralose is a safe anesthetic for longitudinal use.

Anesthesia, Intravenous↗
PubMed1980

Effects of alpha-chloralose on the activity of the nigrostriatal dopaminergic system in the cat.

The effects of alpha-chloralose anaesthesia were studied in the cat on the release of 3H-dopamine (#H DA) from the caudate nucleus and the substantia nigra using the push-pull cannula method and continuous labelling of the structures with L-3,5-3H-tyrosine. Results were compared to those obtained under the same experimental conditions in both halothane-anaesthetized animals and 'encéphale isolé' preparations. The alpha-chloralose-anaesthetized preparation showed the lowest level of 3H-DA release, both from dopaminergic nerve terminals in the caudate nucleus and from dendrites of dopaminergic neurons in the substantia nigra. Furthermore, the time required to reach a steady-state release of 3H-DA was longer in alpha-chloralose-anaesthetized cats than in animals under halothane. This indicated that the activity of the dopaminergic neurons is depressed under alpha-chloralose anaesthesia. In the second part of the study, we measured the effects of unilateral somatic stimulation on the release of 3H-DA from the caudate nuclei and substantiae nigrae on both sides of the brain. The results show that under alpha-chloralose anaesthesia, the electric stimulation of the paw of the right forelimb does not significantly affect the release of 3H-DA from any of the above four structures. This contrasts with the changes of 3H-DA release seen in the same experimental conditions under halothane anaesthesia.

Animals↗
PubMed1990

Dissociation by chloralose of the cardiovascular and cerebrovascular responses evoked from the cerebellar fastigial nucleus.

We studied the effects of chloralose anesthesia on the elevation in arterial pressure (AP), heart rate (HR), and regional CBF (rCBF) elicited by stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized with an initial dose of chloralose (40 mg/kg s.c.), paralyzed, and artificially ventilated. The FN was stimulated (50-100 microA, 50 Hz, 1 s on/1 s off) with microelectrodes stereotaxically implanted. During the stimulation AP was carefully maintained within cerebrovascular autoregulation. CBF was measured by the [14C]iodoantipyrine technique with regional dissection. In rats that received only the initial dose of chloralose, FN stimulation elevated rCBF in brain and spinal cord, up to 209 +/- 13% of control in frontal cortex (n = 5; p less than 0.01, analysis of variance). Administration of additional chloralose (10 mg/kg i.v., 30 min prior to measurement of CBF) did not affect resting rCBF (n = 5), the EEG, or the elevation in AP and HR elicited by FN stimulation (n = 4). However, the additional chloralose abolished the elevations in rCBF (n = 5; p greater than 0.05). Thus, the cerebrovasodilation elicited from the FN is more susceptible to the effects of additional anesthesia than the elevation in AP and HR. These results indicate that the cerebrovascular and cardiovascular responses elicited from the FN are functionally distinct and provide additional evidence for the notion that these responses are mediated by different neural pathways and transmitters.

Animals↗
PubMed1982

Differential effect of althesin versus chloralose-urethane anesthesia on in vivo LHRH and LH release in the proestrous rat.

Anesthetic doses of Althesin and chloralose-urethane were compared as to their effects on neuroendocrine reproductive processes in diestrous and proestrous rats. Proestrous rats treated with Althesin experienced a 5-fold increase in immuno-reactive luteinizing hormone releasing hormone (LHRH) concentration in methanolic extracts of pituitary stalk plasma. This LHRH increase was 67% greater than that of proestrous rats administered chloralose-urethane. Moreover, Althesin given before the onset of the critical period did not suppress the proestrous surge of LHRH in stalk plasma. The Duncan's multiple range test indicated stalk plasma LHRH activity was significantly elevated in proestrous rats anesthetized with Althesin (p less than 0.05) but not with chloralose-urethane. However, the luteinizing hormone (LH) concentration in peripheral plasma increased 14 to 18-fold in all proestrous rats, including those anesthetized with chloralose-urethane. Evidently, in chloralose-urethane-treated rats, the smaller LHRH surge during proestrus is sufficient to elicit maximum release of LH from the anterior pituitary gland. This suggest that under normal conditions the amount of LHRH secreted into portal blood during proestrus is approximately 2-fold greater than that necessary to elicit maximum secretion of LH. The results also show that picogram concentrations of LH in the stalk plasma will stimulate the release of nanogram quantities of LH into the peripheral plasma of the same rats. Moreover, the sensitivity of the pituitary gland to LHRH stimulation via the portal circulation increases nearly 3-fold between diestrus and proestrus.

