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Overview movement as an index of anesthetic depth in humans and experimental animals.

Anesthesia is used widely in animal research, but there are diverse opinions regarding acceptable anesthetic depth. Excessive anesthesia is associated with increased morbidity and mortality. Traditionally, researchers have been taught that animal movement during surgical and experimental procedures indicates that the animal is 'underanesthetized.' Complex movement, however, can be initiated and propagated within the spinal cord, with little input from supraspinal structures. For example, frogs with high spinal-cord transections still maintain the wiping reflex, whereby the hindlimb can move to the forelimb to wipe away a noxious stimulus. Rats that have been decerebrated can perform complex tasks, such as grooming. Brain-dead humans can have spontaneous movement of the arms, legs, and head. Consistent with these phenomena, emerging evidence suggests that, in anesthetized animals, movement in response to noxious stimulation is abolished primarily via anesthetic action in the spinal cord. When isoflurane, halothane, or thiopental is delivered selectively to the brain circulation in goats, substantially greater anesthetic concentrations in brain are needed to ablate movement, as compared with those required upon delivery of anesthetic to the entire body. Rats that have had a precollicular decerebration require the same isoflurane concentrations to prevent movement as compared to intact rats. Furthermore, data from both humans and animals indicate that memory and awareness are ablated at anesthetic concentrations that are < 50% of those needed to abolish movement. Collectively, these data indicate that animals can be anesthetized at depths that, although they do not abolish movement, still produce unconsciousness and amnesia.

Amnesia↗

Automatic control of anesthetic delivery and ventilation during surgery.

Use of a closed rebreathing circuit for anesthesia delivery offers several advantages: conservation of anesthetic agent, natural heating and humidification of inspired gases, less pollution, and improved monitoring. However, the technique requires careful control of the fresh gas and anesthetic delivery. An anesthesia delivery system has been developed which automatically controls fresh gas delivery, anesthetic delivery, and ventilation in order to regulate circuit volume, oxygen concentration, end-tidal anesthetic concentration, and end-tidal PCO2. This system makes available the advantages of closed-circuit anesthesia without encumbering the anesthesiologist with its more demanding control tasks. The system has undergone clinical testing in adult surgical patients. Maintenance of circuit volume, oxygen concentration, end-tidal anesthetic concentration, and end-tidal PCO2 was achieved by the system in all patients but the first. The anesthetic delivery controller required tuning on the first patient. No further tuning was required for any of the other patients or controllers. During abdominal surgery, the end-tidal bellows position measurement and end-tidal anesthetic concentration measurement increased in variability. The cause of the variability and its elimination are discussed in the article.

Adult↗

Morphine effects on locus ceruleus neurons are dependent on the state of arousal and availability of external stimuli: studies in anesthetized and unanesthetized rats.

Because the physiological characteristics of noradrenergic locus ceruleus (LC) neurons differ in anesthetized and unanesthetized rats, the effects of morphine on LC activity recorded in both conditions were compared. Intracerebroventricular administration of morphine inhibited spontaneous LC discharge of both anesthetized and unanesthetized rats but morphine was at least 10 times more potent in anesthetized rats. In anesthetized rats LC discharge evoked by sciatic nerve stimulation was insensitive to doses of morphine (0.03 or 0.1 microgram) that inhibited LC spontaneous activity. Only the highest dose of morphine (0.3 microgram) which inhibited completely tonic activity decreased significantly evoked discharge. In parallel experiments in unanesthetized rats, the presentation of auditory stimuli evoked a pattern of LC discharge similar to that evoked by sciatic nerve stimulation in anesthetized rats. Morphine (1.0 and 3.0 micrograms) decreased both spontaneous and evoked activity in these rats; however, spontaneous LC discharge was more sensitive to morphine, as was observed with anesthetized rats. Quantitative analyses of these effects indicated that morphine tends to alter the pattern of LC discharge to sensory stimuli such that the signal-to-noise ratio (ratio of evoked/tonic activity during stimulus presentation) is increased. Morphine effects were reversed by naltrexone (1.0 mg/kg s.c.) in anesthetized rats and 1.0 microgram i.c.v. in unanesthetized rats. The present results indicate that the degree of arousal and the availability of environmental stimuli are important determinants of opiate effects on LC activity.

