bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increases in Coronary Collateral Blood Flow Produced by Sevoflurane Are Mediated by Calcium-activated Potassium (BKCa) Channels In Vivo
Authors: Kehl Franz , Krolikowski John G. , Tessmer John P. , Pagel Paul S. , Warltier David C. , Kersten Judy R. 
Published: November 2003

Background
Sevoflurane enhances coronary collateral blood flow independent of adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that this volatile anesthetic increases coronary collateral blood flow by either opening calcium-activated potassium channels or by directly stimulating nitric oxide synthesis in the canine coronary collateral circulation.

Methods
Twelve weeks after left anterior descending coronary artery ameroid constrictor implantation, barbiturate-anesthetized dogs (n = 22) were instrumented for measurement of hemodynamics and retrograde coronary flow. Dogs received sevoflurane ([0.5 and 1.0 minimum alveolar concentration [MAC]) during intracoronary infusions of drug vehicle (0.9% saline), the calcium-activated potassium channel antagonist iberiotoxin (13 microg/min), or the nitric oxide synthase inhibitor -nitro-l-arginine methyl ester (l-NAME, 300 microg/min). Retrograde coronary collateral blood flow was measured under baseline conditions, during and after administration of sevoflurane, and during intracoronary infusion of bradykinin. Data are mean +/- SEM.

Results
Sevoflurane increased (* < 0.05) retrograde coronary collateral blood flow (from 65 +/- 11 during control to 67 +/- 12* and 71 +/- 12* ml/min during 0.5 and 1.0 MAC, respectively). Iberiotoxin but not l-NAME attenuated these sevoflurane-induced increases in retrograde flow (6 +/- 1*, 7 +/- 2*, and 3 +/- 2 ml/min during vehicle, l-NAME, and iberiotoxin, respectively). After discontinuation of sevoflurane, retrograde flow returned to baseline values in each group. Bradykinin increased retrograde flow in vehicle- (63 +/- 12 to 69 +/- 12* ml/min) but not in iberiotoxin- (61 +/- 7 to 62 +/- 5 ml/min) or l-NAME-treated dogs (64 +/- 11 to 63 +/- 10 ml/min).

Conclusions
The results demonstrate that sevoflurane increases coronary collateral blood flow, in part, through activation of calcium-activated potassium channels. This action occurs independent of nitric oxide synthesis.
Hypercapnia Improves Tissue Oxygenation
Authors: Akça Ozan , Doufas Anthony G. , Morioka Nobutada , Iscoe Steve , Fisher Joseph , Sessler Daniel I. 
Published: November 2003

Background
Wound infections are common, serious, surgical complications. Oxidative killing by neutrophils is the primary defense against surgical pathogens and increasing intraoperative tissue oxygen tension markedly reduces the risk of such infections. Since hypercapnia improves cardiac output and peripheral tissue perfusion, we tested the hypothesis that peripheral tissue oxygenation increases as a function of arterial carbon dioxide tension (PaCO(2)) in anesthetized humans.

Methods
General anesthesia was induced with propofol and maintained with sevoflurane in 30% oxygen in 10 healthy volunteers. Subcutaneous tissue oxygen tension (PsqO(2)) was recorded from a subcutaneous tonometer. An oximeter probe on the upper arm measured muscle oxygen saturation. Cardiac output was monitored noninvasively. PaCO(2) was adjusted to 20, 30, 40, 50, or 60 mmHg in random order with each concentration being maintained for 45 min.(2) (2)

Results
Increasing PaCO(2) linearly increased cardiac index and PsqO(2) : PsqO(2) = 35.42 + 0.77 (PaCO(2)), < 0.001.

Conclusions
The observed difference in PsqO(2) is clinically important because previous work suggests that comparable increases in tissue oxygenation reduced the risk of surgical infection from -8% to 2 to 3%. We conclude that mild intraoperative hypercapnia increased peripheral tissue oxygenation in healthy human subjects, which may improve resistance to surgical wound infections.
Risk of Respiratory Complications and Wound Infection in Patients Undergoing Ambulatory Surgery
Authors: Myles Paul S. , Iacono George A. , Hunt Jennifer O. , Fletcher Helen , Morris John , McIlroy David , Fritschi Lin 
Published: November 2003

Background
Smoking is considered to be a risk factor for patients undergoing surgery and anesthesia, but it is unclear whether this is applicable to patients undergoing ambulatory surgery. The aim of this study was to determine the risk of respiratory complications and wound infection among smokers.

