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PubMed1987

Anesthetic potencies of secondary alcohol enantiomers.

The Meyer-Overton rule has been interpreted to mean that general anesthetics act at a nonpolar site, either in a lipid bilayer or a protein. Optical isomers, also called enantiomers, are pairs of compounds with the same molecular formula and functional groups, but which differ in the arrangement of the groups around an "asymmetric" carbon atom and in the direction they rotate plane-polarized light. By definition, enantiomers that are anesthetics can distinguish between stereoselective and nonselective sites of anesthetic action. We used such enantiomers to determine whether anesthetics are stereoselective in their actions on animals by measuring the potencies of a homologous series of secondary aliphatic alcohols from 2-butanol through 2-octanol in tadpoles, using reversible loss of righting reflex as the endpoint. None of the isomeric pairs exhibited significant differences in potency. Anesthetic potency increased logarithmically with the number of carbon atoms in the hydrocarbon chain of the alcohol. The ED50 +/- SE (mM) for the (+) and (-) forms of the alcohols, respectively, were as follows: 2-butanol 17 +/- 1.2, 17 +/- 1.1; 2-pentanol 4.7 +/- 0.28, 4.8 +/- 0.27; 2-hexanol 1.33 +/- 0.068, 1.42 +/- 0.079; 2-heptanol 0.32 +/- 0.011, 0.33 +/- 0.020; and 2-octanol 0.063 +/- 0.0042, 0.061 +/- 0.0032. These data demonstrate a lack of stereoselectivity in the interactions between the anesthetic secondary alcohols and their site of action in animals.

1-Octanol↗

PubMed1987

Hepatic effects of repeated halothane anesthetics in the hypoxic rat model.

The hepatic effects of repeated anesthesia of phenobarbital-induced Fischer 344 rats with 1% halothane/14% oxygen were investigated, after anesthetics were administered at either 1-day or 5-day intervals. Urinary excretion of fluoride, a product of reductive halothane metabolism, was increased in the 24-h period following anesthesia, but was the same after the first, second, and third anesthetics. Rats killed 24 h after a single anesthetic all had centrilobular hepatocellular necrosis. All animals killed 24 h after the second or third anesthetic also had centrilobular necrosis, but, in most animals, this was no more extensive than that following a single anesthetic, regardless of whether the interval between anesthetics was one or five days.

Anesthesia, Inhalation↗

PubMed1989

Fentanyl-induced muscle rigidity in unanesthetized and ketamine- or thiopental-anesthetized rats.

This study was undertaken to search for an alternative experimental model in the evaluation of fentanyl-induced muscle rigidity. Unanesthetized, spontaneously ventilating Sprague-Dawley rats, and rats anesthetized with either ketamine or thiopental whose ventilation was mechanically controlled, were studied. Intravenous administration of fentanyl (25, 50, or 100 micrograms/kg) caused an increase in electromyographic (EMG) activity in both unanesthetized and ketamine-anesthetized, but not in thiopental-anesthetized, animals. Muscle rigidity was more prominently manifested in the gastrocnemius muscle, when compared with the rectus abdominis muscle. Hypoxemia was exhibited during the course of rigidity by both spontaneously ventilating and ketamine-anesthetized rats, but not by thiopental-anesthetized animals. In addition, unanesthetized, spontaneously ventilating rats developed hypercarbia and respiratory acidosis. The authors suggest that, in addition to using unanesthetized animals, EMG activity in the gastrocnemius muscle of rats anesthetized with ketamine in whom ventilation is controlled may provide an alternative approach in the evaluation of fentanyl-induced muscle rigidity.

Anesthesia↗

PubMed1989

The effects of magnesium salts on the duration of epinephrine-induced ventricular tachyarrhythmias in anesthetized rats.

