Comparative effects of halothane, enflurane, isoflurane and sevoflurane on function and metabolism in the ischaemic rat heart

This study was designed to examine the effects of inhalationanaesthetics on function and metabolism in isolated ischaemicrat hearts. Four volatile anaesthetics in two different concentrations(1.0 to 1.5 MAC) were used before whole heart ischaemia wasinduced for 1 5 mm followed by reperfusion for 30 mm. The datawere compared with a control group in which inhalation anaestheticswere not used. Before ischaemia, volatile anaesthetics depressedventricular function. During reperfusion, ventricular functionand coronary flow in both halothane groups were significantlylower than those in the control group. Myocardial ATP concentrationsin the 1.0 MAC of enflurane and isoflurane groups were significantlyhigher than those in the control group. We conclude that halothanehad more depressant effects than the other anaesthetics andthat enflurane and isoflurane may enhance metabolic recoveryin the ischaemic working rat heart. (Br. J. Anaesth. 1995; 74:569–575)     

安氟醚及异氟醚对阿曲库铵临床药效的影响

目的：观察吸入１％安氟醚或等效浓度异氟醚对阿曲库铵临床药效的影响。方法：３０例择期手术病人随机分为三组，分别吸入６７％Ｎ２Ｏ（Ⅰ组），１％安氟醚（Ⅱ组）或０．６７％异氟醚（Ⅲ组）后观察阿曲库铵临床药效。结果：静注阿曲库铵０．５ｍｇ／ｋｇ后，Ⅰ、Ⅱ和Ⅲ组的起效时间分别是２．２±０．４２分、２．１±０．４２分和２．１±０．３４分（Ｐ＞０．０５），作用时间分别是４５．８５±３．７分、５５．２５±６．４７分和５５．８８±８．２５分（Ｐ＜０．０１）；维持９０％～９５％颤搐抑制所需阿曲库铵的静脉滴注速度分别为６．２７７±１．０９２μｇ·ｋｇ－１·ｍｉｎ－１、４．２７２±０．５８５μｇ·ｋｇ－１·ｍｉｎ－１和４．５０５±０．７１６μｇ·ｋｇ－１·ｍｉｎ－１（Ｐ＜０．０１）。结论：１％安氟醚及等效浓度的异氟醚均可增强阿曲库铵的临床药效，但两者之间的增强无显著差异。     

The volatile anesthetics, halothane, enflurane and isoflurane, influence the distribution of thiopental in man differently

In man, a change of thiopental pharmacokinetics was observed under halothane anesthesia, but not when patients were anesthetized with enflurane and isoflurane. After an initial subanesthetic dose of 50 mg thiopental, the concentrations in serum (T) were determined over 15 min (4 samples). From these T-values the pharmacokinetic parameters Vc (central volume of distribution), t1/2 alpha and Cl were established (control). 16 min after the first thiopental dose, one of the inhalation anesthetics was administered (randomized). After 45 min exposure to the respective inhalation anesthetic (2-3 MAC in combination with N2O, steady-state a second dose of 50 mg thiopental was injected and the T-values were determined again over 15 min. The T-values of the control course varied considerably; the logarithmic frequency distribution revealed two distinct subgroups of patients, A and B, with characteristic Vc and t1/2 alpha. Both subgroups were influenced by the volatile anesthetics in a similar way with regard to pharmacokinetic parameters. With halothane, Vc was decreased and t1/2 alpha was shortened. In contrast, enflurane and isoflurane did not affect the pharmacokinetic parameters.     

Inhibitory effects of intravenous anesthetics on mast cell function

Mast cells play a protective role in the inflammation and auto-tissue injury. The impairment of mast cell function may influence defense against infection. We investigated the effect of four IV anesthetics (thiopental, midazolam, ketamine, and propofol) on the chemotaxis and exocytosis of mast cells. Canine mast cell chemotaxis was measured by the Boyden's blindwell chamber technique using 100 microg/mL of substance P as a stimulator. We measured mast cell exocytosis by measuring released histamine from mast cells using substance P or gamma-monomeric IgG-mediated crosslinking as a stimulator. Thiopental, midazolam, and propofol exerted a dose-dependent inhibitory effect on mast cell chemotaxis. Ketamine, midazolam, and propofol had a dose-dependent inhibitory effect on mast cell exocytosis. In conclusion, midazolam and propofol inhibited both chemotaxis and exocytosis of mast cells, while thiopental only inhibited chemotaxis, and ketamine only inhibited exocytosis. IMPLICATIONS: Mast cells play an important role in the antibacterial host-defense mechanism. Thiopental, midazolam, and propofol exerted a dose-dependent inhibitory effect on mast cell chemotaxis. Ketamine, midazolam, and propofol had a dose-dependent inhibitory effect on mast cell exocytosis. The impairment of mast cell function by IV anesthetics may influence the defense against infection.     

Effects of halothane, isoflurane and enflurane on isolated rat heart muscle

Since the effects in the intact organism are complicated by central as well as peripheral effects, we compared the direct cardiac effects of three commonly used inhalational anaesthetics--halothane, isoflurane and enflurane--on isolated heart muscle. Concentration-response curves for inotropic, chronotropic and ventricular automaticity effects of halothane, isoflurane and enflurane (0.1-2% v/v) on electrically stimulated left atria, right atria and right ventricles of the rat were obtained. All three inhalational anaesthetics significantly decreased contractile force; the inhibitory concentration 50 (IC50) of enflurane was 0.55 +/- 0.06% v/v, significantly lower than halothane (0.96 +/- 0.08% v/v) and isoflurane (0.67 +/- 0.05% v/v). Similar results were obtained on atrial nomotopic rate. Halothane, isoflurane and enflurane produced negative chronotropic effects in this preparation. On the other hand, halothane and isoflurane significantly reduced the ventricular ectopic automaticity. However enflurane (0.3, 0.5, 1% v/v) increased ventricular rate. There were statistically significant differences between the IC50 values of atrial and ventricular rate for halothane and isoflurane. These results indicate: (a) direct negative inotropic and chronotropic effects for the three inhalational anaesthetics tested; (b) anti-dysrhythmic actions for halothane and isoflurane; and (c) dysrhythmogenic effects of enflurane.     

The respiratory effects of isoflurane, enflurane and halothane in spontaneously breathing children

The respiratory effects of halothane, isoflurane and enflurane were assessed during nitrous oxide anaesthesia (N2O 50%) in three groups of unstimulated, spontaneously breathing children who weighed 10-20 kg and were aged 1-6 years. Respiratory variables were measured or calculated from capnographic and pneumotachographic recordings at three multiples of minimal alveolar concentration (MAC). The slope of the carbon dioxide response was measured. Similar increases in end tidal carbon dioxide were found for the three agents at each MAC multiple, and similar decreases in tidal volume and in the slope of the ventilatory response to carbon dioxide. A dose-related tachypnoea occurred with halothane and a significant decrease in the duration of inspiration and the duration of each breath at the deepest level of anaesthesia. A significant increase in both these times occurred with enflurane, and a decrease in respiratory rate. No change in respiratory rate occurred with isoflurane at increasing alveolar concentrations whereas at each level of anaesthesia inspiratory time was significantly reduced.     

In vivo effects of halothane, enflurane, and isoflurane on hepatic sinusoidal microcirculation

Background: It has been proposed that halogenated anaesthetics interfere with the endothelium-dependent circulatory control by attenuating the effects of endothelium-derived relaxing factor (EDRF/NO). This study was designed to determine whether or not volatile anaesthetics in vivo influence the microvascular tone in hepatic sinusoids. Methods: Using epifluorescence videomicroscopy, we compared the effects of the volatile anaesthetics halothane, enflurane, and isoflurane on hepatic microcirculation in ventilated Lewis rats. Animals were initially anaesthetized with pentobarbitone (50 mg-kg^-1 i.p.) to allow instrumentation and laparotomy and were randomly allocated to one of 4 groups (n=5–6 each) to receive either a supplementary dose of i.v. pentobarbitone (25 mg kg^-1; control group) or 0.75 MAC halothane, enflurane or isoflurane (1.5 MAC h). Results: Halothane decreased significantly the volumetric blood flow as compared with isoflurane (P < 0.05) or pentobarbitone controls (P < 0.05). The decrease in sinusoidal blood flow caused by halothane was largely attributable to a decrease in sinusoidal diameter (P < 0.05), while red blood cell velocity remained unchanged. Isoflurane led to a significant decrease in sinusoidal width compared with controls (P < 0.05) but an increase in red cell velocity offset the effect of sinusoidal narrowing on volumetric blood flow, while enflurane had no significant effect on any of the measured parameters. Conclusion: This study provides the first direct evidence that the volatile anaesthetics halothane and isoflurane in vivo shift the hepatic microvascular tone toward a more constricted state; however, flow velocity is enhanced with isoflurane, offsetting this effect. As a result the volumetric flow is at least affected by isoflurane, then enflurane and most significantly by halothane. Furthermore, our data are consistent with the concept that volatile anaesthetics in clinically relevant concentrations may influence the balance between endothelium-derived vasoactive factors which control microvascular tone.     

The effects of diethyl ether, enflurane, and isoflurane at the neuromuscular junction.

The actions of diethyl ether, enflurane, and isoflurane at the neuromuscular junction were examined in isolated guinea pig lumbrical muscles. These anesthetics depressed the ability of carbachol to depolarize the endplate region; this depression of depolarization did not show competitive kinetics. None of the anesthetics altered the affinity of the acetylcholine receptor for d-tubocurarine, i.e., the dissociation constant of d-tubocurarine was unchanged. Since diethyl ether, enflurane, and isoflurane produced no observable alteration of the receptor, the antagonism of the drug-induced depolarization of the neuromuscular junction appears to be exerted at a stage subsequent to reaction with the receptor. (Key words: Anesthetics, volatile, diethyl ethers; Anesthetics, volatile, euflurane; Anesthetics, volatile, isoflurane; Neuromuscular relaxants, d-tubocurarine; Neuromuscular junction.).     

The effect of halothane, enflurane and isoflurane on the circulation

This study, in open-chested dogs, sought to explore the relationship between whole-body oxygen delivery and oxygen consumption during anaesthesia, using increasing concentrations of halothane, enflurane and isoflurane. Results indicate that the cardiac index and oxygen delivery became critical at less than 1 MAC (minimal alveolar concentration of anaesthetic) for the three commonly used vapours. Halothane caused the least depression of contractility, but the stroke volume was reduced by the well-maintained afterload at 1 MAC. Enflurane and isoflurane were associated with more depression of contractility, but the cardiac output was maintained by an increase in heart rate in the case of isoflurane and reduced mean arterial pressure during the use of enflurane.     

The effects of local and intravenous anesthetics on recombinant rat VR1 vanilloid receptors

Capsaicin, acting at the vanilloid 1 receptor (VR1), may potentiate local anesthetic activity, and as a ligand-gated ion channel of the transient receptor potential family, may also be a target for IV general anesthetics. We have examined whether local (lidocaine, prilocaine, and procaine 0.1-10 mM; 10 mM represents 0.25%-0.27% wt/vol) or IV anesthetics (propofol 10 micro M, thiopental 100 micro M, and ketamine 100 micro M) interact with recombinant rat VR1 expressed in human embryonic kidney (HEK293) cells (VR1-HEK293). We have assessed receptor interaction functionally by monitoring intracellular Ca(2+) ([Ca(2+)](i)) in Fura2-loaded cells at 37 degrees C. The addition of capsaicin (60 nM) produced a time-dependent biphasic increase in [Ca(2+)](i) amounting to 50-100 nM above than basal, which was inhibited by capsazepine 10 micro M and was absent in wild type HEK293 cells. Lidocaine and prilocaine alone (e.g., at 10 mM) significantly increased [Ca(2+)](i) by 67 +/- 6 nM and 33 +/- 7 nM, respectively, and concentration-dependently inhibited the capsaicin response. The effects of procaine were obscured by anesthetic-induced quenching of Fura2. In wild type HEK293 cells, lidocaine (10 mM) alone produced a small increase in [Ca(2+)](i). All IV anesthetics failed to modify capsaicin-increased [Ca(2+)](i). In conclusion, the present data suggest that local but not IV general anesthetics interact with recombinant rat VR1 receptors with the former anesthetics having antagonistic activity. IMPLICATIONS: Vanilloid receptors (VR1) are activated by capsaicin, the pain-producing component of hot chili peppers. We suggest that local (but not IV general) anesthetics may have inhibitory actions on this receptor.     

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

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

Different effects of halothane and enflurane on diaphragmatic contractility in vivo

We examined the effects of halothane and enflurane on diaphragmatic contractility in 12 anesthetized, mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. Animals were randomly assigned to two groups, a halothane group (n = 6) and an enflurane group (n = 6). The Pdi stimulus-frequency relationship was compared at anesthetic levels of 1, 1.5, and 2 MAC (minimum alveolar concentration) in each group. The sequence of changing anesthetic concentration was randomized. In addition, the Pdi-frequency relationship was also compared between 1 MAC of halothane and enflurane in 8 of 12 dogs. In animals anesthetized with enflurane, Pdi significantly decreased with 50- and 100-Hz stimulation in the presence of increasing MAC values, whereas Pdi at 10-Hz stimulation was not affected by the depth of anesthesia. Pdi with 20-Hz stimulation during 2 MAC enflurane also decreased significantly below Pdi levels seen at 1 and 1.5 MAC. By contrast, with halothane there was no difference in Pdi at any of the stimulation frequencies during any of the three levels of anesthesia. There was no statistical difference, however, between Pdi-frequency relationships during 1 MAC of halothane and enflurane in eight animals. From these results, we conclude that halothane does not impair diaphragmatic contractility any more than enflurane does, but enflurane decreases force generation of the diaphragm at high stimulation frequencies in a dose-related fashion. This depressant effect of enflurane occurs mainly through the impairment of neuromuscular transmission and/or membrane excitability.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of halothane, enflurane, and isoflurane on calcium current in isolated canine ventricular cells.

The effects of halothane, enflurane, and isoflurane on voltage-dependent Ca2+ channel current (ICa) were compared in canine ventricular cells by the whole-cell voltage-clamp technique. ICa was elicited in each cell by progressively depolarizing pulses, from -80 or -40 mV to more positive membrane potentials. The peak amplitude and inactivation rate of the inward current were analyzed before, during, and after the external application of equianesthetic concentrations (0.5, 1.0, and 2.0 MAC) of halothane, enflurane, or isoflurane. The concentrations of these agents in the Krebs' solution were as follows (percentage in the gas phase): halothane 0.36, 0.68, and 1.50%; isoflurane 0.50, 1.00, and 1.90%; and enflurane 0.66, 1.36, and 2.39%. Halothane, enflurane, and isoflurane rapidly reduced peak ICa amplitude at all voltages studied, resulting in a depression of the entire current-voltage relationship for ICa activation. This depression was concentration-dependent and completely reversible upon wash-out of the anesthetic agents. Quantitatively, the three anesthetic agents produced a similar inhibition of peak ICa at approximately equianesthetic concentrations. Inactivation of ICa during 200-ms depolarizing pulses was not affected by two lower concentrations of the anesthetic agents, but was accelerated by the highest concentration of enflurane used. These findings suggest that the negative inotropic and chronotropic actions of halothane, enflurane, and isoflurane on the ventricular myocardium are related, at least in part, to their inhibition of ICa at the sarcolemma. However, since all three anesthetic agents depressed ICa amplitude similarly, their quantitatively different effects on cardiac performance are due most likely to differences in actions at other cellular sites.     

Effect of isoflurane and enflurane on ICG-clearance

We performed ICG-test (indo-cyanine green test) during surgery to study the effect of isoflurane and enflurane on ICG clearance in human. When the systolic arterial pressure (SAP) was maintained at 70% of the preoperative base line value, a significant decrease in ICG clearance occurred in the patients who received enflurane. Isoflurane, on the contrary, did not cause such a decrease in the ICG clearance. We conclude that isoflurane may restore either the blood flow to the liver or the liver function and the liver may remove ICG from the blood much better under isoflurane than under enflurane.     

The effects of isoflurane and enflurane on cerebral hemodynamics and cerebral oxygen consumption in humans

The effects of isoflurane (1 MAC) and enflurane (1 MAC) on cerebral blood flow and cerebral oxygen consumption were studied in 20 male patients without intracranial disease undergoing coronary artery bypass surgery (mean age 57 and 59 years respectively). The aim of the study was to investigate whether both agents diminish autoregulation of cerebral blood flow and CO2 reactivity of cerebral blood vessels. Patients were randomly assigned to one of two groups (10 patients each) receiving either isoflurane 1.15 vol.% or enflurane 1.68 vol.% endexpiratory. Measurements were performed and blood samples were taken in the awake state (I); 15 min after achievement of steady-state conditions with 1.68 vol.% enflurane or 1.5 vol.% isoflurane without blood pressure support (II); during norepinephrine-induced hypertension at a cerebral perfusion pressure of 110 mmHg (III); and during controlled hyperventilation at a PaCO2 of 27 mmHg and normotension (IV). Cerebral blood flow was measured by the argon wash-in technique. Isoflurane and enflurane produced a significant drop in cardiac index and cerebral perfusion pressure and reduced cerebral blood flow significantly by 35% and 39% respectively. Cerebral oxygen consumption was also significantly decreased by 49% (isoflurane) and 50% (enflurane). Induced hypertension with norepinephrine increased cerebral blood flow significantly by 32% (isoflurane) and 26% (enflurane), while hypocapnia reduced cerebral blood flow significantly by 26% (isoflurane) and 29% (enflurane).(ABSTRACT TRUNCATED AT 250 WORDS)