ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The inhibitory effects of three inhalation anesthetics, i.e., halothane, enflurane, and isoflurane, on superoxide production and the intracellular mobilization of calcium in human neutrophils were studied. The superoxide production induced by N-formyl-methionylleucyl-phcnylalanine (FMLP) was inhibited by the anesthetics, but the binding of FML|3H|P to the cells and the superoxide-forming NADPH oxidasc of the phagocytic vesicles were not inhibited. The inhibition of the cellular superoxide production was partially reversed by the addition of a calcium ionophore, A23187. The increase in intracellular free calcium monitored by a calcium-sensitive fluorescent probe, quin-2 and the release of calcium from hydrophobic environment monitored by chlortetracycline were inhibited dose dependently by the anesthetics. These observations suggest that decreased mobilization of intracellular Ca2+is one of the mechanisms by which the anesthetics inhibited the superoxide production of human neutrophils stimulated by FMLP.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Isolated atria from neonatal (0–5 day old) and adult (50 ± 5 day old) rats were perifused in oxygenated Kreb's Henseleit solution at 30 ± 0.5° C and exposed to four different concentrations of halothane, isoflurane, or enflurane while isometric contractile tension was recorded and compared with control atria. ED50 values (mM of anesthetic required to produce 50% reduction in contractile tension) of neonates for halothane (0.18 ± 0.01), isoflurane (0.41 ± 0.05), and enflurane (0.41 ± 0.04) were significantly lower than those of adults (0.35 ± 0.02, 0.80 ± 0.05, and 1.15 ± 0.05, respectively). Furthermore, neonatal ED50calculated as per cent of adult ED50was significantly less for enflurane (35%) than for halothane (54%) or isoflurane (51%).

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effect of deep isoflurane anesthesia on ischemically induced neuronal damage was evaluated in the rat. Sixteen mechanically ventilated animals were maintained normocapnic and normothermic while subjected to a near complete forebrain ischemia insult induced with systemic hypotension (MAP = 50 ± mmHg) and bilateral carotid artery occlusion. Prior to ischemia, eight of the rats received isoflurane by inhalation until the EEG demonstrated a burst suppression pattern; the other eight were untreated controls. After 10 min of ischemia, the carotid clamps were removed, blood pressure was restored, and, in the treated group, isoflurane administration discontinued. Following the ischemic insult, the animals were observed over a 7-day period, at which time they were killed and the brains prepared for histologic study. Severity of damage was assessed by a direct count of irreversibly damaged neurons, which appear bright red when stained with cresyl violet-acid fuchsin. Areas of particular interest were those that characteristically display vulnerability to ischemic damage, i.e., hippocampus, caudate nuclei, and neocortex. The control group revealed severe damage in the hippocampal CA1 sector (70% cells acidophilic) with more variability in the caudate nuclei and neocortex. The treated group showed a similar extent of damage with approximately 74% cells acidophilic in hippocampus (CA1). Clinical appearance was indistinguishable between groups. The authors conclude that pretreatment with isoflurane shows no beneficial effects on delayed neuronal necrosis following near-complete forebrain ischemia.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects on whole body or cardiac metabolism of carbon dioxide, calcium, potassium, or digoxin were studied in 16 normal swine and 31 swine susceptible to malignant hyperthermia (MHS). Malignant hyperthermia (MH) was defined as an increase in metabolism that occurred in MHS but not in normal pigs. Whole body response: despite a sustained PaCO2greater than 130 mmHg, MH did not develop in four intact MHS swine during thiopental-N2O anesthesia and controlled ventilation. Drugs given during total cardiopulmonary bypass: MH did not develop in five MHS pigs with blood ionized calcium to 15 mEq/1, in four MHS pigs with digoxin levels to 60 ng/ml, or in four normal pigs with potassium to 10 mEq/1. In six MHS pigs, oxygen consumption increased from 6.5 to 11.6 ml O2· Min-1·kg-1when potassium exceeded 6 mEq/l; lactate did not increase. Cardiac response (during extracorporeal right heart bypass): eight pigs (four normal, four MHS) with blood ionized calcium to 5 mEq/l and eight pigs (four normal, four MHS) with digoxin levels above 7.5 ng/ml had increased myocardial oxygen consumption. Cardiac potassium efflux or lactate production did not occur in normal or MHS pigs. Increased arterial potassium (7.4–8.5 mEq/l) did not alter myocardial oxygen consumption or lactate production in four MHS or four normal pigs. MH responses were initiated only by potassium and only in regard to whole body metabolism. Cardiac metabolism increased as a result of specific drugs (calcium, digoxin), unrelated to MH phenomena. Porcine inbreeding resulting in MH susceptibility of skeletal muscle does not imply abnormality in other tissues.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

