bluuebunny/crossref_metadata_2025 huggingface dataset:
No Enhancement of Sensory and Motor Blockade by Neostigmine Added to Mepivacaine Axillary Plexus Block
Authors: Bouaziz Herve , Paqueron Xavier , Bur Marie Lorraine , Merle Michel , Laxenaire Marie Claire , Benhamou Dan
Published: November 2003

Background

Intrathecal neostigmine induces analgesia but also several side effects. Recently, 500 microg neostigmine administered intraarticularly was shown to produce postoperative analgesia without side effects. The authors' goal was to determine whether 500 microg neostigmine added to mepivacaine in axillary plexus block prolongs postoperative analgesia. In addition, they wanted to determine the incidence of side effects in patients undergoing hand surgery.

Methods

Sixty-nine outpatients scheduled for carpal tunnel syndrome repair with axillary plexus block were randomly assigned to one of three groups that received saline solution in the axillary plexus and subcutaneously (group 1), 500 microg neostigmine in the axillary plexus and saline solution subcutaneously (group 2), or saline solution in the axillary plexus and 500 microg neostigmine subcutaneously (group 3). Sensory and motor block in the four hand nerve distributions were assessed every 5 min for 30 min The duration of the sensory and motor blocks were assessed after operation. Side effects were also recorded.

Results

Neostigmine had no effect on sensory and motor block in any of the four nerve distributions, nor did it increase the median duration of sensory block (215 min; range, 120-330 min) compared with group 1 (247 min; range, 190-287 min) or group 3 (236 min; range, 160-280 min). Motor block was slightly shorter (P = 0.045) in group 3 (190 min; range, 135-285 min) compared with group 1 (218 min; range, 145257 min) and group 2 (215 min; range, 105-343 min). Gastrointestinal side effects occurred in 30% of patients in both neostigmine groups but not in group 1 (P < 0.05).

Conclusions

This study suggests that 500 microg neostigmine added to mepivacaine in axillary plexus block does not prolong postoperative sensory block, but it does cause a relatively high incidence of side effects. These two findings raise doubts about the use of neostigmine associated with local anesthetics for plexus neural block.
The Mechanism of Inhibitory Actions of Propofol on Rat Supraoptic Neurons
Authors: Inoue Yoshitaka , Shibuya Izumi , Kabashima Narutoshi , Noguchi Jun , Harayama Nobuya , Ueta Yoichi , Sata Takeyoshi , Shigematsu Akio , Yamashita Hiroshi
Published: November 2003

Background

In the perioperative period, plasma osmotic pressure, systemic blood pressure, and blood volume often change dramatically. Arginine vasopressin is a key factor in the regulation of these parameters. This study was performed to evaluate the direct and the mechanism of the actions of propofol on arginine vasopressin release from magnocellular neurosecretory neurons in the rat supraoptic nucleus.

Methods

Somatodendritic arginine vasopressin release from supraoptic nucleus slice preparations was measured by radioimmunoassay. Ionic currents were measured using the whole-cell mode of the patch-clamp technique in supraoptic nucleus slice preparations or in single dissociated supraoptic nucleus neurons of the rat.

Results

Propofol at concentrations greater than 10(-5) M inhibited the arginine vasopressin release stimulated by potassium chloride (50 mM). This inhibition by propofol was not reversed by picrotoxin, a gamma-aminobutyric acid(A)(GABA(A)) receptor antagonist, whereas arginine vasopressin release induced by glutamate (10(-3) M) was also inhibited by propofol at a clinically relevant concentration (10(-6) M). The latter effect was reversed by picrotoxin. Propofol evoked Cl- currents at concentrations ranging 10(-6) to 10(-4) M. Propofol (10(-6) M) enhanced the GABA (10(-6) M)-induced current synergistically. Moreover, propofol (10(-6) M) prolonged the time constant of spontaneous GABA-mediated inhibitory postsynaptic currents. Furthermore, propofol (10(-5) M and 10(-4) M) reversibly inhibited voltage-gated Ca2+ currents, whereas it did not affect currents induced by glutamate (10(-3) M).

Conclusions

Propofol inhibits somatodendritic arginine vasopressin release from the supraoptic nucleus, and the enhancement of GABAergic inhibitory synaptic inputs and the inhibition of voltage-gated Ca2+ entry are involved in the inhibition of arginine vasopressin release.
Volatile Anesthetics Augment Expression of Proinflammatory Cytokines in Rat Alveolar Macrophages during Mechanical Ventilation
Authors: Kotani Naoki , Takahashi Satoshi , Sessler Daniel I. , Hashiba Eiji , Kubota Takeshi , Hashimoto Hiroshi , Matsuki Akitomo
Published: November 2003

Background

Previous studies indicate that anesthesia and surgery induce an inflammatory reaction in alveolar macro phages. However,they filed to independently evaluate the relative contributions of factors including mechanical ventilation, general anesthesia, and surgical stress. Therefore, the authors tested the hypothesis that inflammatory reactions at the cellular level in alveolar macrophages are induced within 2 h of inhalation of volatile anesthetics under mechanical ventilation.

