PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “ANESTHETICS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

Neurotoxicity of local anesthetics: animal data.

OBJECTIVE: To extract experimental data of importance for the understanding of neurotoxicity of local anesthetics, with special reference to continuous spinal anesthesia. METHODS: Literature on clinical experience of and experimental studies on neurotoxic complications of local anesthetics, especially concerning spinal and continuous spinal anesthesia and long-term peripheral nerve block, was reviewed. The overall incidence of neural complications of central and peripheral nerve blocks was extracted, and the results of animal experimental studies on neurotoxicity of local anesthetics were used to characterize the possible mechanisms behind such complications. RESULTS: Persistent neurologic complications of regional anesthesia varied from 0 to 0.09% for central blockades and from 0 to more than 5% for brachial plexus blocks, depending on the technique used. All local anesthetics seem to be involved in clinical reports of neural complications. Experimental studies indicate that all local anesthetics are potentially neurotoxic and that the neurotoxicity parallels their anesthetic potency. In fact, the nerve conduction block may be an expression of a reversible toxic effect of the local anesthetic (LA). The mechanism is not completely understood, but factors of importance are the concentration of the LA and time of exposure of the neural tissue to the LA. Contributing factors are neural trauma and ischemia, both of which may be deleterious by themselves. CONCLUSIONS: Correctly administered LAs of clinical concentration are safe, but animal data indicate that all LAs are potentially neurotoxic. The neurotoxicity seems to be a function of the concentration of the LA and the time of exposure of the nervous tissue to the LA. Concomitant neural trauma, ischemia, or both, may potentiate the neurotoxic effect of the LA.

Anesthetics, Local↗

Ethanol as a general anesthetic: actions in spinal cord.

Ethanol, usually studied in relation to intoxication, is also capable of producing general anesthesia. The most common standard of anesthetic potency is the concentration which produces immobility in response to a noxious stimulus. This concentration will be referred to as the anesthetic concentration. Immobilization is a spinal effect. Ethanol effects were studied in spinal cord from 2-7-day-old rats at concentrations which included the anesthetic concentration in both adult rats (97 mM) and 6-7-day-old rats (235 mM). At neonatal but not adult anesthetic concentrations, ethanol depressed monosynaptic reflex amplitude (mediated by glutamate AMPA receptors + compound action potential). At both neonatal and adult anesthetic concentrations ethanol reversibly depressed the population excitatory postsynaptic potential (pEPSP) (glutamate AMPA and NMDA receptors), the slow ventral root potential (NMDA + metabotropic receptors), and the dorsal root potential (GABA(A) receptors, via glutamate-excited interneurons). Effects were greater on NMDA receptor-mediated components than on AMPA-receptor-mediated components of the pEPSP and greater on NMDA than on metabotropic receptor-mediated components of the slow ventral root potential. The profile of ethanol effects on spinal cord resembles that of inhalation general anesthetics. The results show that both AMPA and NMDA receptor-mediated transmission are sensitive to ethanol and that enhancement of GABAergic neurotransmission is overridden by depression of excitation to the interneurons. They provide no obvious explanation for ethanol's lower general anesthetic potency in the neonate.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

[Mechanism of action of general anesthetics. Effect on ion channel proteins or on membrane phospholipids?].

General anesthesia is defined by reversible unconsciousness, lack of response to noxious stimuli, and amnesia, induced by chemical agents. Mechanisms underlying the anesthetic effect are not known. The most prevalent belief was that anesthetic drugs acted on the lipid cell membranes, based on the correlation between oil solubility and anesthetic potency. Later, it has been proposed that anesthetic agents act on specific proteins of the cellular membrane of neurons. Voltage-gated ionic channels are inhibited by anesthetic agents, being some subtypes more sensitive. Clinical concentration of anesthetic agents inhibit or stimulate excitatory or inhibitory neurotransmitter receptors, respectively. Specific receptor agonists and antagonists modify this effect. Intercellular channels (gap junctions) are also affected by anesthetic agents through direct interaction with some of their protein subunits. Thus, anesthesia would result from combined effects on specific proteins acting on neural cell excitability as well as transmission and propagation of nerve impulses.

