Halothane, Isoflurane, and Sevoflurane Reduce Postischemic Adhesion of Neutrophils in the Coronary System

Background: Polymorphonuclear neutrophils (PMNs) contribute to postischemic reperfusion damage in many organs and tissues, a prerequisite being adhesion of PMNs to vascular endothelial cells. Because adhesion processes involve orderly interactions of membrane proteins, it appeared possible that "membrane effects" of volatile anesthetics could interfere. We investigated the effects of halothane, isoflurane, and sevoflurane on postischemic adhesion of human PMNs in the intact coronary system of isolated perfused guinea pig hearts.

Methods: The hearts (n = 7-10 per group) were perfused in the "Langendorff" mode under conditions of constant flow (5 ml/min) using modified Krebs-Henseleit buffer equilibrated with 94.4% oxygen and 5.6% carbon dioxide. Global myocardial ischemia was induced by interrupting perfusion for 15 min. In the second minute of reperfusion (5 ml/min), a bolus dose of 6 x 105 PMNs was injected into the coronary system. The number of cells reemerging in the coronary effluent was expressed as a percentage of the total number of applied PMNs. Halothane, isoflurane, and sevoflurane, each at 1 and 2 minimal alveolar concentration (MAC), were vaporized in the gas mixture and applied from 14 min before ischemia until the end of the experiment.

Results: Under nonischemic conditions, 24.7 +/- 1.3% of the injected neutrophils did not reemerge from the perfused coronary system. Subjecting the hearts to global ischemia augmented retention (36.4 +/- 2.8%, P <.05). Application of halothane reduced adhesion of neutrophils to 22.6 +/- 2.1% and 24.2 +/- 1.8% at 1 and 2 MAC, respectively (P < .05). Exposure to 1 and 2 MAC isoflurane was similarly effective, whereas basal adhesion was not significantly influenced. Sevoflurane-treated hearts (1 and 2 MAC) also showed decreased adhesion of PMNs (23 +/- 2.3% and 24.8 +/- 1.8%, respectively; P < .05) and an identical reduction resulted when sevoflurane (1 MAC) was applied only with the onset of reperfusion.     

Ketamine Has Stereospecific Effects in the Isolated Perfused Guinea Pig Heart

Background: S(+)-Ketamine is judged to produce more potent anesthesia than either the racemate or the R(-) ketamine isomer because of differential activation of specific cerebral receptors. Other than central nervous system effects, the most important side effects of ketamine occur in the cardiovascular system. We examined the direct cardiac effects of the isomers and the racemate of ketamine in the isolated perfused guinea pig heart.

Methods: Twenty-three guinea pig hearts were perfused by the Langendorff technique with modified 37 degrees Celsius Krebs-Ringer's solution (97% oxygen and 3% carbon dioxide) at a constant perfusion pressure. Eight animals were pretreated with reserpine to deplete hearts of catecholamines. These pretreated hearts were also perfused with Krebs-Ringer's solution containing propranolol, phenoxybenzamine, and atropine to block any remaining effects of catecholamines and of acetylcholine. Five additional hearts were perfused with naloxone to block cardiac opioid receptors. Ten hearts were not treated. All 23 hearts were then exposed to four increasing equimolar concentrations of each isomer and the racemate of ketamine for 10 min. Heart rate, atrioventricular conduction time (AVCT), left ventricular pressure, coronary flow, and inflow and outflow oxygen tensions were measured. Percentage oxygen extraction, oxygen delivery, and oxygen consumption were calculated.

Results: Both isomers and the racemate caused a concentration-dependent depression of systolic left ventricular pressure and an increase in AVCT. in the untreated hearts, S(+)-ketamine decreased heart rate and left ventricular pressure and, at higher concentrations, oxygen consumption and percentage oxygen extraction significantly less than R(-)-ketamine independent of blocked or unblocked opioid receptors. Racemic ketamine depressed cardiac function to a degree intermediate to that produced by the isomers. Coronary flow and AVCT were equally affected by the isomers and by the racemic mixture. In the catecholamine-depleted hearts both isomers and the racemate caused equipotent depression of all variables. In these hearts cardiac depression was greater, and AVCT, coronary flow, and oxygen delivery were significantly greater than in untreated and opioid receptor-blocked hearts.     

