全麻药物与配体门控离子通道作用的分子机制

配体门控离子通道(LGIC)是全麻药物作用的重要位点之一,近年来生物技术的 发展使LGIC的分类与结构研究进一步深化,全麻药物与LGIC作用一些关键的分子位点也逐 渐被阐明,基因敲除等技术的应用为未来的研究提供了更好的前景。     

Nonhalogenated Alkane Anesthetics Fail to Potentiate Agonist Actions on Two Ligand-gated Ion Channels

Background: Although ether, alcohol, and halogenated alkane anesthetics potentiate agonist actions or increase the apparent agonist affinity of ligand-gated ion channels at clinically relevant concentrations, the effects of nonhalogenated alkane anesthetics on ligand-gated ion channels have not been studied. The current study assessed the abilities of two representative nonhalogenated alkane anesthetics (cyclopropane and butane) to potentiate agonist actions or increase the apparent agonist affinity of two representative ligand-gated ion channels: the nicotinic acetylcholine receptor and [gamma]-aminobutyric acid type A (GABAA) receptor.

Methods: Nicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana, and human GABAA receptors ([alpha]1[beta]2[gamma]2L) were expressed in human embryonic kidney 293 cells. The Torpedo nicotinic acetylcholine receptors apparent agonist affinity in the presence and absence of anesthetic was assessed by measuring the apparent rates of desensitization induced by a range of acetylcholine concentrations. The GABAA receptor's apparent agonist affinity in the presence and absence of anesthetic was assessed by measuring the peak currents induced by a range of GABA concentrations.

Results: Neither cyclopropane nor butane potentiated agonist actions or increased the apparent agonist affinity (reduced the apparent agonist dissociation constant) of the Torpedo nicotinic acetylcholine receptor or GABAA receptor. At clinically relevant concentrations, cyclopropane and butane reduced the apparent rate of Torpedo nicotinic acetylcholine receptor desensitization induced by low concentrations of agonist.     

Respiratory Mechanics during Xenon Anesthesia in Pigs: Comparison with Nitrous Oxide

Background: Because of its high density and viscosity, xenon (Xe) may influence respiratory mechanics when used as an inhaled anesthetic. Therefore the authors studied respiratory mechanics during xenon and nitrous oxide (N2O) anesthesia before and during methacholine-induced bronchoconstriction.

Methods: Sixteen pentobarbital-anesthetized pigs initially were ventilated with 70% nitrogen-oxygen. Then they were randomly assigned to a test period of ventilation with either 70% xenon-oxygen or 70% N2O-oxygen (n = 8 for each group). Nitrogen-oxygen ventilation was then resumed. Tidal volume and inspiratory flow rate were set equally throughout the study. During each condition the authors measured peak and mean airway pressure (Pmax and Pmean) and airway resistance (Raw) by the end-inspiratory occlusion technique. This sequence was then repeated during a methacholine infusion.

Results: Both before and during methacholine airway resistance was significantly higher with xenon-oxygen (4.0 +/- 1.7 and 10.9 +/- 3.8 cm H2O [middle dot] s-1 [middle dot] l-1, mean +/- SD) when compared to nitrogen-oxygen (2.6 +/- 1.1 and 5.8 +/- 1.4 cm H2O [middle dot] s-1 [middle dot] l-1, P < 0.01) and N2O-oxygen (2.9 +/- 0.8 and 7.0 +/- 1.9, P < 0.01). Pmax and Pmean did not differ before bronchoconstriction, regardless of the inspired gas mixture. During bronchoconstriction Pmax and Pmean both were significantly higher with xenon-oxygen (Pmax, 33.1 +/- 5.5 and Pmean, 11.9 +/- 1.6 cm H2O) when compared to N2O-oxygen (28.4 +/- 5.7 and 9.5 +/- 1.6 cm H2O, P < 0.01) and nitrogen-oxygen (28.0 +/- 4.4 and 10.6 +/- 1.3 cm H2O, P < 0.01).     

