bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrous Oxide Impairs the Neutrophil Oxidative Response
Authors: Frohlich Dieter , Rothe Gregor , Wittmann Sigrid , Schmitz Gerd , Schmid Peter , Taeger Kai , Hobbhahn Jonny
Published: November 2003

Background

Nitrous oxide has been shown inconsistently to impair the oxidative function of neutrophils. The choice of the stimulus, receptor agonists, or stimuli acting independent of receptors seems to determine whether nitrous oxide impairs the oxidative functions, suggesting an interference with the cytosolic signaling of neutrophils.

Methods

Production of hydrogen peroxide by neutrophils was assessed using flow cytometric analysis. N-formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, dioctanylglycerol, and phorbol-12-myristate-13-acetate were used as stimuli. In addition, the expression of receptors for FMLP and the cytosolic-free calcium response of cells were measured.

Results

Nitrous oxide depresses C5a- or FMLP-induced generation of reactive oxygen derivatives in a concentration-dependent manner. However, the response with direct activation of protein kinase C was unaffected. Further, the number of FMLP receptors and the cytosolic calcium response were unaffected. Inhibition of the oxidative response was not reversible within the observation period of 4 h.

Conclusions

Nitrous oxide inhibited the intracellular signaling of the investigated G-protein-coupled receptors for chemotactic peptides. No interference of nitrous oxide with reduced nicotinamide adenine dinucleotide phosphate oxidase, the oxidative enzyme system of neutrophils, nor with its activation through protein kinase C was detected.
Halothane, But Not Isoflurane, Impairs the β-adrenergic Responsiveness in Rat Myocardium
Authors: Schotten Ulrich , Schumacher Carlos , Sigmund Martin , Karlein Christian , Rose Horst , Kammermeier Helmut , Sivarajan Murali , Hanrath Peter
Published: November 2003

Background

The aim of this study was to identify the mechanisms by which halothane and isoflurane change the myocardial beta-adrenergic signal transduction pathway.

Methods

The authors investigated the influence of volatile anesthetics on the isometric force of contraction of rat papillary muscles. Concentration-response curves for isoproterenol and epinephrine were studied under control conditions and in the presence of halothane or isoflurane. In radioligand receptor-binding studies, the beta-adrenoceptor affinities for isoproterenol and epinephrine were investigated with and without guanosine triphosphate. In addition, the isoproterenol-induced cyclic adenosine monophosphate accumulations in viable cardiomyocytes in the absence and in the presence of halothane were determined by radioimmunoassays.

Results

The half-maximal positive inotropic effect of isoproterenol was reached at a half-maximal effective concentration (EC50 value) of 68 nM (33-141 nM; n = 10). A minimum alveolar concentration of 1.3 halothane reduced the positive inotropic potency of isoproterenol (EC50 = 158 nM [118-214 nM; n = 10; P < 0.01 vs. control]), whereas isoflurane did not changed it. This observation held true when the force of contraction was stimulated with epinephrine. Halothane (1.3 minimum alveolar concentration) depressed beta-adrenoceptor high-affinity binding and beta-adrenoceptor agonist affinity in radioligand binding assays, an effect not seen with isoflurane. Halothane shifted the intracellular cyclic adenosine monophosphate response curve of isoproterenol to the right.

Conclusion

Halothane, but not isoflurane, impairs the beta-adrenergic responsiveness in rat myocardium by reducing the agonist affinity of the beta-adrenoceptors.
Tissue Heat Content and Distribution during and after Cardiopulmonary Bypass at 31 [degree sign]C and 27 [degree sign]C
Authors: Rajek Angela , Lenhardt Rainer , Sessler Daniel I. , Kurz Andrea , Laufer Gunther , Christensen Richard , Matsukawa Takashi , Hiesmayr Michael
Published: November 2003

Background

Afterdrop following cardiopulmonary bypass results from redistribution of body heat to inadequately warmed peripheral tissues. However, the distribution of heat between the thermal compartments and the extent to which core-to-peripheral redistribution contributes to post-bypass hypothermia remains unknown.

Methods

Patients were cooled during cardiopulmonary bypass to nasopharyngeal temperatures near 31 degrees C (n=8) or 27 degrees C (n=8) and subsequently rewarmed by the bypass heat exchanger to approximately 37.5 degrees C. A nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature.

Results

In the 31 degrees C group, the average peripheral tissue temperature decreased to 31.9+/-1.4 degrees C (means+/-SD) and subsequently increased to 34+/-1.4 degrees C at the end of bypass. The core-to-peripheral tissue temperature gradient was 3.5+/-1.8 degrees C at the end of rewarming, and the afterdrop was 1.5+/-0.4 degrees C. Total body heat content decreased 231+/-93 kcal. During pump rewarming, the peripheral heat content increased to 7+/-27 kcal below precooling values, whereas the core heat content increased to 94+/-33 kcal above precooling values. Body heat content at the end of rewarming was thus 87+/-42 kcal more than at the onset of cooling. In the 27 degrees C group, the average peripheral tissue temperature decreased to a minimum of 29.8 +/-1.7 degrees C and subsequently increased to 32.8+/-2.1 degrees C at the end of bypass. The core-to-peripheral tissue temperature gradient was 4.6+/-1.9 degrees C at the end of rewarming, and the afterdrop was 2.3+/-0.9 degrees C. Total body heat content decreased 419+/-49 kcal. During pump rewarming, core heat content increased to 66+/-23 kcal above precooling values, whereas peripheral heat content remained 70+/-42 kcal below precooling values. Body heat content at the end of rewarming was thus 4+/-52 kcal less than at the onset of cooling.