Direct Cerebral Vasodilatory Effects of Sevoflurane and Isoflurane

Background: The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram.

Methods: Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 [mu]g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels.

Results: Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4 +/- 3 and 17 +/- 3% at 0.5 and 1.5 MAC sevoflurane; 19 +/- 3 and 72 +/- 9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P < 0.05). All patients required phenylephrine (100-300 [mu]g) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia.     

Different Inhibitory Effects of Sevoflurane on Hyperreactive Airway Smooth Muscle Contractility in Ovalbumin-sensitized and Chronic Cigarette-smoking Guinea Pig Models

Background: The authors hypothesized that sevoflurane had different inhibitory effects on hyperreactive airway smooth muscle contractility in different types of hyperreactive airway models.

Methods: The effects of sevoflurane on hyperreactive airways in ovalbumin-sensitized and chronic cigarette-smoking guinea pig models were investigated by measuring (1) total lung resistance, (2) smooth muscle tension and intracellular concentration of free Ca2+, (3) voltage-dependent Ca2+ channel activity, and (4) cyclic adenosine monophosphate levels.

Results: Ovalbumin and muscarinic airway hyperreactivity was seen in ovalbumin-sensitized animals. Enlarged alveolar ducts/alveoli and lesser muscarinic hyperreactivity were observed in chronic cigarette-smoke animals. Although sevoflurane inhibited the acetylcholine-induced increase in total lung resistance in the control and ovalbumin-sensitized models, the anesthetic had a smaller effect in the chronic cigarette-smoking model. Similarly, in the chronic cigarette-smoking model, sevoflurane had a smaller inhibitory effect on carbachol-induced muscle contraction and increase in intracellular concentration of free Ca2+. Sevoflurane also had a smaller inhibitory effect on voltage-dependent Ca2+ channel activity in the chronic cigarette-smoking group than in the other two groups. The sevoflurane-induced increase in cyclic adenosine monophosphate that was seen in the control and ovalbumin-sensitized groups was significantly suppressed in the chronic cigarette-smoking group.     

七氟烷与异氟烷对腹腔镜胆囊切除术中通气功能影响的比较

目的应用旁气流通气监测比较七氟烷与异氟烷对腹腔镜胆囊切除术中通气功能的影响。方法选择ASAⅠ～Ⅱ级40例拟行腹腔镜胆囊切除术的成年患者,随机分成七氟烷组（Ⅰ组）和异氟烷组（Ⅱ组）,各组20例,术前用药、麻醉诱导相同。麻醉维持：分别在气管插管后吸入1%七氟烷或异氟烷,同时持续静脉泵入丙泊酚3～5mg/（kg.h）和阿曲库铵0.3～0.5mg/（kg.h）。计算2组不同时段肺顺应性比值、气道阻力的变化和死腔率。结果①与平卧位插管后相比,2组气腹后0,15和30min的肺动态顺应性（Cdyn）降低,气道压（Paw）升高（P〈0.05）,气腹后30min死腔率（VD/VT）也明显升高（P〈0.05）。②与平卧位插管后相比,2组PaCO2和呼气末CO2分压（PETCO2）在气腹后15,30min以及排除CO2后明显升高（P〈0.05）。③与同一时段七氟烷组相比,异氟烷组排除CO2后的VD/VT、PaCO2明显高于七氟烷组（P〈0.05）,余2组差异无显著性。结论吸入七氟烷的患者在排除CO后的肺部死腔率明显小于吸入异氟烷的患者。     

Stereospecific Effect of Bupivacaine Isomers on Atrioventricular Conduction in the Isolated Perfused Guinea Pig Heart

Background: The local anesthetic bupivacaine is an equal mixture of two optically active isomers known to exert different cardiotoxic profiles in vivo. Enantiomer-specific forms of bupivacaine may have differential effects on cardiovascular function, specifically on cardiac electrophysiology. The authors' aim was to determine if there were any direct functional differences in the cardiac effects of bupivacaine isomers. The isolated heart was used to avoid possible indirect cardiac effects of bupivacaine, such as autonomic nervous and hormonal influences, as well as preload and afterload factors.

