bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desflurane Increases Pulmonary Alveolar-Capillary Membrane Permeability after Aortic Occlusion-Reperfusion in Rabbits
Authors: Nielsen Vance G. , Baird Manuel S. , McAdams Michelle L. , Freeman Bruce A. 
Published: November 2003

Background
Pulmonary injury occurs after vascular surgery, with xanthine oxidase (an oxidant generator) released from reperfusing liver and intestines mediating a significant component of this injury. Because halogenated anesthetics have been observed to enhance oxidant-mediated injury in vitro, the authors hypothesized that desflurane would increase alveolar-capillary membrane permeability mediated by circulating xanthine oxidase after thoracic occlusion and reperfusion.

Methods
Rabbits were assigned to one of five groups: aorta occlusion groups administered desflurane (n=14), desflurane and tungstate (xanthine oxidase inactivator, n=12), fentanyl plus droperidol (n=13), and two sham-operated groups (desflurane, n=7 and fentanyl plus droperidol, n=7). Aortic occlusion was maintained for 45 min with a balloon catheter, followed by 3 h of reperfusion. Alveolar-capillary membrane permeability was assessed by measurement of bronchoalveolar lavage fluid protein. Xanthine oxidase activity was determined in plasma and lung tissue. Ascorbic acid content (an antioxidant) was determined in lung tissue.

Results
Desflurane was associated with significantly increased alveolar-capillary membrane permeability after aortic occlusion-reperfusion when compared with the fentanyl plus droperidol anesthesia or sham-operated groups (P < 0.05). Inactivation of xanthine oxidase abrogated the alveolar-capillary membrane compromise associated with desflurane. Although significantly greater than for sham-operated animals, plasma xanthine oxidase activities released after aortic occlusion-reperfusion were not different between the two anesthetics. There were no anesthetic-associated differences in lung tissue xanthine oxidase activity. However, desflurane anesthesia resulted in a significant reduction in lung ascorbic acid after aortic occlusion-reperfusion compared with the sham-operated animals.

Conclusions
Desflurane anesthesia increased xanthine oxidase-dependent alveolar-capillary membrane compromise after aortic occlusion-reperfusion in concert with depletion of a key tissue antioxidant.
The Effects of Epidural Morphine on Cardiac and Renal Sympathetic Nerve Activity in α-Chloralose-anesthetized Cats
Authors: Mori Takashi , Nishikawa Kiyonobu , Terai Takekazu , Yukioka Hidekazu , Asada Akira 
Published: November 2003

Background
Epidural morphine yields postoperative pain relief and hemodynamic stability. However, the effects of epidural morphine on sympathetic tone are unclear. This study was designed to elucidate the effects of epidural morphine on cardiac (CSNA) and renal (RSNA) sympathetic nerve activity by direct measurement in anesthetized cats.

Methods
Thirty mongrel cats anesthetized with alpha-chloralose were randomly assigned to one of the following five groups: control (0.2 ml/kg thoracic epidural normal saline; n=5); thoracic epidural morphine (n=9); lumbar epidural morphine (n=6); vagotomized, sinoaortic denervated, thoracic epidural morphine (n=5); or intravenous morphine (n=5). Mean arterial pressure (MAP), heart rate (HR), CSNA, and RSNA were measured 0, 15, 30, 60, 90, and 120 min after saline or morphine (200 microg/kg) administration and 15 min after reversal with 200 microg naloxone given intravenously.

Results
In the control group, no changes in measured variables were found after either thoracic epidural saline or intravenous naloxone. Thoracic and lumbar epidural morphine both significantly reduced MAP, HR, CSNA, and RSNA 30 through 120 min after morphine administration (P < 0.05). These changes were reversed by intravenous naloxone. Changes after thoracic epidural morphine administration in vagotomized, baroreceptor-denervated cats were similar to those in intact cats. Intravenous morphine produced no significant changes except for a decrease in MAP, which was reversed by intravenous naloxone.

Conclusion
In contrast to intravenous morphine, thoracic and lumbar epidural morphine both inhibited cardiac and renal sympathetic nerve activity and consequently reduced MAP and HR in alpha-chloralose anesthetized cats.
In Vitro Hypothermia Enhances Platelet GPIIb-IIIa Activation and P-Selectin Expression
Authors: Faraday Nauder , Rosenfeld Brian 
Published: November 2003

Background
A clinical bleeding diathesis is associated with hypothermia. Inhibition of platelet reactivity is the purported cause of this coagulopathy despite inconsistent evidence to support this hypothesis. To clarify the effect of temperature on intrinsic platelet function, platelet GPllb-IIIa activation and P-selectin expression were assessed under normothermic and hypothermic conditions in vitro.