Contrasting Synaptic Actions of the Inhalational General Anesthetics Isoflurane and Xenon

Background: The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon.

Methods: The actions of isoflurane and xenon on [gamma]-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks.

Results: Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and [alpha]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component.     

Subunit-dependent Inhibition of Human Neuronal Nicotinic Acetylcholine Receptors and Other Ligand-gated Ion Channels by Dissociative Anesthetics Ketamine and Dizocilpine

Background: The neuronal mechanisms responsible for dissociative anesthesia remain controversial. N-methyl-D-aspartate (NMDA) receptors are inhibited by ketamine and related drugs at concentrations lower than those required for anesthetic effects. Thus, the authors studied whether ligand-gated ion channels other than NMDA receptors might display a sensitivity to ketamine and dizocilpine that is consistent with concentrations required for anesthesia.

Methods: Heteromeric human neuronal nicotinic acetylcholine receptors (hnAChR channels [alpha]2[beta]2, [alpha]2[beta]4, [alpha]3[beta]2, [alpha]3[beta]4, [alpha]4[beta]2 and [alpha]4[beta]4), 5-hydroxytryptamine3 (5-HT3), [alpha]1[beta]2[gamma]2S[gamma]-aminobutyric acid type A (GABAA) and [alpha]1 glycine receptors were expressed in Xenopus oocytes, and effects of ketamine and dizocilpine were studied using the two-electrode voltage-clamp technique.

Results: Both ketamine and dizocilpine inhibited hnAChRs in a noncompetitive and voltage-dependent manner. Receptors containing [beta]4 subunits were more sensitive to ketamine and dizocilpine than those containing [beta]2 subunits. The inhibitor concentration for half-maximal response (IC50) values for ketamine of hnAChRs composed of [beta]4 subunits were 9.5-29 [mu]M, whereas those of [beta]2subunits were 50-92 [mu]M. Conversely, 5-HT3 receptors were inhibited only by concentrations of ketamine and dizocilpine higher than the anesthetic concentrations. This inhibition was mixed (competitive/noncompetitive). GABAA and glycine receptors were very resistant to dissociative anesthetics.     

Expansion of Gas Bubbles by Nitrous Oxide and Xenon

Background: Nitrous oxide is well known to expand gas bubbles trapped in enclosed spaces and is contraindicated in situations where this may occur. Xenon, an anesthetic gas with similar physical properties to nitrous oxide, is also likely to expand gas bubbles, and it has been predicted that microbubbles in the circulation may expand dramatically when exposed to xenon. Because of the possibility that xenon will be used during cardiopulmonary bypass surgery, a procedure that is likely to introduce microbubbles into the circulation, the authors reinvestigated the extent to which xenon expands gas bubbles in aqueous solution.

Methods: Gas bubbles of either air or oxygen were formed in an aqueous solution, and their size was monitored using optical microscopy when they were exposed to a rapidly flowing solution of xenon, nitrous oxide, or a xenon-oxygen mixture.

Results: Both nitrous oxide and xenon rapidly expanded air bubbles, although nitrous oxide caused a much larger expansion. The observed expansion was not greatly dependent on the initial size of the bubble but was significantly greater at lower temperatures. Under conditions relevant to cardiopulmonary bypass surgery (50% xenon-50% oxygen, 30[degrees]C), the increase in diameter was modest (9.7 +/- 0.8%).     

Diffusion of Xenon and Nitrous Oxide into the Bowel

Background: Nitrous oxide diffuses easily from blood into air filled spaces. Xenon is also a relatively insoluble gas, like nitrous oxide. Therefore, the authors measured xenon diffusion into obstructed bowel segments during xenon anesthesia and compared this with nitrous oxide and nitrogen diffusion.

Methods: Twenty-one pentobarbital-anesthetized pigs were randomly assigned to three groups to receive either xenon-oxygen, nitrous oxide-oxygen, or nitrogen-oxygen (75%-25%), respectively. In each animal, four bowel segments of 15-cm length were isolated. A pressure-measuring catheter was inserted into the lumen, and 30 ml of room air was injected into the segments. Anesthesia with the selected gas mixture was performed for 4 h. Pressure in the segments was measured continuously. The volume of gaseous bowel content was measured on completion of the study.