Methods: The hearts of 12 ketamine-anesthetized guinea pigs were perfused with Krebs-Ringer's solution (97% oxygen, 3% carbon dioxide) at constant perfusion pressure using the Langendorff technique. Atrial and ventricular bipolar electrodes were placed to measure heart rate (HR) and atrioventricular (AV) conduction time. Left ventricular pressure (LVP), coronary flow, and inflow and outflow oxygen tensions were also measured. Oxygen delivery, oxygen consumption (MVO2), and percentage of oxygen extraction were calculated. Each heart was perfused with increasing randomized concentrations (0.5, 1, 5, 10 micro Meter) of both isomers and the racemate of bupivacaine.

Results: Racemic and isomeric bupivacaine equally and dose dependently decreased cardiac function. At 10 micro Meter bupivacaine these changes were HR, -17 +/- 2%; LVP, -50 +/- 3%; coronary flow, -20 +/- 40%; and MVO2, -46 +/- 40%. The (+) isomer significantly prolonged AV conduction compared with the racemate and the (-) isomer at all concentrations. At 10 micro Meter, AV time was 54 +/- 6% longer with the (+) isomer and 30 +/- 4% longer with the (+/-) racemate than with the (-) isomer. The greater delay in AV time with the (+) than the racemate or (-) isomer led to a second-degree AV dissociation in 10 of 12 of hearts treated with (+) bupivacaine.     

Influence of Hemodialysis on Plasma Chemotactic Activity and the Chemotactic Responsiveness of Polymorphonuclear Neutrophils

Thirty patients with chronic renal failure on maintenance hemodialysis (HD) were studied. Plasma chemotactic activity was estimated using the "under agarose" chemotaxis assay during the first 2 h of HD. It was found that in the fifth minute of HD, patients' plasma became chemotactic, reaching the maximum activity at the tenth minute. The chemotactic activity appearance correlated significantly with the decline in the number of the peripheral neutrophils. Patients' neutrophils, after a single passage through the cellophane coil of the dialyzer, revealed significant impairment of directed migration toward both complementary and bacterial chemoattractants. Moreover, the chemotactic properties of neutrophils obtained from dialyzed patients before HD were significantly lower than had been estimated in 15 nondialyzed patients with chronic renal failure. The results confirm HD-induced complement activation and might explain the mechanisms of the increased susceptibility of dialyzed patients to bacterial infections.     

Isoflurane and Sevoflurane Interact with the Nicotinic Acetylcholine Receptor Channels in Micromolar Cconcentrations

Background: This study was performed to elucidate and compare the effects of sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse myotubes. The experiments were done with special reference to anesthetic concentrations considerably less than those used for clinical anesthesia.

Methods: The patch-clamp technique was used to record acetylcholine-activated currents from the embryonic type of the nicotinic acetylcholine receptor in the outside-out mode. A piezo-driven liquid filament switch was used for the ultrafast application of acetylcholine alone or in combination with isoflurane or sevoflurane. In addition, the patches were preexposed to either anesthetic, preceding the activation with acetylcholine.

Results: The current elicited by acetylcholine was reduced reversibly and in a concentration-dependent manner by both anesthetics, which were equally effective. Preexposure of the patches to isoflurane or sevoflurane showed an additional inhibition that was present at micromolar concentrations. The time courses of current decay could be fitted by single exponentials for isoflurane. At higher concentrations of sevoflurane, the current decay became biexponential. In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations.     