Anesthetics, General↗

Densities of dextrose-free intrathecal local anesthetics, opioids, and combinations measured at 37 degrees C.

Dextrose-free anesthetic medications are commonly used to provide subarachnoid anesthesia and analgesia. Hypobaricity has been proposed as a mechanism to explain postural effects on the extent of sensory block produced by these drugs. Densities of dextrose-free solutions of local anesthetics and opioids, and commonly used anesthetic/opioid mixtures were determined at 37.00 degrees C for comparison with the density of human cerebrospinal fluid (CSF). Measurements accurate to 0.00001 g/mL were performed using a mechanical oscillation resonance frequency density meter. All undiluted solutions tested are hypobaric relative to human lumbar CSF with the exception of lidocaine 1.5% and 2.0% with epinephrine 1:200,000. All mixtures of local anesthetics and opioids tested are hypobaric. We observed good agreement between measured densities and calculated weighted average densities of anesthetic mixtures. While the influence of baricity on the clinical effects of dextrose-free intrathecal anesthetics remains controversial, attempts to attribute postural effects to the baricity of these drugs requires establishment of accurate density values. These density data may facilitate elucidation of the mechanisms underlying the behavior of dextrose-free intrathecal anesthetics.

Analgesics, Opioid↗

Potent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics.

The tandem pore domain K channel family mediates background K currents present in excitable cells. Currents passed by certain members of the family are enhanced by volatile anesthetics, thus suggesting a novel mechanism of anesthesia. The newest member of the family, termed TRESK (TWIK [tandem pore domain weak inward rectifying channel]-related spinal cord K channel), has not been studied for anesthetic sensitivity. We isolated the coding sequence for TRESK from human spinal cord RNA and functionally expressed it in Xenopus oocytes and transfected COS-7 cells. With both whole-cell voltage-clamp and patch-clamp recording, TRESK currents increased up to three-fold by clinical concentrations of isoflurane, halothane, sevoflurane, and desflurane. Nonanesthetics (nonimmobilizers) had no effect on TRESK. Various IV anesthetics, including etomidate, thiopental, and propofol, have a minimal effect on TRESK currents. Amide and ester local anesthetics inhibit TRESK in a concentration-dependent manner but at concentrations generally larger than those that inhibit other tandem pore domain K channels. We also determined that TRESK is found not only in spinal cord, but also in human brain RNA. These results identify TRESK as a target of volatile anesthetics and suggest a role for this background K channel in mediating the effects of inhaled anesthetics in the central nervous system.

Anesthetics, Inhalation↗

[Cardioprotection by anesthetics].

Perioperative myocardial ischemia is one of the most important complications associated with significant risk of perioperative cardiac event. Ischemic preconditioning is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the myocardium against a more prolonged ischemic insult, the result of which is a marked reduction in myocardial infarct size, severity of myocardial stunning, or incidence of cardiac arrhythmias. Myocardial stunning is a clinically important ischemia-reperfusion injury described as a prolonged postischemic contractile dysfunction of myocardium salvaged by reperfusion. Experimental data indicate that general anesthetics protect the myocardium against ischemia-reperfusion injury, as shown by decreased infarct size and a more rapid recovery of contractile function on myocardial stunning. This phenomenon is called anesthetic preconditioning. Volatile anesthetics and morphine have a strong preconditioning like effect. The cardioprotective effect of volatile anesthetics has been supported by some clinical studies. Although the cellular mechanism of anesthetic preconditioning is not fully investigated, possible mechanism involves adenosine, adenosine receptors, the ATP-dependent potassium (K(ATP)) channels, protein kinase C, reactive oxygen species and other mediators or substances. Further, mitochondrial K(ATP) channels play the central role in anesthetic preconditioning.

Anesthetics, General↗

Inhibition of anion and glucose permeabilities by anesthetics in erythrocytes. The mechanisms of action of positively and negatively charged drugs.