Methods

After administration of pentobarbital, rats were allocated to the nonventilated control or spontaneous or mechanical ventilation (n = 15/group) for 2 h at a fraction of inspired oxygen (FI(O2)) of 0.21. In a separate series of experiments, rats were mechanically ventilated without volatile anesthesia, or during exposure to halothane, enflurane, isoflurane, or sevoflurane (n = 15/group). Pulmonary lavage was performed, and RNA was extracted from harvested cells. The mRNA for the proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6, macrophage inflammatory protein-2 (MIP-2), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) were measured by semiquantitative reverse transcription-polymerase chain reaction using beta-actin as an internal standard. Pulmonary lavage concentrations of these cytokines were measured by enzyme-linked immunoassay.

Results

The lavage cell count and cytology were similar in each series of the experiment. Gene expression of MIP-2 and TNF-alpha was greater during mechanical than spontaneous ventilation and nonventilation control However, the concentrations of cytokines except MIP-2 and TNF-alpha were less than detection levels. During exposure to volatile anesthetics, gene expression for IL-1beta, MIP-2, IFN-gamma, and TNF-alpha all increased significantly compared with mechanical ventilation alone. Significant increases in lavage concentrations of MIP-2 and TNF-alpha were also observed.

Conclusions

Gene expression of proinflammatory cytokines increase after inhalation of volatile anesthetics under mechanical ventilation. These data indicate that inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response at the transcriptional level within 2 h.
Acetaminophen Inhibits Spinal Prostaglandin E2Release after Peripheral Noxious Stimulation
Authors: Muth-Selbach Uta S. , Tegeder Irmgard , Brune Kay , Geisslinger Gerd
Published: November 2003

Background

Prostaglandin play a pivotal role in spinal nociceptive processing. At therapeutic concentrations, acetaminophen is not a cyclooxygenase inhibitor. inhibitor. Thus, it is antinociceptive without having antiinflammatory or gastrointestinal toxic effects. This study evaluated the role of spinal prostaglandin E2 (PGE2) in antinociception produced by intraperitoneally administered acetaminophen.

Methods

The PGE2 concentrations in the dorsal horn of the spinal cord were measured after formalin was injected into the hind paw of rats. The effect of antinociceptive doses of acetaminophen (100, 200, and 300 mg/kg given intraperitoneally) on PGE2 levels and flinching behavior was monitored Spinal PGE2 and acetaminophen concentrations were obtained by microdialysis using a probe that was implanted transversely through the dorsal horn of the spinal cord at L4. Furthermore, the effects of acetaminophen on urinary prostaglandin excretion were determined.

Results

Intraperitoneal administration of acetaminophen resulted in a significant decrease in spinal PGE2 release that was associated with a significant reduction in the flinching behavior in the formalin test Acetaminophen was distributed rapidly into the spinal cord with maximum dialysate concentrations 4560 min after intraperitoneal administration. Urinary excretion of prostanoids (PGE2, PGF2alpha, and 6-keto-PGF1alpha) was not significantly altered after acetaminophen administration.

Conclusions

The data confirm the importance of PGE2 in spinal nociceptive processing. The results suggest that antinociception after acetaminophen administration is mediated, at least in part, by inhibition of spinal PGE2 release. The mechanism, however, remains unknown. The finding that urinary excretion of prostaglandins was not affected might explain why acetaminophen is antinociceptive but does not compromise renal safety.
Effects of Exogenous Surfactant on Acute Lung Injury Induced by Intratracheal Instillation of Infant Formula or Human Breast Milk in Rabbits
Authors: Nishina Kahoru , Mikawa Katsuya , Takao Yumiko , Maekawa Nobuhiro , Obara Hidefumi
Published: November 2003

Background

An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products.

Methods

The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured.

Results

The acidified milk products increased A-aD(O2)(550+/-52 and 156+/-28 mmHg; mean+/-SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6+/-0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84+/-4% and 8+/-20%), and decreased compliance (0.76+/-0.09 and 1.90+/-0.11 ml/cm H2O). Surfactant improved these variables in a dose-dependent manner (A-aDO2 = 363+/-50 and 237+/-55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it.