Comparative Pharmacodynamic Modeling of the Electroencephalography-slowing Effect of Isoflurane, Sevoflurane, and Desflurane

Background: The most common measure to compare potencies of volatile anesthetics is minimum alveolar concentration (MAC), although this value describes only a single point on a quantal concentration-response curve and most likely reflects more the effects on the spinal cord rather than on the brain. To obtain more complete concentration-response curves for the cerebral effects of isoflurane, sevoflurane, and desflurane, the authors used the spectral edge frequency at the 95th percentile of the power spectrum (SEF95) as a measure of cerebral effect.

Methods: Thirty-nine patients were randomized to isoflurane, sevoflurane, or desflurane groups. After induction with propofol, intubation, and a waiting period, end-tidal anesthetic concentrations were randomly varied between 0.6 and 1.3 MAC, and the EEG was recorded continuously. Population pharmacodynamic modeling was performed using the software package NONMEM.

Results: The population mean EC50 values of the final model for SEF (95) suppression were 0.66 +/- 0.08 (+/- SE of estimate) vol% for isoflurane, 1.18 +/- 0.10 vol% for sevoflurane, and 3.48 +/- 0.66 vol% for desflurane. The slopes of the concentration-response curves were not significantly different; the common value was [Greek small letter lambda] = 0.86 +/- 0.06. The Ke0 value was significantly higher for desflurane (0.61 +/- 0.11 min-1), whereas separate values for isoflurane and sevoflurane yielded no better fit than the common value of 0.29 +/- 0.04 min (-1). When concentration data were converted into fractions of the respective MAC values, no significant difference of the C50 values for the three anesthetic agents was found.     

Effects of Low-flow Sevoflurane Anesthesia on Renal Function: Comparison with High-flow Sevoflurane Anesthesia and Low-flow Isoflurane Anesthesia

Background: The safety of low-flow sevoflurane anesthesia, during which CF2 = C(CF3)-O-CH2 F (compound A) is formed by sevoflurane degradation, in humans has been questioned because compound A is nephrotoxic in rats. Several reports have evaluated renal function after closed-circuit or low-flow sevoflurane anesthesia, using blood urea nitrogen (BUN) and serum creatinine as markers. However, these are not the more sensitive tests for detecting renal damage. This study assessed the effects of low-flow sevoflurane anesthesia on renal function using not only BUN and serum creatinine but also creatinine clearance and urinary excretion of kidney-specific enzymes, and it compared these values with those obtained in high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia.

Methods: Forty-eight patients with gastric cancer undergoing gastrectomy were studied. Patients were randomized to receive sevoflurane anesthesia with fresh gas flow of 1 l/min (low-flow sevoflurane group; n = 16) or 6-10 l/min (high-flow sevoflurane group; n = 16) or isoflurane anesthesia with a fresh gas flow of 1 l/min (low-flow isoflurane group; n = 16). In all groups, the carrier gas was oxygen/nitrous oxide in the ratio adjusted to ensure a fractional concentration of oxygen in inspired gas (FiO2) of more than 0.3. Fresh Baralyme was used in the low-flow sevoflurane and low-flow isoflurane groups. Glass balls were used instead in the high-flow sevoflurane group, with the fresh gas flow rate adjusted to eliminate rebreathing. The compound A concentration was measured by gas chromatography. Gas samples taken from the inspiratory limb of the circle system at 1-h intervals were analyzed. Blood samples were obtained before and on days 1, 2, and 3 after anesthesia to measure BUN and serum creatinine. Twenty-four-hour urine samples were collected before anesthesia and for each 24-h period from 0 to 72 h after anesthesia to measure creatinine, N-acetyl-beta-D-glucosaminidase, and alanine aminopeptidase.

