bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Pentoxifylline on Acid-induced Alveolar Epithelial Injury
Authors: Kudoh Ichidai , Ohtake Mika , Nishizawa Hideo , Kurahashi Kiyoyasu , Hattori Satoshi , Okumura Fukuichiro , Pittet Jean-Francois , Wiener-Kronish Jeanine 
Published: November 2003

Background
Acid instillation into one lung is known to cause an increase in the permeability of the endothelium to protein in both the instilled and the contralateral lungs. Activated neutrophils are believed to be involved in causing this increased permeability. Pentoxifylline, a drug used in clinical practice, has multiple effects on neutrophils, including inhibition of phagocytosis, degranulation, and superoxide generation. This study investigated whether pretreatment with pentoxifylline would protect the alveolar epithelium or lung endothelium from injury.

Methods
The effect of acid instillation into one lung of anesthetized rabbits using several quantitative parameters was investigated. The quantification of the bidirectional movement of the alveolar (125I-albumin) and the circulating protein tracers (131I-albumin) was used as a measurement of the permeabilities of the lung epithelium and the lung endothelium in the acid-instilled lung. Bronchoalveolar lavage and measurement of the entry of the circulating protein tracer were used to assess the permeabilities of these barriers in the noninstilled lung.

Results
The instillation of HCl (pH 1.25, 1.2 ml/kg) into the right lung resulted in an increase in the protein permeability of the right lung's alveolar epithelium and endothelium as well as an increase in the permeability to protein of the left lung's endothelium. Pentoxifylline pretreatment attenuated the increase in the endothelial permeability of both lungs by 50% and restored the PaO2/FIO2 to normal in the pretreated animals exposed to acid injury.

Conclusions
Acid aspiration causes a dramatic increase in the alveolar epithelial permeability of the acid-instilled lung, but the permeability of the alveolar epithelium of the contralateral lung remains normal. In contrast, unilateral acid instillation causes an increase in the permeability of the endothelium of both lungs. The increase in endothelial permeability can be attenuated by pretreatment with pentoxifylline administration, and this leads to restoration of normal gas exchange.
Effects of Sevoflurane on Contractile Responses and Electrophysiologic Properties in Canine Single Cardiac Myocytes
Authors: Hatakeyama Noboru , Momose Yasunori , Ito Yusuke 
Published: November 2003

Background
The effects of sevoflurane was examined on the contractile response, membrane potential, membrane ionic currents, and intracellular cyclic adenosine monophosphate (cAMP) in canine single ventricular myocytes.

Methods
Contraction was measured by a video-edge detector, and membrane ionic currents were recorded using whole-cell voltage clamp technique. Intracellular cAMP was measured with radioimmunoassay method.

Results
Sevoflurane (1.0-4.0%) decreased the contraction of single ventricular cells in a dose-dependent and reversible manner. Also, sevoflurane decreased the action potential plateau and shortened the duration of action potential. Sevoflurane reduced the peak Ca2+ currents (ICa) but did not show the use-dependent block. On the other hand, sevoflurane slightly reduced the Na+ currents (INa) only at a high concentration (4.0%). Intracellular cAMP concentration was reduced only at 4.0% sevoflurane.

Conclusions
The negative inotropic effect of sevoflurane is mediated via the inhibition of ICa in canine ventricular myocyte but not associated with reduced intracellular cAMP except at a high dose (4.0%).
Myocardial Effects of Propofol in Hamsters with Hypertrophic Cardiomyopathy
Authors: Riou Bruno , Lejay Marc , Lecarpentier Yves , Viars Pierre 
Published: November 2003

Background
Propofol is a short-acting intravenous induction agent that induces cardiovascular depression but without significant effect on intrinsic myocardial contractility in various species. However, its effects on diseased myocardium remain unknown.

Methods
The effects of propofol (1, 3, and 10 micrograms.ml-1) on the intrinsic contractility of left ventricular papillary muscles from normal hamsters and those with hypertrophic cardiomyopathy (strain BIO 14.6, aged 6 months) were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca++ 2.5 mmol.l-1, stimulation frequency 3/min).