Methods
Blood was obtained by venipuncture from healthy volunteers. Platelet activation was assessed by aggregometry and by cytometric analysis of platelet binding of fibrinogen, PAC-1, and P-selectin antibodies. Measurements were made at normothermia (37 degrees C), moderate hypothermia (33 degrees C), and profound hypothermia (22 degrees C) after stimulating samples with adenosine diphosphate (ADP), collagen, or thrombin receptor activating peptide.

Results
Agonist-induced platelet aggregation and fibrinogen binding were significantly greater at 22 degrees C and 33 degrees C than at 37 degrees C. Platelet fibrinogen binding values to 20 micro M ADP were 23,400, 14,300, and 9,700 molecules/platelet at 22 degrees C, 33 degrees C, and 37 degrees C, respectively. The aggregation responses of platelets that were cooled and rewarmed were indistinguishable from those of platelets maintained at 37 degrees C throughout the study. Platelet binding of PAC-1 and P-selectin antibodies was greater under hypothermic conditions.

Conclusions
Aggregation, fibrinogen binding, PAC-1 binding, and P-selectin antibody binding studies showed that platelet GPIIb-IIIa activation and alpha-granule release were enhanced at hypothermic temperatures. Thus hypothermia appears to increase the ability of platelets to respond to activating stimuli. The coagulopathy associated with hypothermia is not likely to be the result of an intrinsic defect in platelet function.
Effects of Small Concentrations of Volatile Anesthetics on Action Potential Firing of Neocortical Neurons In Vitro
Authors: Antkowiak Bernd , Helfrich-Forster Charlotte 
Published: November 2003

Background
Volatile general anesthetics depress neuronal activity in the mammalian central nervous system and enhance inhibitory Cl- currents flowing across the gamma-aminobutyric acid A (GABA(A)) receptor-ion channel complex. The extent to which an increase in GABA(A)-mediated synaptic inhibition contributes to the decrease in neuronal firing must be determined, because many further effects of these agents have been reported on the molecular level.

Methods
The actions of halothane, isoflurane, and enflurane on the firing patterns of single neurons were investigated by extracellular recordings in organotypic slice cultures derived from the rat neocortex.

Results
Volatile anesthetics depressed spontaneous action potential firing of neocortical neurons in a concentration-dependent manner. The estimated median effective concentration (EC50) values were about one half the EC50 values for general anesthesia. In the presence of the GABA(A) antagonist bicuculline (20 microM), the effectiveness of halothane, isoflurane, and enflurane in reducing the discharge rates were diminished by 48-65%, indicating that these drugs act via the GABA(A) receptor.

Conclusions
Together with recent investigations, our results provide evidence that halothane, isoflurane, and enflurane reduced spontaneous action potential firing of neocortical neurons in cultured brain slices mainly by increasing GABA(A)-mediated synaptic inhibition. At concentrations, approximately one half the EC50 for general anesthesia, volatile anesthetics increased overall GABA(A)-mediated synaptic inhibition about twofold, thus decreasing spontaneous action potential firing by half.
Role of the Renal Cysteine Conjugate β-Lyase Pathway in Inhaled Compound A Nephrotoxicity in Rats
Authors: Kharasch Evan D. , Hoffman Gary M. , Thorning David , Hankins Douglas C. , Kilty Cormac G. 
Published: November 2003

Background
The sevoflurane degradation product compound A is nephrotoxic in rats and undergoes metabolism to glutathione and cysteine S-conjugates, with further metabolism by renal cysteine conjugate beta-lyase to reactive intermediates. Evidence suggests that toxicity is mediated by renal uptake of compound A S-conjugates and metabolism by beta-lyase. Previously, inhibitors of the beta-lyase pathway (aminooxyacetic acid and probenecid) diminished the nephrotoxicity of intraperitoneal compound A. This investigation determined inhibitor effects on the toxicity of inhaled compound A.