Results: The average inspired concentration of compound A was 20 +/- 7.8 ppm (mean +/- SD), and the average duration of exposure to this concentration was 6.11 +/- 1.77 h in the low-flow sevoflurane group. Postanesthesia BUN and serum creatinine concentrations decreased, creatinine clearance increased, and urinary N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase excretion increased in all groups compared with preanesthesia values, but there were no significant differences between the low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane groups for any renal function parameter at any time after anesthesia.     

The Invention and Development of Enflurane, Isoflurane, Sevoflurane, and Desflurane

Thirty-six halogenated Me Et ethers have been synthesized for evaluation as volatile anesthetics. Eleven of the ethers were too unstable to test, and, of the remaining 25, 13 had promising anesthetic properties in mice and are suitable for study in larger animals. Those ethers having one H with at least 2 halogens other than F or 2 or more H with at least one Br or Cl were the best anesthetics.     

Interaction of Isoflurane and Sevoflurane with alpha- and beta-adrenoceptor Stimulations in Rat Myocardium

Background: Halothane potentiates the positive inotropic effects of alpha- and beta-adrenoceptor stimulations but impairs the positive lusitropic effect of beta-adrenoceptor stimulations. However, the interactions of isoflurane and sevoflurane with alpha- and beta-adrenoceptor stimulation have not been entirely defined.

Methods: The effects of 1 minimum alveolar concentration isoflurane and sevoflurane on the inotropic responses induced by phenylephrine (10 (-8) to 10-4 M) or isoproterenol (10-8 to 10-4 M) were studied in rat left ventricular papillary muscles in vitro (Krebs-Henseleit solution, 29 [degree sign] Celsius; pH, 7.4; 0.5 mM calcium; stimulation frequency, 12 pulses/min). The positive lusitropic effects of alpha- and beta-adrenoceptor stimulations were studied under isotonic and isometric conditions. Data are mean percentages of baseline +/- SEM.

Results: In control groups, phenylephrine (134 +/- 8%; P < 0.05) and isoproterenol (171 +/- 7%; P < 0.05) induced a positive inotropic effect. Isoflurane enhanced the positive inotropic effects of phenylephrine (185 +/- 10%; P < 0.05) and of isoproterenol (203 +/- 11%; P < 0.05). Sevoflurane enhanced the positive inotropic effects of phenylephrine (187 +/- 10%; P < 0.05) and of isoproterenol (228 +/- 11%; P < 0.05). These potentiations were similar to those previously reported with halothane. Isoflurane and sevoflurane did not modify the positive lusitropic effects under low and high loads of isoproterenol.     

Effects of Isoflurane and Sevoflurane on Intracellular Calcium and Contractility in Pressure-overload Hypertrophy

Background: Depression of myocardial contractility as a result of isoflurane appears to be greater in myocardial hypertrophy, and the cellular basis for this difference in susceptibility is not clear. In this study we examined the effects of isoflurane and sevoflurane on contractility and intracellular calcium in an animal model of pressure-overload hypertrophy.

Methods: Pressure-overload hypertrophy was established in young male ferrets by banding the main pulmonary artery for 1 month and the effects of isoflurane and sevoflurane on contractility and intracellular calcium ([Ca2+]i) were examined in isolated right ventricular papillary muscles, trabeculae, and myocytes. Intracellular calcium was measured with the bioluminescent photoprotein aequorin in isolated papillary muscles, and also with the fluorescent indicator fluo-3 in isolated ventricular myocytes. In addition, Ca2+ sensitivity was assessed in isolated trabeculae after disruption of the surface membrane with a nonionic detergent (skinned fibers).

Results: In the presence of isoflurane and sevoflurane, papillary muscles from banded animals exhibited a greater depression of contractility and isolated ventricular myocytes showed a greater decrease in peak [Ca2+]i. Furthermore, baseline calcium sensitivity was decreased and the slope of the relationship between [Ca2+] and force was increased in skinned trabeculae from banded animals. Isoflurane decreased calcium sensitivity in trabeculae from both normal and banded animals.     