Results: The median volume of bowel gas in animals breathing nitrous oxide was 88.0 ml as compared with 39.0 ml with xenon anesthesia and 21.5 ml in the nitrogen-oxygen group. After 4 h of anesthesia, the intraluminal pressures in the nitrous oxide group were found to be significantly greater than in the control group and in the xenon group.     

Thermoregulatory Thresholds for Vasoconstriction in Patients Anesthetized with Various 1-Minimum Alveolar Concentration Combinations of Xenon, Nitrous Oxide, and Isoflurane

Background: Nitrous oxide limits intraoperative hypothermia because the vasoconstriction threshold with nitrous oxide is higher than with equi-minimum alveolar concentrations of sevoflurane or isoflurane, presumably because of its stimulating actions on the sympathetic nervous system. Xenon, in contrast, does not cause sympathetic activation. Therefore, the authors tested the hypothesis that the vasoconstriction threshold during xenon-isoflurane anesthesia is less than during nitrous oxide-isoflurane anesthesia or isoflurane alone.

Methods: Fifteen patients each were randomly assigned to one of three 1-minimum alveolar concentration anesthetic regimens: (1) xenon, 43% (0.6 minimum alveolar concentration) and isoflurane, 0.5% (0.4 minimum alveolar concentration); (2) nitrous oxide, 63% (0.6 minimum alveolar concentration) and isoflurane 0.5%; or (3) isoflurane, 1.2%. Ambient temperature was maintained near 23[degrees]C and the patients were not actively warmed. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients. A gradient exceeding 0[degrees]C indicated significant vasoconstriction. The core-temperature threshold that would have been observed if skin had been maintained at 33[degrees]C was calculated from mean skin and distal esophageal temperatures at the time of vasoconstriction.

Results: The patients' demographic variables, preinduction core temperatures, ambient operating room temperatures, and fluid balance were comparable among the three groups. Heart rates were significantly less during xenon anesthesia than with nitrous oxide. The calculated vasoconstriction threshold was lowest with xenon (34.6 +/- 0.8[degrees]C, mean +/- SD), intermediate with isoflurane alone (35.1 +/- 0.6[degrees]C), and highest with nitrous oxide (35.7 +/- 0.6[degrees]C). Each of the thresholds differed significantly.     

Halothane, Isoflurane, Xenon, and Nitrous Oxide Inhibit Calcium ATPase Pump Activity in Rat Brain Synaptic Plasma Membranes

Background: Perturbation of neuronal calcium homeostasis may alter neurotransmission in the brain, a phenomenon postulated to characterize the anesthetic state. Because of the central role of plasma membrane Calcium2+ -ATPase (PMCA) in maintaining Calcium2+ homeostasis, the authors examined the effect of several inhalational anesthetics on PMCA function in synaptic plasma membranes (SPM) prepared from rat brain.

Methods: Calcium2+ -ATPase pumping activity was assessed by measurement of ATP-dependent uptake of Calcium2+ by SPM vesicles. ATPase hydrolytic activity was assessed by spectrophotometric measurement of inorganic phosphate (Pi) released from ATP. For studies of anesthetic effects on PMCA activity, Calcium2+ uptake or Pi release was measured in SPM exposed to halothane, isoflurane, xenon, and nitrous oxide at partial pressures ranging from 0 to 1.6 MAC equivalents. Halothane and isoflurane exposures were carried out under a gassing hood. For xenon and nitrous oxide exposures, samples were incubated in a pressure chamber at total pressures sufficient to provide anesthetizing partial pressures for each agent.

