bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propofol Attenuates Hydrogen Peroxide-induced Mechanical and Metabolic Derangements in the Isolated Rat Heart
Authors: Kokita Naohiro , Hara Akiyoshi 
Published: November 2003

Background
Oxygen-derived free radicals are involved in tissue damage during myocardial ischemia and reperfusion. Recent in vitro studies have demonstrated that a beneficial effect of propofol lies on its free radical scavenging properties. The current study, therefore, examined whether propofol is effective against the mechanical and metabolic damage induced by exogenously administered hydrogen peroxide in the isolated rat heart.

Methods
Rat hearts were perfused aerobically with Krebs-Henseleit bicarbonate buffer at a constant flow rate according to Langendorff's technique, while being paced electrically. Hearts were studied in control Krebs-Henseleit bicarbonate buffer, with Intralipid vehicle, with 25 microM or 50 microM propofol for 40 min, and with 50 microM propofol for 30 min followed by Intralipid for 10 min. A similar set of hearts was treated with hydrogen peroxide for 4 min, either in the absence of or beginning 10 min after Intralipid or propofol infusion. Left ventricular pressure was recorded as an index of mechanical function. The tissue concentrations of adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and creatine phosphate were measured as indices of energy metabolism. The tissue concentration of malondialdehyde was measured to evaluate lipid peroxidation.

Results
Hydrogen peroxide (600 microM) significantly increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., it produced mechanical dysfunction), and decreased tissue concentrations of adenosine triphosphate and creatine phosphate (i.e., metabolic damage). Hydrogen peroxide also increased the tissue concentration of malondialdehyde. These mechanical and metabolic alterations induced by hydrogen peroxide were significantly attenuated by propofol (25 microM or 50 microM), while the increase in malondialdehyde was completely suppressed by propofol.

Conclusions
The current study demonstrates that in the isolated heart, propofol attenuates both mechanical and metabolic changes induced by exogenously applied hydrogen peroxide. The beneficial action of propofol is probably correlated with reduction of the hydrogen peroxide-induced lipid peroxidation.
Effect of Blood Pressure Changes on Air Flow Dynamics in the Upper Airway of the Decerebrate Cat
Authors: Mayor Alexander H. , Schwartz Alan R. , Rowley James A. , Willey Shannon J. , Gillespie Boyd M. , Smith Philip L. , Robotham James L. 
Published: November 2003

Background
Previous studies suggest that upper airway neuromuscular activity can be affected by changes in blood pressure via a baroreceptor-mediated mechanism. It was hypothesized that increases in blood pressure would increase upper airway collapsibility predisposing to airway obstruction at a flow-limiting site in the hypopharynx.

Methods
To examine the effect of blood pressure on upper airway function, maximal inspiratory air flow was determined through the isolated feline upper airway before, during, and after intravenous infusion of phenylephrine (10-20 micrograms.kg-1.min) in six decerebrate, tracheotomized cats. Inspiratory flow, hypopharyngeal pressure, and pressure at the site of pharyngeal collapse were recorded as hypopharyngeal pressure was rapidly decreased to achieve inspiratory flow limitation in the isolated upper airway. Pressure-flow relationships were used to determine maximal inspiratory air flow and its mechanical determinants, the upper airway critical pressure (a measure of pharyngeal collapsibility), and the nasal resistance upstream to the site of flow limitation.

Results
An increased mean arterial blood pressure of 71 +/- 16 mmHg (mean +/- SD) was associated with significant decrease in maximal inspiratory air flow from 147 +/- 38 ml/s to 115 +/- 27 ml.sec-1 (P < 0.01). The decrease in maximal inspiratory air flow was associated with an increase in upper airway critical pressure from -8.1 +/- 3.8 to -5.7 +/- 3.7 cm H2O (p < 0.02), with no significant change in nasal resistance. When blood pressure was decreased to baseline by discontinuing the phenylephrine infusion, maximal inspiratory air flow and upper airway critical pressure returned to their baseline values.

Conclusions
Increased blood pressure increased the severity of upper airway air flow obstruction by increasing pharyngeal collapsibility. Previous studies relating baroreceptor activity to neuromuscular regulation of upper airway tone, are consistent with this effect being mediated by afferent activity from baroreceptors. These findings warrant further study because they suggest the possibility that upper airway obstruction in postoperative patients could either be caused or exacerbated by an increase in blood pressure.
Effects of Ventilation on Hemodynamics and Myocardial Blood Flow during Active Compression-Decompression Resuscitation in Pigs
Authors: Prengel Andreas W. , Lindner Karl H. , Pfenninger Ernst G. , Georgieff Michael 
Published: November 2003

Background
Active compression-decompression (ACD) improves hemodynamics and vital organ blood flow during cardiopulmonary resuscitation. The effects of intermittent positive pressure ventilation (IPPV) on ACD have not been studied. This study was designed to compare the effects of ACD with and without IPPV on gas exchange, hemodynamics, and myocardial blood flow.

Methods
After 30 s ventricular fibrillation, 14 tracheally intubated pigs were allocated to receive either ACD combined with IPPV (ACD-IPPV) or ACD alone. In animals treated with ACD-IPPV, the lungs were ventilated using a servo ventilator. Animals treated with ACD received 100% oxygen by a reservoir but ventilation was not assisted.

Results
Minute ventilation (median) was 6.5 and 6.1 l/min after 1 and 7 min of ACD-IPPV, and was 4.2 and 1.6 l/min after 1 and 7 min of ACD. In contrast to ACD-IPPV, PaO2 was less and PaCO2 was greater with ACD. Mean arterial (53 and 40 mmHg; P < 0.05) and mean central venous pressure (25 and 14 mmHg; P < 0.01) were greater during ACD-IPPV as compared with ACD. After administration of epinephrine 0.2 mg/kg, myocardial blood flow increased only in ACD-IPPV treated animals, and 5 min after epinephrine administration, myocardial blood flow was greater during ACD-IPPV (33 ml.min-1.100 g-1) as compared with ACD (15 ml.min-1.100 g-1; P < 0.05). Restoration of spontaneous circulation could be achieved only in animals subjected to ACD-IPPV.

Conclusions
Gas exchange was critically impaired during the late phase of ACD. Compared with ACD-IPPV, myocardial blood flow was less preserved with ACD and was too low to achieve restoration of spontaneous circulation.
Intravenous Opioids Stimulate Norepinephrine and Acetylcholine Release in Spinal Cord Dorsal Horn
Authors: Bouaziz Herve , Tong Chuanyao , Yoon Young , Hood David D. , Eisenach James C. 
Published: November 2003

Background
Opioids produce analgesia by direct effects as well as by activating neural pathways that release nonopioid transmitters. This study tested whether systematically administered opioids activate descending spinal noradrenergic and cholinergic pathways.

Methods
The effect of intravenous morphine on cerebrospinal fluid and dorsal horn microdialysate concentrations of norepinephrine and acetylcholine was examined in 20 sheep. Animals received either intravenous morphine or fentanyl alone, or morphine plus intravenous naloxone or intrathecal idazoxan.

Results
Intravenous morphine (0, 0.5, 1 mg/kg, intravenous) produced dose-dependent increases in cerebrospinal fluid norepinephrine and acetylcholine, but not epinephrine or dopamine. Morphine's effect was blocked by intravenous naloxone and by intrathecal idazoxan. In microdialysis experiments, intravenous morphine increased the concentration of norepinephrine and acetylcholine, but not epinephrine or dopamine, in the dorsal horn. In contrast, intravenous morphine exerted no effect on any of these monoamines in the ventral horn. Intravenous naloxone and cervical cord transection each blocked morphine's effect on dorsal horn norepinephrine.