七氟醚与异氟醚麻醉用于支撑喉镜下声带息肉摘除术的比较

目的探讨七氟醚与异氟醚麻醉在支撑喉镜下声带息肉摘除术的临床效果。方法支撑喉镜下声带息肉摘除术患者40例,ASAⅠ～Ⅱ级,随机分为七氟醚组（S组）与异氟醚组（Ⅰ组）,每组20例。两组静注异丙酚2mg／kg、维库溴胺0．05mg／kg,随即S组吸入8％七氟醚或Ⅰ组吸入4．5％异氟醚2min后行气管插管术,术中分别以七氟醚或异氟醚维持麻醉。监测围术期血压、心率、心电图及脉搏氧饱和度等生命体征,记录术毕自主呼吸恢复、拔管及认知恢复的时间。结果麻醉诱导后,S组与Ⅰ组平均动脉压均明显降低,心率加快（P〈0．01）;气管插管后MAP、HR均升高（P〈0．05或P〈0．01）。七氟醚或异氟醚维持麻醉均满足手术要求,两组麻醉苏醒顺利,不良反应少,但S组自主呼吸恢复、拔管及认知恢复的时间均快于Ⅰ组（P〈0．01）。结论七氟醚或异氟醚全麻均适用于支撑喉镜下声带息肉摘除术,七氟醚的麻醉苏醒比异氟醚快。     

Minimum Alveolar Concentration-Awake of Xenon Alone and in Combination with Isoflurane or Sevoflurane

Background: The minimum alveolar concentration (MAC)-awake is a traditional index of hypnotic potency of an inhalational anesthetic. The MAC-awake of xenon, an inert gas with anesthetic properties (MAC = 71%), has not been determined. It is also unknown how xenon interacts with isoflurane or sevoflurane on the MAC-awake.

Methods: In the first part of the study, 90 female patients received xenon, nitrous oxide (N2O), isoflurane, or sevoflurane supplemented with epidural anesthesia (n = 36 for xenon and n = 18 per group for other anesthetics). In the second part, 72 additional patients received either xenon or N2O combined with the 0.5 times MAC-awake concentration of isoflurane or sevoflurane (0.2% and 0.3%, respectively, based on the results of the first part; n = 18 per group). During emergence, the concentration of an assigned anesthetic (xenon or N2O only in the second part) was decreased in 0.1 MAC decrements every 15 min from 0.8 MAC or from 70% in the case of N2O until the patient followed the command to either open her eyes or to squeeze and release the investigator's hand. The concentration midway between the value permitting the first response to command and that just preventing it was defined as the MAC-awake.

Results: The MAC-awake were as follows: xenon, 32.6 +/- 6.1% (mean +/- SD) or 0.46 +/- 0.09 MAC; N2O, 63.3 +/- 7.1% (0.61 +/- 0.07 MAC); isoflurane, 0.40 +/- 0.07% (0.35 +/- 0.06 MAC); and sevoflurane, 0.59 +/- 0.10% (0.35 +/- 0.06 MAC). Addition of the 0.5 MAC-awake concentrations of isoflurane and sevoflurane reduced the MAC-awake of xenon to 0.50 +/- 0.15 and 0.51 +/- 0.16 times its MAC-awake as a sole agent, but that of N2O to the values significantly greater than 0.5 times its MAC-awake as a sole agent (0.68 +/- 0.12 and 0.66 +/- 0.14 times MAC-awake;P < 0.01, analysis of variance and Dunnett's test).     

Effects of Volatile Anesthetics on Atrial and AV Nodal Electrophysiological Properties in Guinea Pig Isolated Perfused Heart

Background: Knowledge of the anesthetic effects on atrial and atrioventricular (AV) nodal electrophysiologic properties is fundamental to understand the modulatory role of anesthetics on the pathogenesis of supraventricular tachycardias, and to individualize the perioperative management of patients with supraventricular tachycardias or AV nodal conduction disturbances. Therefore the authors studied the effects of three commonly used volatile anesthetics on the electrophysiologic properties of the atrium and AV node.