Results
Cardiac hypertrophy (143 +/- 13%, P < 0.001) was observed in cardiomyopathic hamsters. The contractility of papillary muscles from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in maximum shortening velocity (-29%, P < 0.03) and active isometric force (-51%, P < 0.001). Propofol did not induce any significant effect on contraction, relaxation, and contraction-relaxation coupling under low and high loads in normal hamsters. The effects of propofol were not significantly different between normal hamsters and those with cardiomyopathy. A slight but significant increase in maximum unloaded shortening velocity was observed in cardiomyopathic hamsters at 3 micrograms.ml-1 (4 +/- 6%, P < 0.05) and 10 micrograms.ml-1 (7 +/- 6%, P < 0.05).

Conclusions
Propofol did not modify intrinsic myocardial contractility in normal hamsters, and no significant differences were observed between normal and cardiomyopathic hamsters. These results may be useful because, unlike propofol, most anesthetics decrease myocardial contractility. Nevertheless, indirect cardiac effects of propofol may be more important than its direct cardiac effects in patients with impaired cardiac function.
Effect of Vasoconstrictive Agents Added to Lidocaine on Intravenous Lidocaine-induced Convulsions in Rats
Authors: Yokoyama Masataka , Hirakawa Masahisa , Goto Hiroshi 
Published: November 2003

Background
Epinephrine is reported to decrease the threshold of intravenous lidocaine-induced convulsions. However, the mechanism underlying this effect is not clear. Therefore, we carried out a study to examine the role of vasopressor-induced hypertension.

Methods
Fifty-six awake Wistar rats were assigned to seven groups of eight. All groups received a continuous intravenous infusion of lidocaine at a rate of 4 mg.kg-1.min-1 until generalized convulsions occurred. The control group (group C) received plain lidocaine. The acute hypertensive groups received lidocaine with epinephrine (group E), norepinephrine (group N), or phenylephrine (group P) to increase mean arterial blood pressure (MAP) to 150 +/- 5 mmHg. Sodium nitroprusside (SNP) was added to prevent an increase in mean arterial pressure in the remaining three groups (vasopressor-SNP groups).

Results
The acute hypertensive groups required significantly smaller cumulative doses of lidocaine to produce convulsions compared with control (C = 41.5 +/- 2.9 > E = 24.1 +/- 2.7, N = 27.1 +/- 2.8, P = 26.7 +/- 2.5 mg.kg-1; values are mean +/- SD, P < 0.01). In addition, plasma lidocaine concentrations (C = 11.0 +/- 0.7 > E = 7.4 +/- 0.5, N = 7.9 +/- 0.6, P = 8.1 +/- 0.8 micrograms.ml-1, P < 0.01) and brain lidocaine concentrations (C = 50.9 +/- 4.5 > E = 32.6 +/- 4.2, N = 34.5 +/- 4.8, P = 37.1 +/- 4.5 micrograms.g-1, P < 0.01) were less in the acute hypertensive groups at the onset of convulsions. In the vasopressor-SNP groups, the plasma and brain lidocaine concentrations at the onset of convulsions returned to the control values, although epinephrine and norepinephrine, but not phenylephrine, still decreased cumulative convulsant doses of lidocaine significantly (P < 0.01) compared with control (E + SNP = 30.8 +/- 2.9 < N + SNP = 34.8 +/- 2.8, P < 0.01) < P + SNP = 40.2 +/- 3.0 mg.kg-1, P < 0.01). The brain/plasma concentration ratios were similar for the seven groups.

Conclusions
An equal degree of acute hypertension induced by these three different vasopressors may play a role in reducing the threshold (plasma and brain lidocaine concentrations) as well as the cumulative convulsant doses associated with lidocaine-induced convulsions.
Effects of Perioperative Dexmedetomidine Infusion in Patients Undergoing Vascular Surgery
Authors: Talke P. , Li J. , Jain U. , Leung J. , Drasner K. , Hollenberg M. , Mangano D. T. 
Published: November 2003

Background
Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease.

