ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The effects of intrathecally administered opiates (morphine sulfate and meperidine), α-adrenergic agonists (clonidine and ST-91) and baclofen were examined on the shock titration thesh-old of macaque monkeys chronically prepared with intrathecal (I) or epidural (E) catheters. Spinal opiates produced a long-lasting analgesia which was antagonized by naloxone. The order of potency was I morphine > I meperidine > E meperidine > E morphine. Clonidine and ST-91, also produced a dose-dependent, long-lasting elevation in the shock titration threshold, antagonized by phentolamine, but not naloxone. L-baclofen, but not D-baclofen, resulted in a dose-dependent elevation of shock titration threshold, which was not antagonized by naloxone. Repeated administration at 24-h intervals over a 7-day period of morphine, clonidine or baclofen, resulted in asignificantreduction in the analgetic effects of each drug. Cross tolerance between the three classes of agents was not observed. Intrathecal co-administration of inactive doses of ST-91 and morphine resulted in a near maximal increase in the shock titration threshold, which failed to show any significant tolerance over 21 days.Intrathecal ST-91 and morphine produced no change in either muscle strength, tendon reflexes, respiratory rate, urine formation, or the ability to locomote. Baclofen, in contrast, produced a dose-dependent decrease in muscle strength. That the intrathecal drugs did not produce anesthesia was demonstrated by their failure to block the avoidance response to ensuing ear shock cued by a light tactile stimulus applied to the hind paw. These results clearly indicate that a powerful analgesia can be produced by selectively activating adrenergic, opiate, and baclofenergic receptor systems in the spinal cord.

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The pharmacokinetics and plasma protein binding of thiopental were investigated in 5 female patients who received a bolus intravenous dose of the drug for induction of anesthesia for gynecologic surgery. Blood samples were collected for 3 to 4 days after the dose. Plasma protein binding determinations were also carried out by ultrafiltration and equilibrium dialysis on samples from a panel of healthy volunteers. Plasma concentrations of thiopental were determined by reverse-phase, high-performance liquid chromtography. The coefficient of variation of the method was 2.8 per cent (n = 10). In healthy volunteers, the plasma protein binding of thiopental was concentration dependent. Percentage bound ranged from 96.7 (n = 4, SD = 0.8) at a thiopental concentration of 0.2 μg/ml to 60.4 (n = 5, SD = 0.8) at 150 μg/ml. Therefore, saturation of binding sites on rapid administration of the drug may occur, exposing vital organs to unexpectedly high concentrations of free drug. Values of the fraction of thiopental bound in plasma obtained from the surgical patients during the hour following drug administration were similar to values obtained in healthy volunteers at comparable concentrations. Mean pharmacokinetic parameters obtained for thiopental in the surgical patients were as follows: initial distribution volume 13.81 (SD = 9.4), apparent volume of distribution 233 1 (SD = 98), volume of distribution at steady state 97.5 1 (SD = 40), elimination half-life 11.5 h (SD = 1.0) and systemic plasma clearance 0.150 1/min (SD = 0.063). None of these parameters correlated with body weight. Values reported by other workers vary from ours and this variation may be explained by the much shorter duration of blood collection used in those studies.

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

This study was undertaken to investigate the effect of pregnancy on the disposition of thiopental and to determine the major factors which influence the placental transfer of the drug to the fetus. Maternal venous (MV) and umbilical venous (UV) and arterial (UA) blood samples were collected at delivery from 11 pregnant women at term who received thiopental for induction of anesthesia for elective cesarian section. A detailed study of the pharmacokinetics of thiopental was carried out in 7 of these subjects and blood samples were collected for 80 to 100 hours following thiopental administration. A transient rise in thiopental plasma concentration was observed at delivery. Mean values of pharmacokinetic parameters (±SD) were: initial distribution volume (V1) 17.3 1 (±8.5), apparent volume of distribution (V***β) 564 1 (±343), volume of distribution at steady state (Vss) 288 1 (±180), systemic plasma clearance (Clp) 0.286 1/min (±0.156), rate of change of volume of distribution at zero time (RVd0) 1.03 1/min (±0.36) and elimination half-life (t1/2) 26.1 h (±12.6). Comparison of these data with our previously reported data in nonpregnant surgical patients shows that Vdβ, Vss, and T1/2are significantly greater at cesarian section (P< 0.05) and that systemic plasma clearance shows a similar trend.UAand UVvalues at delivery were similar within individuals. There was no correlation between the ratio UV/MVat delivery and the dosing-delivery interval (δt), or between UVand the administered dose or δt. There were good correlations between UV(corrected for dose) and the reciprocals of V1, Vdβ, Vss, and plasma clearance of thiopental. This demonstrates that differences in maternal distribution and elimination characteristics of thiopental may be more important determinants of intersubject differences in fetal drug exposure than differences in dose or δt.

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Acute myocardial infarction in the intraor perioperative period may be accompanied by either bradycardia and hypotension or tachycardia and hypertension. Different degrees of activation of cardiac and arterial receptors stimulated by the infarction may produce the seemingly dichotomous results. When infarction occurs intraoperatively, the effects of anesthesia may also play a role on the reflex responses observed. This study was performed for two reasons: 1) to study the effects of acute coronary artery occlusion (ACO) on vascular resistance; and 2) to study the effects of halothane (H) anesthesia on this ACO reflex. Snare occlusions of the left coronary arteries were performed in pentothal-anesthetized mongrel dogs, and changes in arterial pressure, left ventricular length, hindlimb vascular resistance, and lumbar sympathetic efferent nerve activity were measured during 30− to 60-s occlusions at 0, 0.5, 1.0, and 1.5 per cent end tidal halothane concentrations.ACO produced a consistent depressor response, produced by withdrawal of sympathetic efferent activity, that was significantly attenuated by vagotomy. Increasing levels of H blunted the reflex depression in vascular resistance, and also produced decreases in baseline resistance and increases in left ventricular end diastolic length (LVEDL). Vagotomy blunted the dose-dependent decrease in baseline resistance with H. Therefore, the study has shown that: 1) ACO activates vagal afferents to initiate a reflex decrease in vascular resistance; 2) this reflex dilation is attenuated with increasing levels of H; and 3) by producing increases in LVEDL, H stimulates cardiac receptors and reflexly reduces vascular resistance.

