bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic and vascular actions of endothelin‐1 are inhibited by insulin‐mediated vasodilation in perfused rat hindlimb muscle
Authors: Kolka Cathryn M , Rattigan Stephen , Richards Stephen , Clark Michael G 
Published: May 2005

Endothelin‐1 (ET‐1) is a potent endothelium‐derived vasoactive peptide and may be involved in the microvascular actions of insulin for the normal delivery of nutrients to muscle, although higher levels may be antagonistic.
Our aim was to observe the interaction between ET‐1 and insulin. Initially, we attempted to distinguish the vascular from the metabolic effects of ET‐1 in the constant‐flow pump‐perfused rat hindlimb by using various doses of ET‐1 and measuring changes in perfusion pressure (PP), oxygen consumption (VO2), glucose uptake (GU) and lactate release (LR). Sodium nitroprusside (SNP) was used to block vasoconstriction and to thus assess the relationship between vascular and metabolic effects. Insulin was included in later experiments to determine the interaction between insulin and ET‐1 on the above parameters.
ET‐1 caused a dose‐dependent increase in PP. Effects on VO2 were biphasic, with low doses increasing VO2, and higher doses leading to a net inhibition. GU and LR were increased at lower doses (ET‐1 1 nM), but this effect was lost at higher doses (10 nM ET‐1).
SNP (50 μM) fully blocked the increase in pressure and metabolism due to low‐dose ET‐1 and partly blocked both pressure and metabolic responses by the high dose. ET‐1 vasodilatory activity was minimal at high or low dose. Insulin (15 nM) alone caused GU, which was not affected by ET‐1. Of the other parameters measured, insulin behaved essentially the same as SNP, inhibiting the pressure and oxygen effects.
Overall, these results show that ET‐1 has a biphasic dose‐dependent vasoconstrictor effect on hindlimb blood vessels, able to modulate flow to cause both the stimulation and inhibition of metabolism, although these effects are blocked by insulin, which is able to vasodilate against both low and high doses of ET‐1.

British Journal of Pharmacology (2005) 145, 992–1000. doi:10.1038/sj.bjp.0706263
Effect of Low-dose Droperidol on the QT Interval during and after General Anesthesia
Authors: White Paul F. , Song Dajun , Abrao Joao , Klein Kevin W. , Navarette Bryan 
Published: May 2005

Background
Since the effects of antiemetic doses of droperidol on the QT interval have not been previously studied, the authors designed a randomized, double-blind, placebo-controlled study to evaluate the intraoperative and postoperative effects of small-dose droperidol (0.625 and 1.25 mg intravenous) on the QT interval when used for antiemetic prophylaxis during general anesthesia.

Methods
One hundred twenty outpatients undergoing otolaryngologic procedures with a standardized general anesthetic technique were enrolled in this study. After anesthetic induction and before the surgical incision, 60 patients were given either saline or 0.625 or 1.25 mg intravenous droperidol in a total volume of 2 ml. A standard electrocardiographic lead II was recorded immediately before and every minute after the injection of the study medication during a 10-min observation period. The QTc (QT interval corrected for heart rate) was evaluated from the recorded electrocardiographic strips. In 60 additional patients, a 12-lead electrocardiogram was obtained before and at specific intervals up to 2 h after surgery to assess the effects of droperidol and general anesthesia on the QTc. Any abnormal heartbeats or arrhythmias during the operation or the subsequent 2-h monitoring interval were also noted.

Results
Intravenous droperidol, 0.625 and 1.25 mg, prolonged the QT interval by an average of 15 +/- 40 and 22 +/- 41 ms, respectively, at 3-6 min after administration during general anesthesia, but these changes did not differ significantly from that seen with saline (12 +/- 35 ms) (all values mean +/- SD). There were no statistically significant differences among the three study groups in the number of patients with greater than 10% prolongation in QTc (vs. baseline). Although general anesthesia was associated with a 14- to 16-ms prolongation of the QTc interval in the early postoperative period, there was no evidence of droperidol-induced QTc prolongation after surgery. Finally, there were no ectopic heartbeats observed on any of the electrocardiographic rhythm strips or 12-lead recordings during the perioperative period.

Conclusion
Use of a small dose of droperidol (0.625-1.25 mg intravenous) for antiemetic prophylaxis during general anesthesia was not associated with a statistically significant increase in the QTc interval compared with saline. More importantly, there was no evidence of any droperidol-induced QTc prolongation immediately after surgery.
Intubating Laryngeal Mask Airway in Morbidly Obese and Lean Patients
Authors: Combes Xavier , Sauvat Stéphane , Leroux Bertrand , Dumerat Marc , Sherrer Emanuel , Motamed Cyrus , Brain Archie , D’Honneur Gilles 
Published: May 2005

Background
The intubating laryngeal mask airway (ILMA) was designed using the characteristics of healthy-weight subjects but was shown to be an effective airway device in morbidly obese patients. The authors compared airway management quality in morbidly obese and lean patients with use of the ILMA.

Methods
Fifty morbidly obese and 50 lean patients (mean body mass indexes, 42 and 27 kg/m, respectively) were enrolled in this prospective study. After induction of general anesthesia, characteristics of airway management were judged on safety and efficiency parameters, including success rate at ventilation and intubation and airway management quality criteria, such as the number of patients who required adjustment maneuvers, the number of failed tracheal intubation attempts, the total duration of airway management, and an overall difficulty visual analog scale score.

Results
The ILMA was successfully inserted and adequate ventilation through the ILMA was achieved in all 100 patients. The success rates of tracheal intubation through the ILMA were similar in obese and lean patients (96% and 94%, respectively). The numbers of failed blind tracheal access attempts and patients who required airway-adjustment maneuvers were significantly reduced in obese patients as compared with lean patients. Four obese patients experienced transient episodes of oxygen desaturation (oxygen saturation < 90%) before adequate bag ventilation was established with the ILMA.

Conclusion
The authors confirmed that the ILMA was an efficient airway device for airway management of both lean and obese patients. In the conditions of this study, the authors observed that airway management with the ILMA was simpler in obese patients as compared with lean patients.
Preoxygenation Is More Effective in the 25° Head-up Position Than in the Supine Position in Severely Obese Patients
Authors: Dixon Benjamin J. , Dixon John B. , Carden Jennifer R. , Burn Anthony J. , Schachter Linda M. , Playfair Julie M. , Laurie Cheryl P. , O’Brien Paul E. 
Published: May 2005

Background
Class III obese patients have altered respiratory mechanics, which are further impaired in the supine position. The authors explored the hypothesis that preoxygenation in the 25 degrees head-up position allows a greater safety margin for induction of anesthesia than the supine position.

Methods
A randomized controlled trial measured oxygen saturation and the desaturation safety period after 3 min of preoxygenation in 42 consecutive (male:female 13:29) severely obese (body mass index > 40 kg/m) patients who were undergoing laparoscopic adjustable gastric band surgery and were randomly assigned to the supine position or the 25 degrees head-up position. Serial arterial blood gases were taken before and after preoxygenation and 90 s after induction. After induction, ventilation was delayed until blood oxygen saturation reached 92%, and this desaturation safety period was recorded.

Results
The mean body mass indexes for the supine and 25 degrees head-up groups were 47.3 and 44.9 kg/m, respectively (P = 0.18). The group randomly assigned to the 25 degrees head-up position achieved higher preinduction oxygen tensions (442 +/- 104 vs. 360 +/- 99 mmHg; P = 0.012) and took longer to reach an oxygen saturation of 92% (201 +/- 55 vs. 155 +/- 69 s; P = 0.023). There was a strong positive correlation between the induction oxygen tension achieved and the time to reach an oxygen saturation of 92% (r = 0.51, P = 0.001). There were no adverse events associated with the study.

Conclusion
Preoxygenation in the 25 degrees head-up position achieves 23% higher oxygen tensions, allowing a clinically significant increase in the desaturation safety period--greater time for intubation and airway control. Induction in the 25 degrees head-up position may provide a greater safety margin for airway control.
Development and Validation of a Perioperative Satisfaction Questionnaire
Authors: Auquier Pascal , Pernoud Nicolas , Bruder Nicolas , Simeoni Marie-Claude , Auffray Jean-Pierre , Colavolpe Christian , François Georges , Gouin François , Manelli Jean-Claude , Martin Claude , Sapin Christophe , Blache Jean-Louis 
Published: May 2005

Background
Satisfaction is considered a valuable measure of outcome of healthcare processes. Only a few anesthesia-related validated questionnaires are reported. Because their scope is restricted to specific clinical contexts, their use remains limited. The objective of the current study was to develop and validate a self-reported questionnaire, Evaluation du Vecu de l'Anesthesie Generale (EVAN-G), assessing the satisfaction of the perioperative period surrounding general anesthesia.

Methods
Development of the EVAN-G questionnaire comprised a phase of item generation and a phase of psychometric validation. The patient sample was generated to be proportionally matched to the population of patients undergoing general anesthesia in France. The structure of the questionnaire was identified studying interitem, item-dimension, and interdimension correlations and factor analyses. Data were concurrently gathered to assess external validity. The discriminant validity was determined by comparison of scores across well known patient groups. Reliability was assessed by computation of Cronbach alpha coefficients and by test-retest.

Results
Eight hundred seventy-four patients were recruited in eight anesthesia departments. The EVAN-G includes 26 items; six specific scores and one global index score are available. Correlations between EVAN-G scores and other concurrent measures supported convergent validity. The EVAN-G correlated poorly with age, American Society of Anesthesiologists physical status, total anesthesia time, and number of previous anesthesias. Significantly higher satisfaction was reported by patients older than 65 yr, belonging to the laryngeal mask group. Reliability and reproducibility were shown.

Conclusion
The EVAN-G adds important information oriented toward patients' perceptions. The authors' approach provides a novel, valid, and reliable tool that may be used in anesthesia practice.
Involvement of Adenosine in the Antiinflammatory Action of Ketamine
Authors: Mazar Julia , Rogachev Boris , Shaked Gad , Ziv Nadav Y. , Czeiger David , Chaimovitz Cidio , Zlotnik Moshe , Mukmenev Igor , Byk Gerardo , Douvdevani Amos 
Published: May 2005

Background
Ketamine is an anesthetic drug. Subanesthetic doses of ketamine have been shown to reduce interleukin-6 concentrations after surgery and to reduce mortality and the production of tumor necrosis factor alpha and interleukin 6 in septic animals. Similarly, adenosine was shown to reduce tumor necrosis factor alpha and mortality of septic animals. The aim of this study was to determine whether adenosine mediates the antiinflammatory effects of ketamine.

Methods
Sepsis was induced in mice by lipopolysaccharide or Escherichia coli inoculation. Leukocyte recruitment and cytokine concentrations were used as inflammation markers. Adenosine concentrations were assayed by high-performance liquid chromatography, and the involvement of adenosine in the effects of ketamine was demonstrated by adenosine receptor agonists and antagonists.

Results
Ketamine markedly reduced mortality from sepsis, leukocyte recruitment, and tumor necrosis factor-alpha and interleukin-6 concentrations. Ketamine administration in mice and rats was associated with a surge at 20-35 min of adenosine in serum (up to 5 microm) and peritoneal fluid. The adenosine A2A receptor agonist CGS-21680 mimicked the effect of ketamine in peritonitis, whereas the A2A receptor antagonists DMPX and ZM 241385 blocked its antiinflammatory effects. In contrast, A1 and A3 receptor antagonists had no effect. ZM 241385 reversed the beneficial effect of ketamine on survival from bacterial sepsis.

Conclusions
The current data suggest that the sepsis-protective antiinflammatory effects of ketamine are mediated by the release of adenosine acting through the A2A receptor.
Opposing Effects of Isoflurane and Sevoflurane on Neurogenic Pulmonary Edema Development in an Animal Model
Authors: Kandatsu Nobuhisa , Nan Yong-Shan , Feng Guo-Gang , Nishiwaki Kimitoshi , Hirokawa Mitsuru , Ishikawa Kiyonori , Komatsu Toru , Yokochi Takashi , Shimada Yasuhiro , Ishikawa Naohisa 
Published: May 2005

Background
The current study was undertaken to investigate the effects of pretreatment with isoflurane and sevoflurane on the development of neurogenic pulmonary edema in an animal model.