The effects of MgSO4 or MgCl2 infusion on the duration of epinephrine-induced cardiac arrhythmia were evaluated in male rats anesthetized with either halothane or pentobarbital. In addition, the duration of epinephrine-induced arrhythmia in pentobarbital (50 mg/kg) anesthetized rats was compared with the duration of arrhythmia in halothane (1.5%) anesthetized rats. During halothane anesthesia MgSO4 or MgCl2 infused at a dose rate of 8 mg.kg-1.min-1 for 20 min caused a significant reduction in the duration of arrhythmia (100% and 80%, respectively) following a 4-microgram/kg injection of epinephrine and a significant threefold reduction in arrhythmia duration for each salt following an 8- or 16-micrograms/kg injection of epinephrine. Significantly shorter periods of arrhythmia after each dose of epinephrine were seen in rats anesthetized with pentobarbital than were seen in rats anesthetized with halothane. No significant difference was seen between MgSO4 or MgCl2 infusions in any of these studies. Twenty-minute infusions of MgSO4 (8 mg.kg-1.min-1) were compared with propranolol (0.03 mg.kg-1.min-1) and verapamil (0.5 micrograms.kg-1.min-1) infusions on the duration of arrhythmia after epinephrine (8 micrograms/kg) injections in halothane anesthetized rats. MgSO4 and propranolol infusion caused a significant reduction in the duration of arrhythmia (81% and 70%, respectively). Verapamil infusion caused only a 48% reduction in arrhythmia duration. While there was no significant difference between MgSO4 or propranolol, both caused a significantly greater reduction in arrhythmia than verapamil. CaCl2 (0.15 mM.kg-1.min-1) infusion for 5 min caused a significant fivefold increase in the duration of arrhythmia during halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Pertussis toxin and 4-aminopyridine differentially affect the hypnotic-anesthetic action of dexmedetomidine and pentobarbital.

Dexmedetomidine, a highly selective and potent agonist at alpha-2 adrenoceptors, produces a hypnotic-anesthetic action in rats. The mechanism for this response may involve an inhibitory G-protein and increased conductance through a potassium channel. To investigate this, the effects of pertussis toxin, a specific inactivator of inhibitory G-proteins, and 4-aminopyridine, a blocker of potassium channels, on the hypnotic-anesthetic response to dexmedetomidine were studied in rats. Pertussis toxin and 4-aminopyridine both decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. To preclude the possibility that pertussis toxin and 4-aminopyridine attenuated the hypnotic-anesthetic action of dexmedetomidine via indirect central nervous system excitation, the effects of pertussis toxin and 4-aminopyridine on the hypnotic-anesthetic action of pentobarbital also were assessed. Pentobarbital-induced hypnosis was not attenuated by either treatment. These results suggest that the receptor-effector mechanism for the hypnotic-anesthetic action of dexmedetomidine involves an inhibitory G-protein and increased conductance through a potassium channel.

4-Aminopyridine↗

PubMed1991

Oral clonidine preanesthetic medication augments the pressor responses to intravenous ephedrine in awake or anesthetized patients.

To evaluate the possible interaction between clonidine and ephedrine, the authors studied hemodynamic responses to intravenous ephedrine in 80 patients who received either clonidine pre-anesthetic medication of approximately 5 micrograms.kg-1 orally (n = 40) or no medication (n = 40). The patients were studied while they were either awake (n = 40) or anesthetized with enflurane and nitrous oxide in oxygen (n = 40). Hemodynamic measurements were made at 1-min intervals for 10 min after ephedrine 0.1 mg.kg-1 was injected as a bolus. Although the responses to ephedrine were always greater in anesthetized patients, the magnitudes of mean blood pressure increases in patients who received clonidine (10 +/- 8% for awake and 27 +/- 11% for anesthetized subjects, mean +/- standard deviation [SD]) were significantly greater (P less than 0.05) than in patients not receiving clonidine (4 +/- 5% for awake and 17 +/- 11% for anesthetized subjects). The enhanced pressor responses to ephedrine observed in both awake and anesthetized patients in the presence of clonidine may be attributed to increased catecholamine storage at sympathetic nerve endings due to clonidine, enhanced sensitivity of tissue receptors to which ephedrine binds, potentiation of alpha-adrenoceptor mediated vasoconstriction of both agents, or all of these. It is concluded that oral clonidine preanesthetic medication of 5 micrograms.kg-1 does augment rather than attenuate the pressor responses to intravenous ephedrine in patients both prior to and during general anesthesia.

Administration, Oral↗

PubMed1992

The effects of volatile anesthetics on calcium regulation by malignant hyperthermia-susceptible sarcoplasmic reticulum.