Alfaxalone Alfadolone Mixture↗
PubMed1984

Comparison of the effects of Althesin, chloralose-urethane, urethane, and pentobarbital on mammalian physiologic responses.

Physiological responses to anesthetic doses of four chemically dissimilar agents, namely, Althesin, urethane, chloralose-urethane, and pentobarbital sodium were compared in rats. The tail-flick test revealed Althesin had greater antinociceptive potency than urethane, chloralose-urethane, and pentobarbital, but its duration of action was shorter than that of chloralose-urethane. Althesin produced minimal or no suppression of core body temperature and mean arterial pressure, and only moderate reduction of mean pulse pressure. The heart rate and respiratory rate of Althesin-treated rats were slower than those of chloralose-urethane and urethane-treated counterparts, respectively, but were not significantly decreased from normal controls. It is concluded that Althesin is a suitable anesthetic for short-term surgery and for studies of body temperature, heart rate, and mean arterial pressure. Because release of gonadotropin-releasing hormone into hypophysial portal blood can be observed under Althesin but is suppressed or blocked by chloralose-urethane, urethane, and pentobarbital, Althesin is the anesthetic of choice in studies concerned with the neural control of ovulatory hormone release.

Alfaxalone Alfadolone Mixture↗
PubMed1992

A time-course study of the effects of pentobarbital, fentanyl, and morphine chloralose on myocardial mechanics.

Cardiovascular physiological studies in anesthetized animals may be confounded by the hemodynamic actions of the anesthetic agents themselves. To identify an anesthetic regimen that does not significantly influence cardiovascular physiology, the hemodynamic responses of 28 dogs were studied. Animals were equally divided among groups with 1) no anesthesia (i.e., trained conscious preparation), 2) pentobarbital sodium, 3) fentanyl citrate, and 4) a combination of morphine sulfate and alpha-chloralose. Anesthesia was maintained for 3 h. Data were acquired with the use of ultrasound imaging of the heart in conjunction with invasive pressure measurements. Left ventricular ejection phase indexes and end-systolic force-velocity relations were used to evaluate the effects of each anesthetic agent on overall systolic performance and myocardial contractility. Compared with the conscious animals, pentobarbital profoundly depressed systolic performance (P less than 0.05 vs. control) because of a reduction in myocardial contractility (P less than 0.01) and an increase in left ventricular afterload (end-systolic wall stress, P less than 0.05). Fentanyl increased myocardial contractility (P less than 0.05) but also tended to increase afterload with the net result that overall systolic performance remained unchanged. Morphine-chloralose did not affect overall ventricular systolic performance or its individual determinants. Pentobarbital and fentanyl also caused progressive time-dependent deteriorations in all parameters of systolic function during prolonged anesthesia. In contrast, cardiac function was stable for greater than or equal to 3 h after induction of morphine-chloralose anesthesia. The hemodynamic profile of dogs anesthetized with morphine-chloralose most closely resembled that of the conscious animals. Morphine-chloralose is recommended when prolonged anesthesia is required for studies of cardiovascular physiology.

Anesthetics↗
PubMedDate not supplied

Regional blood flow in canine brain during nicotine infusion: pentobarbital vs. chloralose anesthesia.

We compared vasoactive effects of intravenous nicotine (36 micrograms/kg/min) in regional cerebral circulations under pentobarbital and chloralose anesthesia. Experiments were conducted in three groups of dogs: Group I, pentobarbital anesthesia with fixed ventilation; Group II, chloralose anesthesia with fixed ventilation; Group III, chloralose anesthesia with free breathing. Values for regional cerebral blood flow measured with 15 mu radioactive microspheres were used to compute regional cerebral vascular resistance (rCBR). In Group I, nicotine had no effect on rCVR in cerebral cortex, and it increased significantly rCVR in cerebellum (+17%), pons (+13%), medulla (+23%), and spinal cord (+19%). Using chloralose instead of pentobarbital in dogs with fixed ventilation (Group II), caused a significant reduction in rCVR in the cerebral cortex during nicotine, although it did not alter significantly nicotine-induced changes in rCVR in other regions of the brain. Hypocapnic alkalosis during nicotine-induced hyperventilation (Group III) resulted in significant increases in rCVR in all regions of the brain; however, the increases in rCVR in non-cortical regions more than doubled those in the cerebral cortex. The present results indicate: Nicotine-induced vasodilation in cerebral cortex was blunted by pentobarbital anesthesia. Nicotine-induced vasodilation in cerebral cortex under chloralose anesthesia was sufficient to nullify in part the potent vasoconstrictor effect of hypocapnic alkalosis.

