bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms Underlying the Inhibitory Effect of Propofol on the Contraction of Canine Airway Smooth Muscle
Authors: Lin Chih-Chung , Shyr Ming-Hwang , Tan Peter P. C. , Chien Chin-Sung , Pan Shiow-Lin , Wang Chuan-Chwan , Chiu Chi-Tso , Yang Chuen-Mao 
Published: November 2003

Background
Propofol has been shown to produce relaxation of preconstricted airway smooth muscle. Although the inhibition of calcium mobilization is supposed to be the major mechanism of action, the whole picture of the mechanisms is not completely clear.

Methods
Contractile response was performed using canine tracheal rings. The effects of propofol on carbachol-induced mobilization of intracellular Ca2+ and phosphoinositide hydrolysis were measured using cultured canine tracheal smooth muscle cells by monitoring fura-2 signal and assessing the accumulation of [3H]-inositol phosphates. To detect the effect of propofol on muscarinic receptor density and affinity, [3H]N-methyl-scopolamine was used as a radioligand for receptor binding assay.

Results
Pretreatment with propofol shifts the concentration-response curves of carbachol-induced smooth muscle contraction to the right in a concentration-dependent manner without changing the maximal response. Propofol not only decreased the release of Ca2+ from internal stores but also inhibited the calcium influx induced by carbachol. In addition, carbachol-induced inositol phosphate accumulation was attenuated by propofol; the inhibitory pattern was similar to the contractile response. Moreover, propofol did not alter the density of muscarinic receptors. The dissociation constant value was not altered by pretreatment with 100 microM propofol but was significantly increased by 300 microM (propofol, 952+/-229 pM; control, 588+/-98 pM; P<0.05).

Conclusions
Propofol attenuates the muscarinic receptor-mediated airway muscle contraction. The mechanism underlying these effects was attenuation of inositol phosphate generation and inhibition of Ca2+ mobilization through the inhibition of the receptor-coupled signal-transduction pathway.
Stereoselectivity of Bupivacaine in Local Anesthetic–sensitive Ion Channels of Peripheral Nerve
Authors: Nau Carla , Vogel Werner , Hempelmann Gunter , Bräu Michael E. 
Published: November 2003

Background
The local anesthetic bupivacaine exists in two stereoisomeric forms, R(+)- and S(-)-bupivacaine. Because of its lower cardiac and central nervous system toxicity, attempts were made recently to introduce S(-)-bupivacaine into clinical anesthesia. We investigated stereoselective actions of R(+)-and S(-)-bupivacaine toward two local anesthetic-sensitive ion channels in peripheral nerve, the Na+ and the flicker K+ channel.

Methods
In patch-clamp experiments on enzymatically demyelinated peripheral amphibian nerve fibers, Na+ and flicker K+ channels were investigated in outside-out patches. Half-maximum inhibiting concentrations (IC50) were determined. For the flicker K+ channel, simultaneous block by R(+)-bupivacaine and S(-)-bupivacaine was analyzed for competition and association (k1) and dissociation rate constants (k(-1)) were determined.

Results
Both channels were reversibly blocked by R(+)- and S(-)-bupivacaine. The IC50 values (+/- SEM) for tonic Na+ channel block were 29+/-3 microM and 44+/-3 microM, respectively. IC50 values for flicker K+ channel block were 0.15+/-0.02 microM and 11+/-1 microM, respectively, resulting in a high stereopotency ratio (+/-) of 73. Simultaneously applied enantiomers competed for a single binding site. Rate constants k1 and k(-1) were 0.83+/-0.13x10(6) M(-1) x S(-1) and 0.13+/-0.03 s(-1), respectively, for R(+)-bupivacaine and 1.90+/-0.20x10(6) M(-1) x s(-1) and 8.3+/-1.0 s(-1), respectively, for S(-)-bupivacaine.