Anesthesia↗

Prolongation of the QT interval by volatile anesthetics in chronically instrumented dogs.

The influence of volatile anesthetics on ventricular repolarization in vivo (QT interval) has not been studied in a systematic fashion. The purpose of this investigation was to characterize the electrocardiographic and hemodynamic actions of the volatile anesthetics halothane, isoflurane, and enflurane in chronically instrumented dogs. Because autonomic nervous system tone may influence ECG findings, experiments were completed with and without concomitant pharmacologic autonomic nervous system blockade. In six groups comprising 50 experiments with 21 instrumented dogs, anesthesia was mask-induced with nitrous oxide, oxygen, and one of the volatile anesthetics and maintained with the volatile anesthetic in 100% oxygen for 2 hours. Changes in the ECG and in hemodynamics were compared to the conscious state. In the absence of autonomic nervous system blockade, halothane and isoflurane significantly prolonged the QT interval (0.24 +/- 0.01 to 0.30 +/- 0.01 second and 0.22 +/- 0.01 to 0.28 +/- 0.01 second, respectively), whereas enflurane produced no change in ventricular repolarization (0.24 +/- 0.01 to 0.26 +/- 0.01 second). All of the volatile anesthetics increased the QT interval corrected for changes in basal heart rate (QTc), and all agents decreased intravascular pressure and dP/dt. Following autonomic nervous system blockade, halothane, isoflurane, and enflurane significantly increased the QT interval and QTc. The results demonstrate that ventricular repolarization is directly altered by the volatile anesthetics independent of changes in autonomic nervous tone. Whether or not such effects are additive with other congenital or acquired forms of QTc prolongation has yet to be examined. The present results indicate that caution should be used during the administration of volatile anesthetics to patients with abnormalities of the QT interval.

Animals↗

Effect of age on the solubility of volatile anesthetics in human tissues.

To determine the effect of age on the solubility of volatile anesthetics in human tissues, the authors measured the solubilities of isoflurane, enflurane, halothane, and methoxyflurane in vitro at 37 degrees C in 35 postmortem human tissue specimens. Specimens were taken from neonates, and young (20-50 yr), middle-aged (50-70 yr), and elderly adults (greater than 70 yr). Brain/gas, heart/gas, and liver/gas partition coefficients for all four anesthetics increased significantly (P less than 0.05) between birth and adulthood, although brain/gas partition coefficients in young adults tended to be higher than those in middle-aged and elderly adults. Heart/gas and liver/gas partition coefficients tended to increase with aging. Muscle/gas partition coefficients for the four anesthetics increased linearly with age. Fat/gas partition coefficients did not change significantly with age. Tissue/blood solubilities for the four anesthetics were of the same order of magnitude for a given tissue and age group. Tissue/blood solubilities for enflurane were 30% lower than those for isoflurane in the same tissue and age group. In summary: the solubility of volatile anesthetics in human tissues increases with age; the lower solubility of anesthetics in neonates partially explains the more rapid increase of alveolar and tissue anesthetic partial pressures in neonates; despite the higher blood solubility of enflurane, its lower tissue solubility may explain a rate of recovery comparable with that of isoflurane.

Adipose Tissue↗

Renin response to hemorrhage in awake and anesthetized rats.