Conclusions

Peripheral tissues failed to fully rewarm by the end of bypass in the patients in the 27 degrees C group, and the afterdrop was 2.3+/-0.9 degrees C. Peripheral tissues rewarmed better in the patients in the 31 degrees C group, and the afterdrop was only 1.5+/-0.4 degrees C.
Nonanesthetic Volatile Drugs Obey the Meyer-Overton Correlation in Two Molecular Protein Site Models
Authors: Forman Stuart A. , Raines Douglas E.
Published: November 2003

Background

Nonanesthetic volatile compounds fail to inhibit movement in response to noxious stimulation at concentrations predicted to induce anesthesia from their oil-water partitioning. Thus they represent tools to determine whether molecular models behave like the targets that mediate in vivo anesthetic actions. The effects of volatile anesthetics and nonanesthetics were examined in two experimental models in which anesthetics interact directly with proteins: the pore of the nicotinic acetylcholine receptor and human serum albumin.

Methods

Wild-type mouse muscle nicotinic receptors and receptors containing pore mutations (alphaS252I + betaT263I) were studied electrophysiologically in membrane patches from Xenopus oocytes. Patch currents evoked by brief pulses of acetylcholine were measured in the presence of enflurane and two nonanesthetics, 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane. Nonanesthetic interactions with human serum album were assessed by quenching of intrinsic protein fluorescence.

Results

Both anesthetic and nonanesthetic volatile compounds inhibited wild-type and alphaS252I + betaT263I mutant nicotinic channels but displayed different selectivity for open versus resting receptor states. Median inhibitory concentrations (IC50s) in wild-type nicotinic receptors were 870+/-20 microM for enflurane, 37+/-3 microM for 1,2-dichlorohexafluorocylcobutane, and 11.3+/-5.6 microM for 2,3-dichlorooctafluorobutane. For all three drugs, ratios of wild-type IC50s to mutant IC50mut ranged from 7-10, and ratios of wild-type IC50s to predicted anesthetic median effective concentrations (EC50s) ranged from 1.8-2.3. 1,2-Dichlorohexafluorocyclobutane quenched human serum albumin with an apparent dissociation constant (Kd) of 160+/-11 microM. The ratios of dissociation constants to predicted EC50s for the nonanesthetics were within a factor of two of the dissociation constant:EC50 ratios calculated for halothane and chloroform from previous published results.

Conclusions

In two models in which anesthetics bind to protein sites, both anesthetic and nonanesthetic volatile drugs cause similar steady state effects with potencies that are predicted by hydrophobicity. These protein sites do not sterically discriminate between anesthetic and nonanesthetic drugs. However, differential state-selective actions on ion channel targets may underlie the distinct in vivo effects of anesthetics and nonanesthetics.
The Effects of Extracellular pH with and without Bicarbonate on Intracellular Procaine Concentrations and Anesthetic Effects in Crayfish Giant Axons
Authors: Ibusuki Shoichiro , Katsuki Hiroshi , Takasaki Mayumi
Published: November 2003

Background

The potentiating effect of sodium bicarbonate on local anesthetic action is attributed to two mechanisms: (1) an increase in the un-ionized local anesthetic due to extracellular alkalinization, and (2) an accelerated conversion of local anesthetic from un-ionized to ionized form with intracellular acidification caused by bicarbonate. To evaluate these hypotheses, the intracellular pH, intracellular ionized procaine concentration, and evoked action potentials were measured in crayfish giant axons.

Methods

In all measurements, axon preparations from crayfish were perfused extracellularly for 15 min with either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH was measured using a pH-sensitive microelectrode. Intracellular anesthetic concentration was measured using a specially designed procaine-sensitive microelectrode with each of three solutions containing 1 mM procaine hydrochloride. Membrane potential was measured and, as an index of anesthetic action, the dV/dt of evoked action potential was calculated during perfusion with procaine.

Results

Mean intracellular pH was significantly lower in the bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08 mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6 (0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately coincident with the mean intracellular procaine concentration in each solution.

Conclusion

The presence of bicarbonate or extracellular alkalinization increased the intracellular concentration of ionized procaine and the anesthetic effect.
Effect of Propofol on Norepinephrine-induced Increases in [Ca2+](i) and Force in Smooth Muscle of the Rabbit Mesenteric Resistance Artery
Authors: Imura Nami , Shiraishi Yoshihisa , Katsuya Hirotada , Itoh Takeo
Published: November 2003

Background

Propofol (2,6-diisopropylphenol) possesses vasodilating activity in vivo and in vitro. The propofol-induced relaxation of agonist-induced contractions in small resistance arteries has not been clarified.

Methods

The effect of propofol was examined on the contractions induced by norepinephrine and high K+ in endothelium-denuded rabbit mesenteric resistance artery in vitro. The effects of propofol on the [Ca2+]i mobilization induced by norepinephrine and high K+ were studied by simultaneous measurement of [Ca2+]i using Fura 2 and isometric force in ryanodine-treated strips.