Conclusion

Exogenous surfactant improved physiologic, histologic, and biochemical lung injury induced by acidified milk products in a dose-dependent manner. The effectiveness of surfactant may be caused, in part, by inhibition of neutrophils' sequestration and activation. These data indicate that intratracheal instillation of surfactant may be a promising therapeutic modality in acute lung injury resulting from aspiration of acidified milk products.
A Matter of Life and Death
Authors: Van Norman Gail A.
Published: November 2003

Accurate criteria for death are increasingly important as it becomes more difficult for the public to distinguish between patients who are still alive from those who, through the aid of medical technology, merely look like they are alive even though they are dead. Patients and their families need to know that a clear line can be drawn between life and death, and that patients who are alive will not be unintentionally treated as though they are dead. For the public to trust the pronouncements of medical doctors as to whether a patient is dead or alive, the criteria must be unambiguous, understandable, and infallible. It is equally important to physicians that accurate, infallible criteria define death. Physicians need to know that a clear line can be drawn between life and death so that patients who are dead are not treated as though they are alive. Such criteria enable us to terminate expensive medical care to corpses. Clear criteria for death also allow us to ethically request the gift of vital organs. Clear, infallible criteria allow us to assure families and society that one living person will not be intentionally or unintentionally killed for the sake of another. The pressure of organ scarcity must not lead physicians to allow the criteria for life and death to become blurred because of the irreparable harm this would cause to the patient-physician relationship and the devastating impact it could have on organ transplantation. As the cases presented here illustrate, anesthesiologists have an important responsibility in the process of assuring that some living patients are not sacrificed to benefit others. Criteria for declaring death should be familiar to every anesthesiologist participating in organ retrieval. Before accepting the responsibility of maintaining a donor for vital organ collection, the anesthesiologist should review data supplied in the chart supporting the diagnosis of brain death and seriously question inconsistencies and inadequate testing conditions. Knowledge of brain death criteria and proper application of these criteria could have changed the course of each of the cases presented.
Ulnar Nerve Pressure
Authors: Prielipp Richard C. , Morell Robert C. , Walker Francis O. , Santos Carlos C. , Bennett Judy , Butterworth John
Published: November 2003

Background

Although the ulnar nerve is the most frequent site of perioperative neuropathy, the mechanism remains undefined. The ulnar nerve appears particularly susceptible to external pressure as it courses through the superficial condylar groove at the elbow, rendering it vulnerable to direct compression and ischemia However, there is disagreement among major anesthesia textbooks regarding optimal positioning of the arm during anesthesia.

Methods

To determine which arm position (supination, neutral orientation, or pronation) minimizes external pressure applied to the ulnar nerve, we studied 50 awake, normal volunteers using a computerized pressure sensing mat. An additional group of 15 subjects was tested on an operating table with their arm in 30 degrees, 60 degrees, and 90 degrees of abduction, as well as in supination, neutral orientation, and pronation. To determine the onset of clinical paresthesia compared to the onset and severity of somatosensory evoked potential (SSEP) electrophysiologic changes, we studied a separate group of 16 male volunteers while applying intentional pressure directly to the ulnar nerve. Data are presented as mean (median; range).

Results

Supination minimizes direct pressure over the ulnar nerve at the elbow (2 mmHg [0; 0-23]; n = 50), compared with both neutral forearm orientation (69 mmHg [22; 0-220]; P < 0.0001), as well as pronation (95 mmHg [61; 0-220]; P < 0.0001). Neutral forearm orientation also results in significantly less pressure over the ulnar nerve compared to pronation (P < or = 0.04). The estimated contact area of the ulnar nerve with the weight-bearing surface was significantly (P < 0.0001) smaller in the supine position (2.2 cm2 [0.5; 0-9]; n = 50) compared with both neutral orientation (5.5 cm2 [5.0; 0-13]) and pronation (5.8 cm2 [6; 0-12]). With the forearm in neutral orientation, ulnar nerve pressure decreased significantly (P < or = 0.01; n = 15) as the arm was abducted at the shoulder from 0 degrees to 90 degrees. In the 16 male subjects tested, notable alterations in ulnar nerve SSEP signals (decrease > or = 20% in N9-N9' amplitude) were detected in 15 of 16 awake males during application of intentional pressure to the ulnar nerve. However, eight of these subjects did not perceive a paresthesia, even as SSEP waveform amplitudes were decreasing 23-72%. Two of these eight subjects manifested severe decreases in SSEP amplitude (> or = 60%).

Conclusions

Extrapolating these results to the clinical setting, the supinated arm position is likely to minimize pressure over the ulnar nerve. With the forearm in neutral orientation, pressure over the ulnar nerve decreases as the arm is abducted between 30 degrees and 90 degrees. In addition, up to one half of male patients may fail to perceive or experience clinical symptoms of ulnar nerve compression sufficient to elicit SSEP changes.
Platelet-activated Clotting Time Does Not Measure Platelet Reactivity during Cardiac Surgery
Authors: Shore-Lesserson Linda , Ammar Tameshwar , DePerio Marietta , Vela-Cantos Frances , Fisher Cherie , Sarier Kaya
Published: November 2003

Background

Platelet dysfunction is a major contributor to bleeding after cardiopulmonary bypass (CPB), yet it remains difficult to diagnose. A point-of-care monitor, the platelet-activated clotting time (PACT), measures accelerated shortening of the kaolin-activated clotting time by addition of platelet activating factor. The authors sought to evaluate the clinical utility of the PACT by conducting serial measurements of PACT during cardiac surgery and correlating postoperative measurements with blood loss.