Methods
Fischer 344 rats underwent 3 h of nose-only exposure to compound A (0-220 ppm in initial dose-response experiments and 100-109 ppm in subsequent inhibitor experiments). The inhibitors (and targets) were probenecid (renal organic anion transport mediating S-conjugate uptake), acivicin (gamma-glutamyl transferase), aminooxyacetic acid (renal beta-lyase), and aminobenzotriazole (cytochrome P450). Urine was collected for 24 h, and the animals were killed. Nephrotoxicity was assessed by histology and biochemical markers (serum BUN and creatinine; urine volume; and excretion of protein, glucose, and alpha-glutathione-S-transferase, a predominantly proximal tubular cell protein).

Results
Compound A caused dose-related proximal tubular cell necrosis, diuresis, proteinuria, glucosuria, and increased alpha-glutathione-S-transferase excretion. The threshold for toxicity was 98-109 ppm (294-327 ppm-h). Probenecid diminished (P < 0.05) compound A-induced glucosuria and excretion of alpha-glutathione-S-transferase and completely prevented necrosis. Aminooxyacetic acid diminished compound A-dependent proteinuria and glucosuria but did not decrease necrosis. Acivicin increased nephrotoxicity of compound A, and aminobenzotriazole had no consistent effect on nephrotoxicity of compound A.

Conclusions
Nephrotoxicity of inhaled compound A in rats was associated with renal uptake of compound A S-conjugates and cysteine conjugates metabolism by renal beta-lyase. Manipulation of the beta-lyase pathway elicited similar results, whether compound A was administered by inhalation or intraperitoneal injection. Route of administration does not apparently influence nephrotoxicity of compound A in rats.
Assessment of Clinical Performance during Simulated Crises Using Both Technical and Behavioral Ratings
Authors: Gaba David M. , Howard Steven K. , Flanagan Brendan , Smith Brian E. , Fish Kevin J. , Botney Richard 
Published: November 2003

Background
Techniques are needed to assess anesthesiologists' performance when responding to critical events. Patient simulators allow presentation of similar crisis situations to different clinicians. This study evaluated ratings of performance, and the interrater variability of the ratings, made by multiple independent observers viewing videotapes of simulated crises.

Methods
Raters scored the videotapes of 14 different teams that were managing two scenarios: malignant hyperthermia (MH) and cardiac arrest. Technical performance and crisis management behaviors were rated. Technical ratings could range from 0.0 to 1.0 based on scenario-specific checklists of appropriate actions. Ratings of 12 crisis management behaviors were made using a five-point ordinal scale. Several statistical assessments of interrater variability were applied.

Results
Technical ratings were high for most teams in both scenarios (0.78 +/- 0.08 for MH, 0.83 +/- 0.06 for cardiac arrest). Ratings of crisis management behavior varied, with some teams rated as minimally acceptable or poor (28% for MH, 14% for cardiac arrest). The agreement between raters was fair to excellent, depending on the item rated and the statistical test used.

Conclusions
Both technical and behavioral performance can be assessed from videotapes of simulations. The behavioral rating system can be improved; one particular difficulty was aggregating a single rating for a behavior that fluctuated over time. These performance assessment tools might be useful for educational research or for tracking a resident's progress. The rating system needs more refinement before it can be used to assess clinical competence for residency graduation or board certification.
Persistent Alterations of the Autonomic Nervous System after Noncardiac Surgery
Authors: Amar David , Fleisher Martin , Pantuck Carol B. , Shamoon Harry , Zhang Hao , Roistacher Nancy , Leung Denis H. Y. , Ginsburg Ilana , Smiley Richard M. 
Published: November 2003

Unlabelled
BACKGROUND. Changes in the sympathetic nervous system may be a cause of postoperative cardiovascular complications. The authors hypothesized that changes in both beta-adrenergic receptor (betaAR) function (as assessed in lymphocytes) and in sympathetic activity (assessed by plasma catecholamines and by heart rate variability [HRV] measurements obtained from Holter recordings) occur after operation.

Methods
The HRV parameters were measured in 28 patients having thoracotomy (n = 14) or laparotomy (n = 14) before and for as long as 6 days after operation. Transthoracic echocardiography was performed before and on postoperative day 2. Lymphocytes were also isolated from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). They were used to examine betaAR number (Bmax) and cyclic adenosine monophosphate (cAMP) production after stimulation with isoproterenol and prostaglandin E1. In addition, plasma epinephrine, norepinephrine, and cortisol concentrations were determined at similar intervals.

Results
After abdominal and thoracic surgery, most time and all frequency indices of HRV decreased significantly, as did Bmax and basal and isoproterenol-stimulated cAMP production. The decrements in HRV correlated with those of Bmax and isoproterenol-stimulated cAMP throughout the first postoperative week and inversely correlated with the increase in heart rate. Plasma catecholamine concentrations did not change significantly from baseline values, but plasma cortisol levels did increase after operation in both groups. Left ventricular ejection fraction was normal in both groups and unaffected by surgery.

Conclusions
Persistent downregulation and desensitization of the lymphocyte betaAR/adenylyl cyclase system correlated with decrements in time and frequency domain indices of HRV throughout the first week after major abdominal or thoracic surgery. These physiologic alterations suggest the continued presence of adaptive autonomic regulatory mechanisms and may explain why the at-risk period after major surgery appears to be about 1 week or more.
A Comparison of the Respiratory Effects of Sevoflurane and Halothane in Infants and Young Children
Authors: Brown Karen , Aun Cindy , Stocks Janet , Jackson Elizabeth , Mackersie Angela , Hatch David 
Published: November 2003

Background
This study compared the respiratory effects of sevoflurane with those of halothane in anesthetized infants and young children.

Methods
Infants were randomized to receive 1 minimum alveolar concentration (MAC) halothane or sevoflurane in a mixture of nitrous oxide and oxygen. Anesthetic management included the use of a laryngeal mask. Flow, airway pressure, and the end-tidal carbon dioxide pressure (PETCO2) were measured during spontaneous ventilation and airway occlusions. Respiratory inductive plethysmography was used to assess chest wall motion.

Results
Measurements were obtained in 30 infants and young children (mean (SD) age, 14.5 (5.9) months), 15 of whom received sevoflurane and 15 received halothane. Some respiratory depression, as indicated by a PETCO2 of 45 mmHg (6 kPa), was present in both groups. Minute ventilation and respiratory frequency were significantly lower during sevoflurane than halothane anesthesia (4.5 compared with 5.4 (1/ m2)/min, and 37.5 compared with 46.7 breaths/min, respectively, P < 0.05). There was no difference in respiratory drive, but the shape of the flow waveform differed according to anesthetic agent, with peak inspiratory flow reached later, and peak expiratory flow reached earlier, in the sevoflurane group. There was also significantly less thoracoabdominal asynchrony during sevoflurane anesthesia.

Conclusions
Minute ventilation and respiratory frequency were lower in infants during 1 MAC sevoflurane in nitrous oxide than during halothane anesthesia. However, these differences may not be clinically relevant at these concentrations, given the modest increase in PETCO2. Differences in parameters of breath timing and shape between sevoflurane and halothane suggest different effects of these anesthetic agents on ventilatory control.
The Effect of Propofol on Isolated Human Pregnant Uterine Muscle
Authors: Shin Young K. , Kim Young D. , Collea Joseph V. 
Published: November 2003

Background
Propofol is an alternative to thiopental as an intravenous induction agent for cesarean section. Because it has relaxant effects on vascular and other smooth muscles, the authors set out to determine whether propofol has any effect on pregnant human uterine smooth muscle in an isolated preparation.

Methods
Myometrial specimens were excised from 10 parturients undergoing elective cesarean section. The muscle strips were suspended in tissue baths and isometric tension was recorded. After establishment of rhythmic contractions in the buffer solution as a control, propofol (0.5 to 10 microg/ml) in fat emulsion was applied cumulatively to the bath. The effect of the fat emulsion at equivalent concentrations was also examined.

Results
Propofol concentrations of 2.7 x 10(-6) M (0.5 microg/ml) and 1.1 x 10(-5) M (2 microg/ml) had no significant effect on the active tension developed by muscle contraction. However, propofol at concentration of 5.5 x 10(-5) M (10 microg/ml) reduced the active tension by 45% (P < 0.02) compared with the control value. The fat emulsion had no effects on the active tension.

Conclusions
These results imply that the decline in the active tension of muscle contraction was most likely caused by propofol and not by the fat emulsion. However, the propofol concentrations needed to produce a significant reduction in the uterine muscle tension appear to be much greater than the free propofol concentrations reported by others during cesarean section.
Comparison of pH-state and Alpha-stat Cardiopulmonary Bypass on Cerebral Oxygenation and Blood Flow in Relation to Hypothermic Circulatory Arrest in Piglets
Authors: Kurth Dean C. , O'Rourke Maureen M. , O'Hara Irene B. 
Published: November 2003

Background
Deep hypothermic circulatory arrest is used in neonatal cardiac surgery. Recent work has suggested improved neurologic recovery after deep hypothermic arrest with pH-stat cardiopulmonary bypass (CPB) compared with alpha-stat CPB. This study examined cortical oxygen saturation (ScO2), cortical blood flow (CBF), and cortical physiologic recovery in relation to deep hypothermic arrest with alpha-stat or pH-stat CPB.

