bluuebunny/crossref_metadata_2025 huggingface dataset:
Equianalgesic Doses of Subcutaneous but Not Intrathecal Morphine Alter Phenotypic Expression of Cell Surface Markers and Mitogen-induced Proliferation in Rat Lymphocytes
Authors: Hamra Jena G. , Yaksh Tony L.
Published: November 2003

Background

Surgical trauma and opioids are linked with suppression of immune function. Evidence suggests a probable supraspinal action of morphine in altering immune function, although the role of spinal systems have not been evaluated. Therefore, this study compared the effect of equianalgesic doses of subcutaneous and intrathecal morphine on lymphocyte proliferative responses and phenotypic expression of lymphocyte cell surface markers in rats.

Methods

Equianalgesic doses of subcutaneous (10 mg/kg) or intrathecal (30 micrograms, by a chronic intrathecal catheter) morphine were given twice for 5 h (time 0 and 2.5 h). Immediately after the 5-h period or 24 h after the initial injection, spleens were harvested and lymphocytes isolated. Mitogen-induced (phytohemagglutinin, concanavalin A, pokeweed, lipopolysaccharide) lymphocyte proliferation and monoclonal antibody labeling of cell surface markers (T cell, B cell, CD4+, CD8+) were then performed.

Results

Subcutaneous morphine acutely suppressed lymphocyte proliferation to the mitogens phytohemagglutinin, pokeweed, and concanavalin A by 37%, 21%, and 20% respectively; however, proliferative responses returned to baseline within 24 h. Morphine treatment did not alter the response to lipopolysaccharide. The number of splenic lymphocytes also decreased, whereas the percentage of lymphocytes expressing the CD4+ marker (T helper/inducer cells) modestly increased. Intrathecal morphine did not alter lymphocyte proliferative responses, nor did it change phenotypic expression of cell surface markers.

Conclusions

Subcutaneous morphine inhibited lymphocyte proliferation, decreased splenic lymphocyte number, and altered phenotypic expression of cell surface markers, whereas equianalgesic doses of intrathecal morphine did not. Although these results suggest that spinal opioids may have theoretical benefits for the analgesic management of immunocompromised patients, further studies are clearly indicated.
Effect of Cranial Surgery and Brain Tumor Size on Emergence from Anesthesia
Authors: Schubert Armin , Mascha Edward J. , Bloomfield Eric L. , DeBoer Glenn E. , Gupta Manjula K. , Ebrahim Zeyd Y.
Published: November 2003

Background

Knowing which neurosurgical patients are at risk for delayed awakening may lead to better utilization of intensive care resources and avoid the risk and cost of pharmacologic reversal and diagnostic tests.

Methods

The authors compared anesthetic emergence from complex spinal surgery (spine; n = 47) with that from craniotomy for supratentorial nonfrontal (n = 22), frontal (n = 34), or posterior fossa tumor (n = 28). A further comparison involved patients with small versus large (diameter > 30 mm, mass effect) tumors. The standardized anesthetic regimen consisted of induction with 2-4 mg/kg-1 thiopental and 1-2 micrograms/kg-1 sufentanil, followed by maintenance with nitrous oxide, 0.2-0.5 micrograms.kg-1.h-1 sufentanil and < or = 0.5% isoflurane. Sufentanil administration was terminated on dural or spinal muscle closure, isoflurane during skin closure, and nitrous oxide during dressing application. After discontinuing nitrous oxide, a minineurologic examination was performed every 15 min for 1 h, then hourly for 4 h and at 24 h.

Results

Craniotomy patients performed less well than spinal surgery patients on the minineurologic examination 15 and 30 min after discontinuing nitrous oxide. At 15 min, fewer patients with large (vs. small) tumors were oriented to time (58% vs. 87%; P < 0.01) or place (67% vs. 90%; P < 0.01). Forty-two percent of patients with large tumors still had an abnormal minineurologic examination score versus 15% of patients with small tumors. At 30 min, these values were 28% and 8%, respectively (P < 0.05). Seventy-one percent of patients with large tumors were oriented to time compared to 97% for small lesions (P < 0.01). Emergence from anesthesia was similar for spinal surgery patients and patients with small brain tumors.

Conclusion

Patients undergoing craniotomy for large intracranial mass lesions awaken more slowly than patients after spinal surgery or craniotomy for small brain tumor.
Reduction of Isoflurane Minimal Alveolar Concentration by Remifentanil
Authors: Lang E. , Kapila A. , Shlugman D. , Hoke J. F. , Sebel P. S. , Glass P. S. A.
Published: November 2003

Background

Remifentanil is a new micro-specific opioid receptor agonist currently under investigation. The interaction between opioids and volatile anesthetics is complex. Defining this interaction provides a basis for more rational dosing schemes when such combinations are used for anesthesia and allows the anesthetic potency of remifentanil relative to other opioids to be determined.

Methods

Two centers enrolled a total of 220 patients. Patients were randomized to receive a target concentration of remifentanil via a computer-assisted continuous infusion device of either 0.0, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 16.0, and 32.0 ng/ml initiated before the administration of isoflurane. Patients were also stratified by groups 18-30, 31-55, and 56-65 yr. After induction of anesthesia with isoflurane the initial patient in each dose group was assigned an age-adjusted isoflurane concentration. The isoflurane concentration for each subsequent patient was adjusted according to the up/down technique until a minimum of 12 patients were enrolled in each group. Arterial blood samples for remifentanil whole blood concentrations were obtained. The patient was observed for purposeful movement for up to 1 min after skin incision. The minimum alveolar concentration (MAC) of isoflurane (0 ng/ml remifentanil group) and MAC reduction of isoflurane by remifentanil were determined.