Methods
Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively.

Results
Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results.

Conclusions
Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate.
Comparison of the Neuromuscular Blocking Effect of Atracurium and Vecuronium on the Adductor Pollicis and the Geniohyoid Muscle in Humans
Authors: D'Honneur G. , Guignard B. , Slavov V. , Ruggler R. , Duvaldestin P. 
Published: November 2003

Background
Residual paralysis of suprahyoid muscles may occur when the adductor pollicis response has completely recovered after the administration of a neuromuscular blocking agent. The response of the geniohyoid muscle to intubating doses of muscle relaxants is evaluated and compared to that of adductor pollicis.

Methods
Sixteen patients undergoing elective surgery under general anesthesia were given 5-7 mg.kg-1 thiopental and 2 micrograms.kg-1 fentanyl intravenously for induction of anesthesia. Eight (half) patients then received 0.5 mg.kg-1 atracurium, and the other eight received 0.1 mg.kg-1 vecuronium. The evoked response (twitch height, TH) of the adductor pollicis was monitored by measuring the integrated electromyographic response (AP EMG) on one limb and the mechanical response, using a force transducer (AP force), on the other. The activity of geniohyoid muscle (GH EMG) was measured using submental percutaneous electrodes. The following variables were measured: maximal TH depression; onset time for neuromuscular blockade to 50%, 90%, and maximal TH depression (OT50, OT90, and OTmax); times between administration of neuromuscular blocking agent and TH recovery to 10%, 25%, 50%, 75%, and 90% of control; and time for return of train-of-four ratio to return to 0.7.

Results
The principal findings were (1) OTmax was significantly (P < 0.01) shorter for geniohyoid than for adductor pollicis after either atracurium or vecuronium (OTmax was 216, 256, and 175 s for AP force, AP EMG, and GH EMG, with atracurium and 181, 199, and 144 s with vecuronium, respectively), and (2) the evoked EMG of geniohyoid recovered at the same speed as the EMG of adductor pollicis after an intubating dose of atracurium or vecuronium (recovery of TH to 75% of control at 50, 48, 42 min with AP force, AP EMG, and GH EMG with atracurium and 46, 45, and 42 min with vecuronium, respectively).

Conclusions
Once the adductor pollicis response has returned to normal values after a single intubating dose of atracurium or vecuronium, the risk of residual depression of the TH of the geniohyoid muscle, one of the principal muscles contributing to airway patency, appears unlikely.
Optimal Duration and Temperature of Prewarming
Authors: Sessler Daniel I. , Schroeder Marc , Merrifield Benjamin , Matsukawa Takashi , Cheng Christi 
Published: November 2003

Background
Core hypothermia developing immediately after induction of anesthesia results largely from an internal core-to-peripheral redistribution of body heat. Although difficult to treat, redistribution can be prevented by prewarming. The benefits of prewarming may be limited by sweating, thermal discomfort, and efficacy of the warming device. Accordingly, the optimal heater temperature and minimum warming duration likely to substantially reduce redistribution hypothermia were evaluated.

Methods
Sweating, thermal comfort, and extremity heat content were evaluated in seven volunteers. They participated on two study days, each consisting of a 2-h control period followed by 2 h of forced-air warming with the heater set on "medium" (approximately 40 degrees C) or "high" (approximately 43 degrees C). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, ten skin temperatures, and "deep" foot temperature.

Results
Half the volunteers started sweating during the second hour of warming. None of the volunteers felt uncomfortably warm during the first hour of heating, but many subsequently did. With the heater set on "high," arm and leg heat content increased 69 kcal during the first 30 min of warming and 136 kcal during the first hour of warming, representing 38% and 75%, respectively, of the values observed after 2 h of warming. The increase was only slightly less when the heater was set to "medium."

