bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Lamotrigine Inhibits Extracellular Glutamate Accumulation during Transient Global Cerebral Ischemia in Rabbits
Authors: Bacher Andreas , Zornow Mark H. 
Published: November 2003

Background
During cerebral ischemia, an influx of Na+ may be partially responsible for the release of the excitatory amino acid glutamate. When glutamate is released in excessive concentrations during ischemia, it may become neurotoxic. The ability of the Na+ channel blocker lamotrigine to inhibit glutamate release during episodes of transient global cerebral ischemia was investigated.

Methods
After approval was given by the animal care and use committee, 24 New Zealand white rabbits were randomly assigned to one of four groups each containing six animals (control, L20, L50, and a hypothermic group). After anesthesia (1% halothane) was induced, the tracheas were intubated and the lungs mechanically ventilated before microdialysis probes were placed in the hippocampus. Ninety minutes before the onset of ischemia, either 20 or 50 mg/kg lamotrigine was administered intravenously (in the L20 and L50 groups). Esophageal temperature was maintained at 38 degrees C in the control. L20 and L50 groups, whereas the animals in the hypothermic group were cooled to 30 degrees C. Two 10-min periods of cerebral ischemia, separated by a 90-min interval, were generated by inflating a neck tourniquet. High-performance liquid chromatography was used to determine the glutamate concentration in the microdialysate. Analysis of variance and Dunnett's test were used for statistical analysis. Data are presented as means +/- SD.

Results
During the first ischemic period, glutamate concentration increased only slightly from baseline. A significant increase was observed during the second ischemic period for the control (sixfold) and the L20 (threefold) groups. Glutamate concentrations in the L50 and the hypothermic groups were significantly lower than in the other two groups and remained at the baseline level during the entire experiment.

Conclusions
This study shows that the Na+ channel blocker lamotrigine is effective in inhibiting extracellular glutamate accumulation during transient global cerebral ischemia. This attenuation of ischemia-induced glutamate release may explain the previously reported neuroprotective properties of Na+ channel blockers.
Hyperlocomotion during Recovery from Isoflurane Anesthesia Is Associated with Increased Dopamine Turnover in the Nucleus Accumbens and Striatum in Mice
Authors: Irifune Masahiro , Sato Tomoaki , Nishikawa Takashige , Masuyama Takashi , Nomoto Masahiro , Fukuda Takeo , Kawahara Michio 
Published: November 2003

Background
It was recently reported that isoflurane increases dopamine release in the striatum in rats both in vivo and in vitro, and that isoflurane inhibits uptake of dopamine in the rat brain synaptosomes. However, the functional role of these effects of isoflurane on dopamine neurons is uncertain. Dopaminergic mechanisms within the nucleus accumbens and striatum play an important role in the control of locomotor activity, and a change in dopamine turnover depends essentially on a change in impulse flow in the dopamine neurons. In this study, the effects of isoflurane on locomotor activity and on dopamine turnover were investigated in discrete brain regions in mice.

Methods
Mice were placed in individual airtight clear plastic chambers and spontaneously breathed isoflurane in 25% oxygen and 75% nitrogen (fresh gas flow, 4 l/min). Locomotor activity was measured with an Animex activity meter. Animals were decapitated after treatments with or without isoflurane, and the concentrations of monoamines and their metabolites in different brain areas were measured by high-performance liquid chromatography.

Results
During the 10 min after the cessation of the 20-min exposure to isoflurane, there was a significant increase in locomotor activity in animals breathing 1.5% isoflurane but not 0.7% isoflurane. This increase in locomotor activity produced by 1.5% isoflurane was abolished by a low dose of haloperidol (0.1 mg/kg), a dopamine receptor antagonist. Regional brain monoamine assays revealed that 1.5% isoflurane significantly increased the 3,4-dihydroxyphenylacetic acid:dopamine ratio (one indicator of transmitter turnover) in the nucleus accumbens and striatum, but a concentration of 0.7% did not. This significant increase in dopamine turnover in these regions continued during 20 min after the cessation of the administration of 1.5% isoflurane.