Results

The MAC of isoflurane alone was 1.3%. Remifentanil caused an exponential reduction in the MAC of isoflurane with 1.37 ng/ml remifentanil a 77% reduction and 32 ng/ml a 91% reduction of isoflurane MAC.

Conclusion

The MAC reduction of isoflurane by remifentanil is similar to that produced by other opioids. Although remifentanil was given at extremely high concentrations in the absence of isoflurane, it did not provide adequate anesthesia. A 50% isoflurane MAC reduction is produced by 1.37 ng/ml remifentanil whole blood concentration compared to previously published plasma concentrations of fentanyl of 1.67 ng/ml or sufentanil of 0.14 ng/ml.
Dose-Response Characteristics of Spinal Bupivacaine in Volunteers
Authors: Liu Spencer S. , Ware Paul D. , Allen Hugh W. , Neal Joseph M. , Pollock Julia E.
Published: November 2003

Background

Small doses of bupivacaine may be a reasonable choice for spinal anesthesia for patients having ambulatory surgery. However, few dose-response data are available to guide the selection of reasonable doses of bupivacaine for different ambulatory procedures.

Methods

Eight volunteers per group were randomized to receive 3.75, 7.5, or 11.25 mg of 0.75% bupivacaine with 8.25% dextrose in a double-blind manner. Sensory block was assessed with pinprick, transcutaneous electrical stimulation equivalent to surgical incision at the ankle, knee, pubis, and umbilicus, and with duration of tolerance to pneumatic thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was assessed with isometric force dynamometry. Times until recovery from spinal anesthesia were recorded. Dose-response relationships were determined by linear regressions. Mean (95% confidence intervals) for durations of sensory and motor block per milligram of bupivacaine administered were calculated from linear regressions.

Results

Significant dose-response relationships (P < 0.006) were determined for sensory block, motor block, and time until recovery (R from 0.6 to 0.9). Within the range of doses studied, each additional milligram of bupivacaine was associated with an increase in duration of tolerance to transcutaneous electrical stimulation of 10 (7 to 13) min, an increase in tolerance to tourniquet of 7 (2 to 11) min, an increase in duration of motor block of 8 (5 to 12) min, and an increase in time until recovery of 21 (17 to 25) min.

Conclusions

These dose-response data may guide the selection of reasonable doses of bupivacaine for various outpatient procedures, although individual responses vary.
Effect of Acute Respiratory Acidosis on the Limits of Oxygen Extraction during Hemorrhage
Authors: Ward Michael E.
Published: November 2003

Background

Hypercapnia can impair cells' capacity to maintain energy status anerobically and enhances the risk of hypoxic injury when oxygen availability is reduced. The ability to maintain tissue oxygenation is determined by both bulk blood flow and the efficiency of oxygen extraction. Bulk blood flow is maintained during hypercapnia through increased sympathetic activity. The effect of hypercapnia on oxygen extraction, however, is unknown. This study evaluates the effect of hypercapnia on cells' capacity to adapt to reductions in oxygen availability by increasing oxygen extraction.

Methods

In three groups of paralyzed, mechanically ventilated dogs that were anesthetized with alpha-chloralose, the concentration of carbon dioxide in the inhaled gas mixture was adjusted to achieve normocapnia, moderate hypercapnia (Paco2 = 72 +/- 3 [SE] mmHg) or severe hypercapnia (Paco2 = 118 +/- 4 [SE] mmHg). Stepwise hemorrhage was induced until each dog's blood pressure was destabilized. At each stage in the hemorrhage protocol, the oxygen delivery, oxygen consumption, and oxygen extraction ratios (ratio of arteriovenous oxygen content difference to arterial oxygen content) were determined.

Results

At the point of onset of delivery dependence of oxygen consumption, the oxygen delivery rate (critical oxygen delivery) was 7.8 +/- 1.5 (SE) ml.kg-1.min-1 and the oxygen extraction ratio (critical oxygen extraction ratio) was 0.72 +/- 0.04 (SE) in the normocapnic dogs. Moderate hypercapnia had no effect on these parameters. In the severely hypercapnic dogs, the critical values for oxygen delivery and extraction ratios were 12.5 +/- 1.8 (SE) ml.kg-1.min-1 and 0.54 +/- 0.035 (SE), respectively (P < 0.05 for differences from the normocapnic dogs).

Conclusions

The results identify a previously unrecognized threat to tissue oxygenation and emphasize the importance of ensuring adequate oxygen delivery when adopting mechanical ventilatory strategies that permit respiratory acidosis to develop.
Ipratropium Decreases Airway Size in Dogs by Preferential M2Muscarinic Receptor Blockade In Vivo
Authors: Groeben Harald , Brown Robert H.
Published: November 2003

Background

Two major groups of drugs are available to prevent bronchoconstriction: beta-agonists and muscarinic blocking agents. Ipratropium is the most commonly used anticholinergic agent to treat chronic obstructive pulmonary disease. The authors studied anti-muscarinic agents to determine if they are as effective bronchodilators as beta-adrenergic agents and if not to identify the mechanism of their reduced effectiveness.

