bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic Inflammation Leads to Resistance to Atracurium without Increasing Membrane Expression of Acetylcholine Receptors
Authors: Fink Heidrun , Luppa Peter , Mayer Barbara , Rosenbrock Hilkea , Metzger Jochen , Martyn J. A. Jeevendra , Blobner Manfred 
Published: February 2004

Background
Systemic inflammation may be associated with resistance to nondepolarizing neuromuscular blocking drugs, the mechanisms of which are, however, uncharacterized. The authors therefore investigated the pharmacodynamics of atracurium and its relation to the expression of nicotinic acetylcholine receptors and alpha1 -acid glycoprotein in a rat model of systemic inflammation.

Methods
To induce a systemic inflammation, male CD rats received 56 mg/kg corynebacterium parvum intravenously. On days 2, 4, 6, 8, 10, 12, 14, or 16 after infection, neuromuscular transmission was measured. The individual effective dose of atracurium was determined, followed by an atracurium infusion at a rate to establish a steady state neuromuscular block of 50%. Total and unbound plasma concentrations of atracurium for 50% paralysis were measured using high-performance liquid chromatography. Acetylcholine receptors were quantitated using 125I-alpha-bungarotoxin. alpha1 -Acid glycoprotein concentrations in the serum were measured using a competitive chemiluminescence immunoassay.

Results
The effective dose of atracurium was increased on days 4, 6, and 8. Total atracurium plasma concentrations at 50% neuromuscular paralysis were increased on days 4, 6, 8, and 10, with a peak at day 8 (8.0 +/- 1.3 micro g/ml) compared with control rats (4.23 +/- 0.82 micro g/ml). The alpha1 -acid glycoprotein concentrations were increased between days 2 and 10, with a peak on day 4 (6.52 +/- 1.45 mg/ml), and recovered to control values (0.61 +/- 0.33 mg/ml) on day 12. Unbound plasma concentrations of atracurium to achieve 50% depression, as well as the expression of acetylcholine receptors, did not differ between groups.

Conclusion
Resistance to atracurium during corynebacterium parvum-induced systemic inflammation is due to increased drug binding to alpha1 -acid glycoprotein and is unrelated to changes in acetylcholine receptor expression.
Hemodynamic and Cardiac Electrophysiologic Effects of Lidocaine–Bupivacaine Mixture in Anesthetized and Ventilated Piglets
Authors: Lefrant Jean-Yves , Muller Laurent , de La Coussaye Jean E. , Lalourcey Laurent , Ripart Jacques , Peray Pascale A. , Mazoit Xavier , Dauzat Michel , Sassine Antoine , Eledjam Jean-Jacques 
Published: February 2004

Background
The sensory blockade induced by a lidocaine-bupivacaine mixture combines the faster onset of lidocaine and the longer duration of bupivacaine. The current study compared the effects of large doses lidocaine (16 mg/kg), bupivacaine (4 mg/kg), and a mixture of 16 mg/kg lidocaine-4 mg/kg bupivacaine on hemodynamic and cardiac electrophysiologic parameters in anesthetized and ventilated piglets.

Methods
After carotid artery cannulation, a double micromanometer measured mean aortic pressure, left ventricular end diastolic pressure, and the first derivative of left ventricular pressure. Electrocardiogram recording and a bipolar electrode catheter measured RR, PQ, QRS, QT C, JT C, AH, and HV intervals. Lidocaine, bupivacaine, or the mixture was administered intravenously over 30 s, and studied parameters were measured throughout 30 min.

Results
Mean aortic pressure decreased in all groups ( P < 0.05). The first derivative of left ventricular pressure was decreased in all groups ( P < 0.001) but to a greater extent with the mixture compared with lidocaine ( P < 0.04). RR, QT C, and JT C intervals were similarly increased in all groups ( P < 0.05). In all groups, PQ, AH, HV, and QRS intervals were widened ( P < 0.001). The lengthening of PQ was greater with bupivacaine ( P < 0.02). The lengthening of AH was greater and delayed with bupivacaine compared with lidocaine ( P < 0.03). The lengthening of HV and the widening of QRS were greater and delayed with bupivacaine ( P < 0.01). The widening of QRS was greater with the mixture than with lidocaine ( P < 0.01).