Methods
Rats were exposed to room air (control), 1.5% isoflurane, or 2.5% sevoflurane for 4 h. They were then anesthetized with intraperitoneal injections of pentobarbital sodium, and fibrinogen and thrombin were injected into the cisterna magna to induce neurogenic pulmonary edema.

Results
Consecutive injections of fibrinogen and thrombin caused increases in blood pressure, with the peak values obtained in the isoflurane and sevoflurane groups being lower than the control values. The incidence of significant neurogenic pulmonary edema was 58%, 100%, and 8% in the control, isoflurane, and sevoflurane groups, respectively. The lung water ratio, an index of severity of edema, was 4.86 +/- 0.78, 6.15 +/- 0.64, and 4.40 +/- 0.32 in the control, isoflurane, and sevoflurane groups, respectively. Furthermore, immunohistochemical staining for vascular endothelial growth factor demonstrated an increase of expression in the rat lungs exposed to isoflurane. Treatment with an anti-vascular endothelial growth factor antibody during exposure to isoflurane completely inhibited the effect of isoflurane to promote neurogenic pulmonary edema in this model.

Conclusion
Exposure to 1.5% isoflurane enhances the development of neurogenic pulmonary edema development in this animal model, most likely via release of vascular endothelial growth factor from bronchial epithelial cells, an effect not observed with sevoflurane.
Effect of Postoperative Epidural Analgesia on Rehabilitation and Pain after Hip Fracture Surgery
Authors: Foss Nicolai Bang , Kristensen Morten Tange , Kristensen Billy Bjarne , Jensen Pia Søe , Kehlet Henrik 
Published: May 2005

Background
Hip fracture surgery usually carries a high demand for rehabilitation and a significant risk of perioperative morbidity and mortality. Postoperative epidural analgesia may reduce morbidity and has been shown to facilitate rehabilitation in elective orthopedic procedures. No studies exist on the effect of postoperative epidural analgesia on pain and rehabilitation after hip fracture surgery.

Methods
Sixty elderly patients were included in a randomized, double-blind study comparing 4 days of continuous postoperative epidural infusion of 4 ml/h bupivacaine, 0.125%, and 50 mug/ml morphine versus placebo. Both patient groups received balanced analgesia and intravenous nurse-controlled analgesia with morphine. All patients followed a well-defined multimodal rehabilitation program. Pain, ability to participate in four basic physical functions, and any factors restricting participation were assessed on the first 4 postoperative days during physiotherapy.

Results
Epidural analgesia provided superior dynamic analgesia during all basic physical functions, and patients were significantly less restricted by pain, which was the dominating restricting factor in the placebo group. Motor blockade was not a restricting factor during epidural analgesia. Despite improved pain relief, scores for recovery of physical independence were not different between groups.

Conclusion
Postoperative epidural analgesia after hip fracture surgery provides superior analgesia attenuating pain as a restricting factor during rehabilitation without motor dysfunction. However, superior analgesia did not translate into enhanced rehabilitation. Future studies with multimodal rehabilitation are required to establish whether superior analgesia can be translated into enhanced rehabilitation and reduced morbidity in hip fracture patients.
Median Effective Dose (ED50) of Nefopam and Ketoprofen in Postoperative Patients
Authors: Delage Noémie , Maaliki Hilal , Beloeil Hélène , Benhamou Dan , Mazoit Jean-Xavier 
Published: May 2005

Background
The analgesic efficacy of ketoprofen has been shown after moderate- and severe-pain surgery, and the analgesic efficacy of nefopam has been shown after moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and to determine whether the interaction of nefopam and of ketoprofen is synergistic.

Methods
Seventy-two patients scheduled to undergo moderately painful surgery were enrolled in one of three groups. The dose of nefopam and ketoprofen received by a particular patient was determined by the response of the previous patient of the same group, using an up-and-down technique. Initial doses were 18 and 40 mg, with dose adjustment intervals of 2 and 5 mg, in the nefopam and ketoprofen groups, respectively. The initial doses of nefopam and ketoprofen were 8 and 20 mg, respectively, in the nefopam-ketoprofen group, with the same dose adjustment intervals. Analgesic efficacy was defined as a decrease to less than 3 on a 0-10 numeric pain scale, 45 min after the beginning of drug infusion.