Methods

Six anesthetized dogs were studied using high-resolution computed tomography to measure changes in the cross-sectional area of conducting airways induced by cumulative doses of ipratropium with and without gallamine, a selective M2 muscarinic receptor blocker, and after metaproterenol.

Results

Metaproterenol dilated the airways and ipratropium constricted the airways. Ipratropium in concentrations of 0.01 and 0.1 mg/ml constricted the airways to 22 +/- 2% and 20 +/- 3% of control, respectively (P < 0.01), whereas larger concentrations caused bronchodilation. After complete blockade of the M2 receptors by pretreatment with intravenous gallamine, the bronchoconstrictor effect of ipratropium was abolished, and ipratropium dilated the airways by 16 +/- 8% and 27 +/- 10% of pre-gallamine baseline after doses of 0.01 and 0.1 mg/ml, respectively (P < 0.01).

Conclusion

Low-dose ipratropium can decrease airway size by the initial, preferential blockade of neuronal M2 muscarinic receptors, whereas a larger dose of ipratropium blocks M3 muscarinic receptors on airway smooth muscle, resulting in bronchodilation.
Epidural Catheter Reconnection
Authors: Langevin Paul B. , Gravenstein Nikolaus , Langevin Sharon O. , Gulig Paul A.
Published: November 2003

Background

An in vitro model of epidural catheter contamination was used to determine if disconnected catheters can be safely reconnected.

Methods

Epidural catheters were filled with brain-heart infusion (BHI) broth or preservative-free saline containing 5 micrograms/ml fentanyl. Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus (1.10(5) colony-forming units) was injected into the initial 1.1 +/- 0.24 inch (2.75 +/- 0.60 cm) of the catheters. To study the effect of bacteria settling in a vertically oriented catheter on the advancement of bacteria along the catheter, bacteria were incubated with catheters in the vertical and the horizontal positions. To determine if bacteria are swept further into a catheter when fluid in it is displaced, catheters were inclined 30 degrees and the fluid in them was allowed to drain from the distal end to various extents. Bacteria were incubated with the catheter held horizontally. After incubation, the catheters were serially sectioned, and the resulting segments were eluted with buffered saline-containing gelatin (BSG), which was collected on BHI agar plates for colony counts. This determined if a segment of the catheter remained internally sterile distal to the point of disconnection. Effectiveness of decontaminating the exterior of the catheter was also tested as follows: Catheters (n = 10) were first immersed in BSG containing 1.10(5) S, aureus, immediately immersed in betadine for 2 min, exposed to air for 3 min, cut with a sterile instrument, and reconnected to a sterile screw cap catheter connector. Reconnected catheters were perfused with 10 ml BSG for 1 hr. Collected perfusate (100 microliters) was removed for direct colony count; the remaining perfusate was mixed with an equal volume of BHI and incubated overnight. A 100 microliters aliquot of BHI-BSG mixture was sampled the next day. No bacteria were cultured from either the perfusate or BHI-BSG mixture.

Results

Eight hours after contamination, as long as the fluid in the catheter was static, no bacteria were detected more than 13 inches (32.5 cm) from the contaminated end of catheters filled with BHI and no more than 8 inches (20 cm) from the end of those filled with fentanyl solution. This finding was not affected by incubation of the catheter in the vertical position. Fluid displacement less than 8 inches (20 cm) had no effect on dissemination, but when fluid was displaced 13 inches (32.5 cm), bacteria were found at the end of the catheter, 35 inches (87.5 cm) away. No bacteria were recovered from the perfusate of reconnected catheters after the catheters were cleaned with betadine and cut with a sterile instrument.

Conclusions

There may be an area distal to the disconnected end of an epidural catheter where its interior remains sterile for at least 8 hr. Such an area exists only when the fluid in the catheter remains static. Furthermore, the exterior of the catheter can be adequately cleaned to prevent bacteria from entering the catheter when reconnected at that point.
Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans
Authors: Crowder Michael C. , Shebester Laynie D. , Schedl Tim
Published: November 2003

Background

The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans.

Methods

The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C.

Results

The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations.

Conclusions

Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.
Eye Injuries after Nonocular Surgery
Authors: Roth Steven , Thisted Ronald A. , Erickson John P. , Black Susan , Schreider Bruce D.
Published: November 2003

Background

Eye injuries after anesthesia, although infrequent, may result in visual impairment. Previous studies have not defined the risk factors associated with these injuries. To study the cause of these injuries and to determine incidence data, the authors reviewed the records from a 4.5-y period of patients who sustained eye injuries after anesthesia and nonocular surgery.

Methods

The records were surveyed of 60,965 patients who underwent anesthesia for nonocular surgery at our institution from January 1988 to July 1992. Eye injuries were identified by examining several sources of information, including quality improvement data, postoperative visits or telephone calls, and examination of medical records of postoperative patients who required an ophthalmology consultation. Records were reviewed to determine the types and causes of eye injuries. Logistic regression, with univariate and multivariate analysis, was used to identify the importance of possible risk factors.