Conclusions
The alterations of ventricular conduction parameters are greater with 4 mg/kg bupivacaine than with a mixture of 16 mg/kg lidocaine-4 mg/kg bupivacaine, whereas the hemodynamic parameters are similarly altered.
Inhibitory Effects of Etomidate and Ketamine on Adenosine Triphosphate–Sensitive Potassium Channel Relaxation in Canine Pulmonary Artery
Authors: Sohn Ju-Tae , Murray Paul A. 
Published: February 2004

Background
The authors recently demonstrated that etomidate and ketamine attenuated endothelium-dependent pulmonary vasorelaxation mediated by nitric oxide and Ca -activated K + channels. In the current study, they tested the hypothesis that these intravenous anesthetics inhibit pulmonary vasorelaxation mediated by adenosine triphosphate-sensitive potassium (K + ATP ) channel activation.

Methods
Endothelium intact and denuded pulmonary arterial rings were suspended in organ chambers for isometric tension recording. The effects of etomidate (5 x 10(-6) and 5 x 10(-5) m) and ketamine (5 x 10(-5) and 10(-4) m) on vasorelaxation responses to lemakalim (K + ATP channel activator), prostacyclin, and papaverine were assessed in phenylephrine-precontracted rings. The effect of cyclooxygenase inhibition with indomethacin was assessed in some protocols.

Results
Etomidate (5 x 10(-6) m) only inhibited the vasorelaxant response to lemakalim in endothelium intact rings, whereas a higher concentration of etomidate (5 x 10(-5) m) inhibited relaxation in both intact and endothelium-denuded rings. Pretreatment with indomethacin abolished the endothelium-dependent attenuation of lemakalim-induced relaxation caused by etomidate. Ketamine (5 x 10(-5) and 10(-5) m) inhibited the relaxation response to lemakalim to the same extent in both endothelium-intact and -denuded rings, and this effect was not prevented by indomethacin pretreatment. Etomidate and ketamine had no effect on the relaxation responses to prostacyclin or papaverine.

Conclusions
These results indicate that etomidate, but not ketamine, attenuates the endothelium-dependent component of lemakalim-induced pulmonary vasorelaxation an inhibitory effect on the cyclooxygenase pathway. Both anesthetics inhibit K + ATP -mediated pulmonary vasorelaxation a direct effect on pulmonary vascular smooth muscle.
Isoflurane Sensitizes the Cardiac Sarcolemmal Adenosine Triphosphate–Sensitive Potassium Channel to Pinacidil
Authors: Gassmayr Susanne , Stadnicka Anna , Suzuki Akihiro , Kwok Wai-Meng , Bosnjak Zeljko J. 
Published: February 2004

Background
Cardioprotective effects of isoflurane are partially mediated by the sarcolemmal adenosine triphosphate-sensitive potassium (sarcK ATP ) channel. The authors tested the hypothesis that isoflurane sensitizes sarcK ATP channels to a potassium channel opener, pinacidil, adenosine- and phospholipid-mediated pathways.

Methods
Activation by pinacidil of the K ATP current (I KATP ) was monitored in guinea pig ventricular myocytes at 0.5 and 5 mm intracellular ATP in the whole cell configuration of the patch clamp technique. The sensitization effect was evaluated by pretreating each myocyte with isoflurane (0.57 +/- 0.04 mm) before application of pinacidil (5 micro m) in the continued presence of the anesthetic. To investigate whether intracellular signaling pathways may be involved in isoflurane sensitization, the authors used the adenosine receptor antagonist theophylline (100 micro m) and the phosphatidylinositol kinase inhibitor wortmannin (100 micro m).

Results
The density of pinacidil-activated I KATP was higher at 0.5 mm ATP (20.7 +/- 3.2 pA/pF) than at 5 mm ATP (2.0 +/- 0.3 pA/pF). At 0.5 mm ATP, pretreatment with isoflurane caused an increase in density of pinacidil-activated I KATP (42.4 +/- 6.2 pA/pF) and accelerated the rate of current activation (from 5.4 +/- 1.2 to 39.0 +/- 7.9 pA. pF(-1). min(-1) ). Theophylline attenuated current activation by pinacidil (9.4 +/- 3.9 pA/pF) and abolished the sensitization effect of isoflurane on I KATP (10.0 +/- 2.5 pA/pF). Wortmannin did not alter pinacidil activation of I KATP (13.2 +/- 1.7 pA/pF) but prevented sensitization by isoflurane (15.8 +/- 4.5 pA/pF).