To clarify the mechanism by which volatile anesthetics initiate malignant hyperthermia (MH), we examined the effect of halothane, isoflurane, and enflurane on Ca2+ uptake and release by sarcoplasmic reticulum vesicles isolated from MH-susceptible (MHS) and normal pig muscle. Clinical concentrations of these anesthetics (0.1-0.5 mM) stimulated sarcoplasmic reticulum ATP-dependent Ca2+ uptake (maximal at approximately 4 mM), whereas 10-20 times the clinical anesthetic concentration inhibited Ca2+ uptake. There was no significant difference between MHS and normal sarcoplasmic reticulum in any aspect of Ca2+ uptake. Ca2+ release from 45Ca(2+)-filled sarcoplasmic reticulum vesicles in a 10(-8) M Ca(2+)-containing medium (pH 7.0) was significantly stimulated at clinical concentrations of all three volatile anesthetics (anesthetic concentration for the 50% stimulation of Ca2+ release = 0.096-0.22 mM); however, the rate constant for Ca2+ release from MHS sarcoplasmic reticulum was in all cases significantly greater than that from normal sarcoplasmic reticulum. Furthermore, 0.5 mM halothane had no effect on Ca2+ release from normal sarcoplasmic reticulum at pH values less than 6.8, although it could still significantly stimulate Ca2+ release from MHS sarcoplasmic reticulum even at pH 6.4; similar results were obtained for isoflurane and enflurane. These studies thus demonstrate that the interaction of volatile anesthetics with the sarcoplasmic reticulum Ca(2+)-release channel is altered in MHS porcine muscle such that the channel may be activated even at a Ca2+ concentration or pH that would be expected to maintain the channel in the closed state.

Animals↗

PubMed1994

Volatile anesthetics and agonist-induced contractions in porcine coronary artery smooth muscle and Ca2+ mobilization in cultured immortalized vascular smooth muscle cells.

BACKGROUND: These experiments addressed four specific questions. Do isoflurane and halothane (0.5-3.0% in the gas phase) inhibit contractions evoked in isolated porcine coronary artery rings (without endothelium) by the specific Ca2+ mobilizing agonists serotonin, endothelin-1, and F-? Are contractions evoked by phorbol-activated protein kinase C inhibited by the anesthetics? In a well-characterized vascular smooth muscle cell culture model (A7r5 and A10), do the anesthetics attenuate serotonin- and endothelin-induced Ca2+ mobilization? Do the anesthetics inhibit intracellular Ca2+ mobilization via facilitated cAMP formation? METHODS: Tension was measured in rings suspended in organ chambers. Apparent intracellular Ca2+ was estimated in cells using indo-1 and flow cytometry. Cyclic AMP was measured by radioimmunoassay. RESULTS: At the anesthetic concentrations examined, isoflurane attenuated contractions evoked by serotonin and F- but not those induced by endothelin-1 or phorbol dibutyrate. In cells, isoflurane 2% attenuated 3 x 10(-5) M serotonin-induced Ca2+ mobilization by about 26%, whereas Ca2+ responses evoked by endothelin 10(-8) M were more resistant to anesthetic inhibitory effect. Halothane attenuated contractions in rings evoked by serotonin, endothelin, and F- but lacked effect on phorbol-induced responses. In cells, halothane 2% inhibited Ca2+ mobilization induced by serotonin by about 43% and that induced by endothelin by about 31%. Neither anesthetic facilitated cAMP formation. CONCLUSIONS: Isoflurane and halothane variably attenuated contractions evoked by Ca2+ mobilizing agonists--by a cellular action beyond the receptor level--but did not inhibit phorbol activated protein kinase C. Serotonin- and endothelin-induced Ca2+ mobilization was inhibited by isoflurane and halothane--but the mechanism does not depend upon increased cAMP.

Aluminum Compounds↗

PubMed1994

Critical respiratory events in the postanesthesia care unit. Patient, surgical, and anesthetic factors.