Results

Of 34 patients who sustained eye injuries (0.056%), the most common was corneal abrasion (n = 21). Other injuries were conjunctivitis, blurred vision, red eye, chemical injury, direct trauma, and blindness. Independent factors associated with a higher relative risk of eye injury were long surgical procedures (odds ratio, 1.16 per hour of anesthetic care; CI, 1.1 to 1.3), lateral positioning during surgery (odds ratio, 4.7; CI, 2 to 11), operation on the head or neck (odds ratio, 4.4; CI, 2.2 to 9.0), general anesthesia (odds ratio, 3.0; CI, 2.2 to 38), and surgery on a Monday (odds ratio, 2.7; CI, 1.4 to 5.3). In only 21% of cases was a specific cause of injury identified.

Conclusions

For reasons not understood, eye injuries are more common in patients who are older or who undergo lengthier procedures. The cause of injury was usually not determined by the authors' methods. Until the mechanisms producing perioperative eye injuries are better understood, it is difficult to identify strategies to prevent this type of injury.
Differential Effects of Etomidate, Propofol, and Midazolam on Calcium and Potassium Channel Currents in Canine Myocardial Cells
Authors: Buljubasic Nediljka , Marijic Jure , Berczi Viktor , Supan Darko F. , Kampine John P. , Bosnjak Zeljko J.
Published: November 2003

Background

Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown.

Methods

The effects of intravenous anesthetics on L-type Ca2+, transient outward and inward-rectifier K+ channel currents (ICa, IKto, and IK1) were compared in canine ventricular cells using the whole-cell voltage-clamp technique. ICa and IK were elicited by progressively depolarizing cells from -40 to +40 mV, and from -90 to +60 mV, respectively. The peak amplitude and time-dependent inactivation rate of ICa and IK were measured before, during, and after the administration of equimolar concentrations (5, 30, or 60 microM) of etomidate, propofol, or midazolam.

Results

Exposure to etomidate, propofol, and midazolam produced a concentration-dependent inhibition of ICa. Midazolam was the most potent intravenous anesthetic; at 60 microM, etomidate, propofol, and midazolam decreased peak ICa by 16 +/- 4% (mean +/- SEM), 33 +/- 5%, and 47 +/- 5%, respectively. Etomidate, propofol, and midazolam given in a 60-microM concentration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respectively. IK1 was decreased by 60 microM etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1.

Conclusions

At equimolar concentrations, intravenous anesthetics decreased the peak ICa, IKto, and IK1 with various degrees of potency. Effects of anesthetics on ICa were significantly greater compared with their effects on K+ currents. These findings suggest that the negative inotropic actions of etomidate, propofol, and midazolam are related, at least in part, to decreased ICa. Some effects, such as IK inhibition, may partially antagonize effects of decreased ICa. Indeed, the final effect of these intravenous anesthetics on myocardium will be the sum of these and other sarcolemmal and intracellular effects.
Role of the Endocardial Endothelium in the Negative Inotropic Effects of Thiopental
Authors: Bettens Karin M. , De Hert Stefan G. , Sys Stanislas U. , Brutsaert Dirk L.
Published: November 2003

Background

Myocardial function is regulated by endocardial endothelium (EE). Several studies have demonstrated the involvement of vascular endothelium in regulating the vasoactive effects of anesthetic agents. Because vascular endothelium and EE form a contiguous layer, it was postulated that EE might also be involved in regulating the inotropic effects of anesthetics. The effects of thiopental on isolated feline papillary muscle with and without EE were examined.

Methods

The study was performed on isolated cat papillary muscles (n = 48). The effects of increasing doses of thiopental (1.5, 3, 6, 9, 12, and 24 micrograms/ml) on isometric and isotonic muscle contraction parameters were evaluated in three protocols under different experimental conditions. In the first protocol, the effects of thiopental were studied in the muscles with an intact EE (group A, n = 8) and muscles in which the EE was selectively damaged by a 1-s immersion in 0.5% Triton X-100 (group B, n = 8). In the second protocol, cumulative concentration responses for thiopental were obtained in muscles with (group C, n = 8) and without (group D, n = 8) EE, pretreated with 10(-3) M of the blocking NG-nitro-L-arginine methyl ester (L-NAME). In the third protocol, the same cumulative concentration responses were obtained for thiopental in muscles with (group E, n = 8) and without (group F, n = 8) EE after pretreatment with 5 x 10(-4) M L-arginine.

Results

In the presence of an intact EE, thiopental induced a dose-dependent decrease in myocardial function. With the EE removed, low doses of thiopental (1.5 to 6 micrograms/ml) no longer altered myocardial function. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental and mimicked the response obtained after EE was removed. Pretreatment with L-arginine slightly accentuated the negative inotropic effects of low doses of thiopental.

Conclusions

The negative inotropic actions of small doses of thiopental depend on the presence of an intact EE. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental, suggesting possible involvement of the nitric oxide pathway.
Nitrict Oxide Synthase Inhibitors, 7-Nitro Indazole and Nitro sup G -L-Arginine Methyl Ester, Dose Dependently Reduce the Threshold for Isoflurane Anesthesia
Authors: Pajewski Thomas N. , DiFazio Cosmo A. , Moscicki Jeffrey C. , Johns Roger A.
Published: November 2003

Background

Nitric oxide (NO), a recognized cell messenger for activating soluble guanylate cyclase, is produced by the enzyme NO synthase in a wide variety of tissues, including vascular endothelium and the central nervous system. The authors previously reported the possible involvement of the NO pathway in the anesthetic state by showing that a specific NO synthase inhibitor, nitroG-L-arginine methyl ester (L-NAME), dose dependently and reversibly decreases the minimum alveolar concentration (MAC) for halothane anesthesia. The availability of a structurally distinct inhibitor selective for the neuronal isoform of NO synthase, 7-nitro indazole (7-NI), allowed for the possibility of dissociating the central nervous system effects of neuronal NO synthase inhibition from the cardiovascular effects of endothelial NO synthase inhibition.

