摘要:

BackgroundPerfluorocarbon liquids are being used experimentally and in clinical trials for the treatment of acute lung injury. Their resemblance to inhaled anesthetic agents suggests the possibility of application by vaporization. The authors' aim was to develop the technical means for perfluorocarbon vaporization and to investigate its effects on gas exchange and lung function in an ovine model of oleic acid‐induced lung injury.MethodsTwo vaporizers were calibrated for perfluorohexane and connected sequentially in the inspiratory limb of a conventional anesthetic machine. Twenty sheep were ventilated in a volume controlled mode at an inspired oxygen fraction of 1.0. Lung injury was induced by intravenous injection of 0.1 ml oleic acid per kilogram body weight. Ten sheep were treated with vaporized perfluorohexane for 30 min and followed for 2 h; 10 sheep served as controls. Measurements of blood gases and respiratory and hemodynamic parameters were obtained at regular intervals.ResultsVaporization of perfluorohexane significantly increased arterial oxygen tension 30 min after the end of treatment (P < 0.01). At 2 h after treatment the oxygen tension was 376 +/‐ 182 mmHg (mean +/‐ SD). Peak inspiratory pressures (P < 0.01) and compliance (P < 0.01) were significantly reduced from the end of the treatment interval onward.ConclusionVaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid‐induced lung injury.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThis was a study of the relative effects on directly recorded sympathetic activity of desflurane, isoflurane, and halothane.MethodsRenal sympathetic nerve activity (RSNA) was recorded with bipolar electrodes in renal nerves exposed retroperitoneally in anesthetized ([Greek small letter alpha]‐chloralose), paralyzed (succinylcholine), and artificially ventilated dogs. Somatosympathetic responses were evoked by supramaximal electrical stimulation of radial nerves (0.33 Hz, 30 V, 0.5 ms). Spontaneous and evoked activity were rectified, averaged, and integrated to allow quantitative comparison of the effects of 3–12% desflurane, 0.6–2.4% isoflurane, and 0.4–1.6% halothane.ResultsIncreasing concentrations of isoflurane progressively depressed mean RSNA, A [Greek small letter delta], and C reflexes by 40% (P < 0.01), 50% (P < 0.01) and 70% (P < 0.001) respectively at 2.4% concentration. Halothane depressed both reflexes equally by approximately 60% (P < 0.01) at 1.6% concentration, without significant depression of spontaneous RSNA. Desflurane increased and subsequently decreased RSNA by 37% (P < 0.02) and 65% (P < 0.001) at concentrations of 6% and 12% respectively, and although somatosympathetic reflexes remained unchanged up to 9%, both were depressed equally by 70% (P < 0.01) at 12% concentration.ConclusionAfter equilibration, lower concentrations of desflurane remained excitatory, but, like isoflurane, higher concentrations depressed RSNA. The effect of halothane on RSNA was insignificant. Isoflurane depressed C more than A [Greek small letter delta] somatosympathetic reflexes, which is uncorrelated with lipid solubility because desflurane and halothane, which have the highest and lowest minimum alveolar concentration, respectively, depressed both equally.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe effects of adrenergic agonists, often used as local anesthetic additives or spinal analgesics, on spinal vessels have not been firmly established. The authors investigated the effects of [Greek small letter alpha]2‐and [Greek small letter alpha]1‐adrenergicagonists on spinal and cerebral pial vessels in vivo.MethodsPentobarbital‐anesthetized dogs (n = 28) were prepared for measurement of spinal pial‐vessel diameter in a spinal‐window preparation. The authors applied dexmedetomidine, clonidine, phenylephrine, or epinephrine in three different concentrations (0.5, 5.0, and 50 [micro sign]g/ml; [2.1, 1.9, 2.5, and 2.3] x [10‐6, 10‐5, and 10‐4] M, respectively) under the window (one drug in each dog) and measured spinal pial arteriolar and venular diameters in a sequential manner. To enable the comparison of their effects on cerebral vessels, the authors also administered these drugs under a cranial window.ResultsOn topical administration, each drug constricted spinal pial arterioles in a concentration‐dependent manner. Phenylephrine and epinephrine induced a significantly larger arteriolar constriction than dexmedetomidine or clonidine at 5 [micro sign]g/ml (8%, 11%, 0%, and 1%, respectively). Spinal pial venules tended to be less constricted than arterioles. In cerebral arterioles, greater constrictions were induced by dexmedetomidine and clonidine than those induced by phenylephrine and epinephrine (14%, 8%, 0%, and 1%, respectively). Cerebral pial venules tended to exhibit larger constrictions than cerebral arterioles (unlike in spinal vessels).ConclusionDexmedetomidine and clonidine constricted spinal vessels in a concentration‐dependent manner, but such vasoconstrictions were smaller than those induced by phenylephrine and epinephrine.