A quantitative, in situ experimental method was developed employing the rat sciatic nerve to study the neurotoxicity of local anesthetic solutions applied directly to an intact peripheral nerve bundle. One-milliliter volumes of 2-chloroprocaine, 3%; tetracaine, 1 %; lidocaine, 2%; bupivacaine, 0.75%; or sodium chloride, 0.2%; were injected with a 30-gauge needle beneath the mesoneurium but exterior to the epineurium. The wound was closed and the animals were normally maintained until the nerves were reexposed for quantitative biophysical and morphologic testing 24 h to 4 weeks later. The results indicate that topically applied 2-chloroprocaine and tetracaine produce significant endoneurial edema 48 h after treatment. Horseradish peroxidase was used to verify increased permeability of the perineurium. Endoneurial fluid pressure was significantly increased in edematous nerves. Electron microscopy revealed abnormal mast cells and proliferation of endoneurial fibro-blasts in addition to Schwann cell injury and axonal dystrophy. This study shows that extrafascicular administration of clinically used concentrations of local anesthetic solutions can alter perineurial permeability, producing changes in the endoneurial environment that are associated with neurotoxic injury. Perineurial and endoneurial fibrolic changes may be a late consequence of peripheral nerve injury with anesthetic solutions producing altered perineurial permeability with endoneurial edema.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of clonidine, a centrally acting α2-adrenergic receptor agonist, on depth of fentanyl anesthesia and on cardiovascular response to laryngoscopy and intubation were studied. Twenty-four patients undergoing aortocoronary bypass surgery (ACBS) with a history of arterial hypertension, coronary artery disease (NYHA class 3–4), and well-preserved left ventricular function were assigned randomly to either Group 1 (n = 12), who received standard pre-medication, or Group 2 (n = 12), who received clonidine 5 μ;g·kg-1po in addition to standard premedication 90 min before estimated induction time. Depth of anesthesia was assessed by on-line aperiodic computerized analysis of the electroencephalogram (Lifescan EEG Monitor®). Fentanyl was administered in 250-μ;g increments to shift the EEG to the 0.5–3-Hz frequency range (delta activity) in all subjects. In both groups, the anesthetic regimen effectively prevented hyperdynamic cardiovascular responses to laryngoscopy and intubation. No significant differences in measured or derived hemodynamic variables were observed between the two groups during the awake control period, except for stroke volume index (SVI), which was significantly greater in Group 1,44 ± 9 ml · beat-1· M-2compared with Group 2, 35 ± 3.3 ml · beat-1· m-2(P< 0.05). By contrast, fentanyl requirements in Group 2 were significantly reduced by 45% when compared with Group 1, i.e., from 110 ± 23 to 61 ± 19 μ;g· kg-1(P< 0.001). The authors conclude that at a similar anesthetic depth, as assessed by the EEG shift into the lower frequency range (0.5–3 Hz), a markedly reduced fentanyl dose effectively prevented the hyperdynamic cardiovascular response to laryngoscopy and intubation in the group of patients premedicated with clonidine. This is likely explained by the known synergistic inhibitory action of opiates and α2-adrenoceptor agonists on central sympathetic outflow.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

A new technique of epidural catheterization in rats is described. The pharmacologic characterizations of the model were established after epidural injection of bupivacaine, morphine, fentanyl, lofentanil, and D-Ala2-D-Leu5-enkephalin (DADL) on hot plate (HP) and tail flick (TF). In addition, rostral spread, motor function, behavior, and reproducibility of the effects over time were assessed. The time-response curves showed an almost immediate onset of action for bupivacaine, fentanyl, and lofentanil and a delayed onset for morphine and DADL. Morphine and lofentanil displayed a significantly longer duration of action than bupivacaine, fentanyl, and DADL. The dose-response curves were monotonic and the slopes were log-linear. Based on the ED50values, the following rank order of potency was obtained 1 day after catheterization for both HP and TF: lofentanil ≫ fentanyl > morphine ≫ DADL > bupivacaine. Intraperitoneal (IP) administration of naloxone antagonizes the agonist effects of epidural morphine, fentanyl, and lofentanil. To assess the role in analgesia played by epidural vascular uptake after epidural administration of morphine, fentanyl, and lofentanil, the lowest maximally effective epidural dose of these agents was given intravenously. After iv fentanyl and lofentanil, the analgesic and behavioral effects were not different from the values obtained after epidural administration. By contrast, the effects were negligible after iv morphine when compared with the epidural route. Epidural vascular uptake is thought to be low for morphine and high for fentanyl and lofentanil. The reproducibility of the analgesic and behavioral effects over time was assessed by epidurally injecting the lowest maximally effective dose of bupivacaine, morphine, fentanyl, and lofentanil 1 day and 10 days after catheterization. After 10 days, a significant reduction of analgesic and behavioral effects was noted and was thought to be due to a complete fibrotic sheath surrounding the epidural catheter.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

In rats, intrathecal alfentanil, lofentanil, sufentanil, fentanyl, and morphine produced dose-dependent elevations in the hot-plate and tail-flick latencies and a powerful suppression of the writhing response. The slopes of the monotonic dose-response curves for the Five opioids did not differ significantly. In terms of the hot-plate ED50after intrathecal injection, the order of potency was as follows: lofentanil (210), sufentanil (29), fentanyl (3), morphine (1), and alfentanil (1). Comparable results were observed in the tail flick. The duration of action was proportional to dose. However, at doses that produced an equal magnitude of inhibition, the duration of action was lofentanil > morphine > sufentanil > alfentanil ≥ fentanyl. Systemically administered naloxone (0.03–1 mg/kg, sc) resulted in dose-dependent antagonism of the antinociceptive effect of intrathecal morphine, fentanyl, alfentanil, and sufentanil. In contrast, intrathecal lofentanil was extremely resistant to antagonism by naloxone. In cats, similar dose-dependent blockade of the thermally evoked skin-twitch response was observed after intrathecal morphine, sufentanil, alfentanil, and fentanyl. As in the rat, the slope of the monotonic dose-response curves did not differ. The relative potency and duration of action after equipotent intrathecal doses were similar to those observed in the rodent. These results suggest that sufentanil, alfentanil, and fentanyl exert their analgesic effectsin vivoat a spinal cord site that has properties comparable to those of the site acted upon by morphine. Except for catalepsy in rats, no major behavioral dysfunctions were noted at the ED50dose of any of the drugs administered. No abnormal morphologic effects of acutely or chronically administered alfentanil and sufentanil were seen, aside from an inflammatory reaction secondary to catheter placement.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The so-called membrane fluidizing effect of anesthetics as a cause of anesthesia has been questioned, mainly because the magnitude of the increase in “fluidity” is insignificant at clinically relevant anesthetic pressures. However, the term “fluidity” has an unfortunate history of being misrepresented in membrane biology. It is often expressed as the ease of movement of probe molecules incorporated into the hydrophobic region of the membrane, thereby representing the property of the microenvironment where the probe molecules reside. In surface chemistry, “membrane fluidity” means inverse viscosity. Membrane viscosity is an integral property of a total membrane (not a part of membrane), and membrane molecules must dislocate and flow against resistance. The ease of motion of probe molecules, therefore, is not fluidity, and is now expressed by the order parameter. The present study measured the effect of halothane on surface viscosity of a phospholipid monolayer spread on a water surface by an oscillating pendulum surface viscometer. The results indicate a significant decrease of about 31% in the surface viscosity by the clinical pressure of halothane; anesthetics do fluidize membranes. Two factors contribute to the surface viscosity of the lipid monolayer; the property of the membrane proper (association between phospholipid molecules) and dragging of water (association between phospholipid and water molecules). The association between phospholipid molecules is in large part related to the order parameter. The fact that anesthetics show little effect on the order parameter, whereas halothane shows a significant effect on the membrane viscosity, indicates that halothane releases surface-bound water. It is postulated that the primary effect of anesthetics on membranes is to weaken the lipid-water interaction forces.

ISSN:0003-3022    

出版商:OVID    

年代:1986

数据来源: OVID