bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sevoflurane before or after Ischemia Improves Contractile and Metabolic Function while Reducing Myoplasmic Ca2+Loading in Intact Hearts
Authors: Varadarajan Srinivasan G. , An Jianzhong , Novalija Enis , Stowe David F. 
Published: November 2003

Background
Ca(2+) loading occurs during myocardial reperfusion injury. Volatile anesthetics can reduce reperfusion injury. The authors tested whether sevoflurane administered before index ischemia in isolated hearts reduces myoplasmic diastolic and systolic [Ca(2+)] and improves function more so than when sevoflurane is administered on reperfusion.

Methods
Four groups of guinea pig hearts were perfused with crystalloid solution (55 mmHg, 37 degrees C): (1) no treatment before 30 min global ischemia and 60 min reperfusion (CON); (2) 3.5 vol% sevoflurane administered for 10 min before ischemia (SBI); (3) 3.5 vol% sevoflurane administered for 10 min after ischemia (SAI); and (4) 3.5 vol% sevoflurane administered for 10 min before and after ischemia (SBAI). Phasic myoplasmic diastolic and systolic [Ca(2+)] were measured in the left ventricular free wall with the fluorescence probe indo-1.

Results
Ischemia increased diastolic [Ca(2+)] and diastolic left ventricular pressure (LVP). In CON hearts, initial reperfusion greatly increased diastolic [Ca2+] and systolic [Ca(2+)] and reduced contractility (systolic-diastolic LVP, dLVP/dt(max)), relaxation (diastolic LVP, dLVP/dt(min)), myocardial oxygen consumption (MvO(2)), and cardiac efficiency. SBI, SAI, and SBAI each reduced ventricular fibrillation, attenuated increases in systolic and systolic-diastolic [Ca(2+)], improved contractile and relaxation indices, and increased coronary flow, percent oxygen extraction, MvO(2), and cardiac efficiency during 60 min reperfusion compared with CON. SBI was more protective than SAI, and SBAI was generally more protective than SAI.

Conclusions
Sevoflurane improves postischemic cardiac function while reducing Ca(2+) loading when it is administered before or after ischemia, but protection is better when it is administered before ischemia. Reduced Ca(2+) loading on reperfusion is likely a result of the anesthetic protective effect.
Effects of α2-Adrenoceptor Agonists on Perinatal Excitotoxic Brain Injury
Authors: Laudenbach Vincent , Mantz Jean , Lagercrantz Hugo , Desmonts Jean-Marie , Evrard Philippe , Gressens Pierre 
Published: November 2003

Background
A growing number of children have severe neurologic impairment related to very premature birth. Experimental data suggest that overstimulation of cerebral N-methyl-d-aspartate (NMDA) receptors caused by excessive glutamate release may be involved in the genesis of perinatal hypoxic-ischemic brain injury. alpha(2)-Adrenoceptor agonists are protective in models of brain ischemia in adults. The authors sought to determine whether they prevent perinatal excitotoxic neuronal damage.

Methods
Five-day-old mice were allocated at random to clonidine (4-400 microg/kg), dexmedetomidine (1-30 microg/kg), or saline injected intraperitoneally before an intracerebral stereotactic injection of the NMDA receptor agonist ibotenate; cortical and white matter lesions were quantified 5 days later by histopathologic examination. Cortical neuron cultures exposed to 300 microm NMDA were used to evaluate the effects of clonidine or dexmedetomidine on neuronal death assessed by counting the number of pycnotic nuclei after fluorescent chromatin staining.

Results
In vivo, both clonidine and dexmedetomidine induced significant concentration-dependent reductions in the size of ibotenate-induced lesions in the cortex and white matter. In vitro, the number of neurons damaged by NMDA exposure was significantly decreased by both dexmedetomidine (-28 +/- 12% at 10 microm; P < 0.01) and clonidine (-37 +/- 19% at 100 microm; P < 0.01) as compared with controls. In both models, the selective alpha2-adrenoceptor antagonist yohimbine abolished the neuroprotective effect of clonidine and dexmedetomidine.