Results

Propofol attenuated the contractions induced by high K+ and norepinephrine, the effect being greater on the high K+-induced contraction than on the norepinephrine-induced contraction. In Ca2+-free solution, norepinephrine produced a transient contraction resulting from the release of Ca2+ from storage sites that propofol attenuated. In ryanodine-treated strips, propofol increased the resting [Ca2+]i but attenuated the increases in [Ca2+]i and force induced by both high K+ and norepinephrine. In the presence of nicardipine, propofol had no inhibitory action on the residual norepinephrine-induced [Ca2+]i increase, whereas it still modestly increased resting [Ca2+]i, as in the absence of nicardipine.

Conclusions

In smooth muscle of the rabbit mesenteric resistance artery, propofol attenuates norepinephrine-induced contractions due to an inhibition both of Ca2+ release and of Ca2+ influx through L-type Ca2+ channels. Propofol also increased resting [Ca2+]i, possibly as a result of an inhibition of [Ca2+]i removal mechanisms. These results may explain in part the variety of actions seen with propofol in various types of vascular smooth muscle.
Rebound Swelling of Astroglial Cells Exposed to Hypertonic Mannitol
Authors: McManus Michael L. , Soriano Sulpicio G.
Published: November 2003

Background

Mannitol is widely used in anesthesia and critical care medicine. Although its clinical effects were originally attributed to osmotic dehydration of brain cells, other mechanisms have also been proposed. Osmotic dehydration of astroglial cells is opposed by powerful volume-regulating mechanisms that involve inward transport of electrolytes. These mechanisms have been studied previously by exposing cells to hypertonic saline gradients. Because of its potential clinical relevance, the volume response of astroglial cells exposed to hypertonic mannitol was investigated.

Methods

Rat C6 glioma cells were cultured to confluence, and their volume behavior was observed by laser light scattering. After equilibration at physiologic temperature and pH, cells were abruptly exposed to hypertonic mannitol solutions. In separate experiments, C6 cells were exposed to hypertonic solutions containing radiolabeled mannitol, and its cellular uptake was determined.

Results

Hypertonic mannitol exposure produced initial cell shrinkage followed by rapid volume recovery and rebound swelling. The rebound swelling was similar in magnitude to the initial maximal shrinkage. For +40 mOsm and +70 mOsm mannitol challenges, mean volume recovery was 184+/-31% and 227+/-62%, respectively (where full recovery to baseline volume = 100%). Rebound swelling was substantially inhibited by furosemide. When exposed to mannitol in varying concentrations, uptake was linear, ranging from 82+/-7 nmol/mg to 406+/-26 nmol/mg protein. After 5 min, estimated intracellular concentrations of mannitol were similar to extracellular concentrations.

Conclusions

Unlike hypertonic saline, hypertonic mannitol exposure produces rebound cell swelling. Cellular penetration of mannitol appears to account for much of this phenomenon. The clinical implications of these observations remain to be determined.
A Comparative Evaluation of the Effects of Multiple Vasodilators on Human Internal Mammary Artery
Authors: Huraux Catherine , Makita Tetsuji , Montes Felix , Szlam Fania , Levy Jerrold H.
Published: November 2003

Background

Vasospasm of arterial grafts represents an unpredictable complication of coronary artery surgery and may compromise myocardial revascularization, and treatment is based on empirical therapy with nitroglycerin. Because of the potential for tolerance to nitroglycerin to occur, the authors studied different vasodilators acting through separate pathways on segments of human internal mammary artery.

Methods

Isolated vascular rings were precontracted with norepinephrine (1 microM), KCl, or the thromboxane A2 analogue (U46619, 10 nm). Nitroglycerin (a nitrovasodilator), milrinone (a type III phosphodiesterase inhibitor), papaverine (a phosphodiesterase inhibitor), prostaglandin E1, and isradipine (a dihydropyridine calcium channel blocker) were added in a cumulative fashion.

Results

The analysis of the concentration-response curves showed that vasodilators induced 90-100% relaxation of the constricted segments with norepinephrine or the thromboxane A2 analogue, except prostaglandin E1, which produced 73% relaxation at maximal concentrations. The effective concentrations of vasodilator agent that caused 50% relaxation for nitroglycerin and milrinone were within the range of the reported therapeutic concentrations in plasma. Isradipine was also effective at reversing receptor-mediated contraction (maximal relaxation=100% in internal mammary artery contracted with norepinephrine; maximal relaxation=0% in internal mammary artery contracted with the thromboxane A2 analogue).

Conclusions

Vasodilator drugs acting through multiple pathways are effective at reversing in vitro vasoconstriction.
The Effects of Meperidine and Sufentanil on the Shivering Threshold in Postoperative Patients
Authors: Alfonsi Pascal , Sessler Daniel I. , Du Manoir Bertrand , Levron Jean-Claude , Le Moing Jean-Pierre , Chauvin Marcel
Published: November 2003

Unlabelled

BACKGROUND. Meperidine (pethidine) reportedly treats postoperative shivering better than equianalgesic doses of other mu-receptor agonists. The authors' first goal was to develop a method to accurately determine postoperative shivering thresholds, and then to determine the extent to which meperidine and sufentanil inhibit postoperative shivering.