Conclusions
These results suggest that isoflurane-induced hyperlocomotion during emergence may be associated with increased dopamine turnover in the nucleus accumbens and striatum.
Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions
Authors: Guy John , Hindman Bradley J. , Baker Kristy Z. , Borel Cecil O. , Maktabi Mazen , Ostapkovich Noeleen , Kirchner Jerry , Todd Michael M. , Fogarty-Mack Patricia , Yancy Verna , Sokoll Martin D. , McAllister Alice , Roland Carl , Young William L. , Warner David S. 
Published: November 2003

Background
Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized mu-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.

Methods
Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micrograms.kg.-1. min-1) or remifentanil (n = 31; 1 mu.kg-1.min-1). After tracheal intubation, infusion rates were reduced to 0.03 microgram.kg-1.min-1 (fentanyl) or 0.2 microgram.kg-1.min-1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil (approximately 0.2 microgram.kg-1.min-1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7.

Results
Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar.

Conclusions
Remifentanil appears to be a reasonable alternative to fentanyl during elective supratentorial craniotomy.
Electrocardiographic and Hemodynamic Changes and Their Association with Myocardial Infarction during Coronary Artery Bypass Surgery
Authors: Jain Uday , Laflamme Claude J. A. , Aggarwal Anil , Ramsay James G. , Comunale Mark E. , Ghoshal Sudhanshu , Ngo Long , Ziola Krzysztof , Hollenberg Milton , Mangano Dennis T. 
Published: November 2003

Background
Electrocardiographic (ECG) changes during coronary artery bypass graft surgery have not been described in detail in a large multicenter population. The authors describe these ECG changes and evaluate them, along with demographic and clinical characteristics and intraoperative hemodynamic alterations, as predictors of myocardial infarction (MI) as defined by two sets of criteria.

Methods
Data from 566 patients at 20 clinical sites, collected as part of a clinical trial to evaluate the efficacy of acadesine for reducing MI, were analyzed at core laboratories. Perioperative ECG changes were identified using continuous three-lead Holter ECG. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded each minute during operation. The occurrence of MI by Q wave or myocardial fraction of creatine kinase (CK-MB) or autopsy criteria, and by (Q wave and CK-MB) or autopsy criteria was determined.

Results
During perioperative Holter monitoring, episodes of ST segment deviation, major cardiac conduction changes > or = 30 min, or use of ventricular pacing > or = 30 min occurred in 58% patients, primarily in the first 8 h after release of aortic occlusion. Of the 25% patients who met the Q wave or CK-MB or autopsy criteria for MI, 19% had increased CK-MB as well as ECG changes. (Q wave and CK-MB) or autopsy criteria for MI were met by 4% of patients. The CK-MB concentration generally peaked by 16 h after release of aortic occlusion. In patients with (n = 187) and without a perioperative episode of ST segment deviation, the incidence of MI was 36% and 19%, respectively (P < 0.01), by Q wave or CK-MB or autopsy criteria, and 6% and 3%, respectively (P = 0.055), by (Q wave and CK-MB) or autopsy criteria. Multiple logistic regression analysis showed that intraoperative ST segment deviation, intraventricular conduction defect, left bundle branch block, duration of hypotension (systolic blood pressure < 90 mmHg) after cardiopulmonary bypass, and duration of cardiopulmonary bypass are independent predictors of Q wave or CK-MB or autopsy MI. The independent predictors of (Q wave and CK-MB) or autopsy MI are intraoperative ST segment deviation and duration of aortic occlusion.

Conclusions
Major ECG changes occurred in 58% of patients during coronary artery bypass graft surgery, primarily within 8 h after release of aortic occlusion. Multicenter data collection revealed a substantial variation in the incidence of MI and an overall incidence of up to 25%, with most MI occurring within 16 h after release of aortic occlusion. Intraoperative monitoring of ECG and hemodynamics has incremental value for predicting MI.
Volatile Anesthetics Protect the Ischemic Rabbit Myocardium from Infarction
Authors: Cope Doris K. , Impastato Keyser W. , Cohen Michael V. , Downey James M. 
Published: November 2003

Background
The influence of anesthetic agents on the infarction process in the ischemic myocardium is unclear. This study evaluated the effects of three intravenous and three inhalational anesthetic agents on myocardial infarction within a quantified ischemic risk zone in rabbit hearts subjected to a standardized regional ischemia-reperfusion insult.