Conclusions
Clonidine and dexmedetomidine are potent neuroprotectors that act by stimulating the alpha(2) adrenoceptors. These results obtained in a murine model of perinatal excitotoxic injury may be relevant to some forms of neonatal brain damage in humans.
Isoflurane Activates PKC and Ca2+-Calmodulin-dependent Protein Kinase II via MAP Kinase Signaling in Cultured Vascular Smooth Muscle Cells
Authors: Zhong Li , Su Judy Y. 
Published: November 2003

Background
Protein kinase C (PKC) and Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) have been implicated in isoflurane-increased force in skinned femoral arterial strips. The extracellular signal-regulated kinases (ERK1/2) of mitogen-activated protein kinase have been shown to be target effectors of PKC and CaMKII. This study examined the role of the ERK1/2 signaling pathway in isoflurane activation of PKC and CaMKII using cultured vascular smooth muscle cells.

Methods
Vascular smooth muscle cells were prepared by cell migration from isolated rabbit femoral arterial segments. Growth of passage of vascular smooth muscle cells (80-90% confluence, passage 5-10) was arrested for 48 h before experiments, during which time phorbol 1,3-diaceylester treatment was used to down-regulate PKC. Cells were treated for 30 min with one of the inhibitors of mitogen-activated protein kinase kinase (PD98059), PKC (Go6976 and bisindolylmaleimide), or CaMKII (KN-93 and KN-62) at 10 microm. After administration of isoflurane, vascular smooth muscle cells were frozen rapidly, homogenized, and centrifuged. The homogenates were used for identification of phosphorylated ERK1/2 or for further centrifugation to separate the membrane from the cytosol for identification of PKC isoforms (alpha and epsilon) by Western blotting.

Results
Isoflurane increased ERK1/2 phosphorylation in a dose-dependent manner and reached a plateau at 10 min. PD98059 or down-regulated PKC blocked the increase of phosphorylated ERK1/2 levels by isoflurane, and bisindolylmaleimide, KN-93, or KN-62, but not by Go6976 reduced levels of phosphorylated ERK1/2. The membrane fraction of PKC epsilon but not of PKC alpha was increased by isoflurane.

Conclusions
ERK1/2 signaling is downstream of PKC and CaMKII activated by isoflurane in vascular smooth muscle cells.
Isoflurane Prevents Delayed Cell Death in an Organotypic Slice Culture Model of Cerebral Ischemia
Authors: Sullivan Breandan L. , Leu David , Taylor Donald M. , Fahlman Christian S. , Bickler Philip E. 
Published: November 2003

Background
General anesthetics reduce neuronal death caused by focal cerebral ischemia in rodents and by in vitro ischemia in cultured neurons and brain slices. However, in intact animals, the protective effect may enhance neuronal survival for only several days after an ischemic injury, possibly because anesthetics prevent acute but not delayed cell death. To further understand the mechanisms and limitations of volatile anesthetic neuroprotection, the authors developed a rat hippocampal slice culture model of cerebral ischemia that permits assessment of death and survival of neurons for at least 2 weeks after simulated ischemia.

Methods
Survival of CA1, CA3, and dentate gyrus neurons in cultured hippocampal slices (organotypic slice culture) was examined 2-14 days after 45 min of combined oxygen-glucose deprivation at 37 degrees C (OGD). Delayed cell death was serially measured in each slice by quantifying the binding of propidium iodide to DNA with fluorescence microscopy.

Results
Neuronal death was greatest in the CA1 region, with maximal death occurring 3-5 days after OGD. In CA1, cell death was 80 +/- 18% (mean +/- SD) 3 days after OGD and was 80-100% after 1 week. Death of 70 +/- 16% of CA3 neurons and 48 +/- 28% of dentate gyrus neurons occurred by the third day after OGD. Both isoflurane (1%) and the N-methyl-D-aspartate antagonist MK-801 (10 microm) reduced cell death to levels similar to controls (no OGD) for 14 days after the injury. Isoflurane also reduced cell death in CA1 and CA3 caused by application of 100 but not 500 microm glutamate. Cellular viability (calcein fluorescence) and morphology were preserved in isoflurane-protected neurons.

