bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thiopental Inhibits Increases in [Ca2+]iInduced by Membrane Depolarization, NMDA Receptor Activation, and Ischemia in Rat Hippocampal and Cortical Slices
Authors: Zhan Ren-Zhi , Fujiwara Naoshi , Endoh Hiroshi , Yamakura Tomohiro , Taga Kiichiro , Fukuda Satoru , Shimoji Koki 
Published: November 2003

Background
This study examined the effects of thiopental on intracellular calcium ([Ca2+]i) changes induced by membrane depolarization, N-methyl-D-aspartate (NMDA) receptor activation, and ischemia.

Methods
Experiments were performed in brain slices prepared from Wistar rats. [Ca2+]i measurements were taken on the CA1 pyramidal cell layer of the hippocampus or layers II to III of the somatosensory cortex using the fura-2 fluorescence technique. Membrane depolarization and NMDA receptor activation were induced by exposing slices to 60 mM K+ and 100 microM NMDA, respectively. In vitro ischemia was induced by superfusing slices with glucose-free Krebs solution equilibrated with 95% nitrogen and 5% carbon dioxide. Thiopental was applied 5 min before application of high K+ and NMDA, or before in vitro ischemia.

Results
Ischemia for 15 min produced a characteristic [Ca2+]i increase in both hippocampal and cortical slices. Thiopental prolonged the latency to the appearance of the [Ca2+]i plateau and reduced the magnitudes of increase in [Ca2+]i 8, 10, and 15 min after the onset of ischemia. Thiopental also suppressed the high K+- and NMDA-induced [Ca2+]i increases. The NMDA-induced [Ca2+]i increases were attenuated to a greater extent in cortical slices than were those in hippocampal slices. The inhibition of thiopental on the 200-microM NMDA-mediated [Ca2+]i response was confirmed in cultured cortical neurons.

Conclusions
The results indicate that thiopental attenuates ischemia-induced [Ca2+]i increases in the hippocampus and cortex in vitro, probably because of its inhibition of both voltage-gated calcium channels and NMDA receptors. The regionally different inhibition of thiopental on NMDA receptors may relate to its region-specific action against ischemia.
Remifentanil Pharmacokinetics in Obese versus Lean Patients
Authors: Egan Talmage D. , Huizinga Bernou , Gupta Samir K. , Jaarsma Rudy L. , Sperry Richard J. , Yee James B. , Muir Keith T. 
Published: November 2003

Background
Remifentanil is a short-acting opioid whose pharmacokinetics have been characterized in detail. However, the impact of obesity on remifentanil pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of body weight on remifentanil pharmacokinetics.

Methods
Twelve obese and 12 matched lean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were collected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-compartment model to the concentration versus time curves. Nonlinear mixed-effects population models examining the influence of lean body mass (LBM) and total body weight (TBW) were also constructed. Clinical simulations using the final population model were performed.

Results
The obese patient cohort reached substantially higher remifentanil concentrations. The individual pharmacokinetic parameters of a two-compartment model were not significantly different between the obese versus lean cohorts (unless normalized to TBW). The final population model scaled central clearance and the central and peripheral distribution volumes to LBM. The simulations illustrated that remifentanil pharmacokinetics are not grossly different in obese versus lean subjects and that TBW based dosing in obese patients can result in excessively high remifentanil concentrations.

Conclusions
The essential findings of the study are that remifentanil's pharmacokinetics are not appreciably different in obese versus lean subjects and that remifentanil pharmacokinetic parameters are therefore more closely related to LBM than to TBW. Clinically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.
Epidural Bupivacaine-Morphine Analgesia versus Patient-controlled Analgesia following Abdominal Aortic Surgery
Authors: Boylan John F. , Katz Joel , Kavanagh Brian P. , Klinck John R. , Cheng Davy C. H. , DeMajo Wilfrid C. , Walker Paul M. , Johnston K. Wayne , Sandler Alan N. 
Published: November 2003

Background
The efficacy and effects of epidural analgesia compared with patient-controlled analgesia (PCA) have not been reported in patients undergoing major vascular surgery. We compared the effects of epidural bupivacaine-morphine with those of intravenous PCA morphine after elective infrarenal aortic surgery.