BACKGROUND: Previous studies have noted a high incidence of adverse outcomes in the postanesthesia care unit (PACU), but few have examined associated factors and patient outcomes. To determine the frequency of acute, unanticipated respiratory problems and to examine the associated patient, surgical, and anesthetic factors, we prospectively collected preoperative, intraoperative, and postoperative data on 24,157 consecutive PACU patients who received a general anesthetic during a 33-month period. METHODS: A PACU critical respiratory event (CRE), was defined as any unanticipated hypoxemia (hemoglobin oxygen saturation < 90%), hypoventilation (respiratory rate < 8 breaths/min or arterial carbon dioxide tension > 50 mmHg) or upper-airway obstruction (stridor or laryngospasm) requiring an active and specific intervention (ventilation, tracheal intubation, opioid or muscle relaxant antagonism, insertion of oral/nasal airway or airway manipulation). These problems were documented by PACU nurses whereas data on case-mix, surgical factors, and intraoperative management were retrieved from the anesthetic record. Significant patient, surgical, and anesthetic factors were identified by logistic regression analysis. Other morbidity experienced by patients with a CRE was also noted. RESULTS: For patients given general anesthesia the risk of a CRE was 1.3% (hypoxemia 0.9%, hypoventilation 0.2%, airway obstruction 0.2%). Preoperative factors that increase risk were age > 60 yr, male gender, diabetes, and obesity (P < 0.05). Patients who underwent operative procedures on an emergency basis and whose operation was longer than 4 h were also at increased risk, but those undergoing perineal procedures were at lower risk (P < 0.05). Anesthetic risk factors (P < 0.05) included opioid premedication (relative odds 1.8), sedatives preoperatively (2.0), fentanyl > 2.0 micrograms.kg-1.h-1 as the sole opioid (1.9), fentanyl used in combination with morphine (1.6) and atracurium > or = 0.25 mg.kg-1.h-1 (2.2). Patients in whom anesthesia was induced with thiopental (relative odds 2.5), compared with those who received propofol for induction, were also at increased risk of a CRE. Patients with a CRE stayed longer in PACU, had higher rates of unanticipated admissions to the intensive care unit and were more likely to have PACU cardiac problems (P < 0.01). CONCLUSIONS: A CRE is relatively rare. Multiple patient and surgical factors and specific aspects of anesthetic management are associated with the occurrence of a CRE in the PACU.

Airway Obstruction↗

PubMed1995

General anesthetics modify the kinetics of nicotinic acetylcholine receptor desensitization at clinically relevant concentrations.

BACKGROUND: General anesthetics are thought to induce anesthesia through their actions on ligand-gated ion channels. One such channel, the nicotinic acetylcholine receptor (nAcChoR), can be found in different subtypes in the central nervous system and at the periphery in the neuromuscular junction. The latter subtype of the nAcChoR is a useful model for examining interactions between general anesthetics and ligand-gated ion channels, because it can be isolated and purified in sufficient quantities to allow for biophysical and biochemical studies. This study examines the actions of general anesthetics on agonist-induced conversion of the nAcChoR to inactive desensitized conformational states. METHODS: Nicotinic acetylcholine receptor membranes were purified from the electric organ of Torpedo nobiliana. Agonist-induced desensitization was characterized from the time-dependent increase in fluorescence intensity that results from the binding of the fluorescent acetylcholine analog, Dns-C6-Cho, to the nAcChoR. RESULTS: Mixing Dns-C6-Cho with nAcChoR-rich membranes results in an increase in fluorescence that is characterized by four rate processes. Concentrations of isoflurane and butanol, which range from subclinical to toxic increase the rates of the third and fourth components of fluorescence, corresponding to fast and slow desensitization, respectively. At concentrations that are twice their EC50s for anesthesia, isoflurane, butanol, chloroform, methanol, and cyclopentanemethanol increase the apparent rates of fast and slow desensitization by an average of 92 +/- 22% and 108 +/- 22%, respectively. CONCLUSIONS: The concentration range over which general anesthetics modify the kinetics of nAcChoR desensitization is similar to those reported for anesthetic actions on the GABAA receptor. Thus, the nAcChoR, like other members of this superfamily, is a sensitive target of general anesthetics.

1-Butanol↗

PubMed2001

The effects of CO2 on respiratory mechanics in anesthetized paralyzed humans.