Methods

The effect of two structurally distinct inhibitors of NO synthase, L-NAME and 7-NI, on the MAC of isoflurane was investigated in Sprague-Dawley rats while concurrently monitoring the animals' arterial blood pressure and heart rate. L-NAME (1 to 30 mg/kg given intravenously, dissolved in 0.9% saline) and 7-NI (20 to 1,000 mg/kg given intraperitoneally, dissolved in arachis oil) were administered after determining control MAC and 30 min before determining MAC in the presence of NO synthase inhibitor.

Results

L-NAME and 7-NI caused a dose-dependent decrease from isoflurane control MAC (maximal effect: 35.5 +/- 2.5% and 43.0 +/- 1.7%, respectively) with a ceiling effect observed for both NO synthase inhibitors (above 10 mg/kg and 120 mg/kg, respectively). L-NAME administration significantly increased systolic and diastolic blood pressures (maximal effect: 39.9 +/- 2.2% and 64.3 +/- 4.0%, respectively), which were not accompanied by any changes in heart rate. 7-NI administration resulted in no changes in blood pressure and a small but clinically insignificant decrease in heart rate.

Conclusions

Inhibition of the NO synthase pathway decreased the MAC for isoflurane, which suggests that inhibition of the NO pathway decreases the level of consciousness and augments sedation, analgesia, and anesthesia. The MAC reduction by two structurally distinct NO synthase inhibitors supports that this is a specific effect on NO synthase. Furthermore, the action of the neuronal NO synthase inhibitor 7-NI supports an effect selective for neuronal NO synthase and also avoids the hypertensive response of generalized NO synthase inhibitors.
A Beta-adrenoceptor Agonist Evokes a Nitric Oxide-cGMP Relaxation Mechanism Modulated by Adenylyl Cyclase in Rat Aorta
Authors: Iranami Hiroshi , Hatano Yoshio , Tsukiyama Yoshi , Maeda Hiroshi , Mizumoto Kazuhiro
Published: November 2003

Background

The objective of this study was to characterize the effects of halothane on the agonist-induced nitric oxide-cyclic GMP (NO-cGMP) mechanisms by comparing the intracellular signal transduction mediating isoproterenol- and acetylcholine-induced nitric oxide formation.

Methods

Isoproterenol-induced relaxations of rat aortic rings with and without endothelia were examined in the absence and presence of halothane. Studies were also done in the presence of inhibitors of nitric oxide-synthase, adenylyl cyclase, calmodulin, protein kinase A, and intracellular Ca2+ release mechanism. The relaxations under some of these conditions were compared with those induced by acetylcholine. Cyclic nucleotide contents of the rings were also measured.

Results

Isoproterenol relaxed aortic rings via the endothelium-dependent nitric oxide-cyclic GMP mechanism. Inhibition of adenylyl cyclase or of protein kinase A attenuated the isoproterenol-induced relaxations significantly but did not affect those induced by acetylcholine. Inhibition of intracellular Ca2+ release abolished the acetylcholine-induced relaxations but did not affect those induced by isoproterenol. Calmodulin inhibition attenuated both agonist-induced relaxations significantly. Unlike acetylcholine-induced relaxation, that induced by isoproterenol was not affected by halothane. Isoproterenol increased both the cyclic adenosine monophosphate and cGMP contents of rings significantly when endothelia were intact. Inhibition of nitric oxide synthase attenuated the isoproterenol-induced cGMP content increases significantly but did not affect the cyclic adenosine monophosphate content increases. Halothane (2%) did not affect isoproterenol-induced increases in nucleotide content.

Conclusions

Isoproterenol-induced nitric oxide formation requires the activation of constitutive nitric oxide synthase, but the Ca2+ release mechanism is not involved in activating this enzyme. Halothane can inhibit the nitric oxide-cyclic GMP mechanism only when Ca2+ release is greatly involved in the activation of constitutive nitric oxide synthase.
Sevoflurane Depresses Myocardial Contractility Less than Halothane during Induction of Anesthesia in Children
Authors: Holzman Robert S. , van der Velde Mary E. , Kaus Sarah J. , Body Simon C. , Colan Steven D. , Sullivan Lorna J. , Soriano Sulpicio G.
Published: November 2003

Background

Cardiovascular stability is an important prerequisite for any new volatile anesthetic. We compared echocardiographically derived indices of myocardial contractility during inhalation induction with sevoflurane and halothane in children.

Methods

Twenty children were randomized to receive either halothane or sevoflurane for inhalation induction of anesthesia. No preoperative medications were given. Myocardial contractility was evaluated at baseline and at sevoflurane and halothane end-tidal concentrations of 1.0 minimum alveolar concentration (MAC) and 1.5 MAC.