(1) The mode of action of anesthetics as inhibitors of Cl- and glucose transports in human red cells was studied. The term anesthetic is taken in its broad meaning as defined by Seeman (Seeman, P. (1972) Pharmacol. Rev. 24, 583-655) and covers anionic and cationic liposoluble compounds which reversibly block the rising phase of the action potential, without effect on the resting membrane potential. (2) Phenothiazine derivatives were chosen as prototypes of anesthetics because they represent a set of compounds having the same basic chemical structure, the phenothiazine ring, but with either a positive or a negative charge. (3) The Cl- self-exchange is inhibited by both cationic and anionic derivatives. However, to obtain the same level of inhibition, it is necessary to use a concentration 10-100 times higher with cationic than with anionic drugs. (4) At a concentration which inhibits Cl- permeability, cationic derivatives induce a very strong morphological change (cup-shaped cells: stomatocytes or spherostomatocytes) and protect erythrocytes against osmotic hemolysis, signifying that the membrane is fully expanded. Conversely, with anionic derivatives, inhibition occurs at a concentration which does not induce any apparent shape change or protect against osmotic hemolysis: there is no significant membrane expansion. (5) Glucose permeability, measured by glucose exit, is inhibited by cationic and anionic phenothiazine, but always at a concentration which fully expands the membrane as indicated by morphological changes and anti-hemolytic effects. It is interesting to point out that whilst glucose exit shows inhibition by cationic derivatives, glucose exchange flux is scarcely altered. (6) It is concluded that cationic and anionic anesthetics are general inhibitors of transmembrane solute movements involving a facilitated-diffusion process. However, the mechanism of inhibition is not identical for all: inhibition of glucose permeability by anionic and cationic anesthetics, as well as inhibition of Cl- permeability by cationic anesthetics may be of a non-specific nature and result from their interaction with the bilayer (this indirect effect is discussed); on the other hand, inhibition of Cl- permeability by anionic anesthetics may result from a specific perturbation of the transport mechanism according to recent evidence in some cases (Cousin, J.L. and Motais, R. (1979) J. Membrane Biol. 46, 125-153; Zaki, L., Ruffing, W. Gärtner, E.M., Fasold, H., Motais, R. and Passow, H. (1977) 11th FEBS Meeting, Copenhagen, A4 17-671.

Anions↗

Age, strain and anesthetic dependent differences in the nociceptive responses produced by i.v. 5-HT in the rat.

The intravenous (i.v.) administration of serotonin (5-HT) to rats is a noxious visceral stimulus which produces distinct vagal afferent-mediated pseudaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the tail-flick (TF) reflex and a complex cardiovascular response. In the present study, we examined the effects of age (10 or 16 weeks), strain (Sprague-Dawley, SD; Wistar-Kyoto, WKY; spontaneously hypertensive rats, SHR) and anesthetic (conscious or lightly pentobarbital-anesthetized) on nociceptive (TF reflex and pseudaffective responses) and cardiovascular responses produced by 5-HT (3-288 micrograms/kg, i.v.). There were no age-related differences in baseline TF latencies in the 3 strains. Further, latencies were generally not significantly different whether rats were tested conscious or lightly anesthetized. There were, however, strain differences. Both conscious or lightly pentobarbital-anesthetized SHR and WKY rats at 10 weeks of age had significantly faster response latencies than 10 week old SD rats. At 16 weeks of age, only the lightly pentobarbital-anesthetized WKY and SHR showed faster response latencies than SD rats. The WKY and SHR, but not the SD rats, were more sensitive to the nociceptive effect of i.v. 5-HT at 16 weeks of age compared to 10 weeks of age. At both ages, WKY and SHR, but not SD rats, showed an anesthetic-dependent increase in nociceptive sensitivity to i.v. 5-HT. In addition, at both ages, regardless of the presence of anesthetic, the order of sensitivity to the nociceptive effects of i.v. 5-HT was SD greater than WKY much much greater than SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Muscle atonia can be induced by carbachol injections into the nucleus pontis oralis in cats anesthetized with alpha-chloralose.