Methods

A computer-controlled infusion was started before operation in 30 patients, with target plasma concentrations of 0.15, 0.30, or 0.60 microg/ml meperidine or 0.1, 0.15, or 0.2 ng/ ml sufentanil targeted; patients were randomly assigned to each drug and concentration. The infusion was continued throughout surgery and recovery. Anesthesia was maintained with nitrous oxide and isoflurane. Core temperatures were approximately 34 degrees C by the end of surgery. The compensated core temperature at which visible shivering and a 20% decrease in steady-state oxygen consumption was recorded identified the shivering threshold. A blood sample for opioid concentration was obtained from each patient at this time. The ability of each opioid to reduce the shivering threshold was evaluated using linear regression.

Results

End-tidal isoflurane concentrations were <0.2% in each group at the time of extubation, and shivering occurred approximately 1 h later. Meperidine linearly decreased the shivering threshold: threshold (degrees C) = -2.8 x [meperidine (microg/ml)] + 36.2; r2 = 0.64, P = 0.0005. Sufentanil also linearly decreased the shivering threshold: threshold (degrees C) = -7.8 x [sufentanil (ng/ ml)] + 36.9; r2 = 0.46, P = 0.02.

Conclusions

At a given dose, sufentanil inhibited shivering 2,800 times better than meperidine. However, the equianalgesic ratio of these drugs is approximately 4,900. That is, meperidine inhibited shivering better than would be expected based on the equianalgesic potency ratio. These data are thus consistent with clinical observations suggesting that meperidine indeed possesses special antishivering activity.
Intrathecal Sufentanil Produces Sensory Changes without Hypotension in Male Volunteers
Authors: Riley Edward T. , Hamilton Catherine L. , Cohen Sheila E.
Published: November 2003

Background

Intrathecally administered sufentanil is frequently associated with hypotension and sensory changes in women undergoing labor. In this study, the authors examined whether intrathecally administered sufentanil has similar effects in pain-free individuals with low concentrations of progesterone (i.e., male volunteers).

Methods

Ten male volunteers were randomly assigned to receive an intrathecal injection of either 10 microg sufentanil or saline in a double-blind fashion. Blood pressure, heart rate, oxyhemoglobin saturation, and temperatures from the body core and skin of the calf and ipsilateral great toe were recorded. Cold and pin prick sensation, motor block, and visual analogue scores for sedation, pruritus, and nausea also were assessed. Current perception thresholds using the Neurometer current perception threshold instrument (Neurotron, Inc., Baltimore, MD) were determined for three frequencies (2,000, 250, and 5 Hz, corresponding to stimulation of Abeta, Adelta, and C fibers, respectively) on the upper and lower extremities.

Results

Pruritus and sensory changes to pin prick and cold occurred in the sufentanil group but not the saline group. Neither group had a significant change in blood pressure, heart rate, oxyhemoglobin saturation, sedation, or core temperature. There was a clinically insignificant difference in the calf minus toe temperature index between the saline and sufentanil groups. There was a small increase in the current perception thresholds at 250 Hz in the sufentanil group.

Conclusions

Intrathecally administered sufentanil did not affect blood pressure in male volunteers. The other effects of sufentanil, however, were similar to those observed in women undergoing labor. This suggests that the hypotension occurring in these women after intrathecally administered sufentanil is secondary to relief of pain, rather than to a sympathectomy.
Effect of Epidural Fentanyl on Neonatal Respiration
Authors: Porter Jackie , Bonello Edric , Reynolds Felicity
Published: November 2003

Background

The addition of opioids to epidural infusions for laboring mothers may reintroduce the problem of neonatal depression seen with systemic opioids. The authors studied neonatal respiration and neurobehavior in newborns of mothers randomized to receive epidural analgesia with or without fentanyl.

Methods

One hundred thirty-eight women in labor received loading doses of plain bupivacaine. When pain-free, they received an infusion of either 0.125% bupivacaine alone or 0.0625% bupivacaine with 2.5 microg/ml fentanyl. After delivery, transcutaneous oxygen tension and carbon dioxide tension were recorded in the newborns every 10 s until 90 min after delivery using a transcutaneous oxygen-carbon dioxide monitor. Umbilical venous and arterial acid-base status, Apgar scores, and Neurologic and Adaptive Capacity Scores 2 h and 24 h after delivery were measured. The umbilical venous plasma fentanyl concentration was correlated with indices of neonatal respiration and welfare in the fentanyl group.

Results

One hundred fourteen newborns delivered vaginally were studied. In the fentanyl group, the mean (range) maternal dose of fentanyl was 184 microg (range, 53-400), and the umbilical venous fentanyl concentration was 0.077 ng/ml (range, <0.021 to 0.244). There were no significant differences between the groups for any indices of neonatal respiration or neonatal welfare, and the plasma fentanyl concentration did not correlate with any of these indices.

Conclusions

The results suggest that fentanyl added to epidural bupivacaine infusions during labor does not depress neonatal respiration or adversely affect neurobehavioral scores and other indices of neonatal welfare.
Hyperprocalcitonemia in Patients with Noninfectious SIRS and Pulmonary Dysfunction Associated with Cardiopulmonary Bypass
Authors: Hensel Mario , Volk Thomas , Docke Wolf D. , Kern Florian , Tschirna Dirk , Egerer Karl , Konertz Wolfgang , Kox Wolfgang J.
Published: November 2003

Background

The incidence of noninfectious systemic inflammatory response syndrome (SIRS) associated with coronary artery bypass surgery and the potential role of several inflammatory parameters as early markers of pulmonary dysfunction induced by cardiopulmonary bypass (CPB) were investigated.