Methods
Forty patients classified as American Society of Anesthesiologists physical status 2 or 3 received general anesthesia plus postoperative PCA using morphine sulfate (group PCA; n = 21) or general anesthesia plus perioperative epidural morphine-bupivacaine (group EPI; n = 19) during a period of 48 h. During operation, EPI patients received 0.05 mg/kg epidural morphine and 5 ml 0.25% bupivacaine followed by an infusion of 0.125% bupivacaine with 0.1% morphine (0.1 mg/ ml); group PCA received 0.1 mg/kg intravenous morphine sulfate. Continuous electrocardiographic monitoring (V4 and V5 leads) was performed from the night before surgery until 48 h afterward. Respiratory inductive plethysmographic data were recorded after tracheal extubation. Visual analog pain scores at rest and after movement were performed every 4 h after extubation.

Results
Nurse-administered intravenous morphine and time to tracheal extubation were less in group EPI, as were visual analog pain scores at rest and after movement from 20 to 48 h. Complications and the duration of intensive care unit and hospital stay were comparable. There was a similar, low incidence of postoperative apneas, slow respiratory rates, desaturation, and S-T segment depression.

Conclusions
Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements, more rapid tracheal extubation, and superior analgesia after abdominal aortic surgery, with comparable respiratory effects.
The Effect of Adding a Minidose of Clonidine to Intrathecal Sufentanil for Labor Analgesia
Authors: Mercier Frederic J. , Dounas Mokhtar , Bouaziz Herve , Des Mesnards-Smaja Veronique , Foiret Christine , Vestermann Marie Noelle , Fischler Marc , Benhamou Dan 
Published: November 2003

Background
Preliminary studies have suggested that the addition of clonidine to intrathecal sufentanil prolongs analgesia without producing motor blockade.

Methods
Fifty-three nulliparous women in painful labor were included in this prospective, randomized, double-blinded study. Parturients at 2- to 5-cm cervical dilation received either 5 microg sufentanil plus 30 microg clonidine or 5 microg sufentanil intrathecally, followed by 5 mg bupivacaine epidurally. The primary outcome was time until first request for additional analgesia. Visual analog pain scores, sensory changes, blood pressure, heart rate, ephedrine requirements, motor blockade, sedation, pruritus, and nausea were also recorded.

Results
All parturients but one had effective analgesia in both groups, with similar sensory levels never exceeding T2. The duration (mean +/- SD) of analgesia was longer in the sufentanil-clonidine group: 125+/-46 versus 97+/-30 min (P = 0.007). The incidence of hypotension and the ephedrine requirements (median with range) were higher in the sufentanil-clonidine group: 63% versus 12% (P < 0.001) and 7.5 mg [range, 0-25.5 mg] versus 0 mg [range, 0-6 mg] (P < 0.0001). The incidence of fetal heart rate abnormalities during the first 30 min after intrathecal injection was similar in both groups (17% vs. 19%). No parturient had motor blockade.

Conclusions
The addition of 30 microg clonidine to 5 microg intrathecal sufentanil extended the duration of labor analgesia without producing motor blockade. However, as previously reported with 100-200 microg clonidine, the incidence of hypotension and the ephedrine requirements were also increased, even when 30 microg clonidine only was added.
Diphenhydramine Increases Ventilatory Drive during Alfentanil Infusion
Authors: Babenco H. Daniel , Blouin Robert T. , Conard Pattilyn F. , Gross Jeffrey B. 
Published: November 2003

Background
Diphenhydramine is used as an antipruritic and antiemetic in patients receiving opioids. Whether it might exacerbate opioid-induced ventilatory depression has not been determined.

Methods
The ventilatory response to carbon dioxide during hyperoxia and the ventilatory response to hypoxia during hypercapnia (end-tidal pressure of carbon dioxide [PETCO2] is approximately equal to 54 mmHg) were determined in eight healthy volunteers. Ventilatory responses to carbon dioxide and hypoxia were calculated at baseline and during an alfentanil infusion (estimated blood levels approximately equal to 10 ng/ml) before and after diphenhydramine 0.7 mg/kg.

Results
The slope of the ventilatory response to carbon dioxide decreased from 1.08+/-0.38 to 0.79+/-0.36 l x min(-1) x mmHg(-1) (x +/- SD, P < 0.05) during alfentanil infusion; after diphenhydramine, the slope increased to 1.17+/-0.28 l x min(-1) x mmHg(-1) (P < 0.05). The minute ventilation (VE) at PETCO2 approximately equal to 46 mmHg (VE46) decreased from 12.1+/-3.7 to 9.7+/-3.6 l/min (P < 0.05) and the VE at 54 mmHg (VE54) decreased from 21.3+/-4.8 to 16.6+/-4.7 l/min during alfentanil (P < 0.05). After diphenhydramine, (VE46 did not change significantly, remaining lower than baseline at 9.9+/-2.9 l/min (P < 0.05), whereas VE54 increased significantly to 20.5+/-3.0 l/min. During hypoxia, VE at SpO2 = 90% (VE90) decreased from 30.5+/-9.7 to 23.1+/-6.9 l/min during alfentanil (P < 0.05). After diphenhydramine, the increase in VE90 to 27.2+/-9.2 l/min was not significant (P = 0.06).