BACKGROUND: There is little information concerning the carbon dioxide-related effects on respiratory mechanics in anesthetized, paralyzed subjects; however, hypocapnia or hypercapnia is often permitted in patients with severe brain injury or acute respiratory distress syndrome. Therefore, the carbon dioxide dependence of respiratory mechanics in healthy anesthetized, paralyzed subjects was investigated. METHODS: Interrupter resistance (Rint), additional tissue viscoelastic resistance (deltaR), and quasi-static elastance (Est) of lung (L) and chest wall were assessed by means of the rapid end-inspiratory occlusion method in two groups of seven healthy paralyzed subjects anesthetized with diazepam or isoflurane. They underwent ventilation with a fixed pattern and hyperoxic gas mixtures with different fractions of inspired carbon dioxide (FICO2) to produce a partial pressures of arterial carbon dioxide (PaCO2) of 24.4 +/- 3.4, 39.6 +/- 3.2, and 62 +/- 4.1 (SD) mmHg. RESULTS: Chest wall mechanics and Est,L were unaffected by PaCO2 changes. With diazepam anesthesia, Rint,L decreased linearly, with increasing PaCO2, from 2.3 to 1.4 cm H2O.s.l(-1), whereas deltaR,L decreased from 2 to 1.7 cm H2O.s.l(-1), though not significantly. With isoflurane anesthesia, the decrease of Rint,L (0.2 +/- 0.5 cm H2O.s.l(-1)) was not significant, and deltaRL remained unchanged. With diazepam, Rint,L was 45 (hypercapnia) to 110% (hypocapnia) greater than with isoflurane. CONCLUSIONS: Changes of PaCO2 from 20-65 mmHg cause increasing bronchodilation in anesthetized, paralyzed subjects, this effect being attenuated or abolished by drugs (e.g., halogenated anesthetics) that depress smooth muscle tone substantially. The carbon dioxide bronchodilating effects are probably direct for peripheral structures and are paralleled by a tendency of lung tissue resistance to decrease. Because local PaCO2-related changes in bronchomotor tone promote VA/Q matching, this mechanism should be impaired by anesthetics that cause bronchodilation.

Adult↗

PubMed2001

The effect of prone positioning on intraocular pressure in anesthetized patients.

BACKGROUND: Ocular perfusion pressure is commonly defined as mean arterial pressure minus intraocular pressure (IOP). Changes in mean arterial pressure or IOP can affect ocular perfusion pressure. IOP has not been studied in this context in the prone anesthetized patient. METHODS: After institutional human studies committee approval and informed consent, 20 patients (American Society of Anesthesiologists physical status I-III) without eye disease who were scheduled for spine surgery in the prone position were enrolled. IOP was measured with a Tono-pen XL handheld tonometer at five time points: awake supine (baseline), anesthetized (supine 1), anesthetized prone (prone 1), anesthetized prone at conclusion of case (prone 2), and anesthetized supine before wake-up (supine 2). Anesthetic protocol was standardized. The head was positioned with a pinned head-holder. Data were analyzed with repeated-measures analysis of variance and paired t test. RESULTS: Supine 1 IOP (13 +/- 1 mmHg) decreased from baseline (19 +/- 1 mmHg) (P < 0.05). Prone 1 IOP (27 +/- 2 mmHg) increased in comparison with baseline (P < 0.05) and supine 1 (P < 0.05). Prone 2 IOP (40 +/- 2 mmHg) was measured after 320 +/- 107 min in the prone position and was significantly increased in comparison with all previous measurements (P < 0.05). Supine 2 IOP (31 +/- 2 mmHg) decreased in comparison with prone 2 IOP (P < 0.05) but was relatively elevated in comparison with supine 1 and baseline (P < 0.05). Hemodynamic and ventilatory parameters remained unchanged during the prone period. CONCLUSIONS: Prone positioning increases IOP during anesthesia. Ocular perfusion pressure could therefore decrease, despite maintenance of normotension.

Adolescent↗

PubMed1995

Isotonic saline resuscitation in uncontrolled hemorrhage under various anesthetic conditions.