Conclusions
Bupivacaine block of Na+ channels shows no salient stereoselectivity. Block of flicker K+ channels has the highest stereoselectivity ratio of bupivacaine action known so far. This stereoselectivity derives predominantly from a difference in k(-1), suggesting a tight fit between R(+)-bupivacaine and the binding site. The flicker K+ channel may play an important role in yet unknown toxic mechanisms of R(+)-bupivacaine.
Effect of Epinephrine on Lidocaine Clearance In Vivo
Authors: Bernards Christopher M. , Kopacz Dan J. 
Published: November 2003

Background
Local anesthetic nerve block prolonged by epinephrine is thought to result from local vasoconstriction and consequent decreased local anesthetic clearance from the injection site. However, no study has yet confirmed this directly in humans by measuring tissue concentrations of local anesthetic over time. In addition, recent studies have shown that the alpha2-adrenergic receptor agonist, clonidine, also prolongs nerve block without altering local anesthetic clearance. Because epinephrine is also an alpha2-adrenergic receptor agonist, it is possible that epinephrine prolongs local anesthetic block by a pharmacodynamic mechanism and not a pharmacokinetic one. This study was designed to address this issue.

Methods
Microdialysis probes were placed adjacent to the superficial peroneal nerve in both feet of eight volunteers. Plain lidocaine (1%) was injected along one peroneal nerve and lidocaine with epinephrine (2.5 microg/ml) was injected along the other nerve in a double-blinded, randomized manner. The concentration of lidocaine in tissue was measured at 5-min intervals, and sensory block and cutaneous blood flow were assessed by laser Doppler at 10-min intervals for 5 h. The resulting data for lidocaine concentration versus time were fit to a two-compartment model using modeling software.

Results
Epinephrine prolonged sensory block by decreasing local blood flow and slowing clearance. There was no evidence of a pharmacodynamic effect of epinephrine.

Conclusion
Although epinephrine activates alpha2-adrenergic receptors, its mechanism for prolonging the duration of local anesthetic block rests on its ability to decrease local anesthetic clearance and not on a pharmacodynamically mediated potentiation of local anesthetic effect.
Tooth Pulp– and Facial Hair Mechanoreceptor–evoked Responses of Trigeminal Sensory Neurons Are Attenuated during Ketamine Anesthesia
Authors: Cairns Brian E. , McErlane Shelly A. , Fragoso Miguel C. , Soja Peter J. 
Published: November 2003

Background
Evidence exists that ketamine, administered systemically using a dose required for inducing a state of anesthesia, may antagonize nociceptive but not innocuous input to lumbar dorsal horn neurons. However, it is unclear whether ketamine exerts this selective action on sensory inputs to trigeminal sensory neurons. The current study was undertaken to compare the responses evoked in trigeminal sensory neurons by electrical stimuli applied to the tooth pulp versus air-puff stimuli applied to facial hair mechanoreceptors (FHMs) during quiet wakefulness versus ketamine anesthesia.

Methods
Accordingly, responses of rostral trigeminal sensory nuclear complex (TSNC) and trigeminothalamic tract neurons evoked by tooth pulp (a source of small-diameter fiber input) and FHMs (a source of larger-diameter fiber input) were recorded extracellularly from chronically instrumented cats before, during, and after recovery from the anesthetic state induced by a single (2.2 mg/kg) intravenous injection of ketamine.

Results
Overall, tooth pulp-evoked responses of TSNC neurons were maximally suppressed by 50% within 5 min after the intravenous administration of ketamine. Ketamine also suppressed the FHM-evoked responses of TSNC and trigeminothalamic neurons by 45%. The time course of ketamine's suppressive action was equivalent for tooth pulp- and FHM-evoked responses. However, the recovery of tooth pulp-evoked TSNC neuronal responses at suprathreshold intensities was markedly prolonged compared with neuronal responses driven by threshold stimuli or FHM.