Results
The median effective analgesic dose (median value and 95% confidence interval) of nefopam and ketoprofen were, respectively, 28 mg (17-39 mg) and 30 mg (14-46 mg). The median effective analgesic dose of the combination was 1.75 mg (0.9-2.3 mg) for nefopam and 4.3 mg (2.2-6.5 mg) for ketoprofen.

Conclusion
The isobolographic analysis demonstrated that the combination of the two drugs produces effective analgesia with an important synergistic interaction.
Painful Nerve Injury Decreases Resting Cytosolic Calcium Concentrations in Sensory Neurons of Rats
Authors: Fuchs Andreas , Lirk Philipp , Stucky Cheryl , Abram Stephen E. , Hogan Quinn H. 
Published: May 2005

Background
Neuropathic pain is difficult to treat and poorly understood at the cellular level. Although cytoplasmic calcium ([Ca]c) critically regulates neuronal function, the effects of peripheral nerve injury on resting sensory neuronal [Ca]c are unknown.

Methods
Resting [Ca]c was determined by microfluorometry in Fura-2 AM-loaded neurons dissociated from dorsal root ganglia of animals with hyperalgesia to mechanical stimulation after spinal nerve ligation and section (SNL) at the fifth and sixth lumbar (L5 and L6) levels and from animals after skin incision alone (control group). Axotomized neurons from the L5 dorsal root ganglia were examined separately from adjacent L4 neurons that share the sciatic nerve with degenerating L5 fibers.

Results
After SNL, large (34 mum or larger) neurons from the L4 ganglion showed a 29% decrease in resting [Ca]c, whereas those from the L5 ganglion showed a 54% decrease. Small neurons only showed an effect of injury in the axotomized L5 neurons, in which resting [Ca]c decreased by 30%. A decrease in resting [Ca]c was not seen in neurons isolated from rats in which hyperalgesia did not develop after SNL. In separate experiments, SNL reduced resting [Ca]c in capsaicin-insensitive neurons of the L5 ganglion by 60%, but there was no change in neurons from L4. Resting [Ca]c of capsaicin-sensitive neurons was not affected by injury in either ganglion. SNL injury decreased the proportion of neurons sensitive to capsaicin in the L5 group but increased the proportion in the L4 group.

Conclusions
Painful SNL nerve injury depresses resting [Ca]c in sensory neurons. This is most marked in axotomized neurons, especially the large and capsaicin-insensitive neurons presumed to transmit non-nociceptive sensory information.
Developmental Age Influences the Effect of Epidural Dexmedetomidine on Inflammatory Hyperalgesia in Rat Pups
Authors: Walker Suellen M. , Howard Richard F. , Keay Kevin A. , Fitzgerald Maria 
Published: May 2005

Background
Epidural alpha2-adrenergic agonists produce analgesic effects in children and adults, but efficacy and safety have not been established in neonates and infants. The aim of this study was to determine the effect of epidural dexmedetomidine on sensory processing, reversal of inflammatory hyperalgesia, and sedation during early development in rats.

Methods
In rat pups aged 3, 10, and 21 postnatal days, mechanical withdrawal thresholds of the hind limbs were measured at baseline and after unilateral inflammation due to carrageenan. The effect of epidural dexmedetomidine on withdrawal thresholds was measured for 90 min after injection, and dose-response curves were constructed for each age group. The duration of the righting reflex was measured to assess sedation. The effects of epidural and systemic administration of dexmedetomidine were compared.

Results
At all ages, carrageenan-induced hyperalgesia was reversed by doses of epidural dexmedetomidine that did not affect the threshold of the contralateral paw or prolong the righting reflex. Higher doses of epidural dexmedetomidine affected baseline nociception in the contralateral paw and produced sedation but had no effect when given systemically. Reversal of hyperalgesia and sedation were produced by lower doses of epidural dexmedetomidine in the youngest pups.

Conclusions
Spinally mediated selective reversal of inflammatory hyperalgesia by epidural dexmedetomidine can be achieved at all ages; relatively lower doses are effective in early life, but the therapeutic window is narrow. These data have implications for the use and dosing of epidural alpha2 agonists in neonates and infants.