Conclusions
In an in vitro model of simulated ischemia, 1% isoflurane is of similar potency to 10 microm MK-801 in preventing delayed cell death. Modulation of glutamate excitotoxicity may contribute to the protective mechanism.
Effects of Inspired Hypoxic and Hypercapnic Gas Mixtures on Cerebral Oxygen Saturation in Neonates with Univentricular Heart Defects
Authors: Ramamoorthy Chandra , Tabbutt Sarah , Dean Kurth C. , Steven James M. , Montenegro Lisa M. , Durning Suzanne , Wernovsky Gil , William Gaynor J. , Spray Thomas L. , Nicolson Susan C. 
Published: November 2003

Background
Neonates with functional single ventricle often require hypoxic or hypercapnic inspired gas mixtures to reduce pulmonary overcirculation and improve systemic perfusion. Although the impact of these treatments on arterial oxygen saturation has been described, the effects on cerebral oxygenation remain uncertain. This study examined the effect of these treatments on cerebral oxygen saturation and systemic hemodynamics.

Methods
Neonates with single ventricle mechanically ventilated with room air were enrolled in a randomized crossover trial of 17% inspired oxygen or 3% inspired carbon dioxide. Each treatment lasted 10 min, followed by a 10-20-min washout period. Cerebral and arterial oxygen saturation were measured by cerebral and pulse oximetry, respectively. Cerebral oxygen saturation, arterial oxygen saturation, and other physiologic data were continuously recorded.

Results
Three percent inspired carbon dioxide increased cerebral oxygen saturation (56 +/- 13 to 68 +/- 13%; P < 0.01), whereas 17% inspired oxygen had no effect (53 +/- 13 to 53 +/- 14%; P = 0.8). Three percent inspired carbon dioxide increased the mean arterial pressure (45 +/- 8 to 50 +/- 9 mmHg; P < 0.01), whereas 17% inspired oxygen had no effect. And 3% inspired carbon dioxide decreased arterial pH and increased arterial carbon dioxide and oxygen tensions.

Conclusions
Inspired 3% carbon dioxide improved cerebral oxygenation and mean arterial pressure. Treatment with 17% inspired oxygen had no effect on either.
A Multicenter Study Comparing the ProSeal TMand Classic TMLaryngeal Mask Airway in Anesthetized, Nonparalyzed Patients
Authors: Brimacombe Joseph , Keller Christian , Fullekrug Bernd , Agrò Felice , Rosenblatt William , Dierdorf Stephen F. , Garcia de Lucas Elvira , Capdevilla Xavier , Brimacombe Nick 
Published: November 2003

Background
The laryngeal mask airway ProSeal (PLMA), a new laryngeal mask device, was compared with the laryngeal mask airway Classic (LMA) with respect to: (1) insertion success rates and times; (2) efficacy of seal; (3) fiberoptically determined anatomic position; (4) orogastric tube insertion success rates and times; (5) total intraoperative complications; and (6) postoperative sore throat in nonparalyzed adult patients undergoing general anesthesia, hypothesizing that these would be different.

Methods
Three hundred eighty-four nonparalyzed anesthetized adult patients (American Society of Anesthesiologists physical status I-II) were randomly allocated to the PLMA or LMA for airway management. In addition, 50% of patients were randomized for orogastric tube placement. Unblinded observers collected intraoperative data, and blinded observers collected postoperative data.

Results
First-attempt insertion success rates (91 vs. 82%, P = 0.015) were higher for the LMA, but after three attempts success rates were similar (LMA, 100%; PLMA, 98%). Less time was required to achieve an effective airway with the LMA (31 +/- 30 vs. 41 +/- 49 s; P = 0.02). The PLMA formed a more effective seal (27 +/- 7 vs. 22 +/- 6 cm H2O; P < 0.0001). Fiberoptically determined anatomic position was better with the LMA (P < 0.0001). Orogastric tube insertion was more successful after two attempts (88 vs. 55%; P < 0.0001) and quicker (22 +/- 18 vs. 38 +/- 56 s) with the PLMA. During maintenance, the PLMA failed twice (leak, stridor) and the LMA failed once (laryngospasm). Total intraoperative complications were similar for both groups. The incidence of postoperative sore throat was similar.