Methods

In 50 cardiac surgical patients, blood was sampled at 10 time points to measure PACT. Simultaneously, platelet reactivity was measured by the thrombin receptor agonist peptide-induced expression of P-selectin, using flow cytometry. These tests were temporally analyzed. PACT values, P-selectin expression, and other coagulation tests were analyzed for correlation with postoperative chest tube drainage.

Results

PACT and P-selectin expression were maximally reduced after protamine administration. Changes in PACT did not correlate with changes in P-selectin expression at any time interval. Total 8-h chest tube drainage did not correlate with any coagulation test at any time point except with P-selectin expression after protamine administration (r = -0.4; P = 0.03).

Conclusions

The platelet dysfunction associated with CPB may be a result of depressed platelet reactivity, as shown by thrombin receptor activating peptide-induced P-selectin expression. Changes in PACT did not correlate with blood loss or with changes in P-selectin expression suggesting that PACT is not a specific measure of platelet reactivity.
Diaphragmatic Activity after Laparoscopic Cholecystectomy
Authors: Sharma Rajiv R. , Axelsson Hans , Oberg Ake , Jansson Erica , Clergue Francois , Johansson Goran , Reiz Sebastian
Published: November 2003

Background

Laparoscopic cholecystectomy is presumed to induce a reduction in diaphragmatic activity. Indirect indices of diaphragmatic function based on tidal changes in pressures and cross-section area measurements can be unreliable in the postoperative phase. The present study evaluates diaphragmatic activity by directly recording diaphragmatic EMG (EMGdia) data, along with indirect indices.

Methods

Thirteen adult patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy were examined preoperatively for inspiratory tidal changes in gastric (Pgas-insp) and esophageal (Peso-insp) pressures, and tidal changes in ribcage (Vthor) and abdominal (Vabd) cross-section areas and then again at 1, 6, and 24 h postoperatively combined with EMGdia recordings. Variations in inspiratory gastric (deltaPgas-insp) and inspiratory transdiaphragmatic (deltaPdi-insp) pressures were derived from the above.

Results

Laparoscopic cholecystectomy induced a significant reduction in mean deltaPgas-insp, mean deltaPdi-insp, and mean Vabd indicating a reduction of diaphragmatic activity postoperatively. DeltaPdi-insp decreased from 11.8+/-4.0 cm H2O preoperatively to 5.7+/-5.7 cm H2O at 1 h and 6.6+/-5.1 cm H2O at 6 h postoperatively (mean +/- SD; P < 0.05). Vabd decreased from 327.0+/-113.0 ml preoperatively to 174.0+/-65.0 ml at 1 h and 175.0+/-98.0 ml at 6 h postoperatively (mean +/- SD; P < 0.05). These values had partially recovered at 24 h.

Conclusion

The direct and indirect indices of diaphragmatic activity taken together confirm the presence of reduction in diaphragmatic activity after laparoscopic cholecystectomy followed by its partial recovery at 24 h.
Morphine-sparing Effect of Acetaminophen in Pediatric Day-case Surgery
Authors: Korpela Reijo , Korvenoja Pekka , Meretoja Olli A.
Published: November 2003

Background

Postoperative pain is a major problem in day-case surgery in children. Nonsteroidal antiinflammatory drugs have gained popularity in management of pediatric surgical patients to reduce the need for opioids. The aim of this study was to evaluate the efficacy of different doses of rectal acetaminophen in day-case surgery in children.

Methods

A randomized, double-blinded, placebo-controlled study design was used. Patients (n = 120) were randomized to receive a single dose of 0, 20, 40, or 60 mg/kg of rectal acetaminophen after induction of anesthesia. General anesthesia was induced by mask ventilation with sevoflurane (7%) in nitrous oxide and oxygen and maintained with 2.5-4.0% end-tidal sevoflurane. Opioids or local anesthetics were not used. Postoperative pain was evaluated by behavioral assessment and physiologic measurements every 10 min after arrival at the postanesthesia care unit. The pain intensity was scored using a 0-100 visual analog scale used in the authors' clinic. The need for rescue medication, intravenous morphine 0.1 mg/kg, was decided by the nurse, who was unaware of the rectal acetaminophen dose. The parents were interviewed by phone after 24 h regarding pain and its treatment, nausea, and vomiting. Rescue analgesia at home was rectal ibuprofen, 10 mg/kg.

Results

In the postanesthesia care unit pain scores were significantly lower in the 40- and 60-mg/kg groups compared with placebo and 20-mg/kg groups. Acetaminophen resulted in a dose-related reduction in the number of children who required postoperative rescue opioid, with significance reached with 40 or 60 mg/kg doses. Calculated dose of acetaminophen at which 50% of the children not requiring a rescue opioid was 35 mg/kg. The need for rescue analgesia at home during the first 24 h after surgery was also significantly less in patients in the 40- or 60-mg/kg groups than in the 0- or 20-mg/kg groups (20-17 vs. 80-63%). Thirty-three percent of patients receiving placebo had postoperative nausea and vomiting, compared with 0-3% in groups receiving 40 or 60 mg/kg acetaminophen.