Anesthesia↗
PubMedDate not supplied

Comparative effects of chloralose anesthesia and Sernylan analgesia on cerebral blood flow, CO2 responsiveness, and brain metabolism in the baboon.

A comparison was made between the effects of two different anesthetics, alpha-D-gluco-chloralose and 1-1-phenylcyclohexyl piperidine hydrochloride (Sernylan), on cerebral blood flow (CBF), brain metabolism and cerebrovascular CO2 responsiveness in primates. The experiments were carried out on immobilized and artificially ventilated baboons. Anesthesia was induced either with 100/mg/kg chloralose (i.p.) or with 1 mg/kg Sernylan (i.m.). CBF in 8 different brain regions was measured by the intra-arterial 133Xe clearance technique. The CO2 responsiveness of the cerebrovascular bed was tested by a gas mixture containing 5% CO2. Chloralose depressed total as well as regional CBF compared to the effect of Sernylan. A significant shift occurred toward lower CBF values in the grey matter while white matter flow was identical in the two groups. Brain O2 consumption was significantly higher during Sernylan analgesia (3.35 +/- 0.34 ml/100 g/min) than during chloralose anesthesia (2.42 +/- 0.22 ml/100 g/min). There were no differences in glucose uptake, lactate and pyruvate production, or in arterial and cerebral venous blood gases in the two types of anesthesia. The cerebrovascular CO2 sensitivity of the Sernylan-treated baboons was higher than that of the chloralose-anesthetized animals, in both the grey and white matter.

Animals↗
PubMedDate not supplied

[Graded classification of acute chloralose poisoning. 509 cases].

OBJECTIVE: The annual incidence of chloralose poisoning has exceeded 3 cases per 100,000 inhabitants in Tunisia since 1997. The purpose of this study was to analyze clinical features of chloralose poisoning. METHODS: We reviewed patients admitted to the intensive care unit during the last 5 years to search for chloralose poisoning. The identified cases were classed into 5 grades by clinical features: depth of coma, characteristics of the myoclonia, and cerebral trunk reflex response. RESULTS: We identified 509 cases of chloralose poisoning over the last 5 years. Seventy-five patients (14.7%) were in grade 1: drowsiness alone. Four hundred ten patients (80.8%) were in grades 2 and 3: hypertonic coma and myoclonus. The clinical course was favorable after sedation, tracheal intubation and mechanical ventilation. Twenty-three patients (4.6%) were in grades 4 and 5: hypertonic coma (Glasgow coma score = 3). Three of them died. CONCLUSION: The clinical features of chloralose poisoning depend on the ingested dose. Despite the gravity of the initial clinical presentation, prognosis is excellent if symptomatic treatment is given early, even in grade 5 cases which simulate brain death.

Acute Disease↗
PubMed1986

Supplemental chloralose anesthesia in morphine premedicated dogs.

This study evaluated the cardiorespiratory stability of six dose-regulated, 12-hour, chloralose anesthetic maintenance protocols. Thirty mongrel dogs were premedicated with morphine sulfate (5mg/kg) and anesthetized with an induction dose of chloralose (80mg/kg). Fifteen animals were permitted to breathe spontaneously and 15 animals were ventilated mechanically to maintain a constant arterial pCO2 (40 +/- 5 mmHg). The spontaneously breathing dogs were separated into three groups in which animals (n = 5) were given different bolus doses of supplemental anesthetic. Initially the spontaneously breathing animals were hypoxemic, acidemic and hypercapnic. No consistent hemodynamic difference was noted among these groups. The mechanically ventilated animals were also divided into three groups that received varying doses of supplemental chloralose by constant infusion. Significant (p less than 0.01) myocardial depression was noted in the heavy-dosed animals by the third hour. Systolic pressure decreased 44%, pulse pressure decreased 37% and peak left ventricular dP/dt decreased 52%. All heavy-dosed animals expired before the eighth hour. Although these data suggest that morphine-premedicated, chloralose-anesthetized animals generally provide a stable cardiopulmonary model, high-dose chloralose supplementation depressed ventilation and produced a dose-dependent cardiotoxicity.

Anesthesia↗
PubMed1996

Trichloroethanol is not a metabolite of alpha chloralose.

