[Clinical study of low-flow anesthesia with isoflurane. II. Respiratory effects of isoflurane in low-flow anesthesia and interaction of isoflurane and muscle relaxants].
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Adult↗
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Lack of beta-adrenergic activity of isoflurane in the dog: a comparison of circulatory effects of halothane and isoflurane after propranolol administration.
The studies were undertaken to determine whether isoflurance inhalation is associated with a degree of beta-adrenergic action that is potentially important in clinical situations, and to compare the circulatory tolerance to isoflurane and halothane in dogs following beta blockade. We measured arterial and pulmonary artery pressure, left and right ventricular filling pressure, heart rate and cardiac output, and derived stroke volume and systemic and pulmonary vascular resistances in 13 mongrel dogs. The haemodynamic response to 1 MAC and 2 MAC isoflurane was studied in seven dogs and was similar before and after propranolol 0.1mg/kg i.v. In six dogs, propranolol 0.5mg/kg caused no significant changes in the circulatory response to 1 MAC and 2 MAC isoflurane or 1 MAC halothane. However, in three dogs, administration of 2 MAC halothane after propranolol 0.5mg/kg resulted in such profound circulatory depression as to preclude further study. These data suggest that (a) isoflurane possesses no clinically important beta-adrenergic stimulating activity; (b) there is no adverse drug interaction upon the circulation with the combination of isoflurane and propranolol; (c) in the presence of moderated profound beta-adrenergic blockade, 2 MAC isoflurane may be tolerated better than 2 MAC halothane.
Adrenergic beta-Agonists↗
Anaesthetic induction with isoflurane or halothane. Oxygen saturation during induction with isoflurane or halothane in unpremedicated children.
The authors performed a randomised, prospective trial in which one junior anaesthetist administered gaseous induction of anaesthesia to 50 unpremedicated children with either isoflurane or halothane in nitrous oxide and oxygen. Arterial oxygen saturation and the electrocardiogram were monitored and the incidence of complications noted. Desaturation below 85% occurred in six children, but only with isoflurane. The incidences of complications and desaturation events did not alter throughout the 25 isoflurane inductions. Coughing, movement, laryngospasm and sinus tachycardia occurred more frequently with isoflurane. Isoflurane inductions took longer (7.9 as compared with 5.4 minutes, p less than 0.001) and had 4.25 times the number of complications.
Anesthesia, Inhalation↗
Isoflurane for anaesthesia in the dental chair. a comparison of the incidence of cardiac dysrhythmias during anaesthesia with halothane and isoflurane.
A randomised single-blind trial was performed to compare the effects on cardiac rhythm of isoflurane and halothane in 100 dental outpatients having extractions under general anaesthesia in the dental chair without tracheal intubation. The incidence of supraventricular dysrhythmias did not differ significantly. No patient in the isoflurane group developed a ventricular dysrhythmia, whilst nine of those who received halothane did so (p = 0.0013). The quality of anaesthesia was acceptable in the isoflurane group, but induction time was longer (p less than 0.05) and the maximum heart rate was faster (p less than 0.01). There was no difference in the maximum end tidal carbon dioxide concentrations measured in a further 20 cases.
Adolescent↗
Effects of isoflurane on acetylcholine receptor channels. 1. Single-channel currents.
We studied the effects of the volatile general anesthetic isoflurane on single acetylcholine (ACh) receptor channels from clonal BC3H-1 cells. Excised patches were exposed to concentrations of isoflurane ranging from 0.18% to 4.0%, in the presence of 200 nM ACh. Isoflurane transformed channel behavior from isolated openings into bursts of brief openings. The channel open time decreased monotonically with the concentration of isoflurane; the mean open time was half of control at 0.4% isoflurane. The duration of bursts also decreased in the presence of isoflurane. The duration of brief closures within bursts was 300-400 musec at concentrations above 0.3% isoflurane. The number of openings per burst increased moderately with isoflurane but did not exceed 3. The frequency of bursts increased with the concentration of isoflurane. The apparent single-channel conductance decreased to 75% of control at 4% isoflurane. These results are discussed in terms of models of channel block. The concentration dependence of the open time, the gap duration, and the conductance are consistent with a sequential open-channel blocking mechanism in which most but not all blocking events were resolved. A model that assumes that isoflurane "blocks" both open and closed channels was then considered. This model is consistent not only with the open time data but also with the burst duration and number of openings per burst. These results indicate that isoflurane has effects on closed as well as open ACh receptor channels.