Methods: The concentration-dependent electrophysiologic effects of halothane, isoflurane, and desflurane (0 - 2 minimum alveolar concentration [MAC]) were studied in guinea pig Langendorff-perfused hearts fit with instruments to simultaneously measure atrial and AV nodal conduction times and atrial monophasic action potential duration. Atrial and AV nodal effective refractory periods were measured simultaneously using a computer-assisted premature stimulation protocol. The concentrations of anesthetics in the gas phase were monitor by an infrared gas analyzer.

Results: Volatile anesthetics caused markedly different concentration-dependent effects on atrial conduction, repolarization, and refractoriness, and on AV nodal function. At equianesthetic concentrations, halothane depressed atrial conduction the most, whereas desflurane caused the greatest shortening of atrial monophasic action potential duration. Halothane had no significant effect on atrial refractoriness, whereas at 2 MAC desflurane significantly shortened and isoflurane significantly prolonged atrial effective refractory periods by 18.1 +/- 13.5% and 13.2 +/- 14.7%, respectively. On an equi-MAC basis, the rank order of potency for the anesthetics to prolong AV nodal conduction time and AV nodal ERP was halothane > desflurane > isoflurane.     

Effects of Sevoflurane and Isoflurane on Renal Function and on Possible Markers of Nephrotoxicity

Background: Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans.

Methods: Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n = 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-[small beta, Greek]-glucosaminidase (NAG), [small beta, Greek]2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia.

Results: There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-[small beta, Greek]-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this.     

Halothane Prevents Postischemic Production of Hydroxyl Radicals in the Canine Heart

Background: Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical ([center dot] OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored.

Methods: Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored.

Results: An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P <0.05).

The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion.     

Isoflurane Decreases ATP Sensitivity of Guinea Pig Cardiac Sarcolemmal KATP Channel at Reduced Intracellular pH

Background: Volatile anesthetics can protect the myocardium against ischemic injury by opening the adenosine triphosphate (ATP)-sensitive potassium (KATP) channels. However, direct evidence for anesthetic-channel interaction is still limited, and little is known about the role KATP channel modulators play in this effect. Because pH is one of the regulators of KATP channels, the authors tested the hypothesis that intracellular pH (pHi) modulates the direct interaction of isoflurane with the cardiac KATP channel.

Methods: The effects of isoflurane on sarcolemmal KATP channels were investigated at pHi 7.4 and pHi 6.8 in excised inside-out membrane patches from ventricular myocytes of guinea pig hearts.

Results: At pHi 7.4, intracellular ATP (1-1,000 [mu]m) inhibited KATP channels and decreased channel open probability (Po) in a concentration-dependent manner with an IC50 of 8 +/- 1.5 [mu]m, and isoflurane (0.5 mm) either had no effect or decreased channel activity. Lowering pHi from 7.4 to 6.8 enhanced channel opening by increasing Po and reduced channel sensitivity to ATP, with IC50 shifting from 8 +/- 1.2 to 45 +/- 5.6 [mu]m. When applied to the channels activated at pHi 6.8, isoflurane (0.5 mm) increased Po and further reduced ATP sensitivity, shifting IC50 to 110 +/- 10.0 [mu]m.     

大鼠急性胰腺炎时ICAM-1在胰、肺组织的表达特征与作用的观察

目的：探讨急性坏死性胰腺炎（ANP）时细胞间粘附分子-1（ICAM-1）在胰腺及肺组织的表达特征和作用。方法。用3.5%的牛磺胆酸钠逆行胰胆管注射制备ANP模型，采用免疫组化技术等方法动态观察ANP时胰腺、肺组织ICAM-1的表达改变和PMN组织聚集的变化。结果：胰腺及肺组织ICAM-1的表达分别在ANP造模后3H、6h明显增强，并于12h达高峰。结论：ICAM-1介导的PMN大量组织聚集可能是ANP早期胰腺及肺组织损伤的重要参与因素。