Conclusions
Neither sweating nor thermal discomfort limited heat transfer during the first hour of warming. Thirty minutes of forced-air warming increased peripheral tissue heat content by more than the amount normally redistributed during the first hour of anesthesia. The large increase in arm and leg heat content during prewarming thus explains the observed efficacy of prewarming.
Analysis of Drug Interaction between Intrathecal Clonidine and MK-801 in Peripheral Neuropathic Pain Rat Model
Authors: Lee Youn-Woo , Yaksh Tony L. 
Published: November 2003

Background
Spinally delivered alpha 2-adrenoceptor agonists and N-methyl-D-aspartate antagonists each have been shown to have actions attenuating the hyperesthesia in rat models of nerve injury pain. Using a fixed-dose analysis and an isobolographic paradigm, the spinal interaction between the alpha 2-adrenoceptor agonist clonidine and the N-methyl-D-aspartate antagonist MK-801 is characterized in a rat model of nerve injury-induced tactile hyperesthesia.

Methods
Male Sprague Dawley rats were anesthetized with halothane, and the left L5 and L6 spinal nerves were ligated (Chung model). After 7-10 days' recovery, a Polyethylene tubing catheter was implanted into the lumbar intrathecal space. After recovery from catheter implantations (5-7 days), intrathecal dose-response curves were established for the antihyperesthesia effects of clonidine (3, 6, 10, and 20 micrograms) and MK-801 (1, 3, 10, and 20 micrograms) alone to obtain the ED50 for each agent. In separate studies, three doses of clonidine (1, 3, and 10 micrograms) were injected mixed with one dose of MK-801 (1 microgram) for fixed-dose analysis, and three doses of the two agents (2, 6, and 20 micrograms) were injected jointly in a fraction of the dose ratio 1:1 for isobolographic analysis. Thresholds for left hind paw withdrawal to von Frey hair application were assessed.

Results
Rats with nerve ligation showed a reliable tactile hyperesthesia (mechanical threshold 1-3 g vs. normal > 15 g). Intrathecal clonidine and MK-801 alone produced dose-dependent reductions of tactile hyperesthesia: ED50 9 micrograms and 10 micrograms, respectively. With the fixed-dose analysis, the log dose-response curves showed a left shift that considerably exceeds the theoretical curve made by a simple sum of the effects of clonidine alone and with MK-801 (1 microgram). With the isobolographic analysis, the combination ED50 was found to be statistically less than the theoretical additive dose combination. Intrathecal atipamezole, an alpha 2 antagonist, reversed the effects of clonidine and the clonidine/MK-801 mixture but not MK-801 alone. The side effect of clonidine was sedation and urination and that of MK-801 was motor weakness at doses above 10 micrograms. These effects were considerably less severe in rats after equiactive doses in the combination group.

Conclusions
The neuropathic pain is mediated by low-threshold mechanoreceptors, sympathetically dependent, and sensitive to both alpha 2 agonists and N-methyl-D-aspartate antagonists. Intrathecal clonidine may act to diminish sympathetic outflow, whereas MK-801 blocks the N-methyl-D-aspartate receptor that is associated with other spinal systems related to pain transmission mechanism. The two separate mechanisms may account for the powerful synergy observed in this study. Such combinations might be useful in neuropathic pain states to potentiate the antihyperpathic effects and to reduce the side effects of each agents.
The Membrane Lipid Cholesterol Modulates Anesthetic Actions on a Human Brain Ion Channel
Authors: Rehberg Benno , Urban Bernd W. , Duch Daniel S. 
Published: November 2003

Background
Molecular theories of general anesthesia often are divided into two categories: (1) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.

Methods
Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.

Results
Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half.