Methods
The authors studied a random selection of 489 adult patients undergoing ambulatory surgery. Smoking status was determined by self-report and confirmed with end-expired carbon monoxide analysis. The risk of respiratory complications (i.e., desaturation, cough, laryngospasm, bronchospasm, breath-holding, or apnea) and wound infection (i.e., wound redness or discharge +/- positive microbial culture, requiring antibiotic therapy) in smokers nonsmokers was ascertained. Odds ratios were estimated from multivariable logistic regression and adjusted for age, gender, body mass index, partner's smoking status, domiciliary smoking exposure, and extent and duration of surgery.

Results
Most smokers continued to smoke up until the day of surgery. Smokers had a higher rate of respiratory complications (32.8% vs. 25.9%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.84; = 0.038) and wound infection (3.6% vs. 0.6%; odds ratio, 16.3; 95% confidence interval, 1.58-175; = 0.019). Odds ratios comparing current plus ex-smokers with nonsmokers were of similar magnitude for most of these complications.

Conclusions
Smoking was associated with an increased risk of respiratory complications and postoperative wound infection in ambulatory surgery patients. These findings warrant increased efforts at promoting smoking avoidance and cessation.
Effects of the Nonimmobilizer Hexafluroethane on the Model Membrane Dimyristoylphosphatidylcholine
Authors: Koubi Laure , Tarek Mounir , Bandyopadhyay Sanjoy , Klein Michael L. , Scharf Daphna 
Published: November 2003

Background
Nonimmobilizers are agents that lack anesthetic properties, although their chemical structure is very similar to known anesthetics. The primary action site of both agents, whether at the membrane or target protein level, is still a matter of debate. However, increasing evidence points to the distinct modifications of the membrane physical properties that such agents induce. Such modification may play a role in the mechanism of anesthesia, and may therefore be related to the differences in their clinical behavior.

Methods
Molecular dynamics (MD) computer simulations have been used to investigate the distribution of a nonimmobilizer, hexafluroethane (HFE, C(2)F(6)), in a lipid membrane. The biologically relevant liquid-crystal phase of a hydrated dimyristoyl phosphatidyl choline (DMPC) bilayer was used as a membrane model. Two MD simulations corresponding to HFE mole fractions of 6% and 25% have been performed at room temperature and constant ambient pressure, for a duration of 2 nanoseconds each.

Results
The equilibrium configurations of HFE in the bilayer show that the nonimmobilizer molecules are evenly distributed along the lipid hydrocarbon chains with a slight preference for the bilayer center. This partitioning induces an expansion of the bilayer thickness and a lateral contraction of the membrane (decrease of the area per lipid). The presence of HFE has essentially no effect on the lipid acyl chain conformations in agreement with nuclear magnetic resonance (NMR) measurements of the chain order parameters. The partitioning of the nonimmobilizer does not influence the orientation of the lipid head-group dipole moment.

Conclusions
The modifications induced by the presence of the nonimmobilizer HFE on a model membrane are distinct from those previously found for halothane (CF(3)CHBrCl), its anesthetic analogue, and appear to result from different distributions in the lipid bilayer. The results of the MD simulations show that (1) the changes in the average area per lipid and in the membrane thickness are opposite for the two agents and (2) HFE induces no change in the lipid head-group orientation, in contrast to halothane. These different effects (1) on the physical properties of the lipid bilayer and (2) on the electrostatic properties of the membrane-water interface may be linked to different clinical effects, and thus might contribute to the mechanism of general anesthesia.
Changes in the Effect of Isoflurane on N -methyl-d-aspartic Acid-gated Currents in Cultured Cerebral Cortical Neurons with Time in Culture
Authors: Ming Zhen , Griffith Benjamin L. , Breese George R. , Mueller Robert A. , Criswell Hugh E. 
Published: November 2003

Background
Developmental changes in NR1 splice variants and NR2 subunits of the N-methyl-D-aspartate (NMDA) receptor have been associated with changes in the sensitivity of NMDA receptors to agonists, antagonists, and pharmacologic modulators. The authors have investigated changes in the effect of isoflurane on NMDA-gated currents from cultured cortical neurons with time in culture and related these changes to the subunit composition of the NMDA receptors.

