Experimental arthritis in the rat does not alter the analgesic potency of intrathecal or intraarticular morphine.

To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (i.a.) or intrathecal (i.t) morphine in tests of thermal and mechanical nociception changed during the induction of experimental arthritis in the rat. Thermal nociception by i.t. morphine (3, 10, and 50 micrograms) or i.a. morphine (100, 1000, and 3000 micrograms) was assessed by means of a modified Hargreaves box ever) 28 h. Mechanical antinociception was determined for the largest applied doses of morphine using von Frey hairs. Morphine produced dose-dependent thermal antinociception after i.t. or i.a. administration: a 50% increase in maximum antinociceptive thermal response (50% effective dose) was produced by i.t. doses of 9.7 micrograms at the start and 9.1 micrograms at the end of this 28-h observational interval, whereas after i.a. administration, 50% effective dose values were 553 micrograms at the start and 660 micrograms at the end. The largest applied dose of either i.t. or i.a. morphine produced mechanical antinociception. On Day 1, the antinociceptive effect for mechanical nociception (expressed as the area under the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for i.t. morphine 50 micrograms and 53% for i.a. morphine 3000 micrograms. Neither result differed from the corresponding area under the curve values on Day 2. Naloxone administered either i.t. or i.a. abolished the antinociceptive action of morphine given at the same site. We conclude that, although morphine has a peripheral analgesic site of action in a rat arthritis model, its potency for both i.a. and i.t. routes of administration does not change during the onset of arthritis. Implications: In this animal study, we showed that the administration of morphine modulates thermal and mechanical antinociception at central and peripheral sites in inflammatory pain.     

Pregnancy does not alter the threshold for lidocaine-induced seizures in the rat.

Although altered effects of various anesthetics have been demonstrated during pregnancy, published studies have incompletely defined potential pregnancy-induced changes in the central nervous system toxicity of lidocaine. Accordingly, the seizure threshold for lidocaine was measured in three groups of mechanically ventilated rats breathing 70% N2O-30% O2: male (n = 21), nonpregnant female (n = 19), and pregnant female (n = 23). Lidocaine was administered intravenously at a constant rate of 2.3 mg.kg-1.min-1 while the electroencephalogram was monitored continuously. Total doses of lidocaine and the durations of lidocaine infusion necessary to induce seizure activity were similar among groups. Plasma lidocaine concentrations at the onset of electroencephalographic seizure activity were also similar among groups (male = 10.7 +/- 5.5, nonpregnant female = 12.1 +/- 4.9, pregnant female = 10.8 +/- 4.1 micrograms/mL). In a subset of each group, brain lidocaine concentrations at the onset of seizure activity were also measured, and again no differences among groups were observed (male = 17.4 +/- 6.3, nonpregnant female = 16.8 +/- 4.5, pregnant female = 16.7 +/- 4.2 micrograms/100 g wet wt). The authors conclude that there are no pregnancy-specific alterations in either plasma or brain concentration thresholds for central nervous system toxicity of lidocaine in rats.     

Induced hyperprolactinaemia does not alter FSH binding or ABP secretion in the rat testis

The effects of induced hyperprolactinaemia in male Wistar rats were studied by grafting two pituitary glands under the kidney capsule. Transplants were performed at 15 and 60 days of age, and rats killed 4 weeks later when tissue and serum samples were obtained. Serum concentrations of LH were reduced significantly in rats grafted at 60 days of age, whereas no change was observed in rats grafted at 15 days of age. Serum testosterone levels were slightly suppressed only in the older group of grafted rats. Testicular FSH receptors and the epididymal content of androgen-binding protein (ABP) were not modified by induction of hyperprolactinaemia. The results indicate that hyperprolactinaemia was not associated with changes in at least two functional parameters of the tubular compartment of the rat testis.     