Conclusions

A single dose of 40 or 60 mg/kg of rectal acetaminophen has a clear morphine-sparing effect in day-case surgery in children if administered at the induction of anesthesia. Moreover, children with adequate analgesia with acetaminophen have less postoperative nausea and vomiting.
Different Actions of General Anesthetics on the Firing Patterns of Neocortical Neurons Mediated by the GABAAReceptor
Authors: Antkowiak Bernd
Published: November 2003

Background

In cultured slice preparations of rat neocortical tissue, clinically relevant concentrations of volatile anesthetics mainly decreased action potential firing of neurons by enhancing gamma-aminobutyric acid (GABA(A)) receptor-mediated synaptic inhibition. The author's aim was to determine if other anesthetic agents are similarly effective in this model system and act via the same molecular mechanism.

Methods

The actions of various general anesthetics on the firing patterns of neocortical neurons were investigated by extracellular single-unit recordings.

Results

Pentobarbital, propofol, ketamine, and ethanol inhibited spontaneous action potential firing in a concentration-dependent manner. The estimated median effective concentration (EC50) values were close to or below the EC50 values for general anesthesia. Bath application of the GABA(A) antagonist bicuculline (100 microM) decreased the effectiveness of propofol, ethanol, halothane, isoflurane, enflurane, and diazepam by more than 90%, indicating that these agents acted predominantly via the GABA(A) receptor. The depressant effects of pentobarbital and ketamine were not significantly reduced by bicuculline treatment. Drugs acting mainly via the GABA(A) receptor altered the firing patterns of neocortical cells in different manners. Diazepam reduced the discharge rates by decreasing the number of action potentials per burst, leaving the burst rate unaffected. In contrast, muscimol, GABA, propofol, and volatile anesthetics decreased the burst rate.

Conclusions

Although several anesthetic agents acted nearly exclusively via the GABA(A) receptor, they changed the discharge patterns of cortical neurons in different ways. This finding is explained by GABA-mimetic or benzodiazepine-like molecular interactions.
Analgesic Interaction between Intrathecal Midazolam and Glutamate Receptor Antagonists on Thermal-induced Pain in Rats
Authors: Nishiyama Tomoki , Gyermek Laszlo , Lee Chingmuh , Kawasaki-Yatsugi Sachiko , Yamaguchi Tokio
Published: November 2003

Background

Two major neurotransmitters, gamma-aminobutyric acid (GABA) and the excitatory amino acid, glutamate, may be involved in nociception in the spinal cord. GABA and glutamate receptors may operate in concert to modify signals in the central nervous system. The purpose of this study was to investigate the spinal analgesic interaction between midazolam, a benzodiazepine-GABA(A) receptor agonist, and two glutamate receptor antagonists on acute thermal nociception.

Methods

Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters and were tested for their tail withdrawal response by the tail flick test after intrathecal administration of saline, midazolam (1-100 microg), AP-5 (1-30 microg), or YM872 (0.3-30 microg). AP-5 is an N-methyl-D-aspartate (NMDA) receptor antagonist and YM872 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist. The combination of midazolam and the other two agents were also tested by isobolographic analyses. Motor disturbance and behavioral changes were observed.

Results

Dose-dependent increases in the tail flick latency were observed with midazolam, AP-5, and YM872 with 50% effective dose values of 1.57+/-0.34 (SEM) microg, 5.54+/-0.19 microg, and 1.0+/-0.22 microg, respectively. A potent synergy in analgesia with decreased behavioral changes and motor disturbance was obtained when combining midazolam with AP-5 or YM872.

Conclusions

Spinally administered midazolam and an NMDA- or an AMPA-receptor antagonist exhibited potent synergistic analgesia on acute thermal nociception in rats. Side effects, shown by behavioral changes and motor disturbance, decreased with the combination of the agents. These results point out an important direction for the study of acute nociception.
New Insights into the Pathomechanism of Postintubation Arytenoid Subluxation
Authors: Paulsen Friedrich P. , Rudert Heinrich H. , Tillmann Bernhard N.
Published: November 2003

Background

Impaired movement of the cricoarytenoid joint with hoarseness and immobility of the vocal ligament can occur as a consequence of endotracheal intubation. The biomechanics and pathomechanism of cricoarytenoid subluxation have not been demonstrated to date.

Methods

The present study attempts to simulate the trauma that has been associated with arytenoid cartilage subluxation in intubation trials on 37 unfixed larynges in cadavers from persons aged 25 to 89 years. Larynges were intubated or extubated according to former conceptions of arytenoid subluxation, which assume that the arytenoid tip enters the lumen of the tracheal tube, or that a deflection of the arytenoid occurs during withdrawal of the endotracheal tube with the cuff of the tube only partially deflated. Also, manual attempts were carried out to subluxate the arytenoid cartilage. Subsequently after dissecting the left and right cricoarytenoid joint from each larynx, the morphologic changes induced experimentally were analyzed using gross microscopic and histologic methods.