Animals↗
The interaction of nitrous oxide and isoflurane with incomplete cerebral ischemia in the rat.
In rats with incomplete cerebral ischemia the effects of 70% N2O alone, isoflurane alone (0.5 and 1 MAC), and the combination of N2O + isoflurane on neurologic outcome, neurohistopathology, and EEG were compared. Moderate and severe ischemia were produced by right carotid artery occlusion combined with hemorrhagic hypotension (moderate ischemia, MAP = 30 mmHg, FIO2 = 0.30; severe ischemia, MAP = 25 mmHg, FIO2 = 0.20). Neurologic outcome was evaluated using a graded deficit score from 0 to 5 (0 = normal, 5 = death associated with stroke), and neurohistopathology was evaluated using a 40-point scale from 0 = normal to 40 = total hemisphere infarct at the level of the caudate nucleus in coronal section. Compared with N2O alone, isoflurane (0.5 and 1 MAC) improved neurologic outcome following moderate ischemia (P less than 0.05). Isoflurane also decreased histopathologic damage following moderate ischemia (N2O control = 33 +/- 1 vs. 0.5 MAC isoflurane = 11 +/- 4 and 1 MAC isoflurane = 12 +/- 3, P less than 0.05), whereas only 0.5 MAC isoflurane decreased histopathologic damage following severe ischemia (N2O control = 38 +/- 1 vs. 0.5 MAC isoflurane = 25 +/- 5; P less than 0.05) Adding N2O to 0.5 MAC isoflurane attenuated the neurologic protective effect of isoflurane alone and increased histopathologic damage following both moderate and severe ischemia (moderate = 23 +/- 5, severe = 37 +/- 2; both P greater than 0.05 compared with N2O controls). The effect of adding 70% N2O to isoflurane on cerebral blood flow (CBF) and cerebral oxygen consumption(CMRO2) was also evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, Inhalation↗
Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers.
Awareness, defined as conscious memory during anesthesia, has been a problem in anesthesia practice. To determine the effect of isoflurane and nitrous oxide (N2O) on memory, 17 healthy adult volunteers were randomly assigned to receive isoflurane or N2O and received the alternate agent 1-2 weeks later. Each volunteer was studied at four end-tidal concentrations of each agent, consecutively 0.15, 0.3, 0.45, and 0.15 times the minimum alveolar concentration (MAC) for isoflurane or 0.3, 0.45, 0.6, and 0.3 times MAC for N2O. After 15-min equilibration at each end-tidal concentration, volunteers were tested for voluntary response to command and were presented with verbal information to be recalled after anesthesia. Volunteers were interviewed on the day after the study and tested for conscious and unconscious memory of the information presented during anesthetic administration. MAC-awake (the end-tidal concentration preventing voluntary response in 50% of volunteers) was 0.38 (0.35-0.42) times MAC for isoflurane and 0.64 (0.61-0.68) MAC for N2O (means, 95% confidence limits), indicating isoflurane to be more potent than N2O in suppressing voluntary response (P = .0001). Memory data were analyzed in 12 volunteers who completed the study and in whom the allocation of information to be recalled was counterbalanced among agents and concentrations of agents. Memory was decreased by increasing concentrations of both agents. Conscious memory of the information presented during anesthetic administration was prevented by 0.45 MAC isoflurane but not completely prevented by 0.6 MAC N2O. Unconscious memory (defined as memory of information without conscious recognition) occurred during administration of both agents and was prevented by 0.45 MAC isoflurane but not by 0.6 MAC N2O. Isoflurane was more potent in suppressing memory than MAC-equivalent concentrations of N2O. Using models of the relationship between dose of agent and suppression of memory, a dose of both agents was estimated that suppressed memory by 50% (ED50). The ED50 was 0.20 MAC for isoflurane (95% confidence intervals, 0.15-0.25), and 0.50 MAC for N2O (95% confidence intervals 0.43-0.55). We conclude that isoflurane and N2O suppress memory in a dose-dependent manner, and that isoflurane is more potent in preventing memory and voluntary response to command than MAC-equivalent concentrations of N2O.