Head space capillary gas chromatography was used to detect alpha chloralose and its potent metabolite, trichloroethanol in clinical and forensic cases. Although alpha chloralose was identified in blood and urine in all cases, trichloroethanol was never detected. In a fatal case the alpha chloralose concentration in blood was 151.3 mg/l. It was concluded that trichloroethanol is not a metabolite of alpha chloralose.

Adult↗
PubMed1995

Halothane, but not alpha-chloralose, blocks potassium-evoked cortical spreading depression in cats.

The effects of two anesthetics, halothane and alpha-chloralose, on induction of spreading depression and on extracellular glutamate elevation after intracortical potassium administration were investigated in artificially ventilated (30% oxygen/70% nitrous oxide) cats. High potassium concentrations were achieved using either direct KCl injections (7 microliters, 150 mM via a micropipette) or microdialysis by supplementing 100, 300 or 500 mM KCl, respectively, for 10 min to the perfusion solution (Ringer's). Changes of the cortical DC potential were recorded adjacent (1-2 mm: electrode DC1) and distant (6-7 mm: electrode DC2) to the injection site. Either under halothane (0.75% in the respiratory gas mixture) or under alpha-chloralose (60 mg/kg i.v.) anesthesia, prolonged negative shifts of the DC potential reflecting the elevated potassium levels after KCl injection were measured near the injection site (electrode DC1). In contrast, spreading depressions (transient short DC deflections) were almost exclusively observed under alpha-chloralose. Spreading depressions recorded with electrode DC1 were superimposed on the prolonged negative DC shifts and they propagated frequently to the more distant site (DC2). Upon KCl administration, dose dependent elevations of extracellular glutamate were measured. These elevations were not significantly altered by the type of anesthesia. Our results suggest that in cats, spreading depression induction is affected by anesthesia, i.e., spreading depression induction is inhibited by halothane as compared to alpha-chloralose. Furthermore, factors other than glutamate or high potassium seem to contribute to spreading depression induction.

Animals↗
PubMed1990

The effects of chloralose on the brainstem auditory evoked potential of the rat.

The effects of alpha-chloralose were examined on the brainstem auditory evoked potential of the rat. Subjects were given one of four different doses of chloralose. These were a sedative dose (50 mg/kg), an anaesthetic dose (100 mg/kg), a usually fatal dose (150 mg/kg) or an invariably fatal dose (200 mg/kg). Recordings were made 60 min later. There was no evidence of any dose-dependent increase or decrease in the amplitudes of the four principal components (waves I, II, III and IV) of the brainstem auditory potential. There were only minor dose-dependent increases in latency. These were less than 0.1 msec for waves I, II and III and just over 0.1 msec for wave IV. Wave IV was the component which was most sensitive to chloralose, although this was apparent only at a large dose. In general, the latencies showed little or no difference from those recorded previously from awake animals. The results are discussed in relation to a series of experiments, where animals were initially immobilized with chloralose in order to study the effects of a variety of pharmacological agents on the brainstem auditory potential.

Animals↗
PubMed2005

Confounding effects of anesthesia on functional activation in rodent brain: a study of halothane and alpha-chloralose anesthesia.

Functional magnetic resonance imaging (fMRI) in animal models provides a platform for more extensive investigation of drug effects and underlying physiological mechanisms than is possible in humans. However, it is usually necessary for the animal to be anesthetized. In this study, we have used a rat model of direct cortical stimulation to investigate the effects of anesthesia in rodent fMRI. Specifically, we have sought to answer two questions (i) what is the relationship between baseline neuronal activity and the BOLD response to stimulation under halothane anesthesia? And (ii) how does the BOLD response change after transferring from halothane to the commonly used anesthetic alpha-chloralose? In the first set of experiments, we found no significant differences in the amplitude of the BOLD response at the different halothane doses studied, despite electroencephalography (EEG) recordings indicating a dose-dependent reduction in baseline neuronal activity with increasing halothane levels. In the second set of experiments, a reduction in the spatial extent of the BOLD response was apparent immediately after transfer from halothane to alpha-chloralose anesthesia, although no change in the peak signal change was evident. However, several hours after transfer to alpha-chloralose, a significant increase in both the spatial extent and peak height of the BOLD response was observed, as well as an increased sensitivity to secondary cortical and subcortical activation. These findings suggest that, although alpha-chloralose anesthesia is associated with a greater BOLD response for a fixed stimulus relative to halothane, there is substantial variation in the extent and magnitude of the response over time that could introduce considerable variability in studies using this anesthetic.

Anesthesia, General↗