Cholinergic excitation of structures in the pontine reticular formation appears to be a key step in the generation of active sleep. For example, muscle atonia which occurs as a result of the postsynaptic inhibition of motoneurons during active sleep is also present after carbachol, a cholinergic agonist, is injected into the nucleus pontis oralis. In the present study, in order to obtain information regarding the mechanisms that generate atonia during active sleep and to provide a paradigm for studying atonia in anesthetized cats, we determined whether cholinergically induced atonia could be generated in an animal that was anesthetized with alpha-chloralose. Cats which were initially anesthetized with alpha-chloralose (40 mg/kg, I.V.) exhibited spikes in the EEG, hippocampus and lateral geniculate nuclei. Muscle atonia occurred after carbachol (200 mM) was injected by microiontophoresis (300-500 nA) into the nucleus pontis oralis; the spikes in the EEG, hippocampus and lateral geniculate nuclei were still present. We believe that the atonia induced by carbachol in alpha-chloralose-anesthetized cats is mediated by the same mechanisms that operate during active sleep in the unanesthetized animal for the following reasons. First, in the same cats when they were not anesthetized with alpha-chloralose, carbachol injections in the identical brainstem sites induced active sleep with its accompanying pattern of muscle atonia. Second, after carbachol was injected into the same sites in alpha-chloralose-anesthetized cats, intracellular recordings from lumbar motoneurons revealed that inhibitory postsynaptic potentials were bombarding motoneurons; these inhibitory potentials were similar to those which are present during naturally occurring active sleep. In addition, stimulation of the nucleus reticularis gigantocellularis (NRGc) was found to induce large amplitude depolarizing potentials in lumbar motoneurons in alpha-chloralose-anesthetized cats prior to the administration of carbachol, whereas after its administration, accompanying muscle atonia there were large amplitude hyperpolarizing potentials and a reduction in the amplitude of depolarizing potentials. We therefore conclude that the cholinergically induced processes that initiate and maintain muscle atonia are not blocked by the actions of alpha-chloralose.

Animals↗

Frequency of anesthetic cardiac arrests in infants: effect of pediatric anesthesiologists.

STUDY OBJECTIVE: To determine whether the presence of pediatric anesthesiologists decreases the frequency of anesthetic-related cardiac arrests in infants (children who are 1 year of age or younger). DESIGN: A comparative retrospective study of anesthetics and cardiac arrests during a 7-year period. SETTING: The main operating room (OR) suite of a large university hospital. PATIENTS: All patients age 1 year or less undergoing surgical anesthesia from July 1983 through March 1990. INTERVENTIONS: Computerized anesthetic and operative patients records were queried for patient age, ASA physical status, body weight, surgical procedure, intraoperative complications, and the identity of the attending anesthesiologist. In each case, it was determined whether a pediatric anesthesiologist was in attendance and whether a cardiac arrest due to anesthesia occurred. Pediatric anesthesiologists were identified as those with pediatric fellowship training or the equivalent. The study population was divided into two groups: (1) the pediatric anesthesiologist group, with 2,310 patients whose anesthetics were supervised by pediatric anesthesiologists; (2) the nonpediatric anesthesiologist group, with 2,033 patients. MEASUREMENTS AND MAIN RESULTS: Mean age and weight were comparable in the two groups, and the distribution of physical status did not differ. No anesthesia-related cardiac arrests occurred in the pediatric anesthesiologist group; four anesthetic cardiac arrests occurred in the nonpediatric anesthesiologist group, for a frequency of 19.7 per 10,000 anesthetics. This difference between provider groups is significant (Fisher's exact probability test, p = 0.048). CONCLUSIONS: The results suggest that the use of pediatric anesthesiologists for all infants 1 year of age or younger might decrease anesthetic morbidity in this age-group.

Anesthesia↗

Frequency of anesthetic cardiac arrest and death in the operating room at a single general hospital over a 30-year period.

STUDY OBJECTIVES: To determine the anesthetic cardiac arrest (CA) and death rates in the operating room (OR) and to determine whether anesthetic CA and death are preventable. DESIGN: Prospective study. SETTING: OR suite of a general teaching hospital. PATIENTS: 85,708 patients undergoing surgery over a 30-year period. MEASUREMENTS AND MAIN RESULTS: Anesthetic CAs and deaths were identified, their causes and preventability were determined on the day of occurrence, and they were recorded over the years 1962 to 1992. Four anesthetic CAs (0.5 arrest per 10,000 anesthetics) and 1 death (0.1 death per 10,000 anesthetics) occurred during the 30-year study period. CONCLUSIONS: The results of 30 years' experience do not support the hypothesis that all anesthetic CAs and deaths are preventable. However, careful clinical management can reduce their frequency to a level lower than those reported in the referenced literature.