Conclusion
In anesthetized, nonparalyzed patients, the LMA is easier and quicker to insert, but the PLMA forms a better seal and facilitates easier and quicker orogastric tube placement. The incidence of total intraoperative complications and postoperative sore throat are similar.
Efficacy of Clonidine for Prevention of Perioperative Myocardial Ischemia
Authors: Nishina Kahoru , Mikawa Katsuya , Uesugi Takanobu , Obara Hidefumi , Maekawa Munetaka , Kamae Isao , Nishi Nobuo 
Published: November 2003

Background
There is a belief that clonidine may be effective in reducing perioperative myocardial ischemic events, although the results of several trials are conflicting. The aim of the current study was to provide a systematic review of randomized controlled trials that tested the efficacy of clonidine in this regard.

Methods
Data was collected from a MEDLINE search of English-language studies published from 1980 to 1999 and a manual search of bibliographies from retrieved articles. A total of 28 studies were assessed. According to the selection criteria (study design, population, intervention, and outcome) and a quality scoring system, seven studies were finally included in the meta-analysis. After homogeneity was established by Q value, the data were then combined using the fixed-effects model. The pooled odds ratio was calculated. A subgroup analysis based on the types of surgery and administration route was also performed to qualify the results. The results were expressed as odds ratio and 95% confidence interval.

Results
Heterogeneity of outcome data was negative in the trials. The pooled odds ratio was 0.49 (95% confidence interval 0.34-0.71). In the subgroup analysis, clonidine reduced the incidence of myocardial ischemia in patients undergoing cardiac and noncardiac surgery. Rates of bradycardia were similar in clonidine and placebo groups.

Conclusion
The meta-analysis suggests that perioperative clonidine reduces cardiac ischemic episodes in patients with known, or at risk of, coronary arterial disease without increasing the incidence of bradycardia. Therefore, these findings strongly justify planning and execution of a definitive study seeking the benefits of clonidine.
Use of Dynamic Negative Airway Pressure (DNAP) to Assess Sedative-induced Upper Airway Obstruction
Authors: Litman Ronald S. , Hayes Jennifer L. , Basco Matthew G. , Schwartz Alan R. , Bailey Peter L. , Ward Denham S. 
Published: November 2003

Background
Traditional methods of assessing ventilatory effects of sedative agents do not measure their propensity to cause upper airway obstruction (UAO). The primary objective of this study was to develop a method, using dynamic negative airway pressure (DNAP), for replicating UAO during deep sedation.

Methods
A state of deep sedation (defined as an Observer Assessment of Alertness and Sedation score of 3 and a bispectral index < 80) was attained in 10 healthy volunteers, aged 19-41, using midazolam. Volunteers breathed through a chamber connected to a regulated source of negative pressure that was gradually adjusted downward to produce UAO based on maximal inspiratory flow. The study consisted of three phases: A control phase while awake, a study phase during midazolam deep sedation, and a recovery phase after flumazenil administration.

Results
During the control phase no subject demonstrated airway obstruction at negative pressures to -30-cm H2O. All subjects exhibited complete UAO during DNAP episodes while sedated. Negative pressures required to cause complete UAO (Pcrit) ranged from -2 to -14 cm H2O. After administration of flumazenil, all subjects attained full consciousness within 5 min and did not demonstrate UAO at negative pressures to -30-cm H2O.

Conclusions
Dynamic Negative Airway Pressure is a useful method for provoking midazolam-induced UAO, and may potentially be used to compare the potential for different sedatives and patient factors to cause UAO. Flumazenil was completely effective in reversing the potential for midazolam to cause UAO.
Sympathetic Neural Activation Evoked by μ-Receptor Blockade in Patients Addicted to Opioids Is Abolished by Intravenous Clonidine
Authors: Kienbaum Peter , Heuter Thorsten , Michel Martin C. , Scherbaum Norbert , Gastpar Markus , Peters Jürgen 
Published: November 2003

Background
Mu-opioid receptor blockade by naloxone administered for acute detoxification in patients addicted to opioids markedly increases catecholamine plasma concentrations, muscle sympathetic activity (MSA), and is associated with cardiovascular stimulation despite general anesthesia. The current authors tested the hypothesis that the alpha2-adrenoceptor agonist clonidine (1) attenuates increased MSA during mu-opioid receptor blockade for detoxification, and (2) prevents cardiovascular activation when given before detoxification.