Anesthetic agents have been shown to alter survival in animals subjected to hemorrhage. Since survival after hemorrhage is increased by inhibitors of the renin-angiotensin system, we asked whether anesthetic agents altered renin release during hemorrhage. We studied 33 rats which were subjected to one hour of hemorrhagic hypotension at a mean arterial pressure of 40 mm Hg. Animals were either awake or anesthetized with halothane or ketamine. Anesthesia alone did not alter plasma renin activity (PRA), whereas hemorrhage resulted in approximately a ten-fold increase in PRA in both awake and anesthetized animals. After the shed blood was returned to the animal, intravenous saralasin, an angiotensin II competitive inhibitor, produced a 21-24 mm Hg decrease in blood pressure in all animals, regardless of the severe hemorrhage is unaltered by halothane or ketamine anesthesia, that the renin-angiotensin system provides a similar amount of blood pressure support in both awake and anesthetized animals, and that the anesthetic influence on survival following severe hemorrhage does not result from anesthetic-induced alterations of the renin-angiotensin system.

Animals↗

Enflurane and methoxyflurane metabolism at anesthetic and at subanesthetic concentrations.

In an attempt to determine the importance of concentration of an anesthetic agent as a determinant of the extent of its biotransformation, we measured fluoride excretion in groups of Fischer 344 rats treated with one of several subanesthetic or an anesthetic concentration (1 MAC) of either enflurane or methoxyflurane. Anesthetic administrations (2.0% enflurane or 0.26% methoxyflurane) ranged from 0.15 hours (9 minutes) to 4.8 hours. Subanesthetic exposures, all of 48 hours duration, ranged in concentration from 0.2% enflurane to 0.0016% methoxyflurane. Greatest metabolism occurred at the lowest concentration time (MAC-hours) of subanesthetic administrations and at the shortest duration of anesthetic exposure. Increasing time in the case of anesthetizing exposures, or concentration in subanesthetic exposures, increased the amount of metabolite produced. However, the increased production of metabolite was not proportional to the increase of concentration or duration of exposure. Enzyme induction was ruled out as an important factor in the larger amount of metabolism seen during the subanesthetic exposures. Therefore, the exposure of a patient to the metabolites of an anesthetic is actually low although the anesthetic is administered at a high concentration.

Anesthesia, Inhalation↗

An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion.

Aggregation induced in human platelets by thrombin (TH), collagen (COLL) or the Ca++ ionophore, A23187, was blocked by dibucaine and tetracaine. COLL-induced aggregation was blocked at lower concentrations of anesthetics (0.01-0.5 mM) than TH- or A23187-induced aggregation (0.2-2.0 mM). The rate and magnitude of the release of adenosine diphosphate, Ca++ and serotonin was also decreased by anesthetics. Secretion due to COLL, but not to TH, required extracellular Ca++ and was accompanied by increased uptake of 45Ca which was inhibited by local anesthetics. A23187-induced secretion was partially dependent upon external Ca++ and was accompanied by increased 45Ca uptake. Anesthetics increased 45Ca uptake when added before, but not after, A23187. This effect can be explained by postulating that the anesthetics prevent the release of an internal pool of Ca++, thereby affecting the Ca++ gradient between platelet cytoplasm and extracellular fluid. Platelets degramulated, but not aggregated, by exposure to TH in the presence of ethylene glycol bis(beta--aminoethyl ether)-N, N'-tetraacetic acid and plasmin were isolated by sepharose gel filtration. Such platelets did not aggregate with COLL or TH, but did aggregate with A23187-an effect blocked by local anesthetics. Thus platelet aggregation and secretion are independent Ca++-requiring processes, each of which is inhibitable by local anesthetics, presumable by blocking Ca++ influx or the mobilization of intracellular Ca++ stores.

Adenosine Diphosphate↗

Effect of temperature on volatile anesthetic depression of myocardial contractions.