Methods
Sixteen piglets were cooled with pH-stat or alpha-stat CPB to 19 degrees C (cortex) and subjected to 60 min of circulatory arrest, followed by CPB reperfusion and rewarming and separation from CPB. Near infrared spectroscopy and laser Doppler flowmetry were used to monitor ScO2 and CBF. Cortical physiologic recovery was assessed 2 h after the piglets were separated from CPB by cortical adenosine triphosphate concentrations, cortical water content, CBF, and ScO2.

Results
During CPB cooling, ScO2 increased more with pH-stat than with alpha-stat bypass (123 +/- 33% vs. 80 +/- 25%); superficial and deep CBF were also greater with pH-stat than with alpha-stat bypass (22 +/- 25% vs. -56 +/- 22%, 3 +/- 19% vs. -29 +/- 28%). During arrest, ScO2 half-life was greater with pH-stat than with alpha-stat bypass (10 +/- 2 min vs. 7 +/- 2 min), and cortical oxygen consumption lasted longer with pH-stat than with alpha-stat bypass (36 +/- 8 min vs. 25 +/- 8 min). During CPB reperfusion, superficial and deep CBF were less with alpha-stat than with pH-stat bypass (-40 +/- 22% vs. 10 +/- 39%, -38 +/- 28% vs. 5 +/- 28%). After CPB, deep cortical adenosine triphosphate and CBF were less with alpha-stat than with pH-stat bypass (11 +/- 6 pmole/mg vs. 17 +/- 8 pmole/mg, -24 +/- 16% vs. 16 +/- 32%); cortical water content was greater with alpha-stat than with pH-stat bypass (superficial: 82.4 +/- 0.3% vs. 81.8 +/- 1%, deep: 79.1 +/- 2% vs. 78 +/- 1.6%).

Conclusions
Cortical deoxygenation during hypothermic arrest was slower after pH-stat CPB. pH-stat bypass increased the prearrest ScO2 and arrest ScO2 half-life, to increase the cortical oxygen supply and slow cortical oxygen consumption. Improved cortical physiologic recovery after hypothermic arrest was suggested with pH-stat management.
A Re-examination of Tetrodotoxin for Prolonged Duration Local Anesthesia
Authors: Kohane Daniel S. , Yieh Jamie , Lu Nu T. , Langer Robert , Strichartz Gary R. , Berde Charles B. 
Published: November 2003

Background
Highly potent toxins such as tetrodotoxin that block sodium channels with great specificity have been studied for many years and can provide prolonged blockade when coadministered with vasoconstrictors or conventional local anesthetics. Their utility has been constrained, however, by systemic toxicity. The authors examined the efficacy of tetrodotoxin with and without epinephrine or bupivacaine for producing prolonged-duration sciatic nerve blockade in the rat, and they assessed the degree of concomitant toxicity.

Methods
Rats received percutaneous sciatic nerve blockade using tetrodotoxin with and without epinephrine or bupivacaine. A subset received subcutaneous injections at the nuchal midline. Nociceptive, proprioceptive, and motor blockade were quantified using contralateral leg responses as controls for systemic effects.

Results
Tetrodotoxin without epinephrine produced sciatic nerve blockade, but with considerable toxicity at most effective doses. Epinephrine reduced the median effective concentration of tetrodotoxin for nociception from 37.6 to 11.5 microM and prolonged its duration, such that reversible blocks lasting > 13 h were achieved. Epinephrine reduced measures of systemic distribution and increased the median lethal dose of tetrodotoxin from 40 to 53.6 nmole/kg, thus more than quadrupling the therapeutic index. Bupivacaine increased the local anesthetic potency of tetrodotoxin, reduced its systemic toxicity, and, when coinjected subcutaneously, increased the median lethal dose from 43.7 to 47.7 nmole/kg. The addition of epinephrine did not further improve the effectiveness of the bupivacaine-tetrodotoxin combination.

Conclusion
Combinations of epinephrine or bupivacaine with tetrodotoxin or with other high-potency toxins active on sodium channels should be examined for the potential to provide clinically useful, prolonged nerve blockade.