Conclusions
These results suggest that isoflurane increases sensitivity of cardiac sarcK ATP channels to the potassium channel opener pinacidil. Blockade of adenosine receptors or phosphatidylinositol kinases abolishes the sensitization effect, suggesting that the adenosine and phospholipid signaling pathways may be involved in the actions by isoflurane.
Continuous Interscalene Analgesia with Ropivacaine 2 mg/ml after Major Shoulder Surgery
Authors: Ekatodramis Georgios , Borgeat Alain , Huledal Gunilla , Jeppsson Lennart , Westman Lars , Sjövall Jan 
Published: February 2004

Background
In this open, randomized study, the pharmacokinetics, clinical efficacy, and safety of a 48-h continuous interscalene infusion of 2 mg/ml ropivacaine for postoperative pain relief were investigated in patients undergoing open major shoulder surgery.

Methods
An initial interscalene block with 30 ml ropivacaine, 7.5 mg/ml (225 mg), was performed. After completion of interscalene block, all patients (n = 24) received general anesthesia, and 6 h after interscalene block, a 48-h continuous interscalene infusion of 12 or 18 mg/h using 2 mg/ml ropivacaine was started. Total and unbound plasma concentrations of ropivacaine and 2.6-pipecoloxylidide (PPX; a major active metabolite) were determined during and up to 6 h after the interscalene infusion. Postoperative pain at rest was assessed by a visual analog scale. Supplementary analgesics and adverse events were recorded.

Results
Plasma concentrations of total and unbound ropivacaine were proportional to the total dose. At the end of the interscalene infusion of 9 ml/h, the mean +/- SD plasma concentrations of total and unbound ropivacaine were 1.40 +/- 0.54 and 0.03 +/- 0.01 mg/l, respectively, and of total and unbound PPX were 0.70 +/- 0.38 and 0.30 +/- 0.20 mg/l, respectively. Plasma concentrations of unbound ropivacaine and unbound PPX, added together, remained well below threshold levels for systemic central nervous system toxicity. There were no significant differences between the groups for postoperative pain (median maximum of about 20 mm on the visual analog scale in both groups), analgesic consumption, or quality of pain relief assessed by the patient. No signs or symptoms of systemic local anesthetic toxicity were observed.

Conclusion
A 48-h continuous interscalene infusion of 6 or 9 ml/h ropivacaine, 2 mg/ml, started 6 h after an initial interscalene block of 30 ml ropivacaine, 7.5 mg/ml, provided satisfactory postoperative pain relief after major shoulder surgery and was well tolerated. Unbound plasma concentrations of ropivacaine and PPX remained well below threshold levels for systemic central nervous toxicity.
Comparison of Povidone Iodine and DuraPrep, an Iodophor-in-Isopropyl Alcohol Solution, for Skin Disinfection Prior to Epidural Catheter Insertion in Parturients
Authors: Birnbach David J. , Meadows Warner , Stein Deborah J. , Murray Odessa , Thys Daniel M. , Sordillo Emilia M. 
Published: February 2004

Background
Although rare, infectious sequelae of epidural analgesia can occur. A recently marketed antiseptic solution (DuraPrep) which contains an iodophor in isopropyl alcohol, may provide enhanced and longer-lasting antimicrobial activity and thus be useful in the obstetric setting. The purpose of this study was to evaluate the antisepsis achieved with DuraPrep compared with povidone iodine (PI).

Methods
Sixty women in active labor who requested epidural analgesia were randomly assigned to receive skin preparation with either PI or DuraPrep solution. A total of three cultures were obtained from each subject. The first was obtained just prior to skin disinfection, the second was obtained immediately following antisepsis, and the third was obtained just before removal of the catheter. In addition, the distal tip of the catheter was also submitted for culture.

Results
The clinical characteristics and the risk factors for infection were similar in the two groups. The proportion of subjects with positive skin cultures immediately after skin disinfection differed significantly between the PI and DuraPrep groups (30 3%, respectively, P = 0.01). The number of subjects with any positive skin cultures at the time of catheter removal was greater in the PI group as compared to the DuraPrep group (97 50%, respectively, P = 0.0001), as was the number of organisms cultured from skin (log CFU 1.93 +/- 0.40 0.90 +/- 0.23, respectively, P = 0.03). Six catheters, all from the PI group, yielded positive cultures by the roll-plate technique.