Conclusions
These results support a critical role for the lipid membrane in some anesthetic actions and further indicate that differences in lipid composition must be considered in the interpretation of results when comparing the anesthetic potencies of potential targets in model systems.
Buccal Absorption of Fentanyl Is pH-Dependent in Dogs
Authors: Streisand James B , Zhang Jie , Niu Suyi , McJames Scott , Natte Remco , Pace Nathan L. 
Published: November 2003

Background
Analgesia and sedation have been achieved noninvasively by fentanyl administration through the oral and nasal mucosa. In theory, the transmucosal bioavailability and absorption of fentanyl could be improved by converting more fentanyl to the unionized form by adjusting the surrounding pH. The authors tested this hypothesis in dogs.

Methods
Under general anesthesia, each of six mongrel dogs was given fentanyl on repeated occasions, first intravenously (once), then by application to the buccal mucosa (six times). Buccal fentanyl administration was accomplished by placement of a pH-buffered solution of fentanyl into a specially constructed cell, which was clamped to the dog's buccal mucosa for 60 min. Fentanyl solutions with pHs of 6.6, 7.2, and 7.7 were studied to span a tenfold difference in the unionized fraction of fentanyl. Femoral arterial blood samples were sampled frequently and analyzed for fentanyl using a radioimmunoassay. Peak plasma concentration and the time of its occurrence for each buccal study were noted from the plasma concentration verses time profile. Terminal elimination half-life, bioavailability, and permeability coefficients were calculated using standard pharmacokinetic techniques.

Results
The variables peak plasma concentration, bioavailability, and permeability coefficient increased three- to fivefold as the pH of the fentanyl buccal solution increased and more fentanyl molecules became unionized. There was no difference in terminal elimination half-life after intravenous fentanyl (244 +/- 68 min) or buccal fentanyl administration (pH 7.7, 205 +/- 89 min; pH 7.2, 205 +/- 65 min; pH 6.6, 196 +/- 48 min). In all buccal studies regardless of pH, time to peak plasma concentration occurred within 10 min of removal of the fentanyl solutions from the buccal mucosa.

Conclusions
The buccal absorption, bioavailability, and permeability of fentanyl are markedly increased as the pH of the fentanyl solution becomes more basic. Most likely, this is because of an increase in the fraction of unionized fentanyl.
Cervical Spine Movement during Laryngoscopy with the Bullard, Macintosh, and Miller Laryngoscopes
Authors: Hastings Randolph H. , Vigil A. Christopher , Hanna Richard , Yang Bor-Yau , Sartoris David J. 
Published: November 2003

Background
Direct laryngoscopy requires movement of the head, neck, and cervical spine. Spine movement may be limited for anatomic reasons or because of cervical spine injury. The Bullard laryngoscope, a rigid fiberoptic laryngoscope, may cause less neck flexion and head extension than conventional laryngoscopes. The purpose of this study was to compare head extension (measured externally), cervical spine extension (measured radiographically), and laryngeal view obtained with the Bullard, Macintosh, and Miller laryngoscopes.

Methods
Anesthesia was induced in 35 ASA 1-3 elective surgery patients. Patients lay on a rigid board with head in neutral position. Laryngoscopy was performed three times, changing between the Bullard, Macintosh, and Miller laryngoscopes. Head extension was measured with an angle finder attached to goggles worn by the patient. The best laryngeal view with each laryngoscope was assessed by the laryngoscopist. In eight patients, lateral cervical spine radiographs were taken before and during laryngoscopy with the Bullard and Macintosh blades.

Results
Median values for external head extension were 11 degrees, 10 degrees, and 2 degrees with the Macintosh, Miller, and Bullard laryngoscopy (P < 0.01), respectively. Significant reductions in radiographic cervical spine extension were found for the Bullard compared to the Macintosh blade at the atlantooccipital joint, atlantoaxial joint, and C3-C4. Median atlantooccipital extension angles were 6 degrees and 12 degrees for the Bullard and Macintosh laryngoscopes, respectively. The larynx could be exposed in all patients with the Bullard but only in 90% with conventional laryngoscope (P < 0.01).

Conclusions
The Bullard laryngoscope caused less head extension and cervical spine extension than conventional laryngoscopes and resulted in a better view. It may be useful in care of patients in whom cervical spine movement is limited or undesirable.