Methods

Forty patients undergoing elective coronary artery bypass surgery were studied prospectively. Perioperative lung function was monitored using the lung injury score introduced by Murray and colleagues, by measuring venous admixture (Qs/Qt), and, in some cases, by measuring extravascular lung water. Serum concentrations of the inflammatory parameters (procalcitonin, interleukin-6, sL-selectin, leukocyte elastase, neopterin, leukocyte counts, and C-reactive protein) were determined sequentially. The American College of Chest Physicians-Society of Critical Care Medicine classification system was used to diagnose SIRS.

Results

According to the entry criteria, SIRS developed in 17 (42%) patients after operation. Nine patients of this group showed signs of acute pulmonary impairment, whereas patients without SIRS had no lung injury. In all patients with acute lung injury, distinct increases in procalcitonin concentrations ranging from 5.1 to 14.3 ng/ml were measured. In patients with SIRS but without acute lung injury and in patients without SIRS, none or only negligible increases in serum concentrations of procalcitonin were seen. Compared with procalcitonin, other inflammatory parameters investigated were less sensitive and less specific to indicate pulmonary dysfunction secondary to CPB.

Conclusions

Procalcitonin seems to be an appropriate parameter indicating the early development of severe noninfectious SIRS and for predicting pulmonary dysfunction secondary to CPB.
Isoflurane-induced Dilation of Porcine Coronary Arterioles Is Mediated by ATP-sensitive Potassium Channels
Authors: Zhou Xiping , Abboud Worood , Manabat Nancy C. , Salem Ramez M. , Crystal George J.
Published: November 2003

Background

Isoflurane causes increases in coronary blood flow in vivo, which are mediated by the adenosine triphosphate (ATP)-sensitive potassium channels, but the role of the arterioles (resistance vessels) in these responses is controversial.

Methods

Medium porcine coronary arterioles (internal diameter, 172 +/- 51 [SD] microm) were placed in a chamber supplied with Kreb's buffer, pressurized (40 mmHg), and preconstricted with acetylcholine (10(-8)-10(-6) M). Vascular diameter (VD) was assessed using an optical density video-detection system. Isoflurane (in 95% oxygen and 5% carbon dioxide) was added to buffer using a membrane oxygenator supplied by a calibrated vaporizer. In series 1 (n = 14), 2% isoflurane was administered according to an abrupt (ISO-A) and gradual (ISO-G) protocol. In series 2 (n = 13) and 3 (n = 6), ISO-A (1.5%) was assessed before and after glibenclamide (an ATP-sensitive potassium channel antagonist) or 8-phenyltheophylline (a nonselective adenosine receptor antagonist), respectively. In series 4 (n = 5), validation studies were performed using sodium nitroprusside and adenosine diphosphate to verify that the vascular smooth muscle and endothelium of the vessels were functionally intact. In series 5 (n = 6), ISO-A (0.75 and 1.5%) was compared during preconstriction with acetylcholine and the thromboxane analog U46619 (10(-6) M).

Results

ISO-G caused essentially concentration-dependent increases in VD. At 2% isoflurane, the increases in VD were greater during ISO-A than ISO-G. Glibenclamide, but not 8-phenyltheophylline, attenuated isoflurane-induced increases in VD. Both sodium nitroprusside and adenosine diphosphate caused dose-dependent increases in VD. Isoflurane caused equivalent concentration-dependent increases in VD during acetylcholine and U46619.

Conclusions

Isoflurane is a concentration-dependent dilator of porcine coronary arterioles preconstricted with acetylcholine or U46619. This effect is blunted by gradual administration, suggesting that the vessels may adapt to the relaxing effects of isoflurane. Isoflurane-induced dilation of coronary arterioles is mediated by the ATP-sensitive potassium channels but not by the adenosine receptors.
Peripheral Morphine Administration Blocks the Development of Hyperalgesia and Allodynia after Bone Damage in the Rat
Authors: Houghton Andrea K. , Valdez Joe G. , Westlund Karin N.
Published: November 2003

Background

The current study aimed to assess whether local administration of morphine could block the development of hyperalgesia and allodynia in a rat model of osteotomy or bone damage.

Methods

Withdrawal responses to mechanical and thermal stimuli applied to the plantar surface of the hind paw were measured before and after bone damage. The bone was injured by drilling a 1-mm hole through the tibia during short-lasting general anesthesia. In separate groups of rats, the effects of administering morphine (20-80 microg), either into the marrow cavity or systemically, on the development of hyperalgesia and allodynia after bone damage were assessed. In an additional group of rats, a selective mu-opioid receptor antagonist, clocinnamox (0.15 mg), was administered into the marrow cavity before the administration of morphine (40 microg).

Results

In animals that received no drug treatment, hyperalgesia and allodynia peaked 2 h after injury. Injection of morphine (40 and 80 microg) into the marrow cavity immediately after bone injury prevented the development of hyperalgesia and allodynia. Clocinnamox (0.15 mg) injected into the marrow cavity before administration of morphine blocked the antihyperalgesic effect of morphine.

Conclusion

This study shows that local application of a low dose of morphine effectively blocks the development of hyperalgesia and allodynia in a rat model of bone damage through mu-opioid receptor action. These findings provide further evidence that local application of morphine at the time of orthopedic surgery, bone graft, or bone marrow harvesting may reduce the amount of postoperative pain.
Thiopental Alters Contraction, Intracellular Ca2+, and pH in Rat Ventricular Myocytes
Authors: Kanaya Noriaki , Zakhary Daniel R. , Murray Paul A. , Damron Derek S.
Published: November 2003

Background

Myocardial contractility is regulated by intracellular concentration of free Ca2+ ([Ca2'],) and myofilament Ca2+ sensitivity. The objective of this study was to elucidate the direct effects of thiopental on cardiac excitation-contraction coupling using individual, field-stimulated ventricular myocytes.