Conclusion
As compared to PI, DuraPrep solution was found to provide a greater decrease in the number of positive skin cultures immediately after disinfection, as well as in bacterial regrowth and colonization of the epidural catheters.
Comparison of the Visceral Antinociceptive Effects of Spinally Administered MPV-2426 (Fadolmidine) and Clonidine in the Rat
Authors: Pertovaara Antti , Kalmari Jaakko 
Published: February 2004

Background
The authors determined the visceral antinociceptive effect induced by MPV-2426 (fadolmidine), a selective alpha 2 -adrenoceptor agonist, in rats with and without inflammation of the colon. They also determined whether the sympathetic nervous system or intact descending pathways are critical for the alpha 2 -adrenoceptor-induced visceral antinociception.

Methods
Spinal neuronal responses evoked by colorectal distension were recorded in pentobarbitone-anesthetized rats. MPV-2426 was administered onto the spinal cord. Clonidine was used as a reference alpha 2 -adrenoceptor agonist. Inflammation of the colon was induced by turpentine. Sympathectomy was induced by 6-hydroxydopamine. A midthoracic transection of the spinal cord was performed to study the role of descending pathways.

Results
Spinal administration of MPV-2426 produced a dose-dependent attenuation of responses evoked by colorectal distension, and this effect was of the same percentual magnitude in inflamed as in noninflamed animals. Clonidine and MPV-2426 induced equipotent visceral antinociception. The effect by spinally administered MPV-2426 was enhanced by a chemical sympathectomy but not influenced by spinal transection.

Conclusions
Spinally administered MPV-2426 produces a dose-dependent visceral antinociception as well in animals with an inflammation of the colon as in controls. The visceral antinociceptive effect induced by spinal MPV-2426 is equipotent to that of spinal clonidine. An intact sympathetic nervous system or intact brainstem-spinal pathway is not critical for the MPV-2426-induced visceral antinociception.
Loss of T-type Calcium Current in Sensory Neurons of Rats with Neuropathic Pain
Authors: McCallum J. Bruce , Kwok Wai-Meng , Mynlieff Michelle , Bosnjak Zeljko J. , Hogan Quinn H. 
Published: February 2004

Background
Pathophysiology in the primary sensory neuron may contribute to chronic neuropathic pain. Ca channels play a central role in neuronal processes, and sensory neurons are rich in low-voltage-activated calcium channels (LVACCs). However, the physiologic function of these channels is unknown. Their possible role in rebound burst firing makes them a candidate for increased excitability after neuropathic injury.

Methods
This study uses pharmacological methods to isolate LVACC in cells from the dorsal root ganglia of neuropathic and sham-operated rats, including the blockade of high-voltage-activated Ca channels with fluoride and selective toxins. LVACCs were examined with conventional whole cell patch clamp electrophysiology techniques.

Results
After chronic constriction injury of the peripheral axon, LVACC was significantly reduced compared to sham rats as shown by a 60% reduction in peak current density and an 80% reduction in total calcium influx. A depolarizing shift in the voltage dependence of activation and an increase in the rate of deactivation and inactivation appear to cause this reduction of LVACC. Either Ni2+ or mibefradil, blockers of LVACC, applied in the bath to normal dorsal root ganglion cells during current clamp significantly and reversibly increased excitability.

Conclusions
These results suggest that loss of LVACC may contribute to decreased spike frequency adaptation and increased excitability after injury to sensory neurons. Through decreased Ca2+ influx, the cell becomes less stable and more likely to initiate or transmit bursts of action potentials. Consequently, modulation of Ca2+ currents at the dorsal root ganglion may be a potential method of therapeutic intervention.
Spinal Nitric Oxide Contributes to the Analgesic Effect of Intrathecal [D-Pen2,D-Pen5]-Enkephalin in Normal and Diabetic Rats
Authors: Chen Shao-Rui , Pan Hui-Lin 
Published: February 2004

Background
Spinal nitric oxide (NO) is important for the analgesic actions of morphine and cholinergic agents. Its role in the analgesic effect of delta-opioid receptor agonists is not known. In the present study, the authors determined the role of spinal endogenous NO in the antinociceptive effect of intrathecal [D-Pen2, D-Pen5 ]-enkephalin (DPDPE), a delta-opioid receptor agonist, in normal rats and a rat model of diabetic neuropathic pain.