Adolescent↗
Isoflurane-induced vasodilation: role of the alpha-adrenergic nervous system.
Isoflurane is a potent systemic vasodilator. Because isoflurane vasodilation is clinically significant, we sought to explore whether decreases in systemic vascular resistance caused by isoflurane involve the alpha-adrenergic nervous system in humans. Specifically, we tested the hypothesis that isoflurane systemic vasodilation is mediated via inhibition of vascular alpha 1-adrenergic responsiveness. Phenylephrine pressor dose-response curves were established before anesthesia and during isoflurane/oxygen anesthesia in patients undergoing coronary artery bypass surgery; all patients included in the study (n = 11) demonstrated significant (P = 0.0001) decreases in systemic vascular resistance when isoflurane was given in concentrations adequate to produce a 20% decrease in mean arterial blood pressure. Polynomial regression of the phenylephrine dose-response curve was used to estimate the phenylephrine dose required to increase mean arterial blood pressure 15 mm Hg, designated PD15 mm Hg. Each patient served as his or her own control. Preanesthetic baseline PD15 mm Hg values (115 +/- 23 micrograms [1.4 +/- 0.3 micrograms/kg], mean +/- SEM) were not significantly different from isoflurane PD15 mm Hg values (124 +/- 20 micrograms [1.5 +/- 0.3 micrograms/kg]). End-tidal isoflurane concentration ranged from 0.6%-1.5%; isoflurane PD15 mm Hg was not correlated with end-tidal isoflurane concentration. Patient characteristics and hemodynamics did not affect PD15 mm Hg. These results suggest that isoflurane-induced systemic vasodilation is not mediated via inhibition of alpha 1-adrenergic responsiveness, disproving our hypothesis. This finding has clinical importance because it demonstrates that alpha 1-adrenergic stimulation with phenylephrine is effective in correcting hypotension in patients receiving isoflurane anesthesia.
Adrenergic alpha-Agonists↗
Thiopental and epinephrine-induced dysrhythmias in dogs anesthetized with enflurane or isoflurane.
Epinephrine-induced dysrhythmias were studied in 19 dogs anesthetized with 1.25 MAC enflurane or isoflurane, or the same preceded by thiopental (20 mg/kg). In 11 (group 1) dogs, thiopental reduced the dose of epinephrine required for production of ventricular ectopy, bigeminy and tachycardia with enflurane, and only ventricular tachycardia with isoflurane (P less than 0.05). Thiopental potentiation of epinephrine-induced dysrhythmias with enflurane lasted 4 hr after induction. In eight (group 2) dogs, the arrhythmic dose (ADE in microgram/ml) and plasma level of epinephrine (PLE in ng/ml) for four or more ventricular extrasystoles in 15 sec were determined in the same animal under each of the four test conditions. ADE and PLE values (X +/- SEM) were, respectively, enflurane, 9.1 +/- 1.0 and 141 +/- 24 (8/8 dogs); enflurane-thiopental, 5.0 +/- 0.6 and 63 +/- 16 (8/8 dogs); isoflurane, 28.3 and 330 (1/7 dogs); and isoflurane-thiopental, 15.2 +/- 2.8 and 265 +/- 59 (5/7 dogs). In addition, thiopental had no effect on plasma epinephrine levels reached during epinephrine infusions with 1.0 (enflurane only), 2.0 (enflurane, isoflurane) and 4.0 micrograms X kg-1 X min-1 (isoflurane only). Nor were epinephrine levels reached during enflurane or enflurane-thiopental different from those reached during isoflurane or isoflurane-thiopental. It is concluded that thiopental potentiates several types of epinephrine-induced ventricular dysrhythmias with enflurane, but only ventricular tachycardia with isoflurane. Furthermore, isoflurane or isoflurane-thiopental were less sensitizing than enflurane or enflurane-thiopental. Finally, neither thiopental nor the anesthetic agents affected plasma epinephrine levels reached during epinephrine infusions lasting 3 min.
Animals↗
Washin and washout of isoflurane during cardiopulmonary bypass.