Results: Dose-related inhibition of Calcium2+ -ATPase pumping activity was observed in SPM exposed to increasing concentrations of halothane and isoflurane, confirmed by ANOVA and multiple comparison testing (P < 0.05). Concentrations of halothane and isoflurane equivalent to one minimum effective dose (MED) depressed PMCA pumping approximately 30%. Xenon and nitrous oxide also inhibited Calcium2+ uptake by SPM vesicles. At partial pressures of these two gases equivalent to 1.3 MAC, PMCA was inhibited approximately 20%. Hydrolysis of ATP by SPM fractions was also inhibited in a dose-related fashion. An additive effect occurred when 1 vol% of halothane was added to xenon or nitrous oxide at partial pressures equivalent to 0-1.6 MAC for the latter two agents.     

Nitrous Oxide Augments the Systemic and Coronary Haemodynamic Effects of Isoflurane in Patients with Ischaemic Heart Disease

The effects of 70% nitrous oxide, added to 1% end-tidal isoflurane and administered by intermittent positive pressure ventilation (IPPV), on coronary haemodynamics and myocardial oxygenation were investigated in 10 patients with ischaemic heart disease. Standard methods were used for determination of their central haemodynamic effects. Coronary blood flow was measured by the retrograde thermodilution technique and coronary sinus blood sampled for measurement of myocardial oxygen consumption and lactate extraction. One per cent end-tidal isoflurane decreased systemic blood pressure (-39%) by a combination of systemic vasodilation and reduction in cardiac performance. Coronary blood flow remained unaltered despite the fall in coronary perfusion pressure and myocardial oxygen consumption (-30%) and extraction (-30%) fell significantly. Ischaemic ECG changes parallelled by decreased myocardial lactate extraction or lactate production were recorded in 6 of the 10 patients during steady state isoflurane anaesthesia. When nitrous oxide was added to isoflurane there was a fall in heart rate (-13%), a further reduction in systemic blood pressure (-18%) and myocardial oxygen consumption (-31%) and extraction (-17%) whereas all other variables including coronary blood flow remained unaltered. The myocardial ischaemia was worsened in three of the six patients with ECG and metabolic signs of impaired oxygenation during isoflurane alone. It is concluded that nitrous oxide potentiates the systemic and coronary haemodynamic effects of isoflurane in patients with coronary artery disease. The mechanisms for myocardial ischaemia seem to be decreased coronary perfusion pressure and/or redistribution of coronary blood flow by direct coronary vasodilation.     

Presynaptic and Postsynaptic Effects of the Anesthetics Sevoflurane and Nitrous Oxide in the Human Spinal Cord

Background: Reduced spinal excitability contributes to the suppression of movement responses to noxious stimuli during the anesthetic state. This study examines and compares presynaptic and postsynaptic effects of two anesthetics in the human spinal cord.

Methods: The authors tested two parameters during the administration of 0.8 vol% sevoflurane or 40 vol% nitrous oxide compared with control states before and after drug administration: (1) the size of the soleus H reflex (integrating presynaptic and postsynaptic effects) at increasing stimulus intensities (recruitment curve) and (2) the amount of presynaptic inhibition on Ia afferents of the quadriceps femoris, evaluated by the heteronymous facilitation of the soleus H reflex caused by a conditioning stimulation of the femoral nerve. The study was performed in 10 subjects for each drug.

Results: At the chosen concentrations, the maximum H reflex was reduced by 26.3 +/- 8.4% (mean +/- SD) during sevoflurane and by 33.5 +/- 15.6% during nitrous oxide administration. The averaged recruitment curves were similarly depressed under the influence of the two drugs. The reduction of H-reflex facilitation was significantly stronger for sevoflurane (28.8 +/- 20.0%) than for nitrous oxide administration (6.2 +/- 26.4%).     

The Midlatency Auditory Evoked Potentials Predict Responsiveness to Verbal Commands in Patients Emerging from Anesthesia with Xenon, Isoflurane, and Sevoflurane but Not with Nitrous Oxide

Background: It has recently been demonstrated that the approximately 40-Hz spectral power of the midlatency auditory evoked potential (MLAEP) correlates well with wakefulness during desflurane or propofol anesthesia. The aim of this study was to characterize how other inhalational anesthetics affects the MLAEP as the patients regain responsiveness to simple verbal command during emergence from anesthesia.

