Gastric mucosal perfusion in dogs: effects of halogenated anesthetics and of hemorrhage.

The gastrointestinal tract is one of the first organs affected by hypoperfusion during hemorrhagic shock. The hemodynamics and oxygen transport variables during hemorrhagic shock and resuscitation can be affected by the anesthetics used. In a model of pressure-guided hemorrhagic shock in dogs, we studied the effects of three halogenated anesthetics--halothane, sevoflurane, and isoflurane--at equipotent concentrations on gastric oxygenation. Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of either halothane, sevoflurane, or isoflurane. A gastric tonometer was placed in the stomach to determine mucosal gastric CO(2) (PgCO(2)) and for the calculation of gastric-arterial PCO(2) gradient (PCO(2) gap). The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40-50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamics, systemic oxygenation, and PCO(2) gap were measured at baseline, after 45 min of hemorrhage, and at 15 and 60 min after blood resuscitation. Hemorrhage induced reductions of mean arterial pressure and cardiac index, while systemic oxygen extraction increased (p < .05), without significant differences among groups (p > .05). Halothane group showed significant lower PCO(2) gap values than the other groups (p < .05). After 60 min of shed blood replacement, all groups restored hemodynamics, systemic oxygenation, and PCO(2) gap to the prehemorrhage levels (p > .05), without significant differences among groups (p > .05). We conclude that halothane is superior to preserve the gastric mucosal perfusion in comparison to isoflurane and sevoflurane, in dogs submitted to pressure-guided hemorrhagic shock at equipotent doses of halogenated anesthetics.     

Screening for Decreased Renal Function in Taxi Drivers in Tehran,Iran

Introduction. Halogenated anesthetics can cause changes in the variables that modify the cardiac output necessary to maintain renal hemodynamic during hemorrhagic shock and resuscitation. However, halogenated anesthetics seem to protect against renal ischemia-reperfusion injury. In a model of pressure-guided hemorrhagic shock in dogs, we studied the comparative effects of three halogenated anesthetics—halothane, sevoflurane, and isoflurane—at equipotent concentrations on renal responses after resuscitation. Methods. Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of halothane, sevoflurane, or isoflurane. The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40–50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamic variables were measured at baseline, after 45 min of hemorrhage, and 15 and 60 min after resuscitation. Renal variables were measured at baseline and 15 and 60 min after resuscitation. Results. Hemorrhage induced reductions of mean arterial pressure, filling pressures, and cardiac index (p?<?0.05), without significant differences among groups (p?> 0.05). After 60 min of shed blood replacement, all groups restored hemodynamic and renal variables to the prehemorrhage levels (p?> 0.05), without significant differences among groups (p?> 0.05), with the exception of sodium fractional excretion, the values for which were significantly higher in isoflurane group, in relation to the other groups after 15 min of re-transfusion (p?<?0.05), and renal vascular resistance, the values for which remain lower than baseline in halothane group (p?<?0.05). Conclusions. We conclude that no difference could be detected between choosing equipotent doses of halothane, sevoflurane, or isoflurane in relation to renal variables in dogs submitted to pressure-adjusted hemorrhagic shock and resuscitation.     

The comparative cardiovascular effects of sevoflurane with halothane and isoflurane

Using closed chest dogs, the cardiovascular effects of sevoflurane were compared with those of halothane and isoflurane in equipotent doses of 1.0, 1.5, 2.0, 2.5 and 3.0 MAC. They were evaluated by the changes of arterial blood pressure, central venous pressure, pulmonary artery pressure, maximum rate of left ventricular pressure rise (LV dp/dt), cardiac output and coronary sinus blood flow. The suppression of left cardiac function by sevoflurane was less than that of halothane, but was greater than that of isoflurane. Heart rate, systemic vascular resistance with sevoflurane were slightly lower than that of isoflurance. The coronary sinus blood flows with sevoflurane and isoflurane were significantly (P < 0.05 at 1.0 MAC, P < 0.005 at 2.0 MAC) higher than halothane. There was no significant difference on coronary sinus flow between sevoflurane and isoflurane. The depth of anesthesia could be quickly changed by adjustment of inspired sevoflurane concentration in comparison with the other two anesthetics.(Kazama T, Ikeda K: The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J Anesth 2: 63–68, 1988)     