Conclusions
These results support functional studies that indicate that systematically administered opioids cause spinal norepinephrine and acetylcholine release by a naloxone-sensitive mechanism. Idazoxan blockade of morphine's effects on cerebrospinal fluid norepinephrine was unexpected, and suggests that both norepinephrine and acetylcholine release in the spinal cord may be regulated by alpha 2-adrenoceptors. Microdialysis experiments suggest increased norepinephrine and acetylcholine levels in cerebrospinal fluid resulted from intravenous morphine-induced activation of bulbospinal pathways.
Continuous Intracisternal and High Cervical Intrathecal Bupivacaine Analgesia in Refractory Head and Neck Pain
Authors: Appelgren Lennart , Janson Magnus , Nitescu Petre , Curelaru Ioan 
Published: November 2003

Background
The upper cervical component of the spinomesencephalic tract and cranial nerves V, VII (nervus intermedius), IX, and X are involved in mechanisms of acute and chronic pain from head and neck structures. To date there is no reliable method for relief of refractory pain (i.e., pain that cannot be relieved by conventional pharmacologic therapies) from these structures. Therefore, we explored continuous intracisternal infusion of bupivacaine for the treatment of refractory pain of the head and neck.

Methods
Intracisternal catheters were inserted in 13 adults with refractory nonmalignant (n = 4) and malignant (n = 9) pain from the head, face, mouth, neck, and upper extremities; 0.5% plain bupivacaine was infused continuously at rates of 1-7 (median 1.5) mg/h with optional bolus doses of 0.5-2.0 mg 4-2 times/h. The efficacy was assessed from pain relief (daily VAS(max), VAS(min), and VAS(mean) scores 0-10), daily doses of intracisternal bupivacaine and total opioid (expressed as mg parenteral morphine-eq), amount of nocturnal sleep, and rates of adverse effects.

Results
The 13 patients were treated for 3-182 days (median 37, total 712 days), 3 patients being treated at home for 10-112 days (median 88, total 210 days). In one patient, the efficacy of the treatment could not be estimated because of advanced senility. Eleven of the remaining 12 patients obtained acceptable pain relief with daily doses of intracisternal bupivacaine ranging from 20 to 118 mg (median 37 mg): VAS(mean) scores decreased from 7 to 2, mean pain relief increased for 30% to 80%, total opioid daily dose decreased from 53 to 36 mg parenteral morphine-eq, and nocturnal sleep increased from 2 to >6h (all figures are median values). Speech, eating, walking, and natural functions were generally not affected. Side effects such as tiredness and malaise, somnolence and sleep, feeling of coldness in the neck and skull base, transient post-spinal puncture headache, paresthesias, hoarseness, dysphagia, transient paresis of the upper/lower extremities, episodic miosis and conjunctival hyperemia, and transient orthostatic arterial hypotension were each observed in one or two patients. No patient presented clinical evidence of phrenic nerve paralysis. There was no nausea or vomiting. No persistent neurologic deficit or death could be attributed to the intracisternal pain treatment.

Conclusions
Continuous intracisternal infusion of bupivacaine may be a useful method in exceptional, well selected patients with refractory pain from the head and neck structures. Further studies are necessary to establish the indications and the safety of the method.
Magnetic Resonance Imaging of the Upper Airway
Authors: Mathru Mali , Esch Oliver , Lang John , Herbert Michael E. , Chaljub Gregory , Goodacre Brian , vanSonnenberg Eric 
Published: November 2003

Background
Anesthetic agents inhibit the respiratory activity of upper airway muscles more than the diaphragm, creating a potential for narrowing or complete closure of the pharyngeal airway during anesthesia. Because the underlying mechanisms leading to airway obstruction in sleep apnea and during anesthesia are similar, it was hypothesized that anesthesia-induced pharyngeal narrowing could be counteracted by applying nasal continuous positive airway pressure (CPAP).

Methods
Anesthesia was induced in ten healthy volunteers (aged 25-34 yr) by intravenous administration of propofol in 50-mg increments every 30-s to a maximum of 300 mg. Magnetic resonance images of the upper airway (slice thickness of 5 mm or less) were obtained in the awake state, during propofol anesthesia, and during administration of propofol plus 10 cm nasal CPAP.