Methods
N-methyl-D-aspartate-gated currents were measured using whole-cell voltage clamp recording in cortical neurons cultured for 1-4 weeks and HEK 293 cells transiently expressing NR1-1a + NR2A or NR1-1a + NR2B subunit-containing receptors. NMDA alone or NMDA with treatment agents (isoflurane or ifenprodil) was applied to cells using a U tube.

Results
The effect of isoflurane and the NR2B selective antagonist ifenprodil on NMDA-gated currents from cortical neurons decreased significantly with time in culture. NMDA-gated currents mediated by NR2A-containing receptors were less sensitive to isoflurane than those mediated by NR2B-containing receptors. Tachyphylaxis to repeated application of isoflurane was found in cortical neurons and HEK 293 cells with recombinant NMDA receptors. Hooked tail currents were induced by isoflurane in cultured cortical neurons and HEK 293 cells with expressed NMDA receptors.

Conclusions
Isoflurane inhibits NMDA-gated currents at concentrations well below 1 minimum alveolar concentration (MAC). This effect of isoflurane was subunit dependent with the NR2B-containing receptors more sensitive to isoflurane than the NR2A-containing receptors. A potent tachyphylaxis occurred after brief exposure to isoflurane.
Hemodynamic Benefit of Positive End-expiratory Pressure during Acute Descending Aortic Occlusion
Authors: Johnston William E. , Conroy Brendan P. , Miller Gregory S. , Lin Cheng Y. , Deyo Donald J. 
Published: November 2003

Background
Acute aortic occlusion in vascular surgery patients abruptly increases arterial resistance and blood pressure, which, in turn, makes subsequent volume expansion during cross-clamp application difficult. The use of vasodilatory drugs or volatile anesthetic agents to attenuate this response may have persistent detrimental effects after clamp removal. Another potential therapy that produces rapid effects on myocardial loading conditions is positive end-expiratory pressure (PEEP). In a porcine model of acute aortic clamping, the hemodynamic consequences of 15 cm H(2)O PEEP with and without plasma volume expansion were studied.(2)

Methods
Forty anesthetized pigs underwent 30-min occlusion of the abdominal aorta 1 cm above the origin of the celiac artery. Animals were randomly divided into four treatment groups (n = 10 each) to receive 15 cm H(2)O PEEP or zero end-expiratory pressure (ZEEP) with or without plasma volume expansion using 6% hetastarch (10 ml/kg) during cross-clamp application. Mean aortic pressure was measured with a transducer-tipped catheter placed in the ascending aorta; stroke volume was calculated using thermodilution cardiac output. End-expiratory pressure was discontinued upon aortic declamping, and animals were studied over the ensuing 30-min period.

Results
Aortic occlusion doubled systemic vascular resistance in all groups. Mean aortic blood pressure increased significantly in both ZEEP groups at 1 and 5 min but not in animals treated with 15 cm H(2)O PEEP. The application of PEEP with aortic cross-clamping reduced cardiac output and stroke volume by nearly 50%. Cardiac output and stroke volume increased after volume expansion regardless of end-expiratory pressure. After aortic declamping, aortic blood pressure decreased in all groups but was significantly greater in the PEEP + volume group than in either ZEEP group. Similarly, 5 min after declamping, stroke volume was greatest in the PEEP + volume animals.

Conclusions
Fifteen cm H(2)O PEEP reduces the hypertensive response to acute aortic occlusion and allows concomitant volume expansion. Consequently, stroke volume and blood pressure are better maintained after clamp removal in PEEP + volume animals. The use of PEEP during acute aortic occlusion in patients may allow rapid control of loading conditions to attenuate systemic hypertension while permitting simultaneous volume expansion.
Perineural α2A-Adrenoceptor Activation Inhibits Spinal Cord Neuroplasticity and Tactile Allodynia after Nerve Injury
Authors: Lavand'homme Patricia M. , Ma Weiya , De Kock Marc , Eisenach James C. 
Published: November 2003

Background
Nerve injury in animals increases alpha(2)-adrenoceptor expression in dorsal root ganglion cells and results in novel excitatory responses to their activation, perhaps leading to the phenomenon of sympathetically maintained pain. In contrast to this notion, peripheral alpha(2)-adrenoceptor stimulation fails to induce pain in patients with chronic pain. We hypothesized that alpha(2) adrenoceptors at the site of nerve injury play an inhibitory, not excitatory role.

Methods
Partial sciatic nerve ligation was performed on rats, resulting in a reduction in withdrawal threshold to tactile stimulation. Animals received perineural injection at the injury site of clonidine, saline, or clonidine plus an alpha(2)-adrenergic antagonist, and withdrawal threshold was monitored. Immunohistochemistry was performed on the sciatic nerve ipsi- and contralateral to injury and on the spinal cord.

Results
Clonidine reduced this hypersensitivity in a dose-dependent manner, and this was blocked by an alpha(2A)-preferring antagonist. Perineural clonidine injection had a slow onset (days) and prolonged duration (weeks). Systemic or intrathecal clonidine, or transient neural blockade with ropivacaine, had short lasting or no effect on hypersensitivity. alpha(2A)-adrenoceptor immunostaining was increased near the site of peripheral nerve injury, both in neurons and in immune cells (macrophages and T lymphocytes). Phosphorylated cAMP response element binding protein (pCREB) in lumbar spinal cord was increased ipsilateral to nerve injury, and this was reduced 1 week after perineural clonidine injection.

Conclusions
These data suggest that peripheral alpha(2) adrenoceptors are concentrated at the site of peripheral nerve injury, and their activation receptors produce long-lasting reductions in abnormal spinal cord gene activation and mechanical hypersensitivity.
Detection of Proton Release from Cultured Human Myotubes to Identify Malignant Hyperthermia Susceptibility
Authors: Klingler Werner , Baur Christoph , Georgieff Michael , Lehmann-Horn Frank , Melzer Werner 
Published: November 2003

Background
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. During general anesthesia, a life-threatening hypermetabolic state may occur resulting from increased release of Ca2+ from the sarcoplasmic reticulum in skeletal muscle. Diagnosis of MH susceptibility requires surgical muscle biopsies to measure force in response to chemical stimulation (in vitro contracture test, IVCT). Here, the authors investigated an alternative way of discriminating MH-susceptible (MHS) from normal (MHN) subjects by using cultured human myotubes and measuring proton release as an indicator of cellular metabolism.

Methods
Myotubes were stimulated with the Ca2+ release channel agonist 4-chloro-m-cresol (4-CmC), leading to metabolic activation and proton secretion. The rate of extracellular acidification was recorded with a silicon sensor chip.

Results
A stepwise increase in 4-CmC concentration led to a phasic-tonic increase in the acidification rate. The response, measured at different concentrations of 4-CmC, was considerably larger in cultures from MHS compared with MHN subjects and correlated well with the force response in the IVCT.

Conclusions
The enhanced metabolism of cultured skeletal myotubes, likely originating from an increased myoplasmic Ca2+ concentration, can be monitored by studying the proton secretion rate. Because the method seems to be able to distinguish normal from pathologic phenotypes, it is a promising technique for possible future use in less invasive MH testing.
Presence of Two Different Genetic Traits in Malignant Hyperthermia Families
Authors: Monnier Nicole , Krivosic-Horber Renée , Payen Jean-François , Kozak-Ribbens Geneviève , Nivoche Yves , Adnet Pascal , Reyford Hugo , Lunardi Joël 
Published: November 2003

Background
Malignant hyperthermia susceptibility (MHS), an uncommon syndrome often inherited as an autosomal dominant trait, is characterized by a genetic and clinical heterogeneity. In this article, the authors described six pedigrees in which both parents of MHS patients were diagnosed with MHS by an diagnostic test. Haplotype and mutation analysis revealed that more than one MHS genetic trait was present in these families.

Methods
A panel of 104 MHS families were investigated with a caffeine halothane contracture test on muscle biopsy specimens. When possible, blood creatine kinase concentrations of MHS patients were measured. Haplotyping studies were conducted with chromosome 19q13.2 polymorphic markers and mutations were searched for in patients' DNA.