Results

There were no differences between groups in patient age, sex, physical status, weight, or height. Equilibration times and MAC multiples of sevoflurane and halothane were comparable. Vital signs remained stable throughout the study. Left ventricular end-systolic meridional wall stress increased with halothane but remained unchanged with sevoflurane. Systemic vascular resistance decreased from baseline to 1 MAC and 1.5 MAC with sevoflurane. Halothane depressed contractility as assessed by the stress-velocity index and stress-shortening index, whereas contractility remained within normal limits with sevoflurane. Total minute stress and normalized total mechanical energy expenditure, measures of myocardial oxygen consumption, did not change with either agent.

Conclusions

Myocardial contractility was decreased less during inhalation induction of anesthesia with sevoflurane compared with halothane in children. Although the induction of anesthesia with sevoflurane or halothane was equally well tolerated, the preservation of myocardial contractility with sevoflurane makes it an attractive alternative for inducing anesthesia in children.
N-Butyl Tetracaine as a Neurolytic Agent for Ultralong Sciatic Nerve Block
Authors: Wang G. K. , Vladimirov M. , Quan C. , Mok W. M. , Thalhammer J. G. , Anthony D. C.
Published: November 2003

Background

Neurolytic agents such as phenol (5% to 10%) and absolute alcohol have long been used clinically to destroy the pathogenic nerve regions that manifest pain. Both phenol and alcohol are highly destructive to nerve fibers. However, these agents exert only weak local anesthetic effects and therefore are difficult to administer to alert patients without pain. This report describes a tetracaine derivative that displays both local anesthetic and neurolytic properties. Studies with such a compound may lead to the design of neurolytic agents that are more effective and more easily administered than phenol and alcohol.

Methods

A tetracaine derivative, N-butyl tetracaine quaternary ammonium bromide, was synthesized, and its ability to elicit sciatic nerve block of sensory and motor functions in vivo was tested in rats. A single dose of 0.1 ml N-butyl tetracaine at 37 mM was injected into the sciatic notch. Transverse sections of treated sciatic nerves were subsequently examined to determine the neurolytic effect of this drug. Finally, the local anesthetic properties of N-butyl tetracaine were studied in vitro; both tonic inhibition and use-dependent inhibition of Na+ currents in neuronal GH3 cells were characterized under whole-cell voltage-clamp conditions.

Results

N-butyl tetracaine at 37 mM (equivalent to 1.11% tetracaine-hydrochloric acid concentration) elicited prolonged sciatic nerve block of the withdrawal response to noxious pinch in rats for more than 2 weeks. The withdrawal response was fully restored after 9 weeks. Parallel to sensory block, motor functions of the hind legs were similarly blocked by this drug. Morphologic examinations 3 and 5 weeks after a single injection of drug revealed degeneration of many sciatic nerve fibers, consistent with the results of functional tests. Finally, N-butyl tetracaine was found to be a potent Na+ channel blocker in vitro. It produced strong tonic and use-dependent inhibition of Na+ currents with a potency comparable to that of tetracaine.

Conclusions

A single injection of N-butyl tetracaine produces ultralong sciatic nerve block in rats. This compound possesses both local anesthetic and neurolytic properties and may prove useful as a neurolytic agent in pain management.
Sympathetic and Mesenteric Venous Responses to Baroreceptor or Chemoreceptor Stimulation during Epidural Anesthesia in Rabbits
Authors: Hogan Quinn H. , Kulier Alexander , Bosnjak Zeljko J. , Kampine John P.
Published: November 2003

Background

Baroreceptor and chemoreceptor reflexes maintain homeostasis through mechanisms that involve sympathetic activation. Because sympathetic control of the mesenteric veins plays a central role in hemodynamic responses to stress, the effects of epidural blockade on reflex responses to hypoxia and bilateral carotid occlusion (BCO) were examined by monitoring direct measures of splanchnic sympathetic neural traffic and mesenteric venous capacitance.

Methods

Rabbits were studied during alpha-chloralose anesthesia and mechanical ventilation. Sympathetic efferent nerve activity to the mesenteric vessels was measured by surgically placed electrodes, and mesenteric venous diameter was measured by videomicroscopy. Heart rate and mean arterial pressure were monitored by intraarterial cannulation. Intraluminal venous pressure was monitored by a servo-null micropressure technique. Responses were recorded during repeated administration of three different stresses, F1O2 = 0% for 40 s, F1O2 = 11% for 2.5 min, and BCO for 60 s. Animals received either thoracolumbar epidural blockade (0.4 ml/kg lidocaine 1.5%; n = 7) or 15 mg/kg intramuscular lidocaine (n = 7).

Results

Hypoxia and BCO produced sympathetic stimulation and active constriction of mesenteric veins. Epidural anesthesia accentuated the mean arterial pressure decrease from F1O2 of 0%, caused the 11% response to F1O2 to become depressor instead of pressor, and decreased the pressor effect BCO. Sympathetic efferent nerve activity and venous diameter responses to hypoxia and BCO were attenuated or eliminated.