Methods

Freshly isolated rat ventricular myocytes were loaded with the Ca2+ indicator, fura-2, and placed on the stage of an inverted fluorescence microscope in a temperature-regulated bath. [Ca2+], (340/380 ratio) and myocyte shortening (video-edge detection) were monitored simultaneously in individual cells field-stimulated at 0.3 Hz. Amplitude and timing of myocyte shortening and [Ca2+l, were compared before and after addition of thiopental. Intracellular pH was measured with the pH indicator, BCECF (500/440 ratio). Real-time uptake of Ca2+ into isolated sarcoplasmic reticulum vesicles was measured using fura-2 free acid in the extravesicular compartment. One hundred thirty-two cells were studied.

Results

Field stimulation increased [Ca2+]i from 85 + 10 nM to 355 + 22 nM (mean + SEM). Myocytes shortened by 10% of resting cell length (127 + 5 tlm). Times to peak [Ca2+], and shortening were 139 + 6 and 173 + 7 msec, respectively. Times to 50% recovery for [Ca2+], and shortening were 296 + 6 and 290 + 6 ms, respectively. Addition of thiopental (30-1,000 /lM) resulted in dose-dependent decreases in peak [Ca2+]i and myocyte shortening. Thiopental altered time to peak and time to 50% recovery for [Ca2+], and myocyte shortening and inhibited the rate of uptake of Ca2+ into isolated sarcoplasmic reticulum vesicles. Thiopental did not, however, alter the amount of Ca2+ released in response to caffeine in sarcoplasmic reticulum vesicles or intact cells. Thiopental (100 uM) increased intracellular pH and caused an upward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on peak [Ca2+],. These effects were abolished by ethylisopropyl amiloride, an inhibitor of Na+-H+ exchange.

Conclusion

Thiopental has a direct negative inotropic effect on cardiac excitation-contraction coupling at the cellular level, which is mediated by a decrease in [Ca2+],. Thiopental also increases myofilament Ca2+ sensitivity via alkalinization of the cell, which may partially offset its negative inotropic effect.
Spinal Nitric Oxide Mediates Antinociception from Intravenous Morphine
Authors: Song Ho-Kyung , Pan Hui-Lin , Eisenach James C.
Published: November 2003

Introduction

Spinal nitric oxide (NO) is thought in many circumstances to play a pronociceptive role, because spinal injection of NO synthase inhibitors block hypersensitivity after nerve injury and enhance antinociception from spinal opioids. Conversely, intravenous injection of morphine has been demonstrated to activate descending noradrenergic pathways and to increase spinal synthesis of NO. This study examined the role of spinal NO in antinociception produced by intravenously administered morphine.

Methods

Polyethylene catheters were inserted with tips in the lumbar intrathecal space and in a jugular vein in male rats. Antinociception in response to intravenous injection of morphine was determined by latency to withdrawal of the hind paw from a heat source. Animals received an intrathecal injection of saline, an alpha2-adrenergic antagonist (idazoxan), a muscarinic antagonist (atropine), two NO synthase inhibitors, or an NO scavenger after intravenously administered morphine.

Results

Intravenously administered morphine produced dose-dependent antinociception, which was stable for 45 min and unaffected by intrathecally administered saline or atropine injection. In contrast, idazoxan, each of the NO synthase inhibitors, and the NO scavenger produced dose-dependent attenuation of intravenously administered morphine-induced antinociception.

Discussion

These results confirm a spinal alpha2-adrenergic mechanism of antinociception from intravenously administered morphine, consistent with morphine's activation of descending noradrenergic pathways. Further, these data suggest that spinal NO mediates antinociception produced by intravenous morphine.
Prevalence of Latex Allergy among Anesthesiologists
Authors: Brown Robert H. , Schauble James F. , Hamilton Robert G.
Published: November 2003

Background

Occupational exposure to natural rubber latex has led to sensitization of health-care workers. However, the prevalence of latex allergy among occupationally exposed workers in American hospitals has not been reproducibly determined. The objectives of the current study were to determine the prevalence of and risk factors for latex sensitization among a cohort of highly exposed health-care workers.

Methods

Participants were 168 of 171 eligible anesthesiologists and nurse anesthetists working in the Department of Anesthesiology and Critical Care Medicine. A clinical questionnaire was administered, and testing was performed using a characterized nonammoniated latex reagent for puncture skin testing, a Food and Drug Administration-approved assay to quantify latex-specific immunoglobulin E antibody in serum, and, when required for clarification, a validated two-stage (contact-inhalation) latex glove provocation procedure.

Results

The prevalence of latex allergy with clinical symptoms and latex sensitization without clinical symptoms was 2.4% and 10.1%, respectively. The prevalence of irritant or contact dermatitis was 24%. The risk factors identified for latex sensitization were atopy (odds ratio, 14.1; 95% CI, 1.8-112.1; P = 0.012); history of allergy to selected fruits, such as bananas, avocados, or kiwis (odds ratio, 9.8; 95% CI, 1.6-61.9; P = 0.015); and history of skin symptoms with latex glove use (odds ratio, 4.6; 95% CI, 1.6-13.4; P = 0.006).

Conclusions

The prevalence of latex sensitization among anesthesiologists is high (12.5%). Of these, 10.1% had occult (asymptomatic) latex allergy. Hospital employees may be sensitized to latex even in the absence of perceived latex allergy symptoms. These data support the need to transform the health-care environment into a latex-safe one that minimizes latex exposure to patients and hospital staff.
The Sedative and Analgesic Sparing Effect of Music
Authors: Koch Marc E. , Kain Zeev N. , Ayoub Chakib , Rosenbaum Stanley H.
Published: November 2003

Background

To determine whether music influences intraoperative sedative and analgesic requirements, two randomized controlled trials were performed.

Methods

In phase 1, 35 adults undergoing urologic procedures with spinal anesthesia and patient-controlled intravenous propofol sedation were randomly assigned to hear favorable intraoperative music via headset or to have no music. In phase 2, 43 adults undergoing lithotripsy treatment of renal or ureteral calculi and receiving patient-controlled intravenous opioid analgesia were randomly assigned to either a music or no-music group. The effect of music on sedatives and analgesics requirements, recovery room duration, and adverse outcomes was assessed.

Results

In phase 1, patients in the music group required significantly less propofol for sedation than patients in the control group (0 [0-150] mg vs. 90 [0-240] mg, median[range]; P < 0.001). These findings persisted after adjusting for duration of surgery (0.3+/-0.1 mg/min vs. 1.6+/-0.4 mg/min; P < 0.001). Similarly, in phase 2, patients who listened to music had a significant reduction in alfentanil requirements (1,600 [0-4,250] microg vs. 3,900 [0-7,200] microg; P = 0.005). This persisted after adjusting for duration of surgery (52+/-9 microg/min vs. 119 +/-16 microg/min, mean +/- SD, P < 0.001). Duration of stay in the postanesthesia care unit and the rate of adverse events was similar in both groups (P = NS).

Conclusions

Use of intraoperative music in awake patients decreases patient-controlled sedative and analgesic requirements. It should be noted, however, that patients in the no-music group did not use a headset during operation. Thus, the decrease in sedative and analgesic requirements could be caused by elimination of ambient operating room noise and not by the effects of music.
Quantitative EEG Correlations with Brain Glucose Metabolic Rate during Anesthesia in Volunteers
Authors: Alkire Michael T.
Published: November 2003

Background

To help elucidate the relationship between anesthetic-induced changes in the electroencephalogram (EEG) and the concurrent cerebral metabolic changes caused by anesthesia, positron emission tomography data of cerebral metabolism obtained in volunteers during anesthesia were correlated retrospectively with various concurrently measured EEG descriptors.

Methods

Volunteers underwent functional brain imaging using the 18fluorodeoxyglucose technique; one scan always assessed awake-baseline cerebral metabolism (n = 7), and the other scans assessed metabolism during propofol sedation (n = 4), propofol anesthesia (n = 4), or isoflurane anesthesia (n = 5). The EEG was recorded continuously during metabolism assessment using a frontal-mastoid montage. Power spectrum variables, median frequency, 95% spectral edge, and bispectral index (BIS) values subsequently were correlated with the percentage of absolute cerebral metabolic reduction (PACMR) of glucose utilization caused by anesthesia.

Results

The percentage of absolute cerebral metabolic reduction, evident during anesthesia, trended median frequency (r = -0.46, P = 0.11), and the spectral edge (r = -0.52, P = 0.07), and correlated with anesthetic type (r = -0.70, P < 0.05), relative beta power (r = -0.60, P < 0.05), total power (r = 0.71,P < 0.01), and bispectral index (r = -0.81,P < 0.001). After controlling for anesthetic type, only bispectral index (r = 0.40, P = 0.08) and alpha power (r = 0.37, P = 0.10) approached significance for explaining residual percentage of absolute cerebral metabolic reduction prediction error.

Conclusions

Some EEG descriptors correlated linearly with the magnitude of the cerebral metabolic reduction caused by propofol and isoflurane anesthesia. These data suggest that a physiologic link exists between the EEG and cerebral metabolism during anesthesia that is mathematically quantifiable.
Intrathecal Sufentanil Dose Response in Nulliparous Patients
Authors: Arkoosh Valerie A. , Cooper Matthew , Norris Mark C. , Boxer Louis , Ferouz Fazeela , Silverman Neil S. , Huffnagle Jane , Huffnagle Suzanne , Leighton Barbara L.
Published: November 2003

Background

Intrathecal sufentanil provides effective analgesia during the first stage of labor. A range of doses has been reported to provide adequate pain relief. This study determined the dose of intrathecal sufentanil that produced acceptable pain relief in 50% of nulliparous patients (ED50) who requested labor analgesia.

Methods

With institutional review board approval, 50 nulliparous patients requesting spinal opioid labor analgesia were enrolled into this prospective, randomized, double-blinded study. Each patient was in spontaneous labor at <5 cm cervical dilation. Patients received one of the following doses of intrathecal sufentanil: 1, 2, 3, 5, or 10 microg in 3 ml preservative-free saline (n = 10 for each dose). Pain, pain relief, hemodynamic, respiratory, and side effect data were collected at times 0, 2, 5, 10, 15, 20, 25, and 30 min. Probit analysis of the number of patients in each group who requested additional pain medicine at 30 min was used to determine the ED50.