Methods
Rats were rendered diabetic with streptozotocin (50 mg/kg, intraperitoneal). Intrathecal catheters were implanted in age-matched normal and diabetic rats. Nociceptive thresholds were determined by application of a noxious pressure stimulus to the hind paw. The dose-dependent effect of intrathecal DPDPE was first determined. The role of spinal NO in the analgesic effect of intrathecal DPDPE was then examined through intrathecal treatments with NO synthase inhibitors (NMMA and TRIM) and a specific NO scavenger (carboxy-PTIO).

Results
The diabetic rats developed a sustained mechanical hyperalgesia within 3 weeks after streptozotocin injection. Intrathecal DPDPE, 2-20 micro g, dose-dependently increased the withdrawal threshold in response to the noxious pressure in normal and diabetic rats. However, the ED(50) of DPDPE in diabetic rats was about twofold higher than that in normal rats. Intrathecal pretreatment with NMMA, TRIM, or carboxy-PTIO diminished the analgesic effect of DPDPE in both normal and diabetic rats. Furthermore, the inhibitory effect of NMMA on the action of intrathecal DPDPE was reversed by intrathecal l-arginine but not d-arginine.

Conclusions
Intrathecal DPDPE produces an antinociceptive effect in normal rats and a rat model of diabetic neuropathic pain. Spinal endogenous NO contributes importantly to the analgesic action of intrathecal DPDPE in both normal and diabetic neuropathic pain conditions.
Estimating Times of Surgeries with Two Component Procedures
Authors: Strum David P. , May Jerrold H. , Sampson Allan R. , Vargas Luis G. , Spangler William E. 
Published: February 2004

Background
Variability inherent in the duration of surgical procedures complicates surgical scheduling. Modeling the duration and variability of surgeries might improve time estimates. Accurate time estimates are important operationally to improve utilization, reduce costs, and identify surgeries that might be considered outliers. Surgeries with multiple procedures are difficult to model because they are difficult to segment into homogenous groups and because they are performed less frequently than single-procedure surgeries.

Methods
The authors studied, retrospectively, 10,740 surgeries each with exactly two CPTs and 46,322 surgical cases with only one CPT from a large teaching hospital to determine if the distribution of dual-procedure surgery times fit more closely a lognormal or a normal model. The authors tested model goodness of fit to their data using Shapiro-Wilk tests, studied factors affecting the variability of time estimates, and examined the impact of coding permutations (ordered combinations) on modeling.

Results
The Shapiro-Wilk tests indicated that the lognormal model is statistically superior to the normal model for modeling dual-procedure surgeries. Permutations of component codes did not appear to differ significantly with respect to total procedure time and surgical time. To improve individual models for infrequent dual-procedure surgeries, permutations may be reduced and estimates may be based on the longest component procedure and type of anesthesia.

Conclusions
The authors recommend use of the lognormal model for estimating surgical times for surgeries with two component procedures. Their results help legitimize the use of log transforms to normalize surgical procedure times prior to hypothesis testing using linear statistical models. Multiple-procedure surgeries may be modeled using the longest (statistically most important) component procedure and type of anesthesia.
Functional morphology of the developing alimentary canal in the holothurian Eupentacta fraudatrix (Holothuroidea, Dendrochirota)
Authors: Mashanov V. S. , Dolmatov I. Yu 
Published: February 2004

AbstractDevelopment of the digestive tract of the holothurian Eupentacta fraudatrix was examined using light and transmission electron microscopy. After the blastopore closes, the gut rudiment loses its connection with the blastoderm and becomes an enclosed, tubular chamber, ending blindly at both ends. The differentiation of the digestive and coelomic epithelia is mainly completed by day 12. Since no transient cell types are observed, this differentiation is definitive. By day 20, the mouth and anal openings appear. The cuticular lining in the anterior part of the gut rudiment has an endodermal origin and differentiates before the mouth is formed. The rest of the gut lining is composed of enterocytes typical of holothuroid intestine. At the early stages of development, mitotic figures are encountered among nonspecialized cells of the gut primordium. In more developed digestive epithelium, vesicular enterocytes are capable of mitotic division. Dividing enterocytes retain secretory vacuoles; thus mitosis occurs in actually differentiated cells. After mouth and anus formation, the oesophagus, stomach, intestine and rectum can be distinguished. In the wall of the stomach, powerful musculature is formed.