Methods
Fourteen mono-opioid addicted patients received naloxone during propofol anesthesia. Clonidine (10 microg x kg(-1) administered over 5 min + 5 microg x kg(-1) x h(-1) intravenous) was infused either before (n = 6) or after (n = 6) naloxone administration. Two patients without immediate clonidine administration occurring after naloxone administration served as time controls. Muscle sympathetic activity (n = 8) in the peroneal nerve, catecholamine plasma concentrations (n = 14), arterial blood pressure, and heart rate were assessed in awake patients, during propofol anesthesia before and after mu-opioid receptor blockade, and after clonidine administration.

Results
Mu-receptor blockade markedly increased MSA from a low activity (burst frequency: from 2 burst/min +/- 1 to 24 +/- 8, means +/- SD). Similarly, norepinephrine (41 pg/ml +/- 37 to 321 +/- 134) and epinephrine plasma concentration (13 pg/ml +/- 6 to 627 +/- 146) significantly increased, and were associated with, increased arterial blood pressure and heart rate. Clonidine immediately abolished both increased MSA (P < 0.001) and catecholamine plasma concentrations (P < 0.001). When clonidine was given before mu-opioid receptor blockade, catecholamine plasma concentrations and hemodynamic variables did not change.

Conclusions
Administration of the alpha2-adrenoceptor agonist clonidine decreases both increased MSA and catecholamine plasma concentrations observed after mu-opioid receptor blockade for detoxification. Furthermore, clonidine pretreatment prevents the increase in catecholamine plasma concentration that otherwise occurs during mu-opioid receptor blockade.
Older Age Is the Strongest Predictor of Postoperative Atrial Fibrillation
Authors: Amar David , Zhang Hao , Y. Leung Denis H. , Roistacher Nancy , Kadish Alan H. 
Published: November 2003

Background
Identification of patients vulnerable for atrial fibrillation (AF) after major thoracic surgery will allow targeting those most likely to benefit from prophylactic therapy. The goal of the current study was to evaluate the accuracy of easily available clinical characteristics for the prediction of this complication.

Methods
Patients undergoing major elective thoracic surgery were chosen from an ongoing prospective database.

Results
Postoperative in-hospital AF occurred in 79 (15%) of 527 patients Using cut-point methodology and logistic regression, the authors identified two preoperative risk factors independently associated with AF: age 60 yr or older (P = 0.0007) and heart rate 74 beats/min or greater on preadmission electrocardiogram (P = 0.005). The odds of developing AF increased by a factor of 2.5 (95% confidence interval, 1.7-3.4; P < 0.0001) between incremental age categories (< 60 yr, 60-69 yr, > or = 70 yr) and by a factor of 2.3 (95% confidence interval, 1.4-3.8; P < 0.0007) between heart rate categories (< 74 beats/min, > or = 74 beats/min). The combination of age 60 yr or older and preoperative heart rate 74 beats/min or greater predicted AF with a sensitivity of 73% and specificity of 57%. Maximum P-wave duration as measured from standard electrocardiogram did not differentiate patients who did or did not develop AF. Patients who developed AF had a higher incidence of postoperative pneumonia (14 vs. 4%; P = 0.001), acute respiratory failure (8 vs. 1.6%; P = 0.01), greater hospital stay (17 +/- 17 vs. 10 +/- 9 days; P = 0.001) and 30-day mortality (11 vs. 3%; P = 0.001) when compared with those who did not develop AF, respectively.

Conclusions
Advanced age and preoperative heart rate identify patients at high risk for development of AF after thoracic surgery. Postoperative AF occurs more frequently in patients with greater postoperative morbidity and length of hospitalization.
Estrogen Reduces Efficