Mechanisms of bronchoprotection by anesthetic induction agents: propofol versus ketamine. (1/268)

BACKGROUND: Propofol and ketamine have been purported to decrease bronchoconstriction during induction of anesthesia and intubation. Whether they act on airway smooth muscle or through neural reflexes has not been determined. We compared propofol and ketamine to attenuate the direct activation of airway smooth muscle by methacholine and limit neurally mediated bronchoconstriction (vagal nerve stimulation). METHODS: After approval from the institutional review board, eight sheep were anesthetized with pentobarbital, paralyzed, and ventilated. After left thoracotomy, the bronchial artery was cannulated and perfused. In random order, 5 mg/ml concentrations of propofol, ketamine, and thiopental were infused into the bronchial artery at rates of 0.06, 0.20, and 0.60 ml/min. After 10 min, airway resistance was measured before and after vagal nerve stimulation and methacholine given via the bronchial artery. Data were expressed as a percent of baseline response before infusion of drug and analyzed by analysis of variance with significance set at P< or =0.05. RESULTS: Systemic blood pressure was not affected by any of the drugs (P>0.46). Baseline airway resistance was not different among the three agents (P = 0.56) or by dose (P = 0.96). Infusion of propofol and ketamine into the bronchial artery caused a dose-dependent attenuation of the vagal nerve stimulation-induced bronchoconstriction to 26+/-11% and 8+/-2% of maximum, respectively (P<0.0001). In addition, propofol caused a significant decrease in the methacholine-induced bronchoconstriction to 43+/-27% of maximum at the highest concentration (P = 0.05) CONCLUSIONS: The local bronchoprotective effects of ketamine and propofol on airways is through neurally mediated mechanisms. Although the direct effects on airway smooth muscle occur at high concentrations, these are unlikely to be of primary clinical relevance.  (+info)

Acid-base disturbance during hemorrhage in rats: significant role of strong inorganic ions. (2/268)

The present study tests the hypothesis that changes in the strong inorganic ion concentrations contribute significantly to the acid-base disturbance that develops during hemorrhage in the arterial plasma of rats in addition to lactate concentration ([Lac-]) increase. The physicochemical origins for this acid-base disorder were studied during acute, graded hemorrhage (10, 20, and 30% loss of blood volume) in three groups of rats: conscious, anesthetized with ketamine, and anesthetized with urethan. The results support the hypothesis examined: strong-ion difference (SID) decreased in the arterial plasma of all groups studied because of an early imbalance in the main strong inorganic ions during initial hemorrhagic phase. Moreover, changes in plasma [Lac-] contributed to SID decrease in a later hemorrhagic phase (after 10% hemorrhage in urethan-anesthetized, after 20% hemorrhage in ketamine-anesthetized, and after 30% hemorrhage in conscious group). Inorganic ion changes were due to both dilution of the vascular compartment and ion exchange with extravascular space and red blood cells, as compensation for blood volume depletion and hypocapnia. Nevertheless, anesthetized rats were less able than conscious rats to preserve normal arterial pH during hemorrhage, mainly because of an impaired peripheral tissue condition and incomplete ventilatory compensation.  (+info)

Actions of ketamine and its isomers on contractility and calcium transients in human myocardium. (3/268)

BACKGROUND: Ketamine has a species-dependent inotropic effect on myocardium. The authors' aim was to investigate the direct inotropic effect and the corresponding intracellular Ca2+ transients of ketamine and its isomers on human myocardium. METHODS: Right auricular myocardial strips obtained during open heart surgery were exposed to increasing concentrations (73 microM, 360 microM, and 730 microM) of racemic ketamine (n = 12), S(+)-ketamine (n = 12), or R(-)-ketamine (n = 11). Isometric force, isotonic shortening, contractility, relaxation, and time to maximal isotonic and isometric force were assessed. Ten muscle strips in each group were loaded with the calcium-sensitive fluorescent dye FURA-2/AM for simultaneous measurements of calcium transients. RESULTS: Compared with the initial control maximal isometric developed force, maximal isotonic shortening amplitude, contractility, and relaxation increased by 12.5-22.4% after perfusion with S(+)-ketamine at the concentration of 73 microM (P < 0.05). In contrast, no changes were seen after addition of 73 microM R(-)-ketamine. The effect of racemic ketamine (73 microM) was between that of the two isomers. At the highest concentration (730 microM) ketamine and its isomers decreased maximal isometric developed force, maximal shortening amplitude, contractility, and relaxation by 26.8-57.4% (P < 0.05), accompanied by a significant decrease of the intracellular calcium transient (by 21.0-32.2%, P < 0.05). CONCLUSIONS: In contrast to R(-)-ketamine, S(+)-ketamine increased isometric force, isotonic shortening, contractility, and relaxation at low concentrations (73 microM) compared with the initial control. At higher concentrations (730 microM) a direct negative inotropic action was observed after perfusion with ketamine and its isomers, which was accompanied by a decreased intracellular Ca2+ transient.  (+info)

Comparison of oral chloral hydrate with intramuscular ketamine, meperidine, and promethazine for pediatric sedation--preliminary report. (4/268)

Fifteen consecutive pediatric patients ranging from 3 to 5 years old were selected to receive one of three sedative/hypnotic techniques. Group 1 received oral chloral hydrate 50 mg/kg, and groups 2 and 3 received intramuscular ketamine 2 mg/kg and 3 mg/kg, respectively. In addition to ketamine, patients in groups 2 and 3 received transmucosal intramuscular injections of meperidine and promethazine into the masseter muscle. Sedation for the satisfactory completion of restorative dentistry was obtained for over 40 min on average in the chloral hydrate group, but completion of dental surgery longer than 40 min was achieved in groups 2 and 3 only by intravenous supplements of ketamine.  (+info)

Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain. (5/268)

The effects of diazepam, which acts at GABAA receptors to enhance the effects of GABA, and ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, on local rates of cerebral glucose utilization (ICMRglc) were examined in unrestrained rats. Four groups were studied: vehicle-injected controls; and ketamine-treated, diazepam-treated and combined ketamine- and diazepam-treated animals. Ketamine alone produced a heterogeneous pattern of changes in ICMRglc (e.g. significant increases in the corpus callosum, olfactory tubercle and the entire Papez circuit, in addition to other limbic areas, and significant decreases in lateral habenula and some components of the auditory system). Diazepam alone statistically significantly decreased ICMRglc in the brain as a whole and in most areas of the cerebral cortex, thalamus and limbic system. The most remarkable effects of the two drugs administered together on ICMRglc occurred in the limbic system where the dramatic increases observed with ketamine alone were prevented by treatment with diazepam.  (+info)

Stereospecific effects of ketamine on dopamine efflux and uptake in the rat nucleus accumbens. (6/268)

In addition to being a general anaesthetic, ketamine is a recognized drug of abuse. Many, if not all, drugs of abuse have been shown to increase dopamine efflux in the nucleus accumbens (NAc). As ketamine is optically active, we examined if its actions on dopamine efflux in the NAc were stereoselective. Slices of rat NAc were superfused with artificial CSF at 32 degrees C. Dopamine efflux was evoked by electrical stimulation (1 or 20 pulses, 100 Hz) and measured using fast cyclic voltammetry. (+/-)-Ketamine 100 mumol litre-1 increased dopamine efflux (to mean 174 (SEM 17)% of control, P < 0.05) and slowed dopamine uptake half-time (T1/2) to 164 (17)% of control, as did (+)-ketamine 100 mumol litre-1 (efflux 236 (16)% (P < 0.001); uptake T1/2 177 (25)% (P < 0.05)). The (-)-isomer was inactive. The effect of (+)-ketamine on dopamine efflux did not correlate with its action on dopamine uptake. (+)-Ketamine increased dopamine efflux on single pulse stimulation but to a lesser extent than on 20 pulse trains (P < 0.05). (+)-Ketamine was unable to block the inhibitory effect of quinpirole on single pulse dopamine efflux. Neither MK 801 10 mumol litre-1 nor metoclopramide 1 mumol litre-1 had any effect on dopamine release after short train stimuli (20 pulses, 100 Hz). We conclude that the (+)-isomer is the active form of ketamine and increases NAc dopamine efflux not by block of dopamine uptake; autoreceptors or NMDA receptors, but by mobilization of the dopamine storage pool to releasable sites.  (+info)