Conclusions
These electrophysiologic results in the chronically instrumented cat preparation indicate that a nonselective suppression of orofacial somatosensory information occurs during ketamine anesthesia. The prolonged recovery of suprathreshold responses of TSNC neurons mediated by small-diameter afferent fiber input may partly underlie the analgesic action of ketamine that is clinically relevant at subanesthetic doses.
Perflubron Emulsion Delays Blood Transfusions in Orthopedic Surgery
Authors: Spahn Donat R. , van Brempt Ronald , Theilmeier Gregor , Reibold Jan-Peter , Welte Martin , Heinzerling Hartmut , Birck Katrin M. , Keipert Peter E. , Messmer Konrad 
Published: November 2003

Background
Fluorocarbon emulsions have been proposed as temporary artificial oxygen carriers. The aim of the present study is to compare the effectiveness of perflubron emulsion with the effectiveness of autologous blood or colloid infusion for reversal of physiologic transfusion triggers.

Methods
A multinational, multicenter, randomized, controlled, single-blind, parallel group study was performed in 147 orthopedic patients. Patients underwent acute normovolemic hemodilution with colloid to a target hemoglobin of 9 g/dl with an inspiratory oxygen fraction (FIO2) of 0.40. Patients were then randomized into one of four treatment groups after having reached any of the protocol-defined transfusion triggers including tachycardia (heart rate > 125% of posthemodilution rate or > 110 bpm), hypotension (mean arterial pressure < 75% of posthemodilution level or < or = 60 mmHg), elevated cardiac output (> 150% of posthemodilution level) or decreased mixed venous oxygen partial pressure (PVO2; < 38 mmHg). Treatments in the four groups were 450 ml autologous blood harvested during acute normovolemic hemodilution given at FO2 = 0.40; 450 ml colloid at FIO2 = 1.0; 0.9 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0; and 1.8 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0. The primary endpoint was duration of transfusion-trigger reversal. A secondary end-point was percentage of transfusion-trigger reversal.

Results
Perflubron emulsion was well tolerated with no serious adverse event attributed to drug treatment. Duration of reversal was longest in the 1.8 g/kg perflubron group (median, 80 min; 95% confidence interval, 60-100 min; P = 0.014 vs. autologous blood, P < 0.001 vs. colloid) followed by the 0.9 g/kg perflubron group (median, 59 min; 95% confidence interval, 40-90 min), the autologous blood group (median, 55 min; 95% confidence interval, 30-70 min) and the colloid group (median, 30 min; 95% confidence interval, 27-60 min). Percentage of reversal was also highest in the 1.8 g/kg perflubron group (97%; P < 0.001 vs. autologous blood; P = 0.014 vs. colloid), followed by 0.9 g/kg perflubron (82%), colloid (76%), and autologous blood (60%).

Conclusions
Perflubron emulsion (1.8 g/kg) combined with 100% oxygen ventilation is more effective than autologous blood or colloid infusion in reversing physiologic transfusion triggers.
Caudal Block in Children
Authors: Khalil Samia , Campos Carlos , Farag Adel M. , Vije Hadassah , Ritchey Michael , Chuang Alice 
Published: November 2003

Background
Bupivacaine provides reliable, long-lasting anesthesia and analgesia when given via the caudal route. Ropivacaine is a newer, long-acting local anesthetic that (at a concentration providing similar pain relief) has less motor nerve blockade and may have less cardiotoxicity than bupivacaine.

Methods
In a double-blind trial, 81 healthy children, undergoing ambulatory surgical procedures, were randomly allocated to receive caudal analgesia with either bupivacaine or ropivacaine, 0.25%, 1 mVkg. All blocks were placed by an attending anesthesiologist or an anesthesia fellow after induction of general anesthesia.

Results
Data were available for 75 children. There were no significant differences between the two groups in baseline characteristics or in anesthesia, surgery, recovery room, or day surgery unit durations. The quality and duration of postoperative pain relief did not differ. Motor and sensory effects were similar. Time to first micturition did not differ.

Conclusion
Ropivacaine (0.25%, 1 ml/kg) provided adequate postoperative analgesia with no difference from bupivacaine (0.25%, 1 ml/kg) in quality and duration of pain relief, motor and sensory effects, or time to first micturition in our study children.
Effects of Dobutamine on Hemodynamics and Left Ventricular Performance after Cardiopulmonary Bypass in Cardiac Surgical Patients
Authors: Romson Joseph L. , Leung Jacqueline M. , Bellows Wayne H. , Bronstein Merrill , Keith Fraser , Moores William , Flachsbart Keith , Richter Richard , Pastor Darwin , Fisher Dennis M. 
Published: November 2003

Background
Dobutamine is commonly used to improve ventricular performance after cardiopulmonary bypass. The authors determined the effect of dobutamine on hemodynamics and left ventricular performance immediately after cardiopulmonary bypass in patients undergoing coronary artery bypass graft surgery.