Adolescent↗

Modification of cardiac Na+ channels by batrachotoxin: effects on gating, kinetics, and local anesthetic binding.

The purpose of the present study was to examine the characteristics of Na+ channel modification by batrachotoxin (BTX) in cardiac cells, including changes in channel gating and kinetics as well as susceptibility to block by local anesthetic agents. We used the whole cell configuration of the patch clamp technique to measure Na+ current in guinea pig myocytes. Extracellular Na+ concentration and temperature were lowered (5-10 mM, 17 degrees C) in order to maintain good voltage control. Our results demonstrated that 1) BTX modifies cardiac INa, causing a substantial steady-state (noninactivating) component of INa, 2) modification of cardiac Na+ channels by BTX shifts activation to more negative potentials and reduces both maximal gNa and selectivity for Na+; 3) binding of BTX to its receptor in the cardiac Na+ channel reduces the affinity of local anesthetics for their binding site; and 4) BTX-modified channels show use-dependent block by local anesthetics. The reduced blocking potency of local anesthetics for BTX-modified Na+ channels probably results from an allosteric interaction between BTX and local anesthetics for their respective binding sites in the Na+ channel. Our observations that use-dependent block by local anesthetics persists in BTX-modified Na+ channels suggest that this form of extra block can occur in the virtual absence of the inactivated state. Thus, the development of use-dependent block appears to rely primarily on local anesthetic binding to activated Na+ channels under these conditions.

Animals↗

The influence of anesthetic technique on perioperative complications after carotid endarterectomy.

PURPOSE: This study evaluated the influence of anesthetic techniques on perioperative complications after carotid endarterectomy. METHODS: Perioperative complications, the use of a carotid artery shunt, the duration of the operative procedure and postoperative hospital course were retrospectively compared in 584 consecutive patients undergoing 679 carotid endarterectomies with use of either general anesthesia (n = 361) or cervical block regional anesthesia (n = 318). There was no significant difference in the preoperative medical characteristics between the two anesthetic groups. Symptomatic carotid artery disease was the indication for surgery in 247 (68.4%) patients receiving general anesthetics, whereas 180 (56.6%) patients treated with a cervical block anesthetic had a symptomatic carotid artery stenosis (p = 0.02). RESULTS: The perioperative stroke rate and stroke-death rate for the entire series was 2.4% and 3.2%, respectively, and was not significantly different between the anesthetic groups or between patients with symptomatic or asymptomatic disease. A carotid artery shunt was used in 61 (19.2%) patients receiving a cervical block anesthetic and 152 (42.1%) patients treated with a general anesthetic (p < 0.0001). Use of cervical block anesthesia was associated with a significantly shorter operative time, fewer perioperative cardiopulmonary complications, and a shorter postoperative hospitalization when compared with general anesthesia. Multivariate risk factor analysis indicated that age greater than 75 years, operative time greater than 3 hours, and the use of a carotid artery shunt were all independent risk factors for perioperative cardiopulmonary complications. When a carotid artery shunt was not analyzed as a multivariate risk factor, then general anesthesia became a significant risk factor for perioperative cardiopulmonary complications (risk ratio 2.08; p = 0.04). CONCLUSIONS: We conclude that cervical block anesthesia is safer and results in a more efficient use of hospital resources than general anesthesia in the treatment of patients undergoing carotid endarterectomy.

Aged↗

Anesthetics and high-pressure interaction upon elastic properties of a polymer membrane.