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAspiration pneumonitis is characterized by proteinaceous pulmonary edema and acute infiltration of neutrophils into the alveolar space. This study examined the role of the proinflammatory cytokine, tumor necrosis factor‐[Greek small letter alpha] (TNF‐[Greek small letter alpha]), on the pathogenesis of the injury produced by the different components that may be present in the aspirate, acid, or gastric particles.MethodsRats were injured by intratracheal instillation of a vehicle containing acid or gastric particles. TNF‐[Greek small letter alpha] concentration of bronchoalveolar lavage fluid was determined using a bioassay. upregulation of lung TNF‐[Greek small letter alpha] mRNA was also measured. The effect of intratracheal anti‐rat TNF‐[Greek small letter alpha] treatment was assessed by lung protein permeability, blood gases, and lung myeloperoxidase activity.ResultsInjury vehicle alone and acid injury resulted in a small TNF‐[Greek small letter alpha] peak 1–2 h after injury in the lavage fluid. Both particulate and acidic particulate groups produced a much more robust TNF‐[Greek small letter alpha] signal that reached a plateau at 2–4 h after injury and declined at 8 h. Upregulation of TNF‐[Greek small letter alpha] mRNA was only detected in the particulate‐containing groups. Acidic particulate exposure yielded a synergistic increase in protein permeability and decrease in blood oxygenation. Anti‐TNF‐[Greek small letter alpha] treatment reduced protein permeability and myeloperoxidase activity and increased blood oxygenation in the groups exposed to only acid. Such treatment had no effect on either of the particulate containing injuries.ConclusionsTNF‐[Greek small letter alpha] is differentially manifested according to the components that make up the aspirate but the levels of TNF‐[Greek small letter alpha] expression do not correlate with the severity of the resultant injury. However, the reduction in acid‐induced lung injury by anti‐TNF‐[Greek small letter alpha] treatment indicates that TNF‐[Greek small letter alpha] plays a role in the pathogenesis of aspiration pneumonitis.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundIn cultured slice preparations of rat neocortical tissue, clinically relevant concentrations of volatile anesthetics mainly decreased action potential firing of neurons by enhancing [Greek small letter gamma]‐aminobutyric acid (GABAA) receptor‐mediated synaptic inhibition. The author's aim was to determine if other anesthetic agents are similarly effective in this model system and act via the same molecular mechanism.MethodsThe actions of various general anesthetics on the firing patterns of neocortical neurons were investigated by extracellular single‐unit recordings.ResultsPentobarbital, propofol, ketamine, and ethanol inhibited spontaneous action potential firing in a concentration‐dependent manner. The estimated median effective concentration (EC50) values were close to or below the EC50values for general anesthesia. Bath application of the GABAAantagonist bicuculline (100 [micro sign]M) decreased the effectiveness of propofol, ethanol, halothane, isoflurane, enflurane, and diazepam by more than 90%, indicating that these agents acted predominantly via the GABAAreceptor. The depressant effects of pentobarbital and ketamine were not significantly reduced by bicuculline treatment. Drugs acting mainly via the GABAAreceptor altered the firing patterns of neocortical cells in different manners. Diazepam reduced the discharge rates by decreasing the number of action potentials per burst, leaving the burst rate unaffected. In contrast, muscimol, GABA, propofol, and volatile anesthetics decreased the burst rate.ConclusionsAlthough several anesthetic agents acted nearly exclusively via the GABAAreceptor, they changed the discharge patterns of cortical neurons in different ways. This finding is explained by GABA‐mimetic or benzodiazepine‐like molecular interactions.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundPrevious studies have provided evidence that clinical levels of propofol alter the functions of voltage‐dependent sodium channels, thereby inhibiting synaptic release of glutamate. However, most of these experiments were conducted in the presence of sodium‐channel activators, which alter channel inactivation. This study electrophysiologically characterized the interactions of propofol with unmodified sodium channels.MethodsSodium currents were measured using whole‐cell patch‐clamp recordings of rat brain IIa sodium channels expressed in a stably transfected Chinese hamster ovary cell line. Standard electrophysiologic protocols were used to record sodium currents in the presence or absence of externally applied propofol.ResultsPropofol, at concentrations achieved clinically