Muscle relaxation with succinylcholine or vecuronium does not alter the rate of CSF production or resistance to reabsorption of CSF in dogs

The open ventriculocisternal perfusion method was used to determine the rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) in halothane-anesthetized dogs with and without succinylcholine (n = 6) and with and without vecuronium (n = 6). Both Vf and Ra during the use of either muscle relaxant were not different than Vf and Ra when no muscle relaxant was used. Succinylcholine caused muscle fasciculations and raised CSF pressure transiently (increase of 5.5 +/- 1.0 cm H2O [mean +/- SD]), while vecuronium did not. When muscle relaxants were not used, it became difficult to distinguish the effects of cardiovascular and respiratory activity on the CSF pressure waveform, and the coefficient of variability for determination of cisternal outflow rates was increased, making Ra values less reliable. It is concluded that continuous infusion of succinylcholine or vecuronium do not affect Vf or Ra. When Vf and Ra are determined by the method of ventriculocisternal perfusion, immobilization of respiratory muscles improves both the reliability of Ra values and the usefulness of the CSF pressure waveform. If a muscle relaxant is used, either succinylcholine or vecuronium would be suitable for such studies.     

Sevoflurane does not alter norepinephrine-induced intracellular Ca2+ changes in the diabetic rat aorta

Purpose

The effect of volatile anesthetics on the mechanism(s) of vascular contraction in diabetes mellitus (DM) has not been fully understood. The current study was designed to determine the effects of sevoflurane on the norepinephrine (NE)-induced changes in contractile state and intracellular Ca²⁺ concentrations ([Ca²⁺]_i) in the spontaneously developing type 2 DM rat.

Methods

The effects of sevoflurane on NE (10^?6M)-induced vasoconstriction and increase in [Ca²⁺]_i in the aortas from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 DM model, and from age-matched control Long-Evans Tokushima Otsuka (LETO) rats were investigated using an isometric force transducer and fluorometer with fura-2 as an indicator of [Ca²⁺]_i.

Results

Norepinephrine-induced increases in tension and [Ca²⁺]_i in OLETF rats were 54.8%, 95% confidence interval (CI) 36.9-72.6% and 58.8%, 95% CI 51.5-66.1%, respectively, and in LETO rats they were 46.4%, 95% CI 39.0-53.7% and 53.8%, 95% CI 46.9-60.7%, respectively, when expressed as the percentage relative to that induced by KCl 30 mM. In LETO rats, sevoflurane at a concentration of 3.4% inhibited the vascular contraction (9.4%, 95% CI 6.3-12.6%; P < 0.001) and the increase in [Ca²⁺]_i (33.3%, 95% CI 27.4-39.2%; P = 0.002). In OLETF rats, however, sevoflurane failed to affect either the NE-induced contraction (43.6%, 95% CI 28.3-58.9%; P = 0.68) or the elevation in [Ca²⁺]_i (60.5%, 95% CI 56.3-64.8%; P = 0.93).

Conclusion

Sevoflurane at clinically relevant concentrations inhibited the NE-induced increase in [Ca²⁺]_i in the aortic smooth muscle from normal rats but not in that from type 2 DM rats. Thus, a Ca²⁺- signalling pathway resistant to sevoflurane appears to exist in the type 2 DM rat aorta.     

The potency of succinylcholine in obese adolescents

We constructed a single-dose response curve for succinylcholine in 30 obese adolescents during thiopental-fentanyl anesthesia administration by using 100 microg/kg, 150 microg/kg, or 250 microg/kg IV. The maximal response (percent depression of neuromuscular function) of the adductor pollicis to supramaximal train-of-four stimuli was recorded by using a Datex (Helsinki, Finland) relaxograph. Linear regression and inverse prediction were used to determine doses of succinylcholine to produce 50% (ED(50)), 90% (ED(90)), and 95% (ED(95)) depression of neuromuscular function. The ED(50), ED(90), and ED(95) were 152.8 microg/kg (95% confidence interval: 77.8-299.5), 275.4 microg/kg (95% confidence interval: 142-545.7), and 344.3 microg/kg (95% confidence interval: 175.3-675. 3), respectively. This ED(50) is similar to the dose reported for similarly aged, nonobese adolescents, 147 microg/kg. The previously reported ED(95) for succinylcholine in nonobese adolescents, 270 microg/kg, is within the 95% confidence interval generated for ED(95) in our study. IMPLICATIONS: The potency estimates for succinylcholine in obese (body mass index > 30 kg/m(2)) adolescents are comparable to those in similarly aged nonobese adolescents when dosing is calculated based on total body mass and not lean body mass. When a rapid sequence induction of anesthesia is considered in an obese adolescent, the dose of succinylcholine should be based on actual (not lean) body mass.     