Conclusions

The hemodynamic effects of hypoxia result from a combination of direct depression and reflex activation. Thoracolumbar epidural anesthesia in rabbits impairs compensatory reflexes invoked by chemoreceptor stimulation and eliminates response to baroreceptor stimulation. Loss of splanchnic control of mesenteric capacitance contributes to the inhibition of the hemodynamic response to hypoxia or BCO during epidural anesthesia in rabbits.
Effects of Pre- and Postischemic Administration of Thiopental on Transmitter Amino Acid Release and Histologic Outcome in Gerbils
Authors: Amakawa Kazuhiko , Adachi Naoto , Liu Keyue , Ikemune Keizo , Fujitani Taro , Arai Tatsuru
Published: November 2003

Background

The mechanism by which barbiturates protect neurons against ischemia is unclear, particularly when they are given after ischemia or reperfusion begins. Because an excess release of excitatory neurotransmitters causes postsynaptic membrane depolarization, which triggers neuronal damage in ischemia, the effects of thiopental on histologic outcome, ischemia-induced amino acid release, and anoxic depolarization in gerbils were studied.

Methods

The effects of different doses of thiopental administered before or after ischemia were examined morphologically by assessing delayed neuronal death in hippocampal CA1 pyramidal cells produced by forebrain ischemia for 3 min in gerbils. The ischemia-induced changes in output of aspartate, glutamate, glycine, taurine, and gamma-aminobutyric acid were measured using a microdialysis-high-performance liquid chromatography procedure, and the differences among a halothane-anesthetized group, a thiopental-administered group, and a group given thiopental after a period of ischemia were evaluated. The changes induced in the direct-current potential in the hippocampal CA1 area by forebrain ischemia were compared in animals anesthetized with halothane and those given thiopental.

Results

Preischemic administration of thiopental at all doses decreased the risks for delayed neuronal death (P < 0.01). Post-ischemic administration at a dosage of 2 mg.kg-1.min-1 for 60 min protected neurons, but the same dose for 10 min did not ameliorate the cell injury. Forebrain ischemia produced marked increases in all amino acids 3 to 6 min after the start of recirculation in the halothane-anesthetized gerbils, whereas thiopental anesthesia (2 mg.kg-1.min-1) reduced these increases throughout the experimental period, except for glycine (P < 0.01). The initiation of thiopental after reflow did not markedly diminish these increases. Thiopental anesthesia prolonged the onset of anoxic depolarization and reduced its maximal amplitude.

Conclusions

Thiopental helps protect the brain from ischemia, although treatment with this agent after ischemia requires a larger dose than that before ischemia. The effect of preischemic treatment may be related to the suppression of the excitatory amino acid release and the direct-current potential shift.
Cysteine Conjugate β-Lyase-dependent Biotransformation of the Cysteine S-Conjugates of the Sevoflurane Degradation Product Compound A in Human, Nonhuman Primate, and Rat Kidney Cytosol and Mitochondria
Authors: Iyer Ramaswamy A. , Anders M. W.
Published: November 2003

Background

2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (compound A) is a fluorinated alkene formed by the degradation of sevoflurane in the anesthesia circuit. Compound A is toxic to the kidneys in rats and undergoes glutathione-dependent metabolism in vivo. Several nephrotoxic halogenated alkenes also undergo cysteine conjugate beta-lyase-dependent biotransformation. These experiments were designed to test the hypothesis that cysteine S-conjugates of compound A undergo beta-lyase-dependent biotransformation.

Methods

S-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine 4, S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-L-cysteine 5, and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine 11 were incubated with rat, human, and nonhuman primate (cynomolgus, rhesus, and marmoset) kidney cytosol and mitochondria. beta-Lyase activity was determined by measuring pyruvate formation.

Results

Compound A-derived conjugates 4 and 5 as well as conjugate 11, a positive control, were substrates for cytosolic and mitochondrial beta-lyase from human, nonhuman primate, and rat kidney. For all substrates, beta-lyase activity was highest in the rat and lowest in the human and was higher in cytosol than in mitochondria. Conjugate 11 was a much better substrate than conjugates 4 or 5. The biotransformation of conjugates 4, 5, and 11 was inhibited by the beta-lyase inhibitor (aminooxy)acetic acid and was stimulated by the amino group acceptor 2-keto-4-methylthiolbutyric acid, indicating a role for beta-lyase.

Conclusions

These data confirm the presence of beta-lyase activity in human and rat kidney and show that activity is also present in kidney tissue from nonhuman primates. The data also show that compound A-derived conjugates 4 and 5 undergo beta-lyase-catalyzed biotransformation. beta-Lyase activity in rat and nonhuman primate kidney tissue was 8 to 30 times and one- to three times, respectively, higher than in human kidney tissue.
Local Anesthetic Administration for Awake Direct Laryngoscopy
Authors: Sitzman Todd B. , Rich George F. , Rockwell Jeffrey J. , Leisure George S. , Durieux Marcel E. , DiFazio Cosmo A.
Published: November 2003

Background

Glossopharyngeal nerve (GPN) blocks may provide reliable analgesia for awake direct laryngoscopy, although this has not been evaluated prospectively. This study was designed to determine if GPN blocks provide a superior route of local anesthetic administration for awake direct laryngoscopy as measured by hemodynamic, gag, and subjective pain responses.