Methods: Sixty patients were randomly assigned to receive xenon, isoflurane, sevoflurane, or nitrous oxide (N2O) supplemented with epidural anesthesia. During emergence, the concentration of an anesthetic was decreased in 0.1-minimum alveolar concentration (MAC) decrements from 0.8 MAC or from 70% in the case of N2O, and each new concentration was maintained for 15 min. Every 5 min during each equilibration period, the MLAEP was recorded and the patients were asked to open their eyes and squeeze and release the investigator's hand. This process was repeated until the first response to either of these commands was observed.

Results: Thirteen patients were excluded because of technical reasons. The preanesthetic MLAEP showed a periodic waveform, where the Na-Pa-Nb complex was the most prominent component contributing to the high energy around 29-39 Hz in the power spectrum. Emergence from xenon, isoflurane, and sevoflurane anesthesia produced similar changes in the MLAEP. The spectral power for the frequency 29 Hz or greater was severely suppressed at 0.8 MAC but significantly recovered between the concentration only 0.1 MAC higher that permitting the first response to command and that associated with the first response. In contrast, N2O hardly affected the MLAEPs, even at the concentrations producing unresponsiveness. Two patients did not lose responsiveness even at the highest concentration tested (70%).     

An Evaluation of the Effect of Anesthetic Technique on Reproductive Success after Laparoscopic Pronuclear Stage Transfer: Propofol/Nitrous Oxide Versus Isoflurane/Nitrous Oxide

Background: Laparoscopic pronuclear stage transfer (PROST) is the preferred method of embryo transfer after in vitro fertilization in many infertility programs. There are scant data to recommend the use or avoidance of any particular anesthetic agent for use in women undergoing this procedure. The authors hypothesized that propofol would be an ideal anesthetic for laparoscopic PROST because of its characteristic favorable recovery profile that includes minimal sedation and a low incidence of postoperative nausea and vomiting. The purpose of the study was to compare propofol and isoflurane with respect to postanesthetic recovery and pregnancy outcomes after laparoscopic PROST.

Methods: One hundred twelve women scheduled for laparoscopic PROST were randomized to receive either propofol/nitrous oxide or isoflurane/nitrous oxide for maintenance of anesthesia.

Results: Visual analog scale scores for sedation were lower in the propofol group than in the isoflurane group at all measurements between 30 min and 3 h after surgery. More women experienced emesis and were given an antiemetic during recovery in the isoflurane group than in the propofol group. However, the percentage of pregnancies with evidence of fetal cardiac activity was 54% in the isoflurane group compared with only 30% in the propofol group (P = 0.023). Also, the ongoing pregnancy rate was greater in the isoflurane group than in the propofol group (54% vs. 29%, P = 0.014).     

Interaction of Isoflurane and Nitrous Oxide Combinations Similar for Median Electroencephalographic Frequency and Clinical Anesthesia

Background: The volatile anesthetic sparing effect of nitrous oxide in clinical studies is less than might be expected from the additivity of minimum alveolar concentration values. Other studies identify nonadditive interactions between isoflurane and nitrous oxide. The aim of this study was to quantify the interaction of isoflurane and nitrous oxide at a constant median electroencephalographic frequency.

Methods: Twenty-five patients were studied during laparotomies. Nitrous oxide was randomly administered in concentrations of 0, 20, 40, 60, and 75 vol%, to ten patients for each nitrous oxide concentration. Isoflurane vaporizer settings were chosen so that the median electroencephalographic frequency was held between 2 and 3 Hz. The relationship between nitrous oxide concentrations and required isoflurane concentrations was examined with the method of isoboles.

Results: Nitrous oxide linearly decreased the isoflurane requirement. Addition of every 10 vol% of nitrous oxide decreases the isoflurane requirement by approximately 0.04 vol%. The total anesthetic requirement of isoflurane and nitrous oxide, expressed in terms of previously reported minimum alveolar concentration values, increased significantly with increasing nitrous oxide concentrations.     