To help decide when an inhalational agent should be discontinued during cardiopulmonary bypass (CPB), its rate of washin and washout must be known. Isoflurane one per cent was administered to 14 patients undergoing CPB and isoflurane blood concentrations were measured to determine the time course of washin and washout of this agent. Bubble oxygenators were used for seven patients and membrane oxygenators for the remaining seven. During the administration of isoflurane, isoflurane blood concentrations rose slowly and did not reach a steady state during the time available for washin. Isoflurane blood concentrations decreased by at least 50 per cent within two minutes of turning off the vaporizer, and by 15 minutes the concentration had dropped by 75 per cent. There was a tendency for more rapid elimination of isoflurane in patients undergoing rewarming during this period. There did not appear to be an important difference between bubble and membrane oxygenators in the rate of washin and washout of isoflurane. Within 15 minutes of turning off the vaporizer only 25 per cent of the original blood concentration of isoflurane will remain. The anaesthetist must decide what concentration of isoflurane is acceptable during separation from CPB. Knowledge of the time course of isoflurane washout will allow more accurate determination of when to discontinue its administration in order to reach an acceptable concentration by the time separation from CPB occurs.
Adult↗
Cerebrovascular responses to carbon dioxide in children anaesthetized with halothane and isoflurane.
To determine the effects of isoflurane and halothane on cerebrovascular reactivity to CO2, 30 children aged one to six years were anaesthetized with isoflurane or halothane in an air and oxygen mixture with an FIO2 of 0.3. The end-tidal concentrations (0.5 minimum alveolar concentration (MAC) or 1.0 MAC) of isoflurane or halothane were age-adjusted. After achieving a steady-state at both 0.5 MAC and 1.0 MAC isoflurane and halothane, the end-tidal carbon dioxide tension (PETCO2) was randomly adjusted to 20, 40, or 60 mmHg. Cerebral blood flow velocity (CBFV) and the cerebrovascular resistance index (RI+) in the middle cerebral artery (MCA) were measured by a transcranial Doppler monitor. Three measurements of CBFV and RI+ were obtained at each PETCO2 and isoflurane or halothane concentration. Any rise in the PETCO2 caused an increase in CBFV during both 0.5 MAC (r2 = 0.99 and 0.99) and 1.0 MAC (r2 = 0.96 and 0.95) isoflurane and halothane anaesthesia, respectively (P less than 0.05). The CBFV for isoflurane increased as PETCO2 increased from 20 to 60 mmHg for both 0.5 MAC and 1.0 MAC (P less than 0.05). The CBFV for halothane increased as PETCO2 increased from 20 to 40 mmHg for both 0.5 MAC and 1.0 MAC halothane (P less than 0.05), but did not change as PETCO2 increased from 40 to 60 mmHg for both 0.5 MAC and 1.0 MAC halothane. The RI+ showed an inverse relationship with CBFV at each PETCO2 for 0.5 MAC (r2 = 0.98 and 0.99) and 1.0 MAC (r2 = 0.76 and 0.53) isoflurane and halothane, respectively (P less than 0.05). The CBFV did not differ significantly between 0.5 and 1.0 MAC isoflurane and halothane at corresponding PETCO2 values. The cerebrovascular response to CO2 at 20 mmHg between 0.5 MAC and 1.0 MAC halothane was not significantly different. These data strongly suggest that isoflurane and halothane in doses up to 1.0 MAC do not affect the cerebrovascular reactivity of the MCA to CO2 in anaesthetized, healthy children.
Anesthesia, Inhalation↗
Regional blood flow and tissue oxygen pressures of the collateral-dependent myocardium during isoflurane anesthesia in dogs.
The authors investigated the effects of isoflurane on blood flow and tissue oxygen pressures of a collateral-dependent myocardium. Seventeen dogs divided into two groups were studied 3-4 weeks after implantation of ameroid coronary artery constrictors to completely occlude the proximal part of the left anterior descending artery. Experiments were performed during anesthesia with an opiate that was infused intravenously throughout the experiments. In Group 1 (n = 9), measurements were obtained during control and during isoflurane- (1.6-2.2 vol%) induced hypotension (mean arterial pressure, 60 mmHg). In Group 2 (n = 8), the identical protocol was applied, but norepinephrine was infused to maintain normotension. Dipyridamole effects were studied in five animals of Group 2 after a second control period at least 1 h after discontinuation of isoflurane. Isoflurane-induced hypotension caused reductions of blood flow and surface tissue oxygen pressures in the collateral flow-dependent area. Vasodilation in the normal left ventricular areas was demonstrated by an unchanged blood flow despite a reduced oxygen consumption and by a significantly increased coronary sinus hemoglobin oxygen saturation. When arterial pressure was maintained at its control level by norepinephrine, tissue oxygen pressures remained constant and collateral as well as normal area flow increased significantly during isoflurane. Coronary vascular resistance was lower during administration of isoflurane and norepinephrine compared with that during isoflurane induced hypotension, suggesting a significant contribution of tissue oxygen demand in regulation of coronary vascular resistance. At comparable levels of arterial pressure and left ventricular oxygen consumption, normal zone blood flow was significantly higher during dipyridamole than during isoflurane and norepinephrine. Thus, isoflurane-induced hypotension decreased blood flow and tissue oxygen pressures of collateral flow-dependent myocardial areas. However, neither isoflurane nor dipyridamole caused such alterations when arterial pressure was normal.
Anesthesia, Intravenous↗
Cerebrovascular responsiveness to carbon dioxide in dogs with 1.4% and 2.8% isoflurane.
Cerebral blood flow (CBF) responsiveness to alterations in arterial CO2 tensions (PaCO2) during 1.4% and 2.8% isoflurane anesthesia was assessed. Dogs were initially anesthetized with thiopental (12 mg/kg, iv bolus), their tracheae intubated, after which anesthesia was maintained with 1.4% isoflurane. In eight animals three levels of PaCO2 (25, 40, and 60 mmHg) were studied during 1.4% and 2.8% isoflurane. Mean arterial blood pressure, sagittal sinus pressure, and cerebrospinal fluid pressure were measured and CBF was determined using radiolabeled microspheres. Cerebral perfusion pressure (CPP) was maintained constant at approximately 80 mmHg by inflation of a balloon in the midthoracic aorta. CBF during normocapnia was 70 +/- 14 and 118 +/- 18 ml.min-1.100 g-1 with 1.4% and 2.8% isoflurane, respectively. As PaCO2 was decreased and increased, CBF decreased and increased to 42 +/- 7% and 185 +/- 16% of control, respectively, during 1.4% isoflurane. During 2.8% isoflurane, hypocapnia decreased CBF to 39 +/- 6% of control, but CBF did not increase with hypercapnia. In a second group of animals (n = 8), the effects of changes in CPP during hypercapnia with 1.4% and 2.8% isoflurane were assessed. Increasing CPP approximately 25 mmHg with both 1.4% and 2.8% isoflurane increased CBF but did not change CVR from control. With 1.4% isoflurane, the cerebral vasculature constricts with hypocapnia and dilates with hypercapnia, whereas with 2.8% isoflurane, vasoconstriction to hypocapnia is retained but vasodilation to hypercapnia is absent.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗
Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane, and enflurane in the chronically instrumented dog.
The systemic and coronary hemodynamic effects of desflurane were compared to those of isoflurane, halothane, and enflurane in chronically instrumented dogs. Since autonomic nervous system function may significantly influence the hemodynamic actions of anesthetics in vivo, a series of experiments also was performed in the presence of pharmacologic blockade of the autonomic nervous system. Eight groups comprising a total of 80 experiments were performed on 10 dogs instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. Systemic and coronary hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.25 and 1.75 MAC desflurane, isoflurane, halothane, and enflurane. Desflurane (+79 +/- 12% change from control) produced greater increases in heart rate than did halothane (+44 +/- 12% change from control) or enflurane (+44 +/- 9% change from control) at 1.75 MAC. Desflurane preserved mean arterial pressure to a greater degree than did equianesthetic concentrations of isoflurane. This result was attributed to a smaller effect on peripheral vascular resistance as compared to isoflurane and greater preservation of myocardial contractility as evaluated by peak positive left ventricular dP/dt and the rate of increase of ventricular pressure at 50 mmHg (dP/dt50) compared to other volatile anesthetics. Increases in diastolic coronary blood flow velocity (+19 +/- 6 and +35 +/- 12% change from control at 1.75 MAC, respectively) and concomitant decreases in diastolic coronary vascular resistance (-41 +/- 12 and -58 +/- 6% change from control at 1.75 MAC, respectively) were produced by desflurane and isoflurane. In the presence of autonomic nervous system blockade, the actions of desflurane and isoflurane were nearly identical with the exception of coronary vasodilation. After autonomic nervous system blockade, isoflurane increased coronary blood flow velocity, but desflurane did not. Furthermore, both desflurane and isoflurane continued to produce less depression of myocardial contractility than did halothane and enflurane. In summary, at equianesthetic concentrations, desflurane and isoflurane produced similar hemodynamic effects; however, in the absence of drugs that inhibit autonomic reflexes, desflurane had less negative inotropic activity and produced less decrease in arterial pressure. The coronary vasodilator actions of desflurane and isoflurane within the limitations of this model were not similar. When the increase in heart rate and rate-pressure product produced by desflurane were prevented in dogs with autonomic nervous system blockade, desflurane produced no change in coronary blood flow velocity.
Animals↗
Intracoronary isoflurane causes marked vasodilation in canine hearts.
Previous studies of coronary vasomotor effects of isoflurane were complicated by changes in systemic hemodynamic conditions and in global cardiac work demands. Accordingly, in the current study, the left anterior descending coronary artery (LAD) of 11 open-chest dogs anesthetized with fentanyl and pentobarbital was cannulated and perfused with isoflurane-free arterial blood or with arterial blood equilibrated in an extracorporeal oxygenator with isoflurane (0.5, 1.0, 2.0% in 95.5% oxygen-4.5% carbon dioxide). Steady-state changes in coronary blood flow (CBF) in LAD were measured electromagnetically, and their transmural distribution (endocardium: epicardium ratio) was evaluated with 15-microns radioactive microspheres. Venous blood was obtained from the anterior interventricular vein and analyzed for oxygen tension (PO2) and oxygen content. Myocardial oxygen consumption (MVO2) was calculated using the Fick equation. Cardiac responses during isoflurane were compared to those during maximal vasodilation with intracoronary adenosine. Perfusion pressure was maintained at 100 mmHg. CBF increased 271, 279, and 503% with 0.5, 1.0, and 2.0% isoflurane, respectively, with no change in the endocardium:epicardium ratio. With 2.0% isoflurane, the increase in CBF was 80% of the maximal, adenosine-induced response. The increases in CBF caused by isoflurane were accompanied by greater than proportional increases in venous PO2 and decreases in the arteriovenous oxygen difference, reflecting the reduction (approximately 40% in MVO2. In conclusion, isoflurane has a direct, concentration-dependent relaxing effect on coronary vascular smooth muscle in the canine heart in situ. The ability of isoflurane to increase CBF nearly maximally while also significantly reducing local myocardial oxygen requirements attests to the potency of isoflurane's direct vasodilator action.
Adenosine↗
Halothane and isoflurane increase pulmonary artery endothelial cell sensitivity to oxidant-mediated injury.
Volatile anesthetics inhibit phagocytic cell function, yet little is known about their effects on target tissues or on the target tissue response to stimulated phagocytes. Experiments were performed to determine how exposure to halothane and isoflurane changes rat pulmonary artery endothelial cell (RPAEC) viability in response to the toxic oxygen metabolites produced by stimulated phagocytic cells. RPAECs were grown in monolayer culture. The monolayers were treated with phorbol myristate acetate (PMA) -stimulated human neutrophils at an effector-to-target ratio of 20:1 after equilibration with 0.4% or 1.7% halothane or 0.7% or 2.8% isoflurane. As measured by percent-specific release of incorporated 51Cr label (mean +/- SE), cytotoxicity in the presence of 1.7% halothane (75.3 +/- 3.4%) was significantly greater (P less than 0.02) than cytotoxicity in 5% CO2 in air (44.7 +/- 3.3%) and in 0.4% halothane (57.3 +/- 4.7%). Also, cytotoxicity in 1.7% halothane was significantly greater than in 0.4% halothane (P less than 0.02). The authors found that RPAECs incubated in isoflurane exhibited significantly greater release of 51Cr than cells incubated in the MAC equivalent concentrations of halothane: 78.2 +/- 2.6% in 0.7% isoflurane (P = 0.0004) and 83.8 +/- 1% in 2.8% isoflurane (P = 0.005). Because early neutrophil cytotoxicity has been found to be mediated primarily by hydroxyl radical (HO.) and hydrogen peroxide (H2O2), the authors measured H2O2 production by similar numbers of PMA-stimulated neutrophils under similar exposure conditions. In carrier gas, PMA-stimulated neutrophils produced 20.5 +/- 1.3 nmol H2O2.10(6) cells-1.h-1. At the higher concentrations of halothane, H2O2 production actually was inhibited in comparison with carrier gas (15.4 +/- 1.4 nmol H2O2.10(6) cells-1.h-1 in 1.7% halothane and 16.8 +/- 0.8 in 2.8% halothane), but the degree of inhibition did not reach statistical significance. In