Conclusions
Diphenhydramine counteracts the alfentanil-induced decrease in the slope of the ventilatory response to carbon dioxide. However, at PETCO2 = 46 mmHg, it does not significantly alter the alfentanil-induced shift in the carbon dioxide response curve. In addition, diphenhydramine does not exacerbate the opioid-induced depression of the hypoxic ventilatory response during moderate hypercarbia.
Formulation-dependent Brain and Lung Distribution Kinetics of Propofol in Rats
Authors: Dutta Sandeep , Ebling William F. 
Published: November 2003

Background
Propofol when administered by brief infusion in a lipid-free formulation has a slower onset, prolonged offset and greater potency compared with an emulsion formulation. To understand these findings the authors examined propofol brain and lung distribution kinetics in rats.

Methods
Rats were infused with equieffective doses of propofol in emulsion (n = 21) or lipid-free formulation (n = 21). Animals were sacrificed at various times to harvest brain and lung. Arterial blood was sampled repeatedly from each animal until sacrifice. Deconvolution and moment analysis were used to calculate the half-life for propofol brain turnover (BT) and brain:plasma partition coefficient (Kp). Lung concentration-time profiles were compared for the two formulations.

Results
Peak propofol plasma concentrations for the lipid-free formulation were 50% of that observed for emulsion formulation, whereas peak lung concentrations for lipid-free formulation were 300-fold higher than emulsion formulation. Brain Kp calculated from tissue disposition curve and ratio of brain:plasma area under the curves were 8.8 and 13, and 7.2 and 9.1 for emulsion and lipid-free formulations, respectively. BT were 2.4 and 2.5 min for emulsion and lipid-free formulations, respectively.

Conclusions
Significant pulmonary sequestration and slow release of propofol into arterial circulation when administered in lipid-free vehicle accounts for the lower peak arterial concentration and sluggish arterial kinetics relative to that observed with the emulsion formulation. Higher Kp for the lipid-free formulation could explain the higher potency associated with this formulation. BT were independent of formulation and correlated with values reported for effect-site equilibration half-time consistent with a distribution mechanism for pharmacologic hysteresis.
Treatment of Normal Skeletal Muscle with FK506 or Rapamycin Results in Halothane-induced Muscle Contracture
Authors: Brooksbank Richard L. , Badenhorts Margaret E. , Isaacs Hyam , Savage Nerina 
Published: November 2003

Background
FKBP12 is a protein that is closely associated with the ryanodine receptor type 1 of skeletal muscle and modulates Ca2+ release by the channel. The immunosuppressants FK506 and rapamycin both bind to FKBP12 and in turn dissociate the protein from the ryanodine receptor. By treating healthy human skeletal muscle strips with FK506 or rapamycin and then subjecting the strips to the caffeine-halothane contracture test, this study determined that FK506 and rapamycin alter the sensitivity of the muscle strip to halothane, caffeine, or both.

Methods
Skeletal muscle strips from 10 healthy persons were incubated in Krebs medium equilibrated with a 95% oxygen and 5% carbon dioxide mixture, which contained either 12 microM FK506 (n = 8) or 12 microM rapamycin (n = 6), for 15 min at 37 degrees C. The strips were subjected to the caffeine-halothane contracture test for malignant hyperthermia according to the European Malignant Hyperthermia Group protocol.

Results
Treatment of normal skeletal muscle strips with FK506 and rapamycin resulted in halothane-induced contractures of 0.44+/-0.16 g and 0.6+/-0.49 g, respectively, at 2% halothane.

Conclusions
The results obtained show that pre-exposure of healthy skeletal muscle strips to either FK506 or rapamycin is sufficient to give rise to halothane-induced contractures. This is most likely caused by destabilization of Ca2+ release by the ryanodine receptor as a result of the dissociation of FKBP12. This finding suggests that a mutation in FKBP12 or changes in its capacity to bind to the ryanodine receptor could alter the halothane sensitivity of the skeletal muscle ryanodine receptor and thereby predispose the person to malignant hyperthermia.
Intravenous Almitrine Bismesylate Reversibly Induces Lactic Acidosis and Hepatic Dysfunction in Patients with Acute Lung Injury
Authors: B'chir Afef , Mebazaa Alexandre , Losser Marie-Reine , Romieu Michel , Payen Didier 
Published: November 2003

Background
Intravenous almitrine, which augments hypoxic pulmonary vasoconstriction, is used for short-term improvement of arterial oxygenation. However, recent research has suggested a potentially harmful effect on lactate metabolism and hepatic function.