Anesthetic Doses of Sevoflurane To Block Cardiovascular Responses to Incision when Administered with Xenon or Nitrous Oxide

Background: The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2 O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2 O.

Methods: Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2 O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses.

Results: The MAC-BAR of sevoflurane, including the contribution of Xe or N2 O, was 2.1 +/- 0.2 MAC and 2.7 +/- 0.2 MAC when administered with 1 MAC Xe, respectively, and 2.6 +/- 0.4 MAC when administered with 0.7 MAC N (2) O (mean +/- SD).     

Multicenter Randomized Comparison of Xenon and Isoflurane on Left Ventricular Function in Patients Undergoing Elective Surgery

Background: Volatile anesthetics are commonly used for general anesthesia. However, these can induce profound cardiovascular alterations. Xenon is a noble gas with potent anesthetic and analgesic properties. However, it is uncertain whether xenon alters myocardial function. The aim of this study was therefore to investigate left ventricular function during anesthesia with xenon compared with isoflurane.

Methods: The authors performed a randomized multicenter trial to compare xenon with isoflurane with respect to cardiovascular stability and adverse effects in patients without cardiac diseases scheduled for elective surgery. Two hundred fifty-nine patients were enrolled in this trial, of which 252 completed the study according to the protocol. Patients were anesthetized with xenon or isoflurane, respectively. Before administration of the study drugs and at four time points, the effects of both anesthetics on left ventricular function were investigated using transesophageal echocardiography.

Results: Global hemodynamic parameters were significantly altered using isoflurane (P < 0.05 vs. baseline), whereas xenon only decreased heart rate (P < 0.05 vs. baseline). In contrast to xenon, left ventricular end-systolic wall stress decreased significantly in the isoflurane group (P < 0.05 vs. baseline). Velocity of circumferential fiber shortening was decreased significantly in the xenon group but showed a more pronounced reduction during isoflurane administration (P < 0.05 vs. baseline). The contractile index (difference between expected and actually measured velocity of circumferential fiber shortening) as an independent parameter for left ventricular function was significantly decreased after isoflurane (P < 0.0001) but unchanged using xenon.     

Effects of Desflurane in Rat Myocardium: Comparison with Isoflurane and Halothane

Background: The cardiovascular effects of desflurane have been investigated in several in vivo animal and human studies. To determine the possible contributions of myocardial depression, the effects of desflurane on various contractile parameters in isolated cardiac papillary muscles were compared with those of isoflurane and halothane.

Methods: The effects of desflurane, isoflurane, and halothane (0.5-2.5 minimum alveolar concentration [MAC]) were studied in rat left ventricular papillary muscles (29 [degree sign] Celsius; pH 7.40; stimulation frequency, 12 pulses/min). The inotropic effects were compared under low (isotony) and high (isometry) loads, using the maximum unloaded shortening velocity (Vmax) and maximum isometric active force (AF). The lusitropic effects were compared in isotonic and isometric conditions.

Results: Desflurane has no significant inotropic effect (AF at 2.5 MAC: 95 +/- 11% of control values; NS) in contrast with halothane and isoflurane (AF at 2.5 MAC: 37 +/- 14 vs. 65 +/- 10%, respectively; P <0.05). After alpha- and beta-adrenoceptor blockade or pretreatment with reserpine, desflurane induced a negative inotropic effect (AF at 2.5 MAC: 83 +/- 11 vs. 89 +/- 8%, respectively) that was not significantly different from that of isoflurane (AF at 2.5 MAC: 80 +/- 12%). Halothane induced a negative lusitropic effect under low load, which was significantly greater than those of isoflurane and desflurane. In contrast to halothane, isoflurane and desflurane induced no significant lusitropic effect under high load and did not modify postrest potentiation. These results suggest that desflurane did not impair sarcoplasmic reticulum function.