Results

The groups were demographically similar. The ED50 of intrathecal sufentanil was 1.8 microg (SE, 0.6 microg; 95% CI, 2.96 to 0.54 microg). The incidence of side effects was similar among the groups.

Conclusions

This is the first study to determine the ED50 of intrathecal sufentanil in spontaneously laboring nulliparous patients. As dose-response curves are determined for other labor analgesics, future studies can compare equianalgesic doses or dose combinations.
Atelectasis and Gas Exchange after Cardiac Surgery
Authors: Tenling Arne , Hachenberg Thomas , Tyden Hans , Wegenius Goran , Hedenstierna Goran
Published: November 2003

Background

Sometimes a high intrapulmonary shunt occurs after cardiac surgery, and impairment of lung function and oxygenation can persist for 1 week after operation. Animal studies have shown that postoperative shunt can be explained by atelectasis. In this study the authors tried to determine if atelectasis can explain shunt in patients who have had cardiac surgery.

Methods

Nine patients having coronary artery bypass graft surgery and nine patients having mitral valve surgery were examined using the multiple inert gas elimination technique before and after operation. On the first postoperative day, computed tomography scans were made at three levels of the thorax.

Results

Before anesthesia, the average shunt was low (2+/-3%; range, 0-13%), but on the first postoperative day shunt had increased to 12+/-60% (range, 3-28%). The computed tomography scans showed bilateral dependent densities in all patients but one. The mean area of the densities was 8+/-8% (range, 0-37%) of total lung area, corresponding to a calculated fraction of collapsed lung tissue of 20+/-14% (range, 0-59%). In the basal region, the calculated amount of collapsed tissue was 28+/-19% (range, 0-73%). One mitral valve patient was an outlier and had a large shunt both before and after the operation.

Conclusions

Large atelectasis in the dorsal part of the lungs was found on the first postoperative day after cardiac surgery. However, there was no clear correlation between atelectasis and measured shunt fraction.
Single-breath Vital Capacity Rapid Inhalation Induction in Children
Authors: Agnor Ross C. , Sikich Nancy , Lerman Jerrold
Published: November 2003

Background

The authors compared the speed of induction of anesthesia with sevoflurane with and without nitrous oxide with the speed of halothane and nitrous oxide using a single-breath vital capacity induction.

Methods

With informed parental consent, 51 healthy unpremedicated children aged 5-12 yr were randomized to inhale a single breath of one of three gas mixtures: 8% sevoflurane in 66% nitrous oxide, 8% sevoflurane in oxygen, or 5% halothane in 66% nitrous oxide. A blinded observer recorded the times to loss of the eyelash reflex, return of conjugate gaze, the presence of airway reflex responses, involuntary movement, and hemodynamic responses.

Results

Forty-two children completed the study. The times (mean +/- SD) to loss of the eyelash reflex with sevoflurane/nitrous oxide, 38+/-8 s, and for sevoflurane-oxygen, 34+/-12 s, were less than that with halothane-nitrous oxide, 58+/-17 s (P < 0.01). Movement occurred less frequently during sevoflurane than during halothane anesthesia (P < 0.05). The times to return of conjugate gaze and the incidence of airway reflex responses were similar among the groups. The incidence of dysrhythmias in the sevoflurane groups was less than that in the halothane group (P < 0.01).

Conclusions

Induction of anesthesia with a single breath of 8% sevoflurane with or without 66% nitrous oxide is more rapid than with 5% inspired halothane with 66% nitrous oxide in children. The incidence of movement and dysrhythmias during a single-breath induction with sevoflurane are less than they are with halothane.
Differential Effect of Halothane and Forskolin on Platelet Cytosolic Ca (2+) Mobilization and Aggregation
Authors: Corbin Francois , Blaise Gilbert , Sauve Remy
Published: November 2003

Background

Previous works have suggested that the impairment of platelet aggregation by halothane was partly related to a stimulation of cyclic adenosine monophosphate (cAMP) production, to an inhibitory effect on Ca2+ signaling, or both. Intracellular Ca2+ measurements therefore were undertaken, first to determine the critical steps in the platelet CaZ+ signaling cascade most likely to be affected by halothane or by an increase in cAMP production, and second to establish if the effect of halothane involves aggregation-related biochemical pathways triggered by an increase in internal Ca2+.

Methods

Human washed platelets were treated with halothane or forskolin for 5 min before application of either platelet-activating factor, thrombin, U46619, or thapsigargin. The cytosolic Ca2+ concentration ([Ca2+]i) was measured with the fluorescent Ca2+ indicator fura-2. Nephelometric measurements were also performed to assay the aggregation process.

Results

Our results indicate that pretreating platelets with halothane leads to a partial impairment of the [Ca2+]i increase induced either by U46619, thrombin, or platelet-activating factor, but this had no significant effect on the [Ca2+]i response triggered by thapsigargin. In addition, our results show that halothane inhibits platelet aggregation triggered by U46619, but not by thapsigargin. Conversely, forskolin completely inhibited the [Ca2+]i response to U46619 and thapsigargin and prevented platelet aggregation induced by both agonists.

Conclusions

These results suggest that halothane and cAMP exert their effects on platelet aggregation and Ca2+ signaling through different mechanisms, and that halothane cannot impair platelet aggregation independently of phospholipase C stimulation.