Methods
Arterial oxygenation, hemodynamic parameters, plasma lactate, and hepatic function were monitored prospectively in 25 patients with acute lung injury (defined as a ratio of arterial oxygen pressure to inspiratory oxygen fraction < or = 150 mmHg) who where treated with intravenous almitrine. In 21 of 25 patients, acute lung injury was related to primary lung lesions, including pneumonia, postcardiosurgical atelectasis, and lung contusions.

Results
Intravenous almitrine increased the ratio of arterial oxygen pressure to inspiratory oxygen fraction from 93 +/- 33 mmHg to 207 +/- 107 mmHg (mean +/- SD). In eight patients (three men), the plasma lactate concentration increased by an average of +3.5 +/- 1.8 mM, and the pH and bicarbonate concentration both decreased during the first 24 h of treatment. In this group of patients, the total bilirubin concentration was elevated before almitrine administration, and the results of other hepatic function tests, such as aspartate aminotransferase, alanine aminotransferase, and prothrombin time, were altered by almitrine administration. Therefore, intravenous almitrine was discontinued. Lactic acidosis and hepatic dysfunction improved. In the other 17 patients (14 men), the plasma lactate concentration and the hepatic function tests remained unaltered during intravenous almitrine therapy for > 60 h. Univariate and multivariate analyses revealed that an abnormal plasma concentration of total bilirubin before almitrine administration and female gender were the two factors significantly linked with lactic acidosis during almitrine infusion.

Conclusions
This study confirms that intravenous almitrine greatly improves arterial oxygenation in patients with acute lung injury but may also induce lactic acidosis and hepatic dysfunction. The coexistence of lactic acidosis and hepatic dysfunction in the same patients strongly suggests that the liver is the primary source of intravenous almitrine-induced lactic acidosis.
Cerebrovascular CO2Reactivity during Anesthesia in Patients with Diabetes Mellitus and Peripheral Vascular Disease
Authors: Kawata Ryuichi , Nakakimura Kazuhiko , Matsumoto Mishiya , Kawai Kouji , Kunihiro Mitsuru , Sakabe Takefumi 
Published: November 2003

Background
Diabetes mellitus (DM) and systemic atherosclerosis are risk factors for stroke. Although the origins of increased risk are complex, one possibility is that cerebrovascular reactivity is impaired and does not allow the brain to compensate for aberrations in physiology. The current study tested this issue by evaluating mean blood flow velocity of the middle cerebral artery (Vmca) and carbon dioxide reactivity during anesthesia in patients with DM and peripheral vascular disease (PVD).

Methods
Fifty-two patients were observed: 20 patients with DM (the DM group), 12 patients with PVD (the PVD group), and 20 patients classified as American Society of Anesthesiologists physical status 1 or 2 (the control group). The Vmca was measured using transcranial Doppler ultrasonography during isoflurane-nitrous oxide anesthesia. After measuring baseline Vmca at a partial pressure of carbon dioxide in arterial blood (PaCO2) of 37.7 +/- 4.5 mmHg (mean +/- SD), measurements were repeated at a PaCO of 44.2 +/- 3.8 mmHg, and the carbon dioxide reactivity (absolute value: cm x s(-1) x mmHg(-1); relative value: percentage of baseline Vmca/mmHg) was calculated.

Results
The baseline Vmca of the DM group (51 +/- 12 cm/s) was significantly greater than those of the control group (42 +/- 6 cm/s) and the PVD group (42 +/- 13 cm/s). The absolute and relative values of carbon dioxide reactivity in the DM group (3.1 +/- 1.3 cm x s(-1) x mmHg(-1); 6.3 +/- 2.4%/mmHg) were significantly greater than or equivalent to those of the control group (2.3 +/- 0.8 cm x s(-1) x mmHg(-1); 5.3 +/- 1.7%/mmHg), respectively. In the PVD group, the baseline Vmca was equivalent to the control group, but the carbon dioxide reactivity (1.1 +/- 0.5 cm x s(-1) x mmHg(-1) 2.8 +/- 1.2%/mmHg) was significantly less.