Anesthetics are studied and used under conditions of hypothermia both experimentally and clinically. To determine if myocardial contractile depression by anesthetics is equivalent at different temperatures, depressant effects on guinea pig papillary muscle contractions were compared at 37 degrees C vs 30 degrees C. Stimulation after rest and at rates from 0.1 to 3 Hz was used. After control measurements were established at one temperature, effects due to equi-anesthetic concentrations (equivalent to approximately 0.9 minimum alveolar concentration) of halothane, isoflurane, or enflurane were determined, followed by recovery measurements. The same procedure was then applied at the other temperature. Hypothermia itself had positive inotropic effects: contractions at 30 degrees C developed about twice the tension as at 37 degrees C; the maximum rate of tension development (dT/dt-max) at 30 degrees C was about 50% greater than at 37 degrees C (1-3 Hz stimulation). When anesthetic contractile depression was assessed by the fractional decrease in dT/dt-max, the anesthetics were more depressant at 30 degrees C than at 37 degrees C, an effect which was most prominent at 0.5 Hz. In contrast to the anesthetics, 1 microM ryanodine which decreases sarcoplasmic reticulum (SR) Ca2+ release, and 0.1 microM nifedipine which decreases Ca2+ entry, both depressed dT/dt-max less at 30 degrees C than at 37 degrees C. Furthermore, ryanodine, nifedipine, and a decrease in external [Ca2+] all exhibited distinct rate-dependent contractile depression at 37 degrees C (typically greatest at 2-3 Hz) not seen with anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anesthetic technique influences brain temperature during cardiopulmonary bypass in dogs.

BACKGROUND: Because different anesthetics have different effects on cerebral blood flow and cerebral metabolism, we hypothesized that they also may have different effects on brain temperature during hypothermic cardiopulmonary bypass (CPB) and subsequent rewarming. METHODS: Sixteen dogs were anesthetized either with inhaled halothane, 1.0 minimum alveolar concentration (ie, an anesthetic that should increase cerebral blood flow and minimally affect cerebral metabolism; n = 8), or with intravenous high-dose pentobarbital (ie, an anesthetic that should reduce cerebral blood flow and cerebral metabolism by approximately one half; n = 8). Normocapnia (alpha-stat technique) and a blood pressure near 90 mm Hg were maintained. Thermistors were placed in the esophagus (ie, the body core), in the parietal epidural space, and in the parietal brain parenchyma at depths of 1 and 2 cm. Initially, all temperatures were controlled at 38.0 degrees +/- 0.2 degrees C (mean +/- standard deviation). Thereafter, atrial-femoral artery CPB was initiated, and after 15 minutes at 38 degrees C, the core temperature was decreased to 28 degrees C over approximately 21 minutes. After 30 minutes at 28 degrees C, the core temperature was returned to 38 degrees C over approximately 21 minutes and was maintained at 38 degrees C for the next 30 minutes. RESULTS: In halothane-anesthetized dogs, the mean brain-to-core temperature gradient always was 1.0 degrees C or less for all brain sites during all phases of CPB. In contrast, in pentobarbital-anesthetized dogs, the mean brain temperature during active cooling typically exceeded the core temperature by 1.7 degrees to 2.2 degrees C. This brain-to-core temperature gradient persisted into the period of stable hypothermia. During the rewarming phase of CPB, the mean brain temperature was 2.9 degrees to 3.4 degrees C cooler than the core temperature. This trend of relative cerebral hypothermia persisted well into the period in which the core temperature was 38 degrees C. CONCLUSIONS: Deep barbiturate anesthesia resulted in a brain-to-core temperature gradient during CPB that was of a magnitude greater than the 1 degrees C previously reported to modulate ischemic neurologic injury. We speculate that the timely administration of barbiturates (eg, during the latter stages of CPB) may be useful as part of a cerebroprotective regimen in humans undergoing CPB, in part because the barbiturates influence brain temperature.

Anesthesia↗

An isothermal titration calorimetry study on the binding of four volatile general anesthetics to the hydrophobic core of a four-alpha-helix bundle protein.