Ketamine preserves and propofol potentiates hypoxic pulmonary vasoconstriction compared with the conscious state in chronically instrumented dogs. (7/268)

BACKGROUND: The authors tested the hypothesis that ketamine and propofol anesthesia would alter the magnitude of hypoxic pulmonary vasoconstriction compared with the conscious state. In addition, they assessed the extent to which cyclooxygenase pathway inhibition and adenosine triphosphate-sensitive potassium channel inhibition modulate hypoxic pulmonary vasoconstriction in the conscious state, and whether these pathways are altered during propofol anesthesia. METHODS: Twenty conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow relationship. Pressure-flow plots were measured during normoxia and hypoxia (systemic arterial PO2 reduced to about 60 and about 50 mm Hg) on separate days in the conscious state, during ketamine anesthesia, and during propofol anesthesia. The effects of indomethacin and glibenclamide on the magnitude of hypoxic pulmonary vasoconstriction were also assessed in the conscious and propofol-anesthetized states. RESULTS: Neither ketamine nor propofol had an effect on the baseline pressure-flow relationship during normoxia compared with the conscious state. Hypoxia resulted in stimulus-dependent pulmonary vasoconstriction (P<0.01) in the conscious state. Compared with the conscious state, the magnitude of hypoxic pulmonary vasoconstriction was preserved during ketamine but was potentiated (P<0.01) during propofol anesthesia. Indomethacin enhanced (P<0.01) hypoxic pulmonary vasoconstriction in both the conscious and propofol-anesthetized states. In contrast, glibenclamide only enhanced (P<0.01) hypoxic pulmonary vasoconstriction in the conscious state and had no effect during propofol anesthesia. CONCLUSION: Hypoxic pulmonary vasoconstriction is preserved during ketamine anesthesia but is potentiated during propofol anesthesia. The potentiated response during propofol anesthesia appears to be caused by inhibition of adenosine triphosphate-sensitive potassium channel-mediated pulmonary vasodilation.  (+info)

Tooth pulp- and facial hair mechanoreceptor-evoked responses of trigeminal sensory neurons are attenuated during ketamine anesthesia. (8/268)

BACKGROUND: Evidence exists that ketamine, administered systemically using a dose required for inducing a state of anesthesia, may antagonize nociceptive but not innocuous input to lumbar dorsal horn neurons. However, it is unclear whether ketamine exerts this selective action on sensory inputs to trigeminal sensory neurons. The current study was undertaken to compare the responses evoked in trigeminal sensory neurons by electrical stimuli applied to the tooth pulp versus air-puff stimuli applied to facial hair mechanoreceptors (FHMs) during quiet wakefulness versus ketamine anesthesia. METHODS: Accordingly, responses of rostral trigeminal sensory nuclear complex (TSNC) and trigeminothalamic tract neurons evoked by tooth pulp (a source of small-diameter fiber input) and FHMs (a source of larger-diameter fiber input) were recorded extracellularly from chronically instrumented cats before, during, and after recovery from the anesthetic state induced by a single (2.2 mg/kg) intravenous injection of ketamine. RESULTS: Overall, tooth pulp-evoked responses of TSNC neurons were maximally suppressed by 50% within 5 min after the intravenous administration of ketamine. Ketamine also suppressed the FHM-evoked responses of TSNC and trigeminothalamic neurons by 45%. The time course of ketamine's suppressive action was equivalent for tooth pulp- and FHM-evoked responses. However, the recovery of tooth pulp-evoked TSNC neuronal responses at suprathreshold intensities was markedly prolonged compared with neuronal responses driven by threshold stimuli or FHM. CONCLUSIONS: These electrophysiologic results in the chronically instrumented cat preparation indicate that a nonselective suppression of orofacial somatosensory information occurs during ketamine anesthesia. The prolonged recovery of suprathreshold responses of TSNC neurons mediated by small-diameter afferent fiber input may partly underlie the analgesic action of ketamine that is clinically relevant at subanesthetic doses.  (+info)

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