Results

Within the scope of the experiment, it proved impossible to produce any subluxation of a cricoarytenoid joint. Histologic analysis revealed injuries of synovial folds, joint-surface impressions of the articular cartilage, and fractures in the area of the subchondral bone in some joints.

Conclusions

Based on the morphologic results, it was concluded that intubation trauma of the cricoarytenoid joint does not cause subluxation per se, but rather that formation of a hemarthros or fractures of the joint bodies lead to fixation of the joint surfaces in an abnormal position. Subsequent ankylosis may occur.
Direct Cerebral Vasodilatory Effects of Sevoflurane and Isoflurane
Authors: Matta Basil F. , Heath Karen J. , Tipping Kate , Summors Andrew C.
Published: November 2003

Background

The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram.

Methods

Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 micro/g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels.

Results

Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4+/-3 and 17+/-3% at 0.5 and 1.5 MAC sevoflurane; 19+/-3 and 72+/-9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P<0.05). All patients required phenylephrine (100-300 microg) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia.

Conclusions

In common with other volatile anesthetic agents, sevoflurane has an intrinsic dose-dependent cerebral vasodilatory effect. However, this effect is less than that of isoflurane.
Sevoflurane Mimics Ischemic Preconditioning Effects on Coronary Flow and Nitric Oxide Release in Isolated Hearts
Authors: Novalija Enis , Fujita Satoshi , Kampine John P. , Stowe David F.
Published: November 2003

Background

Like ischemic preconditioning, certain volatile anesthetics have been shown to reduce the magnitude of ischemia/ reperfusion injury via activation of K+ adenosine triphosphate (ATP)-sensitive (K(ATP)) channels. The purpose of this study was (1) to determine if ischemic preconditioning (IPC) and sevoflurane preconditioning (SPC) increase nitric oxide release and improve coronary vascular function, as well as mechanical and electrical function, if given for only brief intervals before global ischemia of isolated hearts; and (2) to determine if K(ATP) channel antagonism by glibenclamide (GLB) blunts the cardioprotective effects of IPC and SPC.

Methods

Guinea pig hearts were isolated and perfused with Krebs-Ringer's solution at 55 mm Hg and randomly assigned to one of seven groups: (1) two 2-min total coronary occlusions (preconditioning, IPC) interspersed with 5 min of normal perfusion; (2) two 2-min occlusions interspersed with 5 min of perfusion while perfusing with GLB (IPC+GLB); (3) SPC (3.5%) for two 2-min periods; (4) SPC+GLB for two 2-min periods; (5) no treatment before ischemia (control [CON]); (6) CON+GLB; and (7) no ischemia (time control). Six minutes after ending IPC or SPC, hearts of ischemic groups were subjected to 30 min of global ischemia and 75 min of reperfusion. Left-ventricular pressure, coronary flow, and effluent NO concentration ([NO]) were measured. Flow and NO responses to bradykinin, and nitroprusside were tested 20-30 min before ischemia or drug treatment and 30-40 min after reperfusion.

Results

After ischemia, compared with before (percentage change), left-ventricular pressure and coronary flow, respectively, recovered to a greater extent (P<0.05) after IPC (42%, 77%), and treatment with SPC (45%, 76%) than after CON (30%, 65%), IPC+GLB (24%, 64%), SPC+GLB (20%, 65%), and CON+GLB (28%, 64%). Bradykinin and nitroprusside increased [NO] by 30+/-5 (means +/- SEM) and 29+/-4 nM, respectively, averaged for all groups before ischemia. [NO] increased by 26+/-6 and 27+/-7 nM, respectively, in SPC and IPC groups after ischemia, compared with an average [NO] increase of 8+/-5 nM (P<0.01) after ischemia in CON and each of the three GLB groups. Flow increases to bradykinin and nitroprusside were also greater after SPC and IPC.

Conclusions

Preconditioning with sevoflurane, like IPC, improves not only postischemic contractility, but also basal flow, bradykinin and nitroprusside-induced increases in flow, and effluent [NO] in isolated hearts. The protective effects of both SPC and IPC are reversed by K(ATP) channel antagonism.
Microcirculatory Basis for Nonuniform Flow Delivery with Intravenous Nitroprusside
Authors: Mustafa Shahzad S. , Rivers Richard J. , Frame Mary D. S.
Published: November 2003

Background

The purpose of this study was to determine the effects of systemic infusions of nitroglycerin and sodium nitroprusside on flow distribution and wall shear stress in the microcirculation.

Methods

With university approval, the cremaster muscle of 28 anesthetized (70 mg/kg pentobarbital given intraperitoneally) hamsters (Harlan Sprague Dawley: Syrian; weight, 121+/-11 g [mean +/- SDD) was observed using in vivo fluorescence microscopy. Arteriolar diameter, erythrocyte flux, and velocity were measured for a feed arteriole and its sequential branches. Observations were made during control (mean arterial pressure, 88+/-4 mm Hg) and after 30 min of intravenous delivery of sodium nitroprusside or nitroglycerin, titrated to decrease mean arterial pressure by 20 mm Hg.