Anesthetics expand cell membranes, and high pressures (about 10-15 MPa) antagonize the anesthetic action. It is also known that inhalation anesthetics expand elastomer membranes. The mechanism of pressure antagonism of anesthetic action on membrane expansion was investigated in the present study with Silastic membranes. Halothane increased the length of Silastic membrane (0.14% per kPa), with an accompanying decrease of Young's modulus (3.7.10(5) Newton/m2 per kPa). High pressure decreased the length of the membrane and increased Young's modulus. The magnitudes of the pressure effect on the length and Young's modulus of the Silastic membrane in the presence of the anesthetic were not identical with those observed in the absence of the anesthetic. In the presence of halothane at pressures common to clinical applications, the bulk modulus of the membrane decreased about 4.6-4.0%. These results suggest that the effects of pressure and anesthetic upon the elastomer may not be completely independent of each other.

Adsorption↗

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. II. Verapamil, enflurane, and isoflurane.

The effects of enflurane and isoflurane on the cardiovascular system and cellular calcium kinetics are somewhat different. Consequently, the interaction with the calcium channel blocking drug, verapamil, may also differ. In order to compare the anesthetics, the authors studied the effects of two infusion doses of verapamil (which produced plasma levels of 90 and 180 ng X ml-1) on cardiovascular dynamics and regional blood flow in awake dogs. On two other days, in the same dogs, the effects of approximately 1.1 and 2 MAC enflurane and isoflurane were first studied and then the same verapamil dose regimens while the same anesthetic concentrations were maintained. Verapamil produced only increases in heart rate and the P-R interval in the awake animal. The high dose of both anesthetics markedly decreased mean aortic pressure and left ventricular rate of tension development (dP/dt), and increased heart rate. However, only enflurane also decreased myocardial segment length shortening and increased left atrial pressure. Neither anesthetic alone affected coronary or renal blood flow, while both increased carotid blood flow at the low dose. Verapamil infusion during 1.2 MAC enflurane was more depressant than during 1.2 MAC isoflurane, but the combination of verapamil with 2 MAC concentration of both anesthetics was equally depressant. Both doses of both anesthetics increased plasma verapamil levels compared with the same verapamil dosing regimen awake. When these results are compared with those previously reported for halothane, the effects of verapamil during all three anesthetics are more similar than different.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Endotracheal↗

Prostaglandin-related microvascular dilation in pentobarbital- and etomidate-anesthetized rats.

Etomidate is characterized by minimal systemic cardiovascular effects, but its effect on the microvasculature has not been assessed. We compared the microvasculature of etomidate-anesthetized animals to that of animals anesthetized with pentobarbital, since its effects on the microvasculature are known. Male Sprague-Dawley rats were anesthetized with etomidate or pentobarbital. The cremaster muscle was prepared for microscopic viewing, leaving the neural and vascular supply intact. Small arterioles were near their maximal diameters in etomidate-anesthetized rats, whereas the pentobarbital group had a large dilator capacity (maximal diameter-basal diameter/basal diameter). The effect on resting arteriolar diameters of endothelium-derived relaxing factor (EDRF) and prostaglandin synthesis inhibitors was tested. Dilator capacity was not affected by the EDRF inhibitor nitro-L-arginine, but it was significantly increased by mefenamic acid and ibuprofen in etomidate-anesthetized animals. To test whether dilator and constrictor mechanisms were normal, serotonin concentration-response curves were obtained in pentobarbital and etomidate-anesthetized animals with and without mefenamate or ibuprofen present. The dilation of small arterioles to serotonin in the etomidate groups with mefenamate or ibuprofen was not significantly different from that of the pentobarbital groups. Serotonin produced a comparable constriction of large arterioles in both anesthetic groups. The topical application of etomidate to the cremaster muscle did not affect arteriolar diameters. Thus, etomidate appears to trigger the release of dilator prostaglandins in striated muscle through a central or indirect mechanism.

Anesthesia, Intravenous↗

Reversal of volatile anesthetic-induced depression of myocardial contractility by extracellular calcium also enhances left ventricular diastolic function.