Results
In six families, the diagnostic test and genetic studies demonstrated that both, apparently unrelated, parents of MHS patients were MHS. In three families, homozygous or compound heterozygous individuals for RYR1 mutations were characterized at a molecular level. In one family, a compound heterozygous patient harboring a RYR1 mutation and a CACNA1S mutation was identified. While patients with two mutated alleles did not show differences in their muscle response to halothane or caffeine, their creatinine kinase concentrations were significantly elevated compared with the heterozygous patients.

Conclusions
Based on genetic and diagnostic test data, more than one MHS allele associated with the MHS phenotype was evidenced in four families. These data should be considered in view of the use of genetics for the diagnosis of MHS and when reaching conclusions of genetic heterogeneity in MHS families. Taking into account the usual dominant mode of transmission of MHS and the size of the investigated population, the authors propose an evaluation of the incidence of the MHS in the general population based on genetic data.
Sleeping Characteristics of Children Undergoing Outpatient Elective Surgery
Authors: Kain Zeev N. , Mayes Linda C. , Caldwell-Andrews Alison A. , Alexander Gerianne M. , Krivutza Dawn , Teague Barbara A. , Wang Shu-Ming 
Published: November 2003

Background
A significant number of children undergoing anesthesia and surgery exhibit new-onset sleep-related problems postoperatively. The aim of this longitudinal cohort study was to expand previous research in this area by using a new objective technology.

Methods
This study compared children undergoing general anesthesia and outpatient surgery (n = 92) to a community-based control group of children (n = 77). Data regarding coping, temperament, anxiety, surgical procedures, and postoperative pain were collected. Subjects underwent actigraphy sleep monitoring for at least 3 nights before surgery and 5 postoperative days (POD). Sleep assessment was performed with actigraphy sleep monitoring and the Post Hospitalization Behavioral Questionnaire (PHBQ).

Results
Forty-three children (47%) in the surgery group experienced postoperative sleeping disturbances as determined by either the actigraphy or the PHBQ. Only 13 children (14.4%), however, experienced a decrease of at least 1 SD in percentage sleep as assessed by actigraphy. Postoperative pain scores on POD 1 and POD 2 were significantly higher among children who exhibited sleep problems as diagnosed by actigraphy (F = 4.283; P= 0.047). Also, children who exhibited actigraph-based sleep problems scored lower sociability-temperament (14.1 +/- 4.3 vs. 17.5 +/- 3.4; P= 0.04) scores compared with the community group and had a higher rate of change in their perioperative anxiety levels (group x time interaction, F = 5.1; P= 0.03).

Conclusion
A significant number of children undergoing outpatient surgery experience postoperative sleep-related problems. The clinical significance of this finding, however, is unclear.
Platelet PlA2Polymorphism and Platelet Activation Are Associated with Increased Troponin I Release after Cardiopulmonary Bypass
Authors: Rinder Christine S. , Mathew Joseph P. , Rinder Henry M. , Greg Howe J. , Fontes Manuel , Crouch Jill , Pfau Stephen , Patel Parag , Smith Brian R. 
Published: November 2003

Background
The PlA2 polymorphism of platelet glycoprotein IIIa has been identified as a prothrombotic risk factor in a number of cardiovascular settings. The aim of this study was to determine whether the PlA2 polymorphism of platelet glycoprotein IIIa and degree of platelet activation were associated with more severe myocardial injury as indicated by troponin I release following cardiopulmonary bypass.

Methods
The PlA2 genotype was determined in 66 patients undergoing elective coronary artery bypass grafting requiring cardiopulmonary bypass. Troponin I concentrations and the percentage of circulating, activated (CD62P+) platelets were measured at predetermined intervals perioperatively.

Results
Forty-six patients were Pl(A1,A1), and 20 were Pl(A1,A2) or Pl(A2,A2). Patients with at least one PlA2 allele had significantly greater postoperative troponin I concentrations than PlA1 homozygotes (P = 0.006, analysis of variance). Peak troponin I concentrations also correlated significantly with the increase in circulating, activated platelets (P = 0.02, Spearman rank correlation).

Conclusions
The PlA2 allele of platelet glycoprotein IIIa is associated with higher troponin I concentrations following cardiopulmonary bypass surgery, suggesting that this platelet polymorphism contributes to perioperative myocardial injury.