Magnesium-deficiency does not alter calcineurin inhibitors activity in mice

Introduction

Tacrolimus (TAC) and cyclosporin (CsA) are commonly responsible for hypomagnesemia that predisposes in turn for hypertension, renal impairment and encephalopathy.

Objective

The effects of TAC on Mg²⁺-homeostasis and of pre-existing Mg²⁺-deficiency on TAC immunosuppressive activity were compared to CsA in mice.

Methods

Mg²⁺ was quantified in plasma, erythrocytes, urine, feces, and femurs from mice treated with TAC 5 mg/kg/day. Immunosuppression was assessed in splenocytes by mixed lymphocyte reaction, IL-2 quantification and CN activity determination.

Results

Plasma and urine Mg²⁺ levels in TAC-treated mice were significantly lower from day 7 until day 21 (p < 0.05 versus control) and returned to control value at day 28. Mg²⁺ levels were unchanged in erythrocyte, feces and femur. Inhibition of allogeneic proliferation, IL-2 production and CN activity were 68, 56 and 30% lower (p < 0.01) after 7 days of TAC-treatment, and 72, 68 and 51% lower (p < 0.01) after 7 days of CsA-treatment with a dose of 50 mg/kg/day. Dietary-induced hypomagnesemia resulted in significant inhibition of CN activity (p < 0.01) without alteration of IL-2 production or allogeneic proliferation. However, it did not alter the effects observed with CsA- or TAC-treatment on allogeneic proliferation, IL-2 production and CN activity.

Conclusion

By contrast with CsA, long-course TAC-treatment induced an early, but transient, and moderate hypomagnesemia without alteration of bone or erythrocyte stocks, intestinal absorption or renal function. Therefore, in clinical use, TAC should be preferred to CsA in patients with pathological or pharmacological conditions which favor Mg²⁺-deficiency. However, dietary-induced hypomagnesemia did not alter the immunosuppressive effects of TAC and CsA.     

Smoking does not alter the dose-requirements and the pharmacodynamics of rocuronium

PURPOSE: Controversial data about the effect of smoking on the dose-requirements and the pharamcodynamics of rocuronium have been reported recently. This study was conducted to evaluate the dose-requirements and the pharmacodynamics of rocuronium in smokers using target controlled infusion. METHODS: The dose-requirements of rocuronium for 60 min relaxation, using target controlled infusion, given under intravenous anaesthesia with propofol, fentanyl and nitrous oxide was studied in 37 smokers and 37 non-smokers. Initially 450 microg x kg(-1) rocuronium were administered, neuromuscular effects were quantified by recording the single twitch response of the adductor pollicis muscle after ulnar nerve stimulation using a force transducer, and the neuromuscular block was kept at 80% by target controlled infusion throughout the procedure. RESULTS: The dose-requirements for one hour relaxation were 867 +/- 116 microg x kg(-1) x hr(-1) for smokers (S) and 839 +/- 149 microg x kg(-1) x hr(-1) for non-smokers (NS). The duration to 10% and the spontaneous recovery from 25% to 75% of the control twitch response also showed no differences between S (17.2 +/- 3.4 min, 10.6 +/- 0.9 min) and NS (18.9 +/- 4.3 min, 10.9 +/- 3.2 min), as well as maximum block, onset time and infusion rate. CONCLUSION: Smoking does not alter the dose-requirements for rocuronium and no effects on the onset time, degree of block, time to maximum block, duration 10% and spontaneous recovery index were observed.     

Cryopreservation does not alter antigenic expression of aortic allografts

Cryopreserved aortic homografts are reportedly viable, but no cross-matching or immunosuppression is utilized. Alterations of the antigenic expression by cryo-preservation must be assumed. We designed a protocol to test this premise. Fisher 344 rats served as recipients in all cases. Lewis rats, a mildly disparate strain, were utilized as donors. Four cohorts of animals were utilized. Group I (N = 11) served as a "first set" control. All animals received a syngeneic skin graft. After 28 days an allogeneic skin graft was placed; rejection was seen at 10.3 +/- 0.5 days. Group II (N = 16) first received allogeneic skin grafts with a similar "first set" rejection pattern of 10.4 +/- 0.47 days. A second skin graft was placed and demonstrated an accelerated rejection response of 6.06 days +/- 0.25 days. Group III (N = 17) received two leaflets from a "fresh" Lewis heart valve inserted into a subcutaneous pouch. Allogeneic skin grafts in this group demonstrated a similar second set rejection at 7.05 +/- 0.82 days. Group IV (N = 22) also underwent implantation of heart valve leaflets, except "cryopreserved" Lewis leaflets were implanted into the subcutaneous pouch. An allogeneic skin graft was placed and demonstrated a second set rejection at 7.18 +/- 0.39 days. A one-way analysis of variance shows no significant difference in Groups III and IV, but a significant difference with respect to Group I (P less than 0.00001). Cryopreservation does not alter the antigenic expression in this model, and at present we strongly recommend that at least ABO compatibility be utilized in all patients undergoing aortic homograft implantation.     

Intravenous bleomycin does not alter the toxic effects of hyperoxia in rabbits

The purpose of this study was to test the hypothesis that bleomycin administration enhances the toxic effects of oxygen on the respiratory system. Twenty-one rabbits, with no evidence of respiratory disease, received intravenous injections of 45 units of bleomycin (Blenoxane), twice a week, for a total dose of 300 units. Fifteen rabbits received an equal volume of saline and served as controls. Treatment with bleomycin resulted in failure to thrive, weight loss, and 30% mortality from nonpulmonary causes, as indicated by the lack of respiratory distress or cyanosis, during or shortly after the injection period. The remainder of the animals were allowed to recover for 21 days following the last injection. At that time, no differences were found between the experimental and the control groups with respect to arterial blood gases, total lung capacity, compliance, and hydroxyproline content. Histologic examination of lung tissue revealed normal lung architecture. When exposed to 100% O2, bleomycin-treated rabbits developed arterial hypoxemia and died from respiratory failure at the same rate as the controls. It was concluded that pretreatment of healthy rabbits with 300 units of intravenous bleomycin did not result in the development of significant amounts of lung fibrosis or enhance the toxic effects of oxygen on the respiratory system.     

Celiac plexus block does not alter hepatic injury in rats

We previously demonstrated that upper abdominal surgery on rats pretreated with phenobarbital and anesthetized with halothane caused centrilobular necrosis of the liver, which may be secondary to hepatic hypoxia induced by vasoconstriction. This study examined the possibility that celiac plexus blockade might decrease the degree of injury seen in the surgical model. Rats, pretreated with phenobarbital, were anesthetized with halothane, enflurane, isoflurane, or fentanyl with 100% oxygen. At the start of the hepatic artery dissection, the celiac plexus was blocked by injection of bupivacaine. Subsequently, the rat livers were evaluated for presence and degree of centrilobular necrosis. Animals anesthetized with halothane or fentanyl had a significantly greater incidence of centrilobular necrosis than controls (rats pretreated with phenobarbital who received no anesthesia or surgery). Hepatic injury in rats anesthetized with isoflurane or enflurane did not differ from that in controls. We conclude that celiac plexus blockade with bupivacaine provides no protection against hepatic necrosis in this model.     

Cardiopulmonary bypass does not alter canine enflurane requirements.

This study determined the effect of cardiopulmonary bypass (CPB) on canine enflurane minimum alveolar concentration (MAC). Fourteen dogs were anesthetized with enflurane in N2O and O2, and after tracheal intubation, the N2O was discontinued. Femoral arterial and pulmonary arterial catheters were placed, and MAC was determined with the tail-clamp method. CPB was initiated via the femoral artery-vein route, with additional venous return obtained from an external jugular vein. Partial CPB was used in the first 10 dogs. In 4 dogs, a membrane oxygenator (group 1) was used, and in the next 6 dogs a bubble oxygenator (group 2) was used. In 4 additional dogs (group 3), using bubble oxygenators, total CPB was achieved by occlusion of the pulmonary artery via a left thoracotomy. The CPB circuit was primed with Ringer's lactate, and circuit blood flows were 70-125 ml.kg-1.min-1, with mean arterial pressures maintained at 50-110 mmHg. MAC was determined again after termination of CPB. In 10 dogs, MAC was also measured during CPB. In 5 dogs MAC was measured after administration of protamine. MAC in all 14 dogs did not change (2.2 +/- 0.3 vs. 2.3 +/- 0.3). MAC remained constant in group 1 (2.4 +/- 0.3 vs. 2.3 +/- 0.4), group 2 (2.2 +/- 0.2 vs. 2.3 +/- 0.3), and group 3 (2.2 +/- 0.1 vs. 2.3 +/- 0.1). Similarly, MAC was unchanged during CPB (2.2 +/- 0.2 vs. 2.2 +/- 0.2) and after protamine (2.3 +/- 0.2 vs. 2.2 +/- 0.3). Temperature was 38.3 +/- 1.2 prebypass and 37.9 +/- 0.9 postbypass.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dexamethasone does not alter in vitro antibacterial efficacy of gentamicin.

OBJECTIVES: Aminoglycoside ototoxicity may be mitigated by administration of dexamethasone; however, dexamethasone could theoretically impair its antibacterial properties. The purpose of this experiment was to determine if dexamethasone decreases the antibacterial activity of gentamicin against Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA). STUDY DESIGN: In vitro microbiological assay. METHODS: Four separate trials of minimum inhibitory concentration (MIC) testing were performed for gentamicin against five PA strains and six SA strains, with and without the addition of high and low concentrations of dexamethasone. RESULTS: MICs were not changed by more than one dilution with the addition of either high or low concentrations of dexamethasone for any of the PA and SA strains. CONCLUSION: Dexamethasone does not impair the antibacterial efficacy of gentamicin for PA and SA. This supports the role of dexamethasone as an oto-protectant with aminoglycoside therapy.     

Interstitial white matter brain oedema does not alter the electroencephalogram.

An experimental study was performed to determine the effects of interstitial white mater oedema on the electroencephalogram (EEG). Using both rodent and feline infusion models of focal brain oedema no difference was found between the EEG waveforms recorded epidurally from the infused and control hemispheres. It is concluded that where focal slow-wave EEG abnormalities overlie oedematous brain the EEG abnormalities are not primarily related to the brain oedema but arise from either local biomechanical or other pathophysiological mechanisms.     

Opioid sedation does not alter intracranial pressure in head injured patients

Purpose

This study aimed to examine the effects of sedative doses of morphine, fentanyl and sufentanil on intracranial pressure (ICP) in head-injured patients in whom changes in mean artenal pressure (MAP) were minimized.

Methods

Fifteen severely head-injured patients (G5C of ≤8) were randomly assigned to receive either fentanyl. sufentanil or morphine, titrating the drug to a maximal 10% decrease in MAP. The patients were subsequently given an infusion of the same opioid. For four hours, ICP MAP and heart rate were recorded. Results: In all groups, there were no increases in ICP. There was a decrease in MAP in the sufentanil group at 10 min (P < 0.05) and 45 min after the initial opioid bolus. These decreases in MAP were not associated with increases in ICP.

Conclusion

The study suggests that when opioids are titrated in head-injured patients, worsening intracranial pressure can be avoided.     

Oral clonidine does not alter vecuronium neuromuscular blockade in anaesthetized patients

Since clonidine, an α₂-agonist, inhibits the release of norepinephrine or acetylcholine which can decrease nondepolarizing muscle relaxant-induced neuromuscular blockade, the authors examined whether clonidine given as an oral preanaesthetic medication would alter the onset, duration or recovery of a vecuronium neuromuscular blockade in lightly anaesthetized patients. Thirty-eight patients (aged 20–73 yr) randomly received oral clonidine either approximately 5 μg · kg^?1 (n = 21) or none (n = 17), 90 min before arrival in the operating room. We measured acceleration of thumb contraction with ulnar nerve stimulation at the wrist to assess neuromuscular blockade. The onset time (the time from injection to decrease to 5% of baseline twitch height), duration (the time interval between injection and return of the first twitch to 25% of the baseline value), and recovery index (the time interval of the first twitch from 25% to 75% of the baseline value) of neuromuscular blockade from a single bolus of vecuronium 0.1 mg · kg^?1 iv were determined and compared between the clonidine-treated and control patients during lower abdominal or extremity surgery under epidural plus general anaesthesia with fentanyl and nitrous oxide in oxygen. No differences were noted between the control and clonidine groups in onset time (100 ± 6 sec (mean ± SE) vs 101 ± 6 sec), duration (44.5 ±2.7 min vs 42.9 ±2.7 min), or recovery index (21.6 ± 2.8 min vs 19.1 ± 1.9 min) of neuromuscular blockade from vecuronium, respectively. These results show that oral preanaesthetic medication of clonidine 5 μg · kg^?1 does not alter neuromuscular blockade induced with vecuronium 0.1 mg · kg^?1 in patients during combined epidural and fentanyl/nitrous oxide general anaesthesia.     

Muscle relaxation does not alter hypnotic level during propofol anesthesia

Electromyographic (EMG) activity can contaminate electroencephalographic signals. Paralysis may therefore reduce the Bispectral Index (BIS) by alleviating artifact from muscles lying near the electrodes. Paralysis may also reduce signals from muscle stretch receptors that normally contribute to arousal. We therefore tested the hypothesis that nondepolarizing neuromuscular block reduces BIS. Ten volunteers were anesthetized with propofol at a target effect site concentration of 3.8 plus/minus 0.4 microg/mL. A mivacurium infusion was adjusted to vary the first twitch (T1) in a train-of-four to 80%, 30%, 20%, 15%, 10%, 5%, or 2% of the prerelaxant intensity. At each randomly assigned T1, we measured BIS and frontal-temporal EMG intensity. BIS averaged 95 plus/minus 4 before induction of anesthesia, and decreased significantly to 40 plus/minus 5 after propofol administration. However, there were no significant differences at the designated block levels. Frontal-temporal EMG intensity averaged 47 plus/minus 3 dB before induction of anesthesia, and decreased significantly to 27 plus/minus 1 dB after propofol administration. However, there were no significant differences at the designated block levels. These data suggest that the BIS level and EMG tone are unaltered by mivacurium administration during propofol anesthesia. IMPLICATIONS: Neuromuscular block level did not alter Bispectral Index (BIS) during propofol anesthesia, either by reducing electromyographic artifact or by decreasing afferent neuronal input. The BIS will thus comparably estimate sedation in deeply unconscious patients who are paralyzed, partially paralyzed, or unparalyzed.     

Heparin pretreatment does not alter heparin requirements during cardiopulmonary bypass

Heparin infusion may cause heparin resistance and may affectmonitoring by measurement of the activated coagulation time(ACT), making the assessment of anticoagulation difficult, withthe risk of over- or undertreatment, especially during cardiacsurgery. We studied two groups of patients undergoing cardiopulmonarybypass (CPB): patients on heparin infusions (group H) and heparin-naivecontrols (group C). All patients received heparin 300 IU kg^–1before CPB and a further dose of 5000 IU if the ACT 5 minafter commencing bypass was less than 400 s. Measurementsof ACT, heparin concentration, antithrombin-3, thrombin–antithrombincomplex, prothrombin fragment F₁₊₂ and D-dimers were made beforeand 5 and 20 min after start of CPB. A second dose of heparinwas given to eight out of 18 patients in group C and 10 outof 24 in group H. Antithrombin-3 in group H was significantlyless than in group C at 5 min [59 (14) vs 52 (9)%, P<0.05].ACT was significantly lower in group H than group C at 20 min[387 (64) vs 431 (67) s, P<0.05]. Despite ACTs of lessthan 400 s in both groups, no coagulation was seen, suggestingthat 300 IU kg^–1 heparin is a safe dose foranticoagulation in CPB even after heparin therapy. Br J Anaesth 2001; 87: 844–7