Results

Sodium nitroprusside significantly dilated select upstream portions of the network (23+/-2.6 to 29+/-2.6 microm); no arterioles were dilated with nitroglycerin. Erythrocyte flux into the feed (i.e., inflow into the arteriolar network) and into the sequential branches (i.e., distribution within the network) were evaluated. With nitroglycerin, inflow decreased significantly from 1,560+/-335 to 855+/-171 cells/s, and flux into the branches decreased evenly. With sodium nitroprusside, inflow increased significantly to 2,600+/-918 cells/s, yet cells were "stolen" from upstream branches (a decrease from 425+/-67 to 309+/-87 cells/s in the first branch). Excess flow passed into a downstream "thorough-fare channel," significantly increasing flux from 347+/-111 to 761+/-246 cells/s. Wall shear stress decreased uniformly with nitroglycerin infusion, with a decrease in the feed from 8.8+/-2.5 to 6+/-1.7 dyn/cm2. With sodium nitroprusside, variable changes occurred that were location specific within the network. For instance, at the inflow point to the network, wall shear stress changed from 8.3+/-2.5 to 4.2+/-3.3 dyn/cm2.

Conclusions

Nitroglycerin infusion promoted homogeneity of flow. Sodium nitroprusside significantly increased the heterogeneity of flow within this arteriolar network; an anatomic location for steal induced by sodium nitroprusside is identified.
High-dose Nitric Oxide Inhalation Increases Lung Injury after Gastric Aspiration
Authors: Nader Nader D. , Knight Paul R. , Bobela Iwona , Davidson Bruce A. , Johnson Kent J. , Morin Frederick
Published: November 2003

Background

Inhaled nitric oxide is often used in patients with adult respiratory distress syndrome. However, nitric oxide also may be significantly toxic, especially if administered concurrently with hyperoxia. The authors evaluated the isolated effect of nitric oxide and the combined effects of nitric oxide and hyperoxia on lung injury in rats after acid aspiration.

Methods

Animals were injured by instillation of 1.2 ml/kg hydrogen chloride in low-pH saline (the acid group) or acidified gastric particles (the casp group) into the lungs under halothane anesthesia via a tracheal catheter. Controls received no injury vehicle but rather underwent the surgical process. After recovery from anesthesia, the animals were exposed to 20% or 90% oxygen with or without 20, 40, or 80 ppm nitric oxide for 5 h. The permeability index, alveolar-arterial oxygen difference, the ratio of oxygen pressure to the inspired fraction of oxygen, and the ratio of wet to dry weight were assessed 5 h after injury as indices of lung injury. Data were assessed using analysis of variance.

Results

Each group included 6-10 rats. Exposure to nitric oxide (80 ppm) in air increased protein permeability in the lungs to a permeability index of 1.42+/-0.12 after acid aspiration. The combination of nitric oxide (80 ppm) and hyperoxia further increased protein leakage to a permeability index of 2.1+/-0.25. Exposure to lower concentrations of nitric oxide (e.g., 20 and 40 ppm) increased the permeability index of the lungs (1.44+/-0.21, 1.75+/-0.29, respectively) in the presence of hyperoxia, although it did not affect the permeability index of the lungs during exposure to air. Pretreatment of animals with deferoxamine and methylene blue partially inhibited the adverse effect of hyperoxia and nitric oxide, which suggested a complex underlying mechanism involving both reactive-species generation and pulmonary vasomotor changes.

Conclusions

These results show that inhaled nitric oxide at 80 ppm for a short duration (5 h) increases the severity of the inflammatory microvascular lung injury after acid aspiration. The pulmonary damage is exacerbated further in the presence of high oxygen concentrations. Although lower concentrations of nitric oxide did not increase the extent of lung injury, longer exposure times need to be assessed.
Ketamine Preserves and Propofol Potentiates Hypoxic Pulmonary Vasoconstriction Compared with the Conscious State in Chronically Instrumented Dogs
Authors: Nakayama Masayasu , Murray Paul A.
Published: November 2003

Background

The authors tested the hypothesis that ketamine and propofol anesthesia would alter the magnitude of hypoxic pulmonary vasoconstriction compared with the conscious state. In addition, they assessed the extent to which cyclooxygenase pathway inhibition and adenosine triphosphate-sensitive potassium channel inhibition modulate hypoxic pulmonary vasoconstriction in the conscious state, and whether these pathways are altered during propofol anesthesia.

Methods

Twenty conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow relationship. Pressure-flow plots were measured during normoxia and hypoxia (systemic arterial PO2 reduced to about 60 and about 50 mm Hg) on separate days in the conscious state, during ketamine anesthesia, and during propofol anesthesia. The effects of indomethacin and glibenclamide on the magnitude of hypoxic pulmonary vasoconstriction were also assessed in the conscious and propofol-anesthetized states.