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

It has previously been shown in rats that diazepam alone has no effect on the cerebral metabolic, rate (CMRO2) but that it interacts with nitrous oxide to produce a 40 per cent reduction in the CMRO2value. In the present study, the effect of sedative doses of diazepam on the cerebral energy state, glycolysis, citric acid cycle, and amino acid metabolism in rats was determined in the presence and absence of a simultaneous administration of 70 per cent nitrous oxide, 45 s to 30 min after the diazepam injection. The metabolic response was very similar in the two groups despite the differences in metabolic rates of oxygen consumption. There were no changes in the cortical concentrations in ATP, ADP, AMP, phosphocreatine and creatine. The brain glycogen concentration was elevated during diazepam sedation, whereas brain glucose levels remained close to normal values except at 30 min after administration of diazepam alone, when the glucose level showed a 30 per cent increase. The onset of diazepam sedation was associated with an inhibition of glycolysis at the phosphofructokinase step in both groups. The reduced pyruvate concentration subsequently lead to a reduction in the pool size of the citric acid cycle intermediates. The concentrations of alanine and glutamate decreased during the period of diazepam sedation, while those of aspartate and glutamine increased. GABA and ammonia concentrations remained unchanged.Based on the cerebral metabolic response, the onset of diazepam sedation appears to be associated with an inhibition of rate of metabolism (glycolysis), both in the presence and absence of nitrous oxide. In that respect, diazepam has a metabolic profile similar to barbiturates.

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Compared to traditional, low-frequency ventilation (LFV), mechanical ventilation at high frequencies (60–200 breaths/min) and low tidal volumes (HFV) is known to: 1) eliminate respiratory-synchronous variations in blood pressure; 2) minimize ventilatory effects on the cardiovascular system; 3) reduce peak airway pressures; and 4) suppress spontaneous respiratory efforts. Since these and other properties may make HFV useful in patients with acute intracranial pathology, we studied the effects of HFV on intracranial pressure (ICP) in cats. Compared with LFV (rate 11/min, tidal volume = 15 ml/kg), HFV (rate 100/min, VT= 3.3 ml/kg) had little effect on mean arterial pressure, heart rate, right atrial pressure, mean ICP or mean cerebral perfusion pressures, even if baseline ICP was raised using an epidural balloon. However, HFV effectively eliminated ventilator-linked fluctuations in both blood pressure and ICP, and at all levels ofmeanICP studied (4.8, 15, and 30 torr), significantly reduced thepeakICP seen during a single respiratory cycle. The reduction in ICP fluctuation and peak pressure was more pronounced as intracranial complicance fell. However, the physiologic significance of such a change in the ICP pressure waveform is unknown.Because of the observed influence of HFV on ICP fluctuations, we also examined its effects on the physical movement of the exposed brain, using a non-contact, inductive displacement measuring device. During LFV, the cortical surface moved “in and out” by 0.36 ± 0.1 (±SD) mm, a distance sufficient to make microscopic focusing difficult. Changing to HFV reduced surface movement to 0.05 ± 0.01 mm, producing a very stable surface. These results suggest that HFV may play a very important role in the intraoperative management of patients undergoing certain neurosurgical procedures, particularly those requiring microsurgical techniques where reduced brain movement may facilitate surgery.

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Reproductive indices and developmental toxicity were evaluated in Swiss/ICR mice chronically exposed to a subanesthetic (0.01 or 0.1 per cent) or an anesthetic (0.5/1.0 per cent) concentration of enflurane. Pregnant mice (443) and fetuses (4743) were examined. In one experiment, groups of females were exposed to 0.01, 0.1, or 0.5/1.0 per cent enflurane for 4 hours per day, seven days per week for 3 weeks; they were then mated with unexposed males. Exposure of females was continued daily throughout pregnancy. No adverse effects on fertility were observed at any dosage. At the highest dosage, 1.0 per cent, minor developmental variations occurred (i.e., lumbar ribs and increased renal pelvic cavitation). In a second experiment, groups of mice were exposed to 0.01, 0.1 or 1.0 per cent enflurane only on days 6 through 15 of pregnancy for 4 hours per day, after having been mated with untreated males. Abnormalities (i.e., increased incidence of cleft palate, minor skeletal and visceral anomalies, and developmental variants) were again seen only at the highest dosage. In a third experiment, male mice were exposed to 0.01, 0.1, or 0.5/1.0 per cent enflurane for 11 weeks for 4 hours per day, 5 days per week, prior to mating with unexposed females; results of this experiment were negative. In general, enflurane treatments did not adversely affect reproductive indices. Effects on fetal development were minimal, being somewhat greater than those reported in previous experiments with methoxyflurane but less than those seen with halothane. The smallest exposure at which effects were seen was approximately 100 times greater than the level of human occupational exposure in unscavenged operating rooms.

ISSN:0003-3022    

出版商:OVID    

年代:1981

数据来源: OVID