Conclusions
The patients with DM have increased baseline cerebral blood flow velocity and normal carbon dioxide reactivity during anesthesia. The patients with PVD have decreased carbon dioxide reactivity, but baseline flow velocity is maintained.
The Pharmacodynamic Interaction between Propofol and Fentanyl with Respect to the Suppression of Somatic or Hemodynamic Responses to Skin Incision, Peritoneum Incision, and Abdominal Wall Retraction
Authors: Kazama Tomiei , Ikeda Kazuyuki , Morita Koji 
Published: November 2003

Background
Sufficient propofol or fentanyl doses necessary to prevent the response to skin incision do not necessarily attenuate hemodynamic responses during surgery. The goal of this study was to characterize the pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses after three stimuli: skin incision, peritoneum incision, and abdominal wall retraction.

Methods
Propofol and fentanyl were administered via computer-assisted continuous infusion to provide equilibration between plasma-blood and biophase concentrations. Patients were randomized to nine groups that received predetermined concentrations of fentanyl (from 0 to 9 ng/ml). Each patient was administered different target concentrations of propofol. Somatic and hemodynamic responses were measured before and after each of three different stimulations: skin incision (si), peritoneum incision (pi), and abdominal wall retraction (ret). The propofol plasma concentrations at which 50% of the patients did not respond to each type of stimulation (Cp50si, Cp50pi, and Cp50ret) were calculated by fitting the Loewe synergistic model.

Results
For propofol alone, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1, and 19.4 microg/ml, respectively. Increasing the fentanyl concentration markedly reduced propofol Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential synergistic interaction of both drugs. During the prestimulation period, fentanyl did not decrease systolic blood pressure; however, propofol specifically decreased systolic blood pressure. Both drugs had a synergistic drug interaction on the systolic blood pressure increase after various surgical stimulations. Fentanyl and propofol concentrations that suppressed both the 50% probability of somatic response and the 50% probability of moderate hemodynamic change defined by the 15% systolic blood pressure increase over the prestimulation value were 3.6 ng/ml and 2.5 microg/ml for skin incision, 8.4 ng/ml and 1.6 microg/ml for peritoneum incision, and 5.9 ng/ml and 5.1 microg/ml for wall retraction, respectively.

Conclusions
The anesthesia requirements for stimuli that are more intense than skin incision should be considered during abdominal surgery. Somatic and hemodynamic responses varied depending on the type of surgical stimuli.
Isoflurane and Sevoflurane Induce Vasodilation of Cerebral Vessels via ATP-sensitive K+Channel Activation
Authors: Iida Hiroki , Ohata Hiroto , Iida Mami , Watanabe Yukinaga , Dohi Shuji 
Published: November 2003

Background
Activation of adenosine triphosphate-sensitive K+ channels causes cerebral vasodilation. To assess their contribution to volatile anesthetic-induced cerebral vasodilation, the effects of glibenclamide, an adenosine triphosphate-sensitive K+ channel blocker, on the cerebral vasodilation induced by isoflurane and sevoflurane were studied.

Methods
Pentobarbital-anesthetized dogs (n = 24) assigned to one of two groups were prepared for measurement of pial vessel diameter using a cranial window preparation. Each dog received three minimum alveolar concentrations (MAC; 0.5, 1, and 1.5 MAC) of either isoflurane or sevoflurane, and the pial arteriolar diameters were measured in the presence or absence of glibenclamide (10(-5) M) infused continuously into the window. Mean arterial pressure was maintained with phenylephrine. Furthermore, to assess the direct effect of isoflurane and sevoflurane on cerebral vessels, artificial cerebrospinal fluid was administered topically by being bubbled with isoflurane or sevoflurane. The blocking effect of glibenclamide on the vasoactive effects of these anesthetics also were evaluated.

Results
Isoflurane and sevoflurane both significantly dilated large (> or = 100 microm) and small (< 100 microm) pial arterioles in a concentration-dependent manner (6% and 10%, 3% and 8% for 0.5 MAC; 10% and 19%, 7% and 14% for 1 MAC; 17% and 28%, 13% and 25% for 1.5 MAC). Glibenclamide attenuated the arteriolar dilation induced by these anesthetics (not significant in isoflurane). Topical application of isoflurane or sevoflurane dilated large and small arterioles both in a concentration-dependent manner. Such vasodilation was inhibited completely by glibenclamide.

Conclusion
The vasodilation of cerebral pial vessels induced by isoflurane and sevoflurane appears to be mediated, at least in part, via activation of adenosine triphosphate-sensitive K+ channels.