BACKGROUND: Volatile anesthetics depress global left ventricular function by altering intracellular calcium (Ca2+) homeostasis at several sites within the myocyte. Although extracellular Ca2+ partially reverses the negative inotropic effects of volatile anesthetics, the actions of extracellular Ca2+ on anesthetic-induced diastolic dysfunction are unexplored. This investigation examined and compared the direct effects of extracellular Ca2+ on left ventricular systolic and diastolic function in conscious and anesthetized dogs. METHODS: Experiments were conducted in the presence of pharmacologic blockade of the autonomic nervous system because autonomic nervous activity may significantly influence the hemodynamic actions of anesthetics and Ca2+ in vivo. Three groups comprised a total of 27 experiments conducted using nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dt, subendocardial segment length, and cardiac output. Myocardial contractility was evaluated using the preload recruitable stroke work relationship slope (Mw). Diastolic function was assessed using a time constant of isovolumic relaxation (tau), a regional chamber stiffness constant (Kp), and maximum segment lengthening velocity during rapid ventricular filling (dL/dtE) and atrial systole (dL/dtA). On 3 separate days, a CaCl2 infusion at 1.25, 2.5, or 5 mg.kg-1 x min-1 was administered. Hemodynamics and ventricular pressure-length loops were recorded after a 20-min equilibration at each dose in the conscious state or during halothane or isoflurane anesthesia. RESULTS: In conscious dogs, CaCl2 produced a significant (P < .05) and dose-dependent increase in contractility as evaluated by Mw. In the presence of halothane anesthesia, CaCl2 increased contractility (Mw of 26 +/- 5 mmHg to 78 +/- 10 mmHg during the high dose of CaCl2), enhanced isovolumic relaxation (tau of 57.9 +/- 4.2 ms to 41.1 +/- 1.9 ms during the high dose of CaCl2), improved rapid ventricular filling (dL/dtE of 11.8 +/- 1.4 mm/s to 20.2 +/- 1.6 mm/s during the high dose of CaCl2), and reduced regional chamber stiffness (Kp of 0.70 +/- 0.18 mm-1 to 0.38 +/- 0.04 mm-1 during the high dose of CaCl2). Similar findings were observed when CaCl2 was administered to dogs anesthetized with isoflurane. CONCLUSIONS: Although CaCl2 produced positive inotropic effects in both the conscious and anesthetized states, CaCl2 did not alter diastolic function in conscious dogs. In contrast, CaCl2 reversed halothane- and isoflurane-induced negative lusitropic actions. The results of the present investigation suggest that improvement of left ventricular performance by CaCl2 during volatile anesthesia may be related to actions in diastole as well as systole.

Anesthesia, Inhalation↗

Inhibition of dopamine transport in rat brain synaptosomes by volatile anesthetics.

BACKGROUND: Volatile anesthetics may depress transmission by altering synaptic concentrations of neurotransmitter. Microdialysis studies have found an increase in brain extracellular dopamine concentration on exposure to volatile anesthetics. We investigated the possibility that synaptosomal dopamine transport is reversibly inhibited by the halothane and isoflurane. METHODS: Rat brain synaptosomes were incubated with 5 nM 3H-DA and increasing concentrations of anesthetic in Teflon-sealed microvials. Cocaine (100 microM) was used to quantify non-specific binding/uptake. Uptake was stopped by vacuum filtration and washing; label incorporation into synaptosomes was determined by liquid scintillation counting. 3H-DA release from preloaded synaptosomes also was studied in the presence of the anesthetic to allow distinction between uptake inhibition and release stimulation in the synaptosomes. RESULTS: Both halothane and isoflurane inhibited the specific 3H-DA uptake in a concentration-dependent fashion with an IC50 of 0.72 +/- 0.14 mM for halothane and 2.24 +/- 0.85 mM for isoflurane. No stereoselectivity of isoflurane's action on Dopamine (DA) uptake was observed. The inhibition produced by halothane and isoflurane was kinetically characterized as noncompetitive, but full reversal was demonstrated after removal of the anesthetic from the incubation mixture. The anesthetics did not stimulate 3H-DA release from preloaded synaptosomes. CONCLUSIONS: These results demonstrate volatile anesthetic-induced inhibition of the dopamine transporter in this preparation of synaptosomes. The calculated IC50S suggest this inhibition occurs with clinically relevant concentrations of halothane but not with isoflurane. The results are consistent with and may explain the increase in extracellular dopamine concentrations demonstrated by microdialysis.

Animals↗