OBJECTIVE: The authors evaluated the effect of early fluid resuscitation with isotonic saline (NaCl, 0.9%) on uncontrolled hemorrhage in rats under different anesthetic conditions. SUMMARY/BACKGROUND DATA: Recently, it has been suggested that administration of fluids to patients during uncontrolled hemorrhage may produce adverse effects, and a postponement of resuscitation until surgical control of bleeding was recommended. Past clinical trials were inconclusive, and the results of recent experimental studies were affected by use of vasoactive anesthetics. METHODS: One hundred thirty-five female Sprague-Dawley rats were randomly divided into three groups: group 1--unanesthetized; group 2--anesthetized with sodium pentobarbital; and group 3--anesthetized with a mixture of droperidol and ketamine. Uncontrolled hemorrhage was initiated with a 75% tail resection, and each group was further subdivided into three subgroups for the following treatment: (A) no resuscitation; (B) 40 mL/kg of isotonic saline; or (C) 80 mL/kg of isotonic saline, administered 15 minutes after the initiation of hemorrhage. Blood loss volume and survival time were recorded, and animals were observed up to 360 minutes. RESULTS: At 6 hours, nonresuscitated animals of all groups exhibited the highest mortality rates (93%, 73%, 100% in groups 1, 2, and 3, respectively). Resuscitation significantly improved the survival; lowest mortality rates were observed after resuscitation with 80 mL/kg in groups 1 and 3 (33%) and 40 mL/kg in group 2 (40%). Fluid infusion increased hemorrhage rates in all anesthetized rats. No such increases in bleeding were observed in group 1. CONCLUSIONS: Resuscitation with isotonic saline improved mortality in uncontrolled hemorrhage, even with concomitant increases in hemorrhage rates, under all three anesthetic conditions tested. Unanesthetized rats bled less than the animals under anesthesia and did not exhibit an increased blood loss in response to fluid infusion.

Anesthesia↗

PubMed2005

The effects of anesthetics on brain activity and cognitive function.

PURPOSE OF THIS REVIEW: This review presents an overview of recent findings related to changes in brain activity with increasing anesthesia mainly obtained with brain imaging and electrophysiological techniques in humans. RECENT FINDINGS: Recent studies have revealed that the brain as a whole is not affected to the same degree by anesthetics, but that specific brain regions (and particular cognitive processes mediated by these regions) are more sensitive to anesthesia and sedation than others. Inhibition of activity in multimodal association cortices (such as parietal and prefrontal association cortices) by sedative concentrations of anesthetics produces amnesia and attention deficits, whereas activity in unimodal cortices and in the thalamus remains largely unaffected by low doses of anesthetics. Activity in the midbrain reticular formation, thalamus, and unimodal cortices appears to be suppressed only by anesthetic concentrations causing unconsciousness. Besides those regional suppressive effects, anesthetics impair functional connections between neurons in distributed cortical and thalamocortical networks, which also contributes to the state of anesthesia. SUMMARY: Anesthetics produce changes in the patient's behavioral state by interacting with brain activity via at least two mechanisms: the dose-dependent global and regionally specific suppression of neuronal activity and the disruption of functional interactivity within distributed neural networks.

Journal Article↗

PubMed2003

Regional cerebral blood flow and BOLD responses in conscious and anesthetized rats under basal and hypercapnic conditions: implications for functional MRI studies.

Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level-dependent [BOLD]) were measured, using the continuous arterial-spin-labeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia (P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 +/- 0.25 and 1.27 +/- 0.29 mL. g-1. min-1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state (P < 0.01). Hypercapnia decreased pH, and increased Pco(2) and Po(2). During 5% CO(2) challenge, under awake and anesthetized conditions, respectively, CBF increased 51 +/- 11% and 25 +/- 4%, and BOLD increased 7.3 +/- 0.7% and 5.4 +/- 0.4%. During 10% CO(2) challenge, CBF increased 158 +/- 28% and 47 +/- 11%, and BOLD increased 12.5 +/- 0.9% and 7.2 +/- 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.

Anesthesia↗

PubMed1989

Effects of volatile anesthetics on cardiac calcium channels.

In order to investigate how volatile anesthetics affect cardiac calcium channels, the effects of halothane, enflurane, and isoflurane on the specific binding of [3H]-nitrendipine to bovine heart sarcolemmal membranes were studied. All three anesthetics added in liquid form inhibited [3H]-nitrendipine binding in a dose-dependent manner, and more interestingly, the order of inhibition by these volatile anesthetics roughly followed that of their anesthetic potencies. The partial pressures, calculated using the gas/water partition coefficients of halothane, enflurane, and isoflurane which inhibited [3H]-nitrendipine binding by 30% at 37 degrees C were about 1.48 x 10(-2) atm. (1.48%), 4.89 x 10(-2) atm. (4.89%) and 2.76 x 10(-2) atm. (2.76%), respectively. One mmol/l halothane altered not only the maximal binding (Bmax) from 189 f mol/mg protein to 136 f mol/mg protein, but also the dissociation constant (Kd) from 0.074 nmol/l to 0.18 nmol/l. Halothane was also added to the reaction mixture in the gaseous form with air. The partial pressure of halothane needed to bring about 30% inhibition was 0.82 x 10(-2) (0.82%), a value almost similar to that for halothane added in the liquid form. These results indicate that all three volatile anesthetics have direct effects on cardiac calcium channels, and that the magnitude of the effects depends on their anesthetic potencies.

Animals↗

PubMed1991

In vivo studies identify 5 alpha-pregnan-3 alpha-ol-20-one as an active anesthetic agent.

Mice were anesthetized with 5 alpha-[3H]pregnan-3 alpha-ol-20-one. Brain levels for 5 alpha-pregnan-3 alpha-ol-20-one and its five major metabolites (5 alpha-pregnanedione, k0, k1, k2, k3) were compared at behavioral endpoints that are characteristic of the anesthetized state. The results support the hypothesis that 5 alpha-pregnan-3 alpha-ol-20-one mediates the anesthetic response, and they weigh against the hypothesis that any of its metabolites is solely responsible for the onset or the maintenance of the anesthetized state. For an administered dose of 3 mg/kg, brain levels (means +/- SEM) for 5 alpha-pregnan-3 alpha-ol-20-one at the time of the loss of the righting response (n = 10) and at the time of the return of the righting response (n = 6) were 7.24 +/- 0.61 pmol/mg of brain tissue and 3.63 +/- 0.26 pmol/mg of brain tissue, respectively. No metabolite level was lower at the return of the righting response than at the loss of the righting response. 5 alpha-Pregnan-3 alpha-ol-20-one brain levels increased consistently with the percentage of anesthetized mice. This was not the case for any of the metabolites. Fifty percent of the mice were anesthetized when the 5 alpha-pregnan-3 alpha-ol-20-one level was 4.5 pmol/mg of brain tissue.

5-alpha-Dihydroprogesterone↗

PubMed1996

Maintenance of atrial fibrillation in anesthetized and unanesthetized sheep using cholinergic drive.

Atrial fibrillation (AF) was induced electrically and the duration of AF was measured in six isoflurane-anesthetized sheep (weight range 54.5-72.7 kg), and in five unanesthetized sheep (weight range 60-75 kg). In the anesthetized sheep, AF was induced by direct electrical stimulation of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostigmine (10 micrograms/kg IV) was administered and the duration of AF was again measured. Then cholinergic drive was increased by bilateral electrical vagal stimulation; AF was induced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF lasted 10 seconds, 11% lasted 20 seconds, and only 1% lasted 200 seconds. However, in one anesthetized animal AF was sustained for 4,800 seconds with no drug or vagal support. The administration of neostigmine alone in 3 anesthetized animals more than doubled the average duration of AF. In the animals with vagal stimulation (after neostigmine), AF persisted throughout stimulation, but ceased shortly after vagal stimulation was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequency ranged from 325-750/min. The unanesthetized sheep were lightly sedated with a small dose (200 micrograms/kg IM) of xylazine to make them less sensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 micrograms/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60-2,000 micrograms of phenylephrine. AF was electrically induced at the time of maximum reflex slowing in heart rate. For the control (no drug) studies, 64% of the AF episodes lasted 10 seconds, 20% lasted 20 seconds, and only 2% of the episodes lasted as long as 140 seconds. When phenylephrine was injected after neostigmine to provide increased cholinergic drive, the duration of fibrillation depended on the dose of phenylephrine. In a 60-kg sheep, the duration of AF increased from 1 second with an intravenous dose of 60 micrograms to 700 seconds with an intravenous dose of 2,000 micrograms. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by the intravenous phenylephrine; for example a single intravenous 500-micrograms dose produced AF ranging from 190-540 seconds among the sheep. The duration of AF was most controllable in the anesthetized sheep, following neostigmine administration and with bilateral vagal stimulation. In the unanesthetized sheep, AF could generally be sustained for more than the duration of the half-life (about 4 minutes) of phenylephrine following neostigmine. However, there was a large variation in the duration of AF among the animals for the same dose of phenylephrine. This study identifies two methods (direct vagal stimulation and reflex vagal stimulation) for providing the cholinergic drive needed to sustain AF in the adult sheep. The duration of AF is sufficiently long to enable the measurement of electrical atrial defibrillation threshold.

Anesthesia, General↗