Results

Neither ketamine nor propofol had an effect on the baseline pressure-flow relationship during normoxia compared with the conscious state. Hypoxia resulted in stimulus-dependent pulmonary vasoconstriction (P<0.01) in the conscious state. Compared with the conscious state, the magnitude of hypoxic pulmonary vasoconstriction was preserved during ketamine but was potentiated (P<0.01) during propofol anesthesia. Indomethacin enhanced (P<0.01) hypoxic pulmonary vasoconstriction in both the conscious and propofol-anesthetized states. In contrast, glibenclamide only enhanced (P<0.01) hypoxic pulmonary vasoconstriction in the conscious state and had no effect during propofol anesthesia.

Conclusion

Hypoxic pulmonary vasoconstriction is preserved during ketamine anesthesia but is potentiated during propofol anesthesia. The potentiated response during propofol anesthesia appears to be caused by inhibition of adenosine triphosphate-sensitive potassium channel-mediated pulmonary vasodilation.
Combining Partial Liquid Ventilation and Prone Position in Experimental Acute Lung Injury
Authors: Max Martin , Kuhlen Ralf , López Frank , Reyle-Hahn Stefan Matthias , Baumert Jan Hinrich , Rossaint Rolf
Published: November 2003

Background

Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI.

Methods

ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position.

Results

In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone.

Conclusions

The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs.
Effects of Halothane on Synaptic Neurotransmission to Medullary Expiratory Neurons in the Ventral Respiratory Group of Dogs
Authors: Stuth Eckehard A. E. , Krolo Mirko , Tonkovic-Capin Mislav , Hopp Francis A. , Kampine John P. , Zuperku Edward J.
Published: November 2003

Background

The activity of canine expiratory neurons is primarily dependent on N-methyl-D-aspartic acid (NMDA)-receptor mediated excitatory chemodrive inputs and a powerful inhibitory gain modulatory mechanism mediated via gamma-aminobutyric acidA (GABA(A)) receptors. We examined whether the depressant effect of halothane on expiratory neuronal activity is primarily caused by a reduction in glutamatergic excitation or a potentiation of the inhibitory mechanism.

Methods

Experiments were performed in halothane-anesthetized, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of a halothane dose increase from one minimum alveolar concentration (MAC) to 2 MAC on extracellularly recorded expiratory neuronal activity was studied before and during complete GABA(A) receptor blockade by localized picoejection of bicuculline close to the neuron. Complete blockade of the inhibitory mechanism allowed differentiation between the effects of halothane on overall NMDA-mediated excitation and on GABA(A)-mediated inhibition.

Results

The spontaneous activity of 12 expiratory neurons was significantly depressed (18.1%) by the 1-MAC halothane dose increase. Overall glutamatergic excitation was depressed 38.3+/-12.3% (mean +/- SD) by the 1-MAC halothane increase. The prevailing GABA(A)ergic attenuation of neuronal output decreased significantly from 49.5+/-10 to 32.0+/-10.4%. Thus overall inhibition was reduced by halothane by 33.5+/-17.2%.

Conclusions

These results suggest that the depressive effect of a 1-MAC halothane dose increase on expiratory neuronal activity in our in vivo preparation with an intact neural network was mainly caused by a reduction of synaptic excitatory mechanisms and not an enhancement of synaptic inhibitory mechanisms.
Preclinical Toxicity Screening of Intrathecal Adenosine in Rats and Dogs
Authors: Chiari Astrid , Yaksh Tony L. , Myers Robert R. , Provencher Jean , Moore Lisa , Lee Choong-Sik , Eisenach James C.
Published: November 2003

Background

Intrathecally administered adenosine receptor agonists have antinociceptive effects in animals, suggesting that intrathecal adenosine might provide analgesia in humans. The authors performed preclinical neurotoxicity studies to define the safety of intrathecally administered adenosine in rats and dogs.

Methods

Eighteen rats with long-term intrathecal catheters received daily injections of saline or 100 microg adenosine for 4 days and were observed for general behavior and thermal nociception before being killed on day 6. Nine beagle dogs were prepared with long-term, lumbar intrathecal catheters and infused continuously with saline or adenosine, 2.4 mg/day for 48 h, then 7.2 mg/day for 26 days. Animals were then anesthetized and perfused with preservative and their spinal cords were examined systematically.

Results

No disturbances in neurologic function were detected in either animal species. intrathecal adenosine caused transient sedation in rats and increased muscle tone in dogs, resolving with continued exposure to drug. Neither adenosine-nor saline-treated rats or dogs showed acute thermal analgesia. Adenosine groups did not differ from saline groups regarding histopathology, although a moderate fibrotic and inflammatory reaction was noted in both, and protein concentrations in cerebrospinal fluid were increased in both.

Conclusion

The current study in rats and dogs failed to provide behavioral or histologic evidence of neurotoxicity from intrathecal administration of adenosine. This provides evidence for the presumption of safety of adenosine in this dose range, and supports phase I safety trials of acute intrathecal adenosine administration in humans.