A molecular understanding of volatile anesthetic mechanisms of action will require structural descriptions of anesthetic-protein complexes. Previous work has demonstrated that the halogenated alkane volatile anesthetics halothane and chloroform bind to the hydrophobic core of the four-alpha-helix bundle (Aalpha(2)-L38M)(2) (Johansson et al., 2000, 2003). This study shows that the halogenated ether anesthetics isoflurane, sevoflurane, and enflurane are also bound to the hydrophobic core of the four-alpha-helix bundle, using isothermal titration calorimetry. Isoflurane and sevoflurane both bound to the four-alpha-helix bundle with K(d) values of 140 +/- 10 micro M, whereas enflurane bound with a K(d) value of 240 +/- 10 micro M. The DeltaH degrees values associated with isoflurane, sevoflurane, and enflurane binding were -7.7 +/- 0.1 kcal/mol, -8.2 +/- 0.2 kcal/mol, and -7.2 +/- 0.1 kcal/mol, respectively. The DeltaS degrees values accompanying isoflurane, sevoflurane, and enflurane binding were -8.5 cal/mol K, -10.4 cal/mol K, and -8.0 cal/mol K, respectively. The results indicate that the hydrophobic core of (Aalpha(2)-L38M)(2) is able to accommodate three modern ether anesthetics with K(d) values that approximate their clinical EC(50) values. The DeltaH degrees values point to the importance of polar interactions for volatile general anesthetic binding, and suggest that hydrogen bonding to the ether oxygens may be operative.

Anesthetics, General↗

Age and anesthetic effects on murine electrocardiography.

Murine models offer potential insights regarding human cardiac disease, but efficient and reliable methods for phenotype evaluation are necessary. We employed non-invasive electrocardiography (ECG) in mice, investigating statistical reliability of these parameters with respect to anesthetic and animal age. Mice (C57BL/6, 8 or 48 weeks) were anesthetized by ketamine/xylazine (K/X, 80/10 mg/kg ip) or by inhalation anesthetic (halothane, HAL; sevoflurane, SEV) and 6 lead ECGs were recorded. P wave duration and QT interval was significantly prolonged with K/X compared to HAL and SEV, indicating slowed atrial and ventricular conduction. P-R interval (atrio-ventricular conduction) was significantly increased in aged mice under all anesthetics. Heart rate was inversely correlated to QT interval and P wave duration. We also detected significant age effects with respect to optimal approaches for QT interval corrections. Power analysis showed 4-fold higher number of mice/group, were required for K/X, to achieve identical statistical sensitivity. These data demonstrate the importance of anesthetic selection for relevant and reliable ECG analysis in mice and illustrate the selective influences of anesthetics and age on cardiac conductance in this species.

Aging↗

GABAergic mechanisms in the action of general anesthetics.

1. The effects of volatile and intravenous anesthetics were studied on evoked field potentials in rat hippocampal CA1 neurons in vitro to determine the role of GABAergic mechanisms in the action of general anesthetics. 2. It was observed that both volatile (halothane, isoflurane, sevoflurane) and intravenous (thiopental, pentobarbital, propofol) anesthetics decreased population spike (PS) amplitudes. 3. Using paired-pulse paradigms, it was revealed that volatile agents enhance paired-pulse facilitation (PPF), and intravenous agents reduce PPF. Use-dependent effects on PS amplitudes were observed following application of the intravenous anesthetics, whereas volatile agents did not show use-dependency. The effects of the intravenous anesthetics were blocked by the GABA(A) receptor antagonist, bicuculline. 4. It is suggested that agent specific actions of general anesthetics are a result of differential effects on GABAergic mechanisms that modulate synaptic transmission.

Anesthetics, General↗

Ultrasonic localization of anesthetic fluid in sub-Tenon's, peribulbar, and retrobulbar techniques.