Methods
One hundred patients received sequential 3-min infusions of dobutamine at 0-40 microg x kg(-1) x min(-1) immediately after cardiopulmonary bypass. Ten additional patients who received no dobutamine served as controls. Hemodynamics and left ventricular performance (fractional area change by transesophageal echocardiography, stroke volume index, and thermodilution cardiac index) were measured. Mixed-effects modeling accounted for repeated-measures data and interindividual differences and allowed for potential effects of covariates.

Results
Heart rate increased in a dose-dependent manner. The slope of HR versus dobutamine dose was steeper in individuals in whom peak dobutamine dose was not reached compared with that in the remaining individuals; slope decreased 2.71 +/- 0.68% per year of age. Dobutamine affected blood pressure minimally, but slightly decreased pulmonary capillary wedge pressure and central venous pressure. Systemic vascular resistance initially increased with dobutamine 10 microg x kg(-1) x min(-1) and remained constant with larger doses. Dobutamine produced a dose-dependent increase in left ventricular performance, primarily by increasing heart rate, because stroke volume index decreased with dobutamine dose.

Conclusion
Our results suggest that the response to graded dobutamine infusion in the post-cardiopulmonary bypass period differs from that previously reported. After cardiopulmonary bypass, the dominant mechanism by which dobutamine improves left ventricular performance is by increasing heart rate. Dobutamine affects blood pressure minimally.
Cardioprotective Effects of Propofol and Sevoflurane in Ischemic and Reperfused Rat Hearts
Authors: Mathur Sanjiv , Farhangkhgoee Parviz , Karmazyn Morris 
Published: November 2003

Background
Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane.

Methods
Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion.

Results
Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment.

Conclusion
HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.
Propofol Has Both Enhancing and Suppressing Effects on Human Platelet Aggregation In Vitro
Authors: Hirakata Hideo , Nakamura Kumi , Yokubol Bencharatana , Toda Hiroshi , Hatano Yoshio , Urabe Nobukata , Mori Kenjiro 
Published: November 2003

Background
Volatile anesthetics are known to suppress platelet aggregation. In contrast, there is conflicting information regarding the effect of propofol on platelet function. The present study was designed to clarify the effects of propofol on platelet function and the mechanisms underlying these effects.

Methods
Propofol or an equivalent volume of 10% Intralipos (as a control) was added to test tubes 5 min before the induction of each reaction. Platelet aggregation induced by epinephrine, arachidonic acid (AA), prostaglandin G2 (PGG2), or STA2 (a thromboxane A2 [TXA2] analog) was measured using an eight-channel aggregometer. To determine type 1 cyclooxygenase activity, AA (0.5 mM) was added to an assay mixture containing type 1 cyclooxygenase, and the concentration of the final product, malonaldehyde, was measured by spectrophotometry. Epinephrine-, adenosine diphosphate-, AA-, and PGG2-induced TXA2 formation was measured using a commercially available radioimmunoassay kit. To estimate TXA2 receptor-binding affinity, 3H-S145, a specific TXA2 receptor antagonist, was added, and the radioactivity of receptor-bound 3H-S145 was determined using a liquid scintillation analyzer. Inositol 1,4,5-triphosphate formation was measured in STA2-stimulated platelets using a commercially available inositol 1,4,5-triphosphate assay kit.

Results
Propofol (40 microM) enhanced, whereas 100 microM suppressed, adenosine diphosphate- and epinephrine-induced secondary aggregation without affecting primary aggregation. Propofol (40 microM) also enhanced, but 100 microM suppressed, AA-induced aggregation. Propofol (100 microM) enhanced PGG2- and STA2-induced aggregation. Propofol (100 microM) suppressed AA-induced TXA2 formation but did not alter that induced by PGG2. Propofol (30-100 microM) suppressed AA-induced malonaldehyde formation, indicating inhibition of type 1 cyclooxygenase activity. Propofol did not alter TXA2 receptor-binding affinity. Propofol (30 and 100 microM) augmented inositol 1,4,5-triphosphate formation in STA2-stimulated platelets.

Conclusions
The present findings clearly indicate that high concentrations of propofol suppress the activity of type 1 cyclooxygenase, the enzyme that converts AA to PGG2. Furthermore, propofol also enhanced STA2-induced inositol 1,4,5-triphosphate formation. These results may explain the inconsistent findings of previous investigators.
Growth of Staphylococcus aureus in Diprivan and Intralipid
Authors: Langevin Paul B. , Gravenstein Nikolaus , Doyle Thomas J. , Roberts Steven A. , Skinner Stacy , Langevin Sharon O. , Gulig Paul A. 
Published: November 2003

Background
The incidence and severity of infections are increased when Intralipid or Diprivan are administered to patients. Intralipid promotes infection, presumably by inhibiting the reticuloendothelial system, thereby suppressing the host's constitutive immunity, whereas Diprivan supposedly promotes infection by supporting bacterial growth and increasing the inoculating dose. This study considers whether bacterial replication alone in Intralipid and Diprivan adequately explains the increased risk of infection associated with these agents or whether other factors might also be involved.

Methods
Staphylococcus aureus was cultured in 10% Intralipid or Diprivan at clinically relevant conditions or in Intralipid containing 0.005% (w/v) sodium EDTA, a current additive, to measure growth. To determine whether Intralipid affected infection, New Zealand white rabbits were injected intravenously with S. aureus with or without Intralipid. Twenty-four hours later, bacteria in lung, liver, spleen, and kidney tissues were enumerated.

Results
S. aureus failed to grow in Diprivan or Intralipid containing 0.005% EDTA. Whereas S. aureus did replicate in plain Intralipid, growth was delayed until the bacteria conditioned the media. Once initiated, growth was slow at clinically relevant temperatures. The administration of Intralipid to rabbits significantly increased the recovery of staphylococci from the kidneys, P < 0.001, relative to the other tissues 24 h after an intravenous inoculation with S. aureus, compared with rabbits receiving S. aureus with no Intralipid.

Conclusions
These results suggest that Diprivan, and possibly Intralipid, represent poor media for the growth of S. aureus and may promote infection through mechanisms other than increased inoculum size.
Which Algorithm for Scheduling Add-on Elective Cases Maximizes Operating Room Utilization?
Authors: Dexter Franklin , Macario Alex , Traub Rodney D. 
Published: November 2003

Background
The algorithm to schedule add-on elective cases that maximizes operating room (OR) suite utilization is unknown. The goal of this study was to use computer simulation to evaluate 10 scheduling algorithms described in the management sciences literature to determine their relative performance at scheduling as many hours of add-on elective cases as possible into open OR time.

Methods
From a surgical services information system for two separate surgical suites, the authors collected these data: (1) hours of open OR time available for add-on cases in each OR each day and (2) duration of each add-on case. These empirical data were used in computer simulations of case scheduling to compare algorithms appropriate for "variable-sized bin packing with bounded space." "Variable size" refers to differing amounts of open time in each "bin," or OR. The end point of the simulations was OR utilization (time an OR was used divided by the time the OR was available).

Results
Each day there were 0.24 +/- 0.11 and 0.28 +/- 0.23 simulated cases (mean +/- SD) scheduled to each OR in each of the two surgical suites. The algorithm that maximized OR utilization, Best Fit Descending with fuzzy constraints, achieved OR utilizations 4% larger than the algorithm with poorest performance.

Conclusions
We identified the algorithm for scheduling add-on elective cases that maximizes OR utilization for surgical suites that usually have zero or one add-on elective case in each OR. The ease of implementation of the algorithm, either manually or in an OR information system, needs to be studied.