Methods

A prospective, randomized, single-blinded, crossover design was used. All participants (n = 11) were anesthesiologists. Three routes of local anesthetic administration were evaluated: 2 min of 2% viscous lidocaine swish and gargle (S&G); S&G combined with 10% lidocaine spray (S&G/spray); and S&G combined with 1% lidocaine bilateral GPN blocks (S&G/block; anterior tonsillar pillar method). Five minutes after the local anesthetic was administered, laryngoscopy was performed and sustained for 20 s. Noninvasive hemodynamic measurements and serum lidocaine concentrations were determined. Visual analogue scale scores and a poststudy questionnaire were used to assess participants' ability to tolerate local anesthetic administration and laryngoscopy and their choice for use in clinical practice.

Results

No significant hemodynamic changes were observed, although there was a modest increase (< 15%) in heart rate in the S&G/block group in the first minute after laryngoscopy. Serum lidocaine concentrations were higher (P < 0.05) in the S&G/block group at 5 and 10 min (0.5 +/- 0.1 and 1.0 +/- 0.2 microgram/ml) compared with the S&G group. Participants' visual analogue scale scores, which assessed their ability to tolerate laryngoscopy, showed that S&G (5.4 +/- 0.9) resulted in more discomfort (P < 0.05) than either S&G/spray (3.5 +/- 0.9) or S&G/block (3.3 +/- 0.7). The laryngoscopist's visual analogue scale scores, which assessed the ease of visualization, revealed a trend (P < 0.08) toward less coughing and gagging with S&G/spray (1.8 +/- 0.9) compared with S&G (4.0 +/- 1.3) and S&G/block (3.7 +/- 1.1). Oropharyngeal discomfort lasting 24 h or more was reported by 91% of participants after S&G/block, whereas no participant reported oropharyngeal discomfort after S&G or S&G/spray. Significantly more participants (73%) indicated their preference for using S&G/spray in future clinical practice compared with S&G (P < 0.01) and S&G/block (P < 0.05).

Conclusions

Glossopharyngeal nerve blocks do not provide a superior route of local anesthetic administration for awake direct laryngoscopy. Two minutes of 2% viscous lidocaine S&G followed by 10% lidocaine spray was the anesthetic route preferred by participants and laryngoscopists.
Isoflurane and Sevoflurane Interact with the Nicotinic Acetylcholine Receptor Channels in Micromolar Cconcentrations
Authors: Scheller Michaela , Bufler Johannes , Schneck Hajo , Kochs Eberhard , Franke Christian
Published: November 2003

Background

This study was performed to elucidate and compare the effects of sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse myotubes. The experiments were done with special reference to anesthetic concentrations considerably less than those used for clinical anesthesia.

Methods

The patch-clamp technique was used to record acetylcholine-activated currents from the embryonic type of the nicotinic acetylcholine receptor in the outside-out mode. A piezo-driven liquid filament switch was used for the ultrafast application of acetylcholine alone or in combination with isoflurane or sevoflurane. In addition, the patches were preexposed to either anesthetic, preceding the activation with acetylcholine.

Results

The current elicited by acetylcholine was reduced reversibly and in a concentration-dependent manner by both anesthetics, which were equally effective. Preexposure of the patches to isoflurane or sevoflurane showed an additional inhibition that was present at micromolar concentrations. The time courses of current decay could be fitted by single exponentials for isoflurane. At higher concentrations of sevoflurane, the current decay became biexponential. In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations.

Conclusions

At the nicotinic acetylcholine receptor, isoflurane and sevoflurane act primarily through the same mechanisms: Both affect the open and the closed state of the channels in concentrations equal to and less than those encountered clinically. The kinetics of desensitization, however, are altered in a different manner. Thus there may be several different sites of interaction.
Role of Adenosine Triphosphate-sensitive Potassium Channels in Coronary Vasodilation by Halothane, Isoflurane, and Enflurane
Authors: Crystal George J. , Gurevicius Juozas , Salem Ramez M. , Zhou Xiping
Published: November 2003

Background

Halothane, isoflurane, and enflurane cause coronary vasodilation and cardiac depression. This study was performed to assess the role of adenosine triphosphate (ATP)-sensitive potassium channels (KATP channels) in these effects.

Methods

Twenty-five thoracotomized dogs were anesthetized with fentanyl and midazolam. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs. One reservoir was supplied with arterial blood free of a volatile anesthetic, and the second reservoir was supplied with arterial blood equilibrated in an oxygenator with a 1 minimum alveolar concentration of either halothane (0.9%, n = 10), isoflurane (1.4%, n = 8), or enflurane (2.2%, n = 7). Coronary blood flow (CBF) was measured using a Doppler flow transducer, and segmental shortening (SS) was measured with ultrasonic crystals. Responses to the volatile anesthetics were assessed under control conditions, during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 micrograms/min), and after cessation of glibenclamide (recovery). The effectiveness of glibenclamide was verified from inhibition of coronary vasodilator responses to the KATP channel opener cromakalim without effect on those to the KATP channel-independent vasodilators, sodium nitroprusside and acetylcholine.

Results

Under control conditions, the volatile anesthetics caused pronounced increases in CBF (isoflurane > halothane = enflurane), and decreases in SS (enflurane > halothane = isoflurane). Glibenclamide blunted significantly (and reversibly) the increases in CBF, but it had no effect on the decreases in SS.

Conclusions

The KATP channels play an important role in coronary vasodilation but apparently are not involved in cardiac depression caused by halothane, isoflurane, and enflurane in canine hearts in situ.