in the brain, significantly altered sodium channel currents by two mechanisms: a voltage‐independent block of peak currents and a concentration‐dependent shift in steady‐state inactivation to hyperpolarized potentials, leading to a voltage dependence of current suppression. The two effects combined to give an apparent concentration yielding a half‐maximal inhibitory effect of 10 [micro sign]M near the threshold potential of action potential firing (about ‐60 mV). Propofol inhibition was also use‐dependent, causing a further block of sodium currents at these anesthetic concentrations.ConclusionsIn these experiments with pharmacologically unaltered sodium channels, propofol inhibition of currents occurred at concentrations about eight‐fold above clinical plasma levels and thus at brain concentrations reached during clinical anesthesia. Therefore, the results indicate a possible role for sodium‐channel suppression in propofol anesthesia.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundPolymorphonuclear neutrophils (PMNs) contribute to reperfusion injury. Because volatile anesthetics can reduce PMN adhesion in the reperfused, nonworking heart, the authors analyzed whether this action of volatile anesthetics affects cardiac performance after ischemia and reperfusion and further clarified the underlying mechanism.MethodsIsolated guinea pig hearts perfused with crystalloid buffer and performing pressure‐volume work were used. Hearts were subjected to 15 min global ischemia and 20 min reperfusion. In the intervention groups an intracoronary bolus of 3 x 106PMNs was applied in the second min of reperfusion, either in the absence or presence of 0.5 or 1 minimum alveolar concentration sevoflurane or isoflurane. The number of sequestered PMNs was calculated from the difference between coronary input and output (coronary effluent) of PMNs. Performance of external heart work, determined pre‐ and postischemically, served as criterion for recovery of myocardial function. Additionally, the expression of the integrin CD11b on the cell surface of PMN was measured before and after coronary passage.ResultsInjection of PMN in the reperfusion phase, but not under nonischemic conditions, reduced recovery of external heart work significantly (from 55 +/‐ 7% to 19 +/‐ 11%). Addition of sevoflurane or isoflurane in concentrations of 0.5 and 1 minimum alveolar concentration to the perfusate reduced postischemic PMN adhesion from 36 +/‐ 8% to basal values (20 +/‐ 7%) and prevented decline of cardiac function. CD11b expression on PMNs increased significantly during postischemic coronary passage under control conditions. Again, both anesthetics in both concentrations inhibited that activation.ConclusionsVolatile anesthetics reduce PMN adhesion in the reperfused coronary system and thereby preserve cardiac function. Reduced expression of the adhesion molecule CD11b on PMNs in the presence of sevoflurane or isoflurane is, at least in part, responsible for the cardioprotective effect.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundTwo major neurotransmitters, [Greek small letter gamma]‐aminobutyric acid (GABA) and the excitatory amino acid, glutamate, may be involved in nociception in the spinal cord. GABA and glutamate receptors may operate in concert to modify signals in the central nervous system. The purpose of this study was to investigate the spinal analgesic interaction between midazolam, a benzodiazepine‐GABAAreceptor agonist, and two glutamate receptor antagonists on acute thermal nociception.MethodsSprague‐Dawley rats were implanted with chronic lumbar intrathecal catheters and were tested for their tail withdrawal response by the tail flick test after intrathecal administration of saline, midazolam (1–100 [micro sign]g), AP‐5 (1–30 [micro sign]g), or YM872 (0.3–30 [micro sign]g). AP‐5 is an N‐methyl‐D‐aspartate (NMDA) receptor antagonist and YM872 is an [Greek small letter alpha]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptor antagonist. The combination of midazolam and the other two agents were also tested by isobolographic analyses. Motor disturbance and behavioral changes were observed.ResultsDose‐dependent increases in the tail flick latency were observed with midazolam, AP‐5, and YM872 with 50% effective dose values of 1.57 +/‐ 0.34 (SEM) [micro sign]g, 5.54 +/‐ 0.19 [micro sign]g, and 1.0 +/‐ 0.22 [micro sign]g, respectively. A potent synergy in analgesia with decreased behavioral changes and motor disturbance was obtained when combining midazolam with AP‐5 or YM872.ConclusionsSpinally administered midazolam and an NMDA‐ or an AMPA‐receptor antagonist exhibited potent synergistic analgesia on acute thermal nociception in rats. Side effects, shown by behavioral changes and motor disturbance, decreased with the combination of the agents. These results point out an important direction for the study of acute nociception.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID