bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Cuffed and Uncuffed Endotracheal Tubes in Young Children during General Anesthesia
Authors: Khine Henry H. , Corddry David H. , Kettrick Robert G. , Martin Thalia M. , McCloskey John J. , Rose John B. , Theroux Mary C. , Zagnoev Michael 
Published: November 2003

Background
Uncuffed endotracheal tubes are routinely used in young children. This study tests a formula for selecting appropriately sized cuffed endotracheal tubes and compares the use of cuffed versus uncuffed endotracheal tubes for patients whose lungs are mechanically ventilated during anesthesia.

Methods
Full-term newborns and children (n = 488) through 8 yr of age who required general anesthesia and tracheal intubation were assigned randomly to receive either a cuffed tube sized by a new formula [size(mm internal diameter) = (age/4) + 3], or an uncuffed tube sized by the modified Cole's formula [size(mm internal diameter) = (age/4) + 4]. The number of intubations required to achieve an appropriately sized tube, the need to use more than 21.min-1 fresh gas flow, the concentration of nitrous oxide in the operating room, and the incidence of croup were compared.

Results
Cuffed tubes selected by our formula were appropriate for 99% of patients. Uncuffed tubes selected by Cole's formula were appropriate for 77% of patients (P < 0.001). The lungs of patients with cuffed tubes were adequately ventilated with 2 1.min-1 fresh gas flow, whereas 11% of those with uncuffed tubes needed greater fresh gas flow (P < 0.001). Ambient nitrous oxide concentration exceeded 25 parts per million in 37% of cases with uncuffed tubes and in 0% of cases with cuffed tubes (P < 0.001). Three patients in each group were treated for croup symptoms (1.2% cuffed; 1.3% uncuffed).

Conclusions
Our formula for cuffed tube selection is appropriate for young children. Advantages of cuffed endotracheal tubes include avoidance of repeated laryngoscopy, use of low fresh gas flow, and reduction of the concentration of anesthetics detectable in the operating room. We conclude that cuffed endotracheal tubes may be used routinely during controlled ventilation in full-term newborns and children during anesthesia.
Halothane and Isoflurane Differentially Affect the Regulation of Dopamine and Gamma-aminobutyric Acid Release Mediated by Presynaptic Acetylcholine Receptors in the Rat Striatum
Authors: Salord Francois , Keita Hawa , Lecharny Jean-Baptiste , Henzel Danielle , Desmonts Jean-Marie , Mantz Jean 
Published: November 2003

Background
General anesthetics are thought to produce their hypnotic effects mainly by acting at ligand-gated ionic channels in the central nervous system (CNS). Although it is well established that volatile anesthetics significantly modify the activity of the acetylcholine nicotinic receptors of the neuromuscular junction, little is known about their actions on the acetylcholine receptors in the CNS. In this study, the effects of halothane and isoflurane on the regulation of dopamine (DA) (gamma-aminobutyric acid [GABA]) depolarization-evoked release mediated by nicotinic (muscarinic) presynaptic receptors were studied in the rat striatum.

Methods
Assay for GABA (dopamine) release consisted of 3H-GABA (3H-DA)-preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml/min, 37 degrees C) and measuring the radioactivity obtained from 1-min fractions for 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with vaporized halothane and isoflurane (0.5-5%, 5 min), and finally with no pharmacologic stimulation (5 min). The depolarizing agents were potassium chloride (KCl; 9 mM) alone or with acetylcholine (10(-6)-10(-4) M) and/or atropine (10(-5) M) for experiments with 3H-GABA, and KC1 (15 mM) and nicotine (10(-7) - 5 x 10(-4) M) alone or with mecamylamine (10(-5) M) for experiments with 3H-DA.

Results
Potassium chloride induced a significant, Ca(2+)-dependent release of both 3H-GABA and 3H-DA. Nicotine produced a concentration-related, mecamylamine-sensitive 3H-DA release that was significantly attenuated by nicotine (10(-7) M) preincubation. Acetylcholine elicited a dose-dependent, atropine-sensitive reduction of the KC1-evoked 3H-GABA release. Halothane and isoflurane significantly decreased the nicotine-evoked 3H-DA release but had only limited depressant effects on the KC1-stimulated 3H-DA and no action on the KC1-induced 3H-GABA release. The effects of acetylcholine on 3H-GABA release were reversed by halothane but not by isoflurane.

Conclusions
Clinically relevant concentrations of halothane and isoflurane significantly, but differentially, alter the presynaptic cholinergic regulation of the release of inhibitory neurotransmitters in the striatum. These results suggest that the cholinergic transmission may represent an important and specific presynaptic target for volatile anesthetics in the CNS.
Differential Inhibition of Lysophosphatidate Signaling by Volatile Anesthetics
Authors: Chan Carrie K. , Durieux Marcel E. 
Published: November 2003

Background
Volatile anesthetics have been found to interfere with the functioning of several G protein-coupled receptors, effects that may be relevant to the mechanism of anesthetic action. Lysophosphatidate (1-acyl-2-sn-glycero-3-phosphate; LP) is the simplest natural phospholipid. It has pronounced biological effects and signals through a specific G protein-coupled receptor. Because of its lipophilicity, the LP receptor is a feasible site of anesthetic interaction. Therefore, the authors investigated the effects of halothane and isoflurane on LP signaling using Xenopus oocytes.

Methods
Mature oocytes were harvested from Xenopus frogs, isolated, and defolliculated manually. Lysophosphatidate receptors are endogenously present in these cells. Angiotensin receptors were expressed recombinantly to study anesthetic effects on intracellular signaling. Oocytes were studied individually with a two-electrode voltage clamp at room temperature. Integrated Ca(2+)-activated Cl- currents (ICl(Ca)) were used to evaluate the effects of anesthetics on changes in intracellular Ca2+ concentration in response to receptor agonists (10(-7) M LP or 10(-7) M angiotensin II) or intracellular inositoltrisphosphate (IP3) injection.

Results
Halothane depressed LP signaling in a concentration-dependent manner, with half-maximal inhibition at 0.23 mM and virtually complete inhibition at 0.34 mM. Responses could be recovered after an anesthetic-free wash. Oocyte injection with heparin, an IP3 receptor antagonist, completely blocked LP and angiotensin signaling, indicating similar IP3- dependent pathways. However, ICl(Ca) induced by angiotensin receptor activation or intracellular IP3 injection were not inhibited by halothane. Isoflurane, at comparable concentrations, did not depress LP responses in oocytes significantly.

Conclusions
Lipid-mediator signaling can be affected profoundly by volatile anesthetics. At clinically relevant concentrations, halothane and isoflurane have different effects on LP signaling. The inhibitory effects of halothane on the LP signaling pathway occur before the IP3 receptor.
Modulation of Cardiac Calcium Channels by Propofol
Authors: Zhou Weiguo , Fontenot Jerrel H. , Liu Shi , Kennedy Richard H. 
Published: November 2003

Background
Propofol elicits a rapid depression of transsarcolemmal Ca2+ influx and myocardial contractility. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that propofol acts as an antagonist of L-type calcium channels.

Methods
Experiments monitored effects of propofol on (1) the binding of [3H]nitrendipine (a 1,4-dihydropyridine calcium channel antagonist) to rat myocardial membranes; (2) L-type calcium current (ICa,L) as determined using whole-cell patch-clamp techniques in intact rat cardiomyocytes; and (3) myocardial contractility as examined in isolated rat papillary muscle.

Results
Propofol, in concentrations as low as 6 microM, increased the apparent dissociation constant (Kd) for [3H]nitrendipine without affecting binding-site density (Bmax). This decrease in dihydropyridine-binding affinity was associated with a depressed ICa,L in cardiomyocytes and diminished myocardial contractility. Other experiments showed that etomidate has no effect on [3H]nitrendipine binding, whereas ketamine enhances dihydropyridine binding.

Conclusion
Results suggest that propofol may inhibit cardiac L-type calcium current by interacting with the dihydropyridine-binding site.
Inhalational Anesthetic Effects on Rat Cerebellar Nitric Oxide and Cyclic Guanosine Monophosphate Production
Authors: Rengasamy Appavoo , Pajewski Thomas N. , Johns Roger A. 
Published: November 2003

Background
Inhalational anesthetics interact with the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway in the central nervous system (CNS) and attenuate excitatory neurotransmitter-induced cGMP concentration. The site of anesthetic action on the NO-cGMP pathway in the CNS remains controversial. This study investigated the effect of inhalational anesthetics on N-methyl-D-aspartate (NMDA)-stimulated NO synthase activity and cyclic cGMP production in rat cerebellum slices.

Methods
The interaction of inhalational anesthetics with NO synthase activation and cGMP concentration was determined in cerebellum slices of 10-day-old rats. Nitric oxide synthase activity in cerebellum slices was assessed by measuring the conversion of L-[3H]arginine to L-[3H]citrulline. The cGMP content of cerebellum slices was measured by radioimmunoassay.

Results
Isoflurane at 1.5% and 3% enhanced the NMDA-stimulated NO synthase activity by two times while halothane at 1.5% and 3% produced no significant effect. However, the NMDA-stimulated cGMP production was inhibited by both anesthetic agents. The anesthetic inhibition of cGMP accumulation was not significantly altered by a mixture of superoxide dismutase and catalase or by glycine, a coagonist of the NMDA receptor.

Conclusions
The enhancement of NMDA-induced NO synthase activity by isoflurane and the inhibition of NMDA-stimulated cGMP production by halothane and isoflurane suggests that inhalational anesthetics interfere with the neuronal NO-cGMP pathway. This inhibitory effect of anesthetics on cGMP accumulation is not due to either their interaction with the glycine binding site of the NMDA receptor or to the action of superoxide anions.
Effect of Body Repositioning after Venous Air Embolism
Authors: Geissler Hans J. , Allen Steven J. , Mehlhorn Uwe , Davis Karen L. , Morris William P. , Butler Bruce D. 
Published: November 2003

Background
Current therapy for massive venous air embolism (VAE) may include the use of the left lateral recumbent (LLR) position, although its effectiveness has been questioned. This study used transesophageal echocardiography to evaluate the effect of body repositioning on intracardiac air and acute cardiac dimension changes.

Methods
Eighteen anesthetized dogs in the supine position received a venous air injection of 2.5 ml/kg at a rate of 5 ml/ s. After 1 min the dogs were repositioned into either the LLR, LLR 10 degrees head down (LLR-10 degrees), right lateral recumbence, or remained in the supine position.

Results
Repositioning after VAE resulted in relocation of intracardiac air to nondependent areas of the right heart. Peak right ventricular (RV) diameter increase and mean arterial pressure decrease were greater in the repositioned animals compared with those in the supine position (P < 0.05). Right ventricular diameter and mean arterial pressure showed an inverse correlation (r = 0.81). Peak left atrial diameter decrease was greater in the LLR and LLR-10 degrees positions compared with the supine position (P < 0.05). Repositioning did not influence peak pulmonary artery pressure increase, and no correlation was found between RV diameter and pulmonary artery pressure. All animals showed electrocardiogram and echocardiographic changes reconcilable with myocardial ischemia.

Conclusions
In dogs, body repositioning after VAE provided no benefit in hemodynamic performance or cardiac dimension changes, although relocation of intracardiac air was demonstrated. Right ventricular air did not appear to result in significant RV outflow obstruction, as pulmonary artery pressure increased uniformly in all groups and was not influenced by the relocation of intracardiac air. The combination of increased RV afterload and arterial hypotension, possibly with subsequent RV ischemia rather than RV outflow obstruction by an airlock appeared to be the primary mechanism for cardiac dysfunction after VAE.
The Rate of Blood Withdrawal Affects the Accuracy of Jugular Venous Bulb
Authors: Matta Basil F. , Lam Arthur M. 
Published: November 2003

Background
Accuracy of jugular venous oxygen saturation (SjvO2) measurement depends on sampling of cerebral venous outflow blood not contaminated by systemic venous blood. The influence of the rate of blood withdrawal has not been determined.

Methods
The authors examined the effect of withdrawing blood at different rates from jugular venous bulb catheters (JVBC) on SjvO2 in 10 mechanically ventilated patients undergoing neurosurgical procedures. All patients received a standardized anesthetic consisting of propofol, fentanyl, vecuronium, and isoflurane. Routine monitors included electrocardiograph (ECG), invasive blood pressure, pulse oximetry, and a JVBC. During a period of stable anesthetic and surgical conditions, JVBC blood samples were drawn at 2, 4, and 10 ml/min using a calibrated pump (Harvard Pump model 900, Harvard Apparatus, South Natick, MA) during mild and moderate hypocapnia (arterial carbon dioxide tension [PaCO2], 26.0 +/- 0.5 and 33.0 +/- 0.5 mmHg).

Results
Faster rates of withdrawal (10 and 4 ml/min vs. 2 ml/min) resulted in significantly higher SjvO2 values at both levels of PaCO2 (66.0 +/- 3% and 61.2 +/- 3% vs. 56.9 +/- 3% at PaCO2 = 26.0 +/- 0.5 mmHg, and 75.0 +/- 3% and 71.3 +/- 3% vs. 68.0 +/- 3% at PaCO2 = 33.0 +/- 0.5 mmHg, respectively; P < 0.01).

Conclusions
The authors conclude that the SjvO2 values measured with intermittent sampling are affected by the rate of withdrawing blood from JVBC, probably as a result of extracranial contamination. They recommend blood samples should be drawn slowly.
A Technique for Population Pharmacodynamic Analysis of Concentration-Binary Response Data
Authors: Bailey James M. , Gregg Keith M. 
Published: November 2003

Background
Pharmacodynamic data frequently consist of the binary assessment (a "yes" or "no" answer) of the response to a defined stimulus (verbal stimulus, intubation, skin incision, and so on) for multiple patients. The concentration-effect relation is usually reported in terms of C50, the drug concentration associated with a 50% probability of drug effect, and a parameter the authors denote gamma, which determines the shape of the concentration-probability of effect curve. Accurate estimation of gamma, a parameter describing the entire curve, is as important as the estimation of C50, a single point on this curve. Pharmacodynamic data usually are analyzed without accounting for interpatient variability. The authors postulated that accounting for interpatient variability would improve the accuracy of estimation of gamma and allow the estimation of C50 variability.

Methods
A probit-based model for the individual concentration-response relation was assumed, characterized by two parameters, C50 and gamma. This assumption was validated by comparing probit regression with the more commonly used logistic regression of data from individual patients found in the anesthesiology literature. The model was then extended to analysis of population data by assuming that C50 has a log-normal distribution. Population data were analyzed in terms of three parameters, (C50), the mean value of C50 in the population; omega, the standard deviation of the distribution of the logarithm of C50; and gamma. The statistical characteristics of the technique were assessed using simulated data. The data were generated for a range of gamma and omega values, assuming that C50 and gamma had a log-normal distribution.

Results
The probit-based model describes data from individual patients and logistic regression does. Population analysis using the extended probit model accurately estimated (C50), gamma, and omega for a range of values, despite the fact that the technique accounts for C50 variability but not gamma variability.

Conclusions
A probit-based method of pharmacodynamic analysis of pooled population data facilitates accurate estimation of the concentration-response curve.
Recombinant Human Hemoglobin Does Not Affect Renal Function in Humans
Authors: Viele Maurene K. , Weiskopf Richard B. , Fisher Dennis MD 
Published: November 2003

Background
Recombinant human hemoglobin (OptroD; rHb1.1) is a genetically engineered protein produced in Escherichia coli. The two alpha-globin polypeptides are genetically joined, resulting in a stable tetramer that does not dissociate into dimers or monomers. Historically, infusion in humans of acellular hemoglobin preparations has resulted in renal toxicity. This study was performed to evaluate the safety and pharmacokinetics of rHb1.1 when infused in humans.

Methods
After giving informed consent, 48 healthy male volunteers were randomly assigned to receive either 0.015-0.32 g/kg 5% rHb1.1 (n = 34) or an equivalent amount of 5% human serum albumin (HSA; n = 14) infused intravenously over 0.8-1.9 h. Serum creatinine, creatinine clearance, urine N-acetyl-beta-glucosaminidase, and serum rHb1.1 concentrations were measured before and at timed intervals after infusion.

Results
Postinfusion urine N-acetyl-beta-glucosaminidase activity did not exceed preinfusion values at any interval in either group. Serum creatinine did not differ from preinfusion values at 1 day, 2-3 days, or 7 days after infusion for either group. Creatinine clearance increased significantly for the HSA group 12 h after infusion (138 +/- 16 ml/min, means +/- SE) and in the rHb1.1 group 1 day after infusion (112 +/- 5 ml/min; P < 0.05). Values for creatinine clearance did not differ from preinfusion values for either group at any other postinfusion interval; serum creatinine and creatinine clearance did not differ between groups at any time. The amount of hemoglobin excreted in the urine did not exceed approximately 0.04% of the administered rHb1.1 dose in any volunteer. Plasma clearance of rHb1.1 decreased and half-life increased as a function of increasing plasma concentration (e.g., the half-life was 2.8 h at a plasma concentration of 0.5 mg/ml and 12 h at 5 mg/ml). The incidence of gastrointestinal symptoms, fever, and chills was greater after infusion of rHb1.1 than after HSA (P < 0.05).

Conclusions
No evidence for rHb1.1-mediated nephrotoxicity was observed in volunteers given doses of rHb1.1 as large as 0.32 g/kg. Because the clearance of rHb1.1 varies inversely with its concentration, additional studies with larger doses are necessary to determine the half-life expected in clinical use. Administration of rHb1.1 to conscious humans is associated with some side effects, such as gastrointestinal upset, fever, chills, headache, and backache.
Halothane-induced Dilatation of Intraparenchymal Arterioles in Rat Brain Slices
Authors: Harkin Christopher P. , Hudetz Antal G. , Schmeling William T. , Kampine John P. , Farber Neil E. 
Published: November 2003

Background
Halothane is a potent dilator of cerebral arteries. The predominant site of cerebrovascular resistance is thought to be intracerebral arterioles, and the effects of halothane on these vessels were not previously examined. This study compared the effects of halothane with those of the vasodilator and nitric oxide donor, sodium nitroprusside, on intraparenchymal microvessel responsiveness in a brain slice preparation.

Methods
Anesthetized Sprague-Dawley rats underwent thoracotomy and intracardiac perfusion and then were decapitated. Hippocampal brain slices were prepared and placed in a perfusion/recording chamber and superfused with artificial cerebrospinal fluid. An arteriole was located within the brain parenchyma and its diameter was monitored with videomicroscopy before, during, and after various concentrations of halothane or sodium nitroprusside were equilibrated in the perfusate. All vessels were preconstricted with prostaglandin F2 alpha before halothane or sodium nitroprusside treatment. An observer blinded to treatment analyzed vessel diameter changes with a computerized videomicrometer.

Results
Baseline microvessel diameter was 18 +/- 2 microns in the halothane group (n = 14) and 15 +/- 1 microns in the sodium nitroprusside group (n = 15). Prostaglandin F2 alpha (0.5 micron) preconstricted vessels by approximately 15% from resting diameter in both groups. Halothane significantly and dose dependently dilated intracerebral microvessels by 54% +/- 6%, 74% +/- 8%, 108% +/- 13%, and 132% +/- 7% (normalized to the preconstricted diameter) at 0.5%, 1.0%, and 2.5% halothane, respectively. This dilatation corresponds to a decrease in a calculated index of cerebrovascular resistance index of up to 117% +/- 2% at 2.5% halothane. Sodium nitroprusside, in concentrations ranging from 10(-8) to 10(-3)M, also dose dependently dilated these intraparenchymal vessels by 129% +/- 7% at the highest concentration. These alterations in microvessel diameter corresponded to a decrease in the cerebrovascular resistance index of up to 116 +/- 4% for the largest dose.

Conclusions
Halothane produces dose-dependent vasodilatation of intraparenchymal cerebral microvessels, thus predicting marked decreases in cerebrovascular resistance in this in vitro brain slice preparation. The effects of halothane on these cerebral microvessels are similar to those of the potent vasodilator sodium nitroprusside. These findings suggest that direct effects of halathane on cerebral microvessels diameter contribute substantially to alterations in cerebrovascular resistance and flow produced by this agent.
Inhaled Nitric Oxide Pretreatment But Not Post-treatment Attenuates Ischemia-Reperfusion-induced Pulmonary Microvascular Leak
Authors: Chetham Paul M. , Sefton William D. , Bridges James P. , Stevens Troy , McMurtry Ivan F. 
Published: November 2003

Background
Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown.

Methods
Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion.

Results
(1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective.

Conclusions
Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.