PURPOSE: To determine the distribution of anesthetic fluid during 3 regional anesthetic techniques routinely used for phacoemulsification. METHODS: Patients having routine cataract extraction by phacoemulsification were studied after informed consent had been obtained. B-scan ultrasonography was performed on the eye before administration of the anesthetic agent. Kinetic echography was used to scan the eye during administration of the anesthesia to show the needle position and location of fluid in the orbit during the injection. Ten minutes after injection, another scan was performed to outline the pattern of fluid distribution. RESULTS: In all patients, the needle and the anesthetic fluid were seen on ultrasonography, with sub-Tenon's the most easily seen. In the sub-Tenon's group, fluid tracked behind the globe in the retrobulbar space, appearing as a dark outline during the injection. The fluid around the optic nerve developed a characteristic T sign. In the retrobulbar technique, the needle was less easily identifiable and fluid localized within the cone. The fluid distributed in the intraconal fat. Identification of the peribulbar needle and fluid was also more difficult; the fluid was, however, seen in the extraconal fat. After 10 minutes, fluid was seen within the cone. CONCLUSION: B-scan ultrasonography was a suitable method of identifying the needle position and the distribution of anesthetic fluid in regional ocular anesthesia. The sub-Tenon's technique appears to be the safest method of introducing anesthetic fluid into the retrobulbar space without the potential complications of sharp-needle techniques.

Anesthesia, Local↗

Functional MRI as a tool to assess vision in dogs: the optimal anesthetic.

Functional magnetic resonance imaging (fMRI) is a recent advance in neuroimaging that provides a picture of brain activity with excellent spatial resolution. Current methods used to evaluate canine vision are poorly standardized and vulnerable to bias. Functional MRI may represent a valuable method of testing vision in dogs if the impacts of anesthesia on fMRI are understood. Six dogs were scanned during visual stimulation, each under three different anesthetic protocols (isoflurane, propofol, fentanyl/midazolam) to address the questions: (1) Can visually evoked fMR signals be reliably recorded in anesthetized dogs? and (2) Which anesthetic agent permits the least suppression of visually induced fMR signal in dogs? This study confirms that visual stimuli reliably elicit neural activity and fMR signal change in anesthetized dogs. No significant differences in images acquired under the three anesthetics were found, and there was no significant relationship between anesthetic dose and brain activity, within the range of doses used in this study. Images obtained during isoflurane anesthesia were more consistent between dogs than those obtained with the other two agents. This reduced variation may reflect the fact that inhalant anesthesia is more easily controlled than intravenous anesthesia under conditions associated with high field fMRI.

Anesthesia↗

Myocardial damage prevented by volatile anesthetics: a multicenter randomized controlled study.

OBJECTIVE: The purpose of this study was to evaluate the effects of volatile anesthesia versus total intravenous anesthesia on cardiac troponin release in off-pump coronary artery bypass grafting (OPCAB). DESIGN: The authors performed a multicenter randomized controlled study to compare cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for cardiac surgery on the beating heart, which is an excellent model of human myocardial ischemia. SETTING: Three university hospitals. PARTICIPANTS: The authors randomly assigned 57 patients to desflurane (volatile anesthetic) and 55 patients to propofol (intravenous anesthetic) in addition to an opiate-based anesthesia for OPCAB. INTERVENTIONS: The 2 groups of patients received either desflurane (volatile anesthetic) or propofol in addition to an opiate-based anesthesia for OPCAB. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. Prolonged hospitalization was considered as a secondary outcome. MEASUREMENTS AND MAIN RESULTS: Patient mean age was 69 years, and 82% were men. There was a significant (p < 0.001) reduction in postoperative median (25th-75th percentiles) peak of troponin I in patients receiving volatile anesthetics, 1.2 (0.9-1.9) ng/dL, compared with patients receiving total intravenous anesthesia, 2.7 (2.1-4.0) ng/dL. This myocardial protection resulted in a reduced (p = 0.04) number (percentage) of patients requiring postoperative inotropes, 20 (35%) versus 31 (56%), and a reduced number (percentage) of patients submitted to prolonged hospitalization (> or =7 days), 7 (12%) versus 20 (36%) in the 2 groups (p = 0.005). One patient receiving total intravenous anesthesia died within 30 days of surgery. CONCLUSIONS: Myocardial damage measured by cardiac troponin release could be reduced by volatile anesthetics during OPCAB. Because patients underwent cardiac surgery on the beating heart, these results could have implications for cardiac patients undergoing noncardiac surgery.

Aged↗

A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation.

General anesthetics allosterically modulate the activity of neuronal gamma-aminobutyric acid, type A (GABAA), receptors. Previous mutational studies from our laboratory and others have shown that the regions in transmembrane domain 1 (M1) and pre-M1 of alpha and beta subunits in GABA receptors are essential for positive modulation of GABA binding and function by the intravenous (IV) general anesthetics. Mutation of beta2Gly-219 to Phe corresponded in rho nearly eliminated the modulatory effect of IV anesthetics in alpha1/beta2/gamma2S combination. However, the general anesthetics retained the ability to directly open the channel of mutant G219F, and the apparent affinity for GABA was increased, and desensitization rate was reduced. In this study, we made additional single mutations such as 219 Ser, Cys, Ile, Asp, Arg, Tyr, and Trp. The larger side chains of the replacement residues produced the greatest reduction in enhancement of GABA currents by IV anesthetics at clinical concentrations (Trp > Tyr = Phe > Arg > Asp > Ile > Cys > Ser = wild type). Compared with a 2-3-fold response in wild type, pentobarbital and propofol enhanced less than 0.5-fold; etomidate and alphaxalone modulation was reduced from more than 4- to 1-fold in G219F, G219Y, and G219W. A linear correlation was observed between the volume of the residue at position 219 and the loss of modulation. An identical correlation was found for the effect of modulation on left-shift in the GABA EC50 value; furthermore, the same rank order of residues, related to size, was found for reduction in the maximal direct channel-gating by pentobarbital (1 mm) and etomidate (100 mum) and for increased apparent affinity for direct gating by the IV anesthetics.

Adjuvants, Anesthesia↗

Pre- versus postinjury effects of intravenous GABAergic anesthetics on formalin-induced Fos immunoreactivity in the rat spinal cord.

UNLABELLED: We evaluated the suppression of spinal Fos-like immunoreactivity (FLI) by i.v. anesthetics in the rat formalin model. Preformalin injection (1.5% subcutaneously) treatment groups included i.v. saline controls and three i.v. GABAergic anesthetic groups (pentobarbital 20 mg/kg, propofol 10 mg/kg, or alphaxalone 1.5 mg/kg; n = 12 per group). After perfusion 2 h postformalin, spinal cords were dissected, sliced at 30 microm, and processed by immunoperoxidase staining with an antibody against the Fos protein. Quantification and determination of the laminar distribution of Fos-labeled nuclei were performed at the L4-5 spinal level ipsilateral to formalin injection. Drug groups demonstrating FLI suppression were comparatively studied in a 5-min postformalin treatment group. Pentobarbital pretreatment failed to suppress FLI. However, significant reductions (percent decrease) of FLI were observed with propofol (63%) and alphaxalone (30%) compared with saline controls. Pre- versus postformalin comparison studies showed that propofol, but not alphaxalone, suppressed FLI more effectively when given preformalin. Given the observed inconsistencies between this study of Fos expression and our previous behavioral study, it is questionable whether anesthetic modulation of noxious stimulus-induced FLI parallels that of behavioral responses. IMPLICATIONS: In this study, we examined whether i.v. general anesthetics (propofol, alphaxalone, and pentobarbital) prevent injury-induced spinal cord changes. We measured spinal Fos protein after rats received anesthetics before versus after a formalin injection. Fos inhibition patterns were inconsistent with behavioral studies of these anesthetics, suggesting that Fos inhibition does not always correlate with behavioral analgesia.

Adjuvants, Anesthesia↗