isoflurane, however, H2O2 production was not different from that seen in carrier gas. In other experiments, the monolayers were treated with 0, 200, 500, and 1,000 microM H2O2 after equilibration with 0.4%, 1.7%, and 2.8% halothane or 0.7%, 2.8%, and 5% isoflurane in 5% CO2 in air. Efficiency of replating was used to measure degree of injury. Both halothane and isoflurane enhance the sensitivity of the RPAEC monolayers to injury by H2O2. The sensitizing effect of halothane was reversed by removing the anesthetic. Halothane and isoflurane thus enhance RPAEC sensitivity to injury by both H2O2 and PMA-stimulated neutrophils. In increasing RPAEC sensitivity to injury by oxygen metabolites, halothane and isoflurane may be inhibiting processes involved in intracellular antioxidant defenses.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Isoflurane and an alpha 2-adrenoceptor agonist suppress nociceptive neurotransmission in neonatal rat spinal cord.
Analgesia is an important component of general anesthesia. alpha 2-adrenoceptor agonists such as clonidine and dexmedetomidine are effective analgesics at the spinal level, and furthermore, they reduce the volatile anesthetic requirement. In order to probe a possible spinal-level contribution to general anesthetic-induced analgesia, the effects of dexmedetomidine were tested in an isolated spinal cord preparation. The effects of dexmedetomidine were compared with those of isoflurane, and dexmedetomidine-isoflurane interactions were explored. The test response was a nociceptive-related slow ventral root potential (slow VRP) recorded from the isolated neonatal rat spinal cord in response to electrical stimulation of a dorsal root. At 0.2-1.28 vol%, isoflurane reversibly depressed the slow VRP. At a lower concentration (0.14 vol%), isoflurane increased the slow VRP in three of five preparations. At 1.0-1.28 vol%, isoflurane also depressed the monosynaptic reflex. Recovery on washout usually was to a level greater than control. The N-methyl-D-aspartate (NMDA) receptor antagonist (DL)-2-amino 5-phosphonovalerate (10 microM) prevented the rebound to levels above control on isoflurane washout. The earlier components of the slow VRP were more sensitive to isoflurane than were the later. Dexmedetomidine (0.5-10 nM) depressed the slow VRP and had no effect on the monosynaptic reflex. The slow VRP depends on both substance P and glutamate NMDA-receptor-mediated neurotransmission; isoflurance and dexmedetomidine depressed responses to both substance P and NMDA. Although the two agents depress responses to the same neurotransmitters, there is no evidence that they act at the same cellular site(s). There was no significant interaction between dexmedetomidine and isoflurane. The results suggest that isoflurane exerts marked inhibitory effects on spinal neurotransmission, depressing both substance P and glutamate-mediated pathways. There is a possible biphasic effect on the NMDA receptor. To the extent that nociception depends on these neurotransmitters, isoflurane may be expected to exert profound analgesic effects at the spinal level. By blocking responses to strongly arousing stimuli, these effects may contribute to general anesthesia. Suppression of nociceptive neurotransmission at the spinal level may contribute to dexmedetomidine's anesthetic-sparing properties as well as to analgesia by this agent.
Adrenergic alpha-Agonists↗
Comparison of kinetics of sevoflurane and isoflurane in humans.
The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%-70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured VE, FA, and FM for 6-7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 +/- 0.003 (mean +/- SD); sevoflurane, 0.850 +/- 0.018; and isoflurane, 0.733 +/- 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 +/- 0.020; isoflurane, 0.223 +/- 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% +/- 7%) equaled recovery of isoflurane (101% +/- 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Inhalation↗