Early Restoration of Cocaine-Induced Splanchnic Hypoperfusion in Anesthetized Dogs

Although cardiovascular effects of cocaine have been well studied, little is known about its effects on splanchnic perfusion. We studied systemic and regional hemodynamic effects of acute cocaine intoxication in dogs under volatile anesthesia. Mechanically ventilated beagle dogs, randomized at 1.5% halothane (n = 7) or 2.25% sevoflurane (n = 7) anesthesia, received an intravenous bolus of cocaine (12 mg/kg over 5 min) followed by 0.22 mg/kg/min infusion over 30 min. They were observed for 60 min thereafter. Cardiac index (CI), heart rate (HR), mean arterial pressure (MAP), portal blood flow (PBF), gastric PCO₂ (gas tonometry), blood gases, and lactate and cocaine levels were assessed. Cocaine bolus promoted significant reductions in CI (～ 50%), HR (～ 20%), MAP (～ 20%), and PBF (～ 50%), accompanied by increase in systemic and splanchnic oxygen extractions and in gastric mucosal–arterial PCO₂ gradient. Those changes were maintained during cocaine infusion and returned to baseline values parallel to plasmatic cocaine clearance. Unlike other shock states, regional parameters, including gastric mucosal–arterial PCO₂ gradient, were restored before systemic variables. A possible local vasodilatory effect of volatile agents could play a role in this phenomenon. Cocaine infusion in anesthetized animals promoted marked systemic and regional hemodynamic derangement, which was rapidly reversible with decay of cocaine plasmatic concentration.     

The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparative evaluation of inhaled halothane, isoflurane, and sevoflurane during acute normovolemic hemodilution in dogs

The hemodynamic response to acute normovolemic hemodilution (ANH) can be affected by the anesthetics used. We randomized 18 mongrel dogs to undergo ANH with 3 different inhaled anesthetics: halothane, isoflurane, or sevoflurane. Hemodynamics, oxygen transport, and gastric pH were measured before blood withdrawal, at the end of hemodilution, and 30 and 60 min after the end of hemodilution. The baseline measurements of all hemodynamic variables were similar among groups, with the exception of heart rate, which was more rapid in the sevoflurane group. Thirty minutes after hemodilution, the cardiac index increased 88%, 86%, and 157% in the halothane, isoflurane, and sevoflurane groups, respectively, whereas arterial-venous oxygen differences and oxygen consumption were larger in the halothane group compared with the isoflurane and sevoflurane groups. Gastric pH obtained by tonometry did not change and was not different among groups. Because the hemodynamic response to ANH was not blunted, all three anesthetics may be safely used for the maintenance of anesthesia.     

Hepatic Effects of Halothane,Isoflurane or Sevoflurane Anaesthesia in Dogs

The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic function and hepatocellular damage were investigated in dogs, comparing the activity of hepatic enzymes and bilirubin concentration in serum. An experimental study was designed. Twenty‐one clinically normal mongrel dogs were divided into three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n = 7) and sevoflurane (n = 7). The dogs were 1–4 years old, and weighed between 13.5 and 27 kg (18.4 ± 3.9). Xylazine HCI (1–2 mg/kg) i.m. was used as pre‐anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The trachea was intubated and anaesthesia maintained with halothane, isoflurane or sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively. Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration rate, 12–14/min) was started immediately after intubation and the anaesthesia lasted for 60 min. Venous blood samples were collected before pre‐medication, 24 and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma‐glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT) activities and bilirubin concentration were measured. Serum AST, ALT and GGT activities increased after anaesthesia in all groups. In the halothane group, serum AST and ALT activities significantly increased all the time after anaesthesia compared with baseline activities. But in the isoflurane group AST and ALT activities increased only between 2 and 7 days, and in the sevoflurane group 7 days after anaesthesia. GGT activity was increased in the halothane group between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after anaesthesia. All dogs recovered from anaesthesia without complications and none developed clinical signs of hepatic damage within 14 days. The results suggest that the use of halothane anaesthesia induces an elevation of serum activities of liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia on the liver in dogs is safer than halothane anaesthesia in dogs.     

Effects of four volatile anesthesics on postanesthetic ventilation: a comparison of halothane,enflurane, isoflurane,and sevoflurane

To investigate the effects of four volatile anesthetics (halothane, enflurane, isoflurane, and sevoflurane) on postanesthetic ventilation and levels of consciousness, we enrolled 24 patients undergoing tympanoplasty in this study. Anesthesia was maintained with 67% nitrous oxide and one of four volatile anesthetics. We measured end-tidal carbon dioxide concentration (C_ETco₂), minute volume ( ) and respiratory rate (RR), and determined the volatile anesthetic concentration in whole arterial blood (C_BAnesth) and arterial carbon dioxide tension (Paco₂) at 20 min and 2h after tracheal extubation. We also observed the level of consciousness (awake, drowsy, and asleep) before the measurement. Ventilatory variables were similar among the four groups at 20 min, although the ratio of volatile anesthetic concentration in the alveoli to the minimum alveolar concentration (MAC) (C_AAnesth/MAC ratio) calculated from C_BAnesth in the halothane group was twice those in the other groups. In the halothane group, Paco₂ was significantly higher, and and RR were significantly lower compared with the isoflurane and sevoflurane groups at 2h. Halothane tended to prolong the recovery of levels of consciousness. We conclude that isoflurane and sevoflurane provide clinical advantages over halothane on postanesthetic ventilation and recovery of levels of consciousness.     

6％的羟乙基淀粉-高渗盐水在失血性休克狗复苏时的作用

背景血流动力学和全身氧输送的变化无法反映内脏低灌注，从而导致无法认识到对失血性休克的处理不足。液体复苏后扩容对改善失血性休克时全身和局部的氧供是必不可少的。我们假设，与传统的代血浆相比，应用少量的扩容剂7．5氯化钠／6％羟乙基淀粉（hydroxyethyl starch．hypertonic saline，HHES）溶液，可能提供较少的全身氧输送和胃血流灌注。我们为失血的狗进行临床上严重出血时常用的固定量液体单次输注，分别观察HHES、乳酸林格液（1actatedRinger，LR）和6％羟乙基淀粉（hydroxyethyl starch，HES）溶液对血管内扩容、早期全身氧合和胃灌注的影响。方法30只狗，出血30ml／kg，保持平均动脉压在40～50mmHg，持续45分钟后，分3组进行复苏：LR组（n=10），输注3倍出血量的液体；HES组（平均分子量130KDa，替代级0．4）（n=10），输注出血量等量的液体；HHES组（n=10），以4ml／kg的速度输注。测定血管内容量增加情况（用Evans蓝和血红蛋白稀释）、血流动力学、全身氧合、静动脉CO2分压差（Pv-aco2）和胃黏膜-动脉血CO2分压差（Pco2间隙）变化，测定时间点为基础值、出血45分钟后以及液体复苏5分钟、45分钟、90分钟时。结果由于HHES的高扩容效力增加了血容量，但它对血管内容量的扩张作用是各溶液中最小的（P〈0．05）。3种溶液对血流动力学影响相同，但相对于LR组和HES组，HHES组相混合静脉血Po，更低，全身氧合、Pv-aco2和胃黏膜Pco2间隙更大（P〈0．05）。结论对狗进行按血压调节的失血性休克和固定容量的复苏，尽管HHES有高效扩容作用，但相比LR和HES，由于输注量受限，它的血管内容量扩充能力较小，全身氧合和胃血流灌注较差。     

Anticonvulsant effects of sevoflurane on amygdaloid kindling and bicuculline-induced seizures in cats: comparison with isoflurane and halothane

Purpose. We compared the anticonvulsant effects of sevoflurane with those of isoflurane and halothane in amygdaloid kindling and bicuculline-induced seizures in cats. Methods. In a crossover design, the effects of 70% nitrous oxide, and 0.3, 0.6, and 1.5 minimum alveolar concentration (MAC) of volatile anesthetics were studied in five cats in which the amygdala was electrically stimulated at the current used for establishing the kindled state. The effects of 0.6 and 1.5 MAC of volatile anesthetics were studied in another five cats, in which 0.2 mg·kg⁻¹ of bicuculline was administered IV. Results. In the amygdaloid kindling model, all four anesthetics decreased the duration of after-discharge (AD), the rise of multiunit activity in midbrain reticular formation (R-MUA), and the behavior scores compared with findings without anesthetics. Halothane, at 1.5 MAC, significantly decreased the number of cats showing AD (P < 0.05). In the bicuculline-induced seizure model, all five cats showed repetitive spikes during 1.5 MAC of sevoflurane, whereas only two and three cats, respectively, showed the repetitive spikes during 1.5 MAC of isoflurane and halothane. All three volatile anesthetics decreased the rise of R-MUA, the duration of the repetitive spikes, and the behavior scores. The suppression of the rise in R-MUA and the behavior scores with 1.5 MAC of sevoflurane was significantly less than that with 1.5 MAC of isoflurane. Conclusion. The anticonvulsant effects of sevoflurane were less potent than those of halothane in the amygdaloid kindling model and less potent than those of isoflurane in the bicuculline-induced seizure model. Received: January 11, 2001 / Accepted: May 9, 2001     

The anticonvulsant effects of volatile anesthetics on penicillin-induced status epilepticus in cats

Volatile anesthetics may be used to treat status epilepticus when conventional drugs are ineffective. We studied 30 cats to compare the inhibitory effects of sevoflurane, isoflurane, and halothane on penicillin-induced status epilepticus. Anesthesia was induced and maintained with one of the three volatile anesthetics in oxygen. Penicillin G was injected into the cisterna magna, and the volatile anesthetic discontinued. Once status epilepticus was induced (convulsive period), the animal was reanesthetized with 0.6 minimum alveolar anesthetic concentration (MAC) of the volatile anesthetic for 30 min, then with 1.5 MAC for the next 30 min. Electroencephalogram and multiunit activity in the midbrain reticular formation were recorded. At 0.6 MAC, all anesthetics showed anticonvulsant effects. Isoflurane and halothane each abolished the repetitive spike phase in one cat; isoflurane reduced the occupancy of the repetitive spike phase (to 27%+/-22% of the convulsive period (mean +/- SD) significantly more than sevoflurane (60%+/-29%; P < 0.05) and halothane (61%+/-24%; P < 0.05), and the increase of midbrain reticular formation with repetitive spikes was reduced by all volatile anesthetics. The repetitive spikes were abolished by 1.5 MAC of the anesthetics: in 9 of 10 cats by sevoflurane, in 9 of 9 cats by isoflurane, and in 9 of 11 cats by halothane. In conclusion, isoflurane, sevoflurane, and halothane inhibited penicillin-induced status epilepticus, but isoflurane was the most potent. IMPLICATIONS: Convulsive status epilepticus is an emergency state and requires immediate suppression of clinical and electrical seizures, but conventional drugs may be ineffective. In such cases, general anesthesia may be effective. In the present study, we suggest that isoflurane is preferable to halothane and sevoflurane to suppress sustained seizure.     

Absence of Direct Antioxidant Effects from Volatile Anesthetics in Primary Mixed Neuronal-Glial Cultures

Background: Volatile anesthetics decrease ischemic brain injury. Mechanisms for this protection remain under investigation. The authors hypothesized that volatile anesthetics serve as antioxidants in a neuronal-glial cell culture system.

Methods: Primary cortical neuronal-glial cultures were prepared from fetal rat brain. Cultures were exposed to iron, H2O2, or xanthine-xanthine oxidase for 30 min in serum-free media containing dissolved isoflurane (0-3.2 mm), sevoflurane (0-3.6 mm), halothane (0-4.1 mm), n-hexanol, or known antioxidants. Cell damage was assessed by release of lactate dehydrogenase (LDH) and trypan blue exclusion 24 h later. Lipid peroxidation was measured by the production of thiobarbituric acid-reactive substances in a cell-free lipid system. Iron and calcium uptake and mitochondrial depolarization were measured after exposure to iron in the presence or absence of isoflurane.