Methods
Both in vitro and in situ rabbit models were used to investigate the effects of anesthetic agents on infarct size. In all rabbits the heart was exposed and a coronary artery surrounded with a suture to form a snare for subsequent occlusion. In in situ preparations, both intravenous and inhalational agents were tested, whereas only the latter were used in isolated hearts. Infarct size was determined by triphenyltetrazolium chloride staining. To determine whether an adenosine-mediated protective mechanism was involved, 8-(p-sulfophenyl)theophylline, an adenosine receptor blocker, was added to halothane-treated isolated hearts. Adenosine concentration in the coronary effluent was also measured in isolated hearts exposed to halothane. In other protocols, chelerythrine, a highly selective protein kinase C inhibitor, was administered to both halothane-treated and untreated isolated hearts.

Results
Infarcts in the three in situ groups anesthetized with halothane, enflurane, and isoflurane were about one half as large as infarcts in rabbits that underwent anesthesia with pentobarbital, ketamine-xylazine, or propofol. Volatile anesthetics also protected isolated hearts by a similar amount. Both adenosine receptor blockade and chelerythrine abolished cardioprotection from halothane in isolated hearts. Halothane treatment did not increase adenosine release.

Conclusions
The volatile anesthetics tested protected the ischemic rabbit heart from infarction, in contrast to the three intravenous agents tested. Protection was independent of the hypotensive effect of the inhalational agents because halothane also protected isolated hearts, in which changing vascular tone is not an issue and coronary perfusion pressure is constant. Cardioprotection by volatile anesthetics depended on both adenosine receptors and protein kinase C, and thus is similar to the mechanism of protection seen with ischemic preconditioning.
Effects of Ropivacaine on a Potassium Channel (hKv1.5) Cloned from Human Ventricle
Authors: Valenzuela Carmen , Delpon Eva , Franqueza Laura , Gay Pilar , Snyders Dirk J. , Tamargo Juan 
Published: November 2003

Background
Ropivacaine, a new amide local anesthetic agent chemically related to bupivacaine, is able to induce early after depolarizations in isolated cardiac preparations. The underlying mechanism by which ropivacaine induces this effect has not been explored, but it is likely to involve K+ channel block.

Methods
Cloned human cardiac K+ channels (hKv1.5) were stably transfected in Ltk cells, and the effects of ropivacaine on the expressed hKv1.5 currents were assessed using the whole-cell configuration of the patch-clamp technique.

Results
Ropivacaine (100 microM) did not modify the initial activation time course of the current, but induced a fast subsequent decline to a lower steady-state current level with a time constant of 12.2 +/- 0.6 ms. Ropivacaine inhibited hKv1.5 with an apparent KD of 80 +/- 4 microM. Block displayed an intrinsic voltage-dependent, consistent with an electrical distance for the binding site of 0.153 +/- 0.007 (n = 6) (from the cytoplasmic side). Ropivacaine reduced the tail current amplitude recorded at -40 mV, and slowed the deactivation time course, resulting in a "crossover" phenomenon when control and ropivacaine tail currents were superimposed.

Conclusions
These results indicate that: (1) ropivacaine is an open channel blocker of hKv1.5; (2) binding occurs in the internal mouth of the ion pore; and (3) unbinding is required before the channel can close. These effects explain the ropivacaine availability of induction early after depolarizations and could be clinically relevant.
Prolonged “Phantom” Square Wave Capnograph Tracing after Patient Disconnection or Extubation
Authors: Ginosar Yehuda , Baranov Dimitry 
Published: November 2003

Background
The authors report on the appearance of misleading square wave "phantom" capnograph tracings for approximately 3 min after disconnection from the Siemens Servo 900c ventilator. A series of experiments are described to examine the mechanism of this phenomenon.

Methods
Patients were ventilated using the Siemens Servo 900c ventilator with the following settings: minute volume, 5 1/min; respiratory rate, 8 breaths/min; PEEP, 0 cm H2O; trigger sensitivity, 20 cm H2O. The ventilator was connected to the Siemens Servo Evac 180 evacuation system (25 1/min on evacuation flowmeter). Airway pressure and capnography were recorded at the Y piece during ventilation and after disconnection. A back-up ventilator was used to support the patient during disconnection of the ventilator being studied.

Results
Initially, the "phantom" capnograph tracing closely resembled the square wave capnograph tracing before disconnection, but the amplitude and shape of the waveform gradually decayed. Based on experiments described in this article, the authors show that the carbon dioxide for the "phantom" capnograph tracing comes from the gas exhaled by the patient in the last breaths before disconnection and which is present in both the expiratory tubing and in the evacuation system. The small pressure gradient between the exhaust reservoir and the atmosphere causes reverse flow of expired gas after disconnection, when both the nonreturn flap valve at the exhaust outlet is open (due to minimal valve incompetence) and when the expiratory servo valve is open (in the absence of positive end-expiratory pressure). This continuous reverse flow is detected by the capnograph but is interrupted intermittently by each attempted positive pressure ventilation, thereby creating a "phantom" capnograph.

Conclusions
After accidental disconnection of the patient from the breathing system, or after accidental extubation of the trachea, the "phantom" capnograph is likely to confuse even an experienced anesthesiologist into the mistaken belief that his rapidly deteriorating patient is being ventilated adequately. Several potential mechanisms to eliminate this phenomenon are outlined, including the avoidance of zero positive end-expiratory pressure. "Phantom" capnography provides an illustration of the dangers of using monitoring techniques, however reliable, as a substitute for vigilant clinical observation.
Relationship of the Train-of-four Fade Ratio to Clinical Signs and Symptoms of Residual Paralysis in Awake Volunteers
Authors: Kopman Aaron F. , Yee Pamela S. , Neuman George G. 
Published: November 2003

Background
Recovery of the train-of-four (TOF) ratio to a value > 0.70 is synonymous with adequate return of neuromuscular function, but there is little information available concerning the subjective experience that accompanies residual neuromuscular block wherein the TOF ratio is in the range of 0.70 to 0.90.

Methods
Ten American Society of Anesthesiologists' (ASA) physical status 1 volunteers were studied. Control measurements including grip strength in kilograms and ability to perform a 5-s head- and leg-lift. In addition, a standard wooden tongue depressor was placed between each subject's incisor teeth, and he or she was told not to let the investigator remove it. All subjects were easily able to retain the device despite vigorous attempts to dislodge it. Neuromuscular function was monitored with a Datex (Datex Medical Instrumentation, Inc., Tewksbury, MA) 221 electromyographic (EMG) monitor. TOF stimulation was given every 20 s, and the measured TOF fade ratio was continuously recorded. A 5 mg/kg bolus of mivacurium was then administered, and an infusion at 2 mg.kg-1.min-1 was begun. The infusion was continued until the TOF ratio decreased to < 0.70 and was adjusted to keep it in the range of 0.65 to 0.75. Signs and symptoms of weakness were recorded when the TOF ratio had been stable +/-0.03 for at least 10 min during an interval when there were no adjustments in the infusion. All tests noted previously were repeated at this time. The TOF ratio was then allowed to recover to 0.85-0.90. When stable at this level, all tests were repeated, and the infusion was discontinued. TOF measurements were continued until a ratio of 1.0 was attained and until a final set of observations was recorded.

Results
The TOF ratio in all subjects was reduced to < 0.70. No volunteers required intervention to maintain a patient airway, and the hemoglobin oxygen saturation while breathing air was > or = 96% at all times. TOF ratios < or = 0.90 were accompanied by diplopia and difficulty in tracking moving objects in all subjects. The ability to strongly oppose the incisor teeth did not return until the TOF ratio (on average) exceeded 0.85. A sustained 5-s head-lift was not achieved until the TOF ratio averaged 0.60 (range, 0.45-0.75). At a TOF ratio of 0.70, grip strength averaged 59% of control (range, 50-75%). With certain exceptions (vision, ability to clench the teeth tightly), there was wide variation in symptomatology between patients for any given TOF ratio. It is impossible to give reliable TOF break-points at which symptoms and signs will be present or absent.

Conclusions
All subjects had significant signs and symptoms of residual block at a TOF ratio of 0.70; none considered themselves remotely "street ready" at this time. The authors believe that satisfactory recovery of neuromuscular function after mivacurium-induced neuromuscular block requires return of the TOF ratio to a value > 0.90 and ideally to unity.