Results
Minimum anteroposterior diameter of the pharynx at the level of the soft palate decreased from 6.6 +/- 2.2 mm (SD) in the awake state to 2.7 +/- 1.5 mm (P < 0.05) during propofol anesthesia and increased to 8.43 +/- 2.5 mm (P < 0.05) after nasal CPAP application. Anteroposterior diameter of the pharynx at the level of the dorsum of the tongue increased from 7.9 +/- 3.5 mm during propofol anesthesia to 12.9 +/- 3.6 mm (P < 0.05) after nasal CPAP. Pharyngeal volume (from the tip of the epiglottis to the tip of the soft palate, assuming this space to be a truncated cone) significantly increased from 2,437 +/- 1,008 mm3 during propofol anesthesia to 5,847 +/- 2,827 mm3 (P < 0.05) after nasal CPAP application.

Conclusions
In contrast to the traditional view that relaxation of the tongue causes airway obstruction, this study suggests that airway closure occurs at the level of the soft palate. Application of nasal CPAP can counteract an anesthesia-induced pharyngeal narrowing by functioning as a pneumatic splint. This is supported by the observed reduction in anteroposterior diameter at the level of the soft palate during propofol anesthesia and the subsequent increase in this measurement during nasal CPAP application.
Inotropic Effects of Propofol, Thiopental, Midazolam, Etomidate, and Ketamine on Isolated Human Atrial Muscle
Authors: Gelissen Harry P. M. M. , Epema Anne H. , Henning Robert H. , Krijnen H. John , Hennis Pim J. , den Hertog Adriaan 
Published: November 2003

Background
Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically.

Methods
Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10(-6) to 10(-2) M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental, midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol.

Results
The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC50s (mean +/- SEM; microM) for inhibition of the contractility were: thiopental 43 +/- 7.6, propofol 235 +/- 48 (group 1), and 246 +/- 42 (group 2), midazolam 145 +/- 54, etomidate 133 +/- 13, and ketamine 303 +/- 54.

Conclusions
This is the first study demonstrating a concentration-dependent negative inotropic effect of intravenous anesthetics in isolated human atrial muscle. No inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. In contrast, thiopental showed strong and ketamine showed slight negative inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol, midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation.
Pharmacokinetics of Propofol after a Single Dose in Children Aged 1–3 Years with Minor Burns
Authors: Murat I. , Billard V. , Vernois J. , Zaouter M. , Marsol P. , Souron R. , Farinotti R. 
Published: November 2003

Background
No complete pharmacokinetic profile of propofol is yet available in children younger than 3 yr, whereas clinical studies have demonstrated that both induction and maintenance doses of propofol are increased with respect to body weight in this age group compared to older children and adults. This study was therefore undertaken to determine the pharmacokinetics of propofol after administration of a single dose in aged children 1-3 yr requiring anesthesia for dressing change.

Methods
This study was performed in 12 children admitted to the burn unit and in whom burn surface area was less than or equal to 12% of total body surface area. Exclusion criteria were: unstable hemodynamic condition, inappropriate fluid loading, associated pulmonary injury, or burn injury older than 2 days. Propofol (4 mg.kg(-1))plus fentanyl (2.5 microg.kg(-1)) was administered while the children were bathed and the burn area cleaned during which the children breathed spontaneously a mixture of oxygen and nitrous oxide (50:50). Venous blood samples of 300 microl were obtained at 5, 15, 30, 60, 90, and 120 min, and 3, 4, 8, and 12 thereafter injection; an earlier sample was obtained from 8 of 12 children. The blood concentration curves obtained for individual children were analyzed by three different methods: noncompartmental analysis, mixed effects population model, and standard two-stage analysis.

Results
Using noncompartmental analysis, total clearance of propofol (+/-SD) was 0.053+/-0.013l.kg(-1).min(-1), volume of distribution at steady state9.5 +/- 3.7l.kg(-1),and residence time 188 +/- 85 min. Propofol pharmacokinetics were best described by a weight-proportional three-compartmental model in both population and two-stage analysis. Estimated and derived pharmacokinetic parameters were similar using these two pharmacokinetic approaches. Results of population versus two-stage analysis are as follow: systemic clearance 0.049 versus 0.048 l.kg(-).min(-1), volume of central compartment 1.03 versus 0.95 l.kg(-1), volume of steady state 8.09 versus 8.17 l.kg(-1).

Conclusions
The volume of the central compartment and the systemic clearance were both greater than all values reported in older children and adults. This is consistent with the increased propofol requirements for both induction and maintenance of anesthesia in children 1-3 yr. (Key words: Anesthesia: pediatric. Pharmacokinetics: propofol.)
Spinal Antinociceptive Action of an N-Type Voltage-dependent Calcium Channel Blocker and the Synergistic Interaction with Morphine
Authors: Omote Keiichi , Kawamata Mikito , Satoh Osamu , Iwasaki Hiroshi , Namiki Akiyoshi 
Published: November 2003

Background
Four different voltage-dependent calcium channels (L-, N-, T-, and P-types) are distinguished in the central nervous system. Both L- and N-type calcium channels have been implicated in the release of neurotransmitters from sensory neurons in the spinal cord. It has been demonstrated that intrathecal L-type calcium channel blockers, which alone do not exhibit any antinociceptive effects, potentiate the antinociceptive effect of intrathecal morphine. The current study was designed to investigate the antinociceptive effects of the intrathecally administered N-type calcium channel blocker, omega-conotoxin GVIA (omega-CgTx). The interaction between morphine and omega-CgTx at the level of the spinal cord also was examined.

Methods
In male Sprague-Dawley rats, lumbar intrathecal catheters were chronically implanted. Tail flick and mechanical paw pressure tests were used to assess thermal and mechanical nociceptive thresholds, respectively. Morphine, omega-CgTx, or a combination of morphine and omega-CgTx was administered intrathecally, and the nociceptive thresholds were determined. Isobolographic analyses were used to define the nature of the functional interactions between morphine and omega-CgTx.

Results
Intrathecal omega-CgTx produced antinociception in a dose- and time-dependent manner. Isobolographic analyses revealed that intrathecal omega-CgTx and morphine interacted synergistically in both nociceptive tests.

Conclusions
This study indicates the importance of the N-type calcium channel in the spinal cord on nociception and suggests the functional interaction between the N-type calcium channel blocker and opioid at the level of the spinal cord.
Cardiovascular Events in the Postanesthesia Care Unit
Authors: Rose D. Keith , Cohen Marsha M. , DeBoer Donald P. 
Published: November 2003

Background
The purpose of this study was to determine the relationship of four postanesthesia care unit (PACU) cardiovascular events to long-term outcomes (unplanned critical care admission or mortality) and to evaluate the contribution of anesthetic management compared with other perioperative factors in predicting these events.

Methods
For patients admitted to the PACU after receiving general anesthesia (n = 18,380), the risk of long-term outcomes was examined for patients in the PACU with hypertension, tachycardia, bradycardia, or hypotension. Using logistic regression (P < 0.05), risk factors (grouped as patients, surgical, anesthetic, operating room observations, and other PACU observations) for each cardiovascular event were determined. For each factor grouping, the relative contributions to each cardiovascular event were compared using maximum likelihood chi-square analysis.

Results
Patients in the PACU with hypertension or tachycardia had more unplanned critical care admissions (2.6% and 4.0% vs. 0.2% for patients with no events) and greater mortality (1.9% and 2.3% vs. 0.3% and 0.4%) (P < 0.01). For PACU hypertension (rate 2.0%), age, smoking, renal disease, female gender, and angina were significant risk factors. For PACU tachycardia (0.9%), intraoperative tachycardia and dysrhythmia were the major contributors. Patient factors also increased the risk of bradycardia (2.5%); namely age, ASA physical status 1 or 2, and preoperative beta blocker therapy. For hypotension (2.2%), duration of surgery > 2 h, completion after 6 PM, and gynecologic intraabdominal procedures were significant risk factors. Compared to patient, surgical, intraoperative, or PACU observations, anesthetic factors studied (premedication, induction agent, ventilation, use of opioids) provided only a small contribution in predicting these events.

Conclusions
Hypertension and tachycardia in the PACU, although infrequent, are associated with increased risk of unplanned critical care admission and mortality. Patient, surgical, intraoperative, or PACU observations contribute more to cardiovascular events in the PACU than do differences in anesthetic management identified in this study.