Results: Deferoxamine reduced LDH release caused by H2O2 or xanthine-xanthine oxidase, but the volatile anesthetics had no effect. Iron-induced LDH release was prevented by the volatile anesthetics (maximum effect for halothane = 1.2 mm, isoflurane = 1.2 mm, and sevoflurane = 2.1 mm aqueous phase). When corrected for lipid solubility, the three volatile anesthetics were equipotent against iron-induced LDH release. In the cell-free system, there was no effect of the anesthetics on thiobarbituric acid-reactive substance formation in contrast to Trolox, which provided complete inhibition. Isoflurane (1.2 mm) reduced mean iron uptake by 46% and inhibited mitochondrial depolarization but had no effect on calcium uptake.     

Comparative effects of halothane, isoflurane, and sevoflurane on the liver with hepatic artery ligation in the beagle.

Recently, there has been increasing interest in the alterations in splanchnic and hepatic circulation and preservation of hepatic oxygenation and function during anesthesia and surgery. However, the effects of volatile anesthetics under a condition of marginal hepatic oxygen supply are not well understood. Using a crossover design, we therefore studied the effects of equianesthetic concentrations (1.5 MAC) of halothane, isoflurane, and sevoflurane on hepatic oxygenation and function in nine beagles in which the hepatic artery had been ligated. Portal blood flow was measured by an electro-magnetic flow meter. Hepatic function was assessed by indocyanine green elimination kinetics. While cardiac output and mean arterial pressure were greater during halothane anesthesia than during isoflurane and sevoflurane anesthesia, portal blood flow and hepatic oxygen supply were significantly less during halothane and sevoflurane anesthesia than during isoflurane anesthesia. With regard to hepatic oxygen uptake, there was a significant difference between halothane (2.7 +/- 1.2 ml.min-1 x 100 g-1) and sevoflurane (3.7 +/- 2.0 ml.min-1 x 100 g-1; P less than 0.05). Consequently, the hepatic oxygen supply/uptake ratio and the hemoglobin oxygen saturation and oxygen partial pressure in hepatic venous blood during sevoflurane anesthesia were significantly less than they were with the other anesthetics. Indocyanine green clearance was better preserved during sevoflurane anesthesia (39.7 +/- 12.0 ml.min-1) than during halothane anesthesia (30.9 +/- 8.4 ml.min-1; P less than 0.05). We conclude that sevoflurane is accompanied by a smaller oxygen supply/uptake ratio than is halothane and isoflurane, while it preserves hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Halothane anesthesia decreases the extracellular level of dopamine in rat striatum: a microdialysis study in vivo

Purpose. In our previous microdialysis study, sevoflurane or isoflurane anesthesia significantly decreased the extracellular level of dopamine in rat striatum in vivo. On the other hand, other investigators demonstrated that halothane anesthesia either increased or did not affect the extracellular dopamine level. To explore the differences among these volatile anesthetics, the effects of halothane and nitrous oxide on the striatal dopamine level were reinvestigated. Methods. Halothane alone, nitrous oxide with or without halothane, or drugs known to affect the dopaminergic pathway were administered to rats. Microdialysates were collected every 20 min and directly applied to an on-line high-performance liquid chromatograph without any pretreatment. The effects of halothane on respiratory and cardiovascular variables were monitored. Results. General anesthesia with halothane alone de-creased the dialysate (extracellular) concentration of dopamine but increased that of dopamine metabolites. Nitrous oxide alone slightly increased dopamine metabolites in dialysates but did not affect the halothane-induced decrease in extracellular dopamine. Apomorphine and haloperidol reproduced reported results, confirming the adequacy of our methodology. Nomifensine- or methamphetamine-induced increase in extracellular dopamine was augmented by halothane. Conclusion. These results suggest that halothane po-tently enhances striatal dopamine release and activates the reuptake or metabolic process, which is consistent with our previous results for sevoflurane or isoflurane. Volatile anesthetics interfere with dopamine regulation, at least in the rat striatum. Received for publication on July 12, 1999; accepted on December 14, 1999     

Halothane suppresses the increase in intracellular calcium concentration of isolated rat myocytes during hydrogen peroxide perfusion

Ischemia-reperfusion injury is probably caused by the generation of oxygen free radicals. The final common pathway to cell injury may be mediated by intracellular calcium overloading induced by oxygen free radicals. Volatile anesthetics have been shown to improve myocardial function following reperfusion. To determine whether or not oxygen radicals are involved in the mechanism by which volatile anesthetics improve myocardial function following reperfusion, we investigated the effects of hydrogen peroxide (H₂O₂) on the intracellular calcium concentration ([Ca²⁺]_i) in isolated rat ventricular cells. First, the effects of volatile anesthetics, halothane, isoflurane, or sevoflurane, on [Ca²⁺]_i were studied in the absence of H₂O₂. Next, myocytes were perfused with volatile anesthetics in the presence of H₂O₂. [Ca²⁺]_i was measured using fura-2, a Ca²⁺-sensitive fluorescent dye. None of the volatile anesthetics changed [Ca²⁺]_i in the absence of H₂O₂. In the presence of H₂O₂, [Ca²⁺]_i gradually increased during H₂O₂ perfusion. Halothane delayed the onset of the increase in [Ca²⁺]_i induced by H₂O₂, whereas sevoflurane and isoflurane accelerated the onset. Furthermore, sevoflurane caused more pronounced accumulation of intracellular calcium than did halothane and isoflurane. Therefore, the reduction of excessive intracellular calcium accumulation caused by halothane may have beneficial effects on myocardial function following reperfusion.     

The effects of isoflurane and sevoflurane on the left ventricular end-systolic pressure-volume relation in dogs

The influence of two inhalational anesthetics, isoflurane and sevoflurane, on the end-systolic pressure-volume relations (ESPVR) of the left ventricle (LV) in situ was investigated in open-chest dogs anesthetized with α-chloralose. The LV volume was measured by a conductance catheter while the LV pressure was measured by a tipmicromanometer. The end-systolic elastance (Ees) of the LV was calculated as the slope of ESPVR which was elicited when the inferior vena cava was transiently occluded. The dogs were randomly assigned to two groups, receiving either 1.3% and 2.6% isoflurane (n=6) or 2.3% and 4.6% sevoflurane (n=6), which are equivalent to 1 and 2 MAC of isoflurane or sevoflurane, respectively. Both isoflurane and sevoflurane produced dose-dependent decreases in the cardiac output to a similar degree. Isoflurane and sevoflurane caused equivalent decreases in Ees of 23% and 16% at 1 MAC, and 48% and 41% at 2 MAC, respectively. Dobutamine 3 μg·kg⁻¹·min⁻¹ produced a simultaneous restoration of Ees and recovery of the cardiac output at 1 and 2 MAC of both isoflurane and sevoflurane. We thus conclude that the depressant effect of sevoflurane on cardiac contractility is almost identical to that of isoflurane in the dog, and they are both reversed by the use of a low dose of dobutamine.     

Local application of halothane, isoflurane or sevoflurane increases the response to an electrical stimulus in humans

Volatile anesthetics may interfere with pain perception. This study investigates the effect of halothane, isoflurane and sevoflurane when applied locally, to the response of an electrical stimulus. METHODS: In this randomized control double-blind crossover study 70 volunteers were studied. In experiment 1 (30 subjects), equipotent liquid volumes of halothane 1 ml, isoflurane 1.5 ml and sevoflurane 2.7 ml were randomly applied on one forearm for 30 minutes. The other forearm received water. Both forearms were exposed to an electrical stimulus. The experiment was repeated the following day in a reverse fashion. In experiments 2 (20 subjects) and 3 (20 subjects) the response to the same stimulus was tested after local application of 2, 4, and 6 ml of halothane or 5 ml of sevoflurane respectively. RESULTS: Low doses of the three anesthetics were associated with an increased response to the electrical stimulus (F = 8.940, df = 1,174, P = 0.003). Higher doses of halothane and sevoflurane had no effect on the response (F = 2.358, df = 1,114, P = 0.127 and t = 0.840, df = 19, P = 0.411 respectively). CONCLUSIONS: Low liquid volumes of volatile anesthetics, when applied locally to the skin enhanced the response to an electrical stimulus but higher volumes had no effect.     

Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral arteries

Purpose

Hypocapnia causes cerebral arterial constriction, whereas volatile anaesthetics cause dilatation. The purpose of this study was to compare the direct effects of halothane, isoflurane and sevoflurane on hypocapniainduced constnction of isolated cerebral arteriesin vitro.

Methods

Basilar and middle cerebral arteries of mongrel dogs (n= 11) were cut into nngs and mounted for isometnc tension recording in organ baths containing Krebs’ bicarbonate solution, aerated with CO₂ 5% and O₂ 95% at 37°C. After constnction with 20 mM KCl, hypocapnia was induced by replacing the aerating gas with CO₂ 2.5% and O₂ 97.5% in the presence or absence of anaesthetics.

Results

Exposure of cerebroartenal rings to the hypocapnic gas produced sustained vasoconstnction (418 ± 19 mg), reaching a plateau within 10 to 15 min. Halothane (0.5, 1, 2 MAC) attenuated the hypocapnia-induced constnction (P< 0.05). In contrast, isoflurane and sevoflurane attenuated this constriction only at 2 MAC (P< 0.05). Attenuation by halothane was greater than that by isoflurane or sevoflurane at each concentration(P< 0.05). N^G-nitro-L-arginine (3 × 10^?5 M) did not alter the contractile response to hypocapnia. When a similar degree of constnction was induced by addition of 10 mM KCl, halothane (1 and 2 MAC) preferentially attenuated the constriction induced by hypocapnia to a greater extent than that induced by 10 mM KCl (P< 0.01)

Conclusion

Hypocapnia-induced vasoconstnction of isolated dog cerebral arteries precontracted with KCl is more susceptible to halothane than isoflurane or sevoflurane. This may account for the greater increase in cerebral blood flow dunng halothane than isoflurane or sevoflurane anaesthesia.     

Strain-differences of sensitivity to volatile anesthetics and their genetic character in mice

Using loss of the righting reflex, we determined the ED₅₀ values for enflurane, isoflurane, sevoflurane and halothane in white-haired ddN mice and black-haired C57BL mice. The ED₅₀s (Mean ± SEM) in ddN and C57BL mice for enflurane were 1.65 ± 0.01 and 1.19 ± 0.01% atm, for isoflurane 1.02 ± 0.01 and 0.74 ± 0.01% atm, for sevoflurane 2.29 ± 0.03 and 1.95 ± 0.03% atm, and for halothane 0.97 ± 0.01 and 0.97 ± 0.01% atm, respectively. The results indicate that the ddN strain is more resistant to enflurane, isoflurane and sevoflurane than the C57BL strain. The sensitivities to enflurane and isoflurane is F1 progeny of reciprocal crosses between ddN and C57BL mice revealed that in the ddN strain enflurane resistance is an incompletely dominant or polygenic character, isoflurane resistance in ddN strain is an autosomal recessive character and both are controlled by genes on the sex (X) chromosome. Enflurane and isoflurane resistances are controlled by at least 2 genes, one on the X chromosome, and each resistance is controlled by a different genetic mode.(Tanaka T, Ogli K, Komatsu H, et al.: Strain-differences of sensitivity to volatile anesthetics and their genetic character in mice. J Anesth 7: 75–81, 1993)     

Interaction of halogenated anesthetics with alpha- and beta-adrenoceptor stimulations in diabetic rat myocardium

BACKGROUND: Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown. METHODS: Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD. RESULTS: Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P < 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P < 0.05) and sevoflurane (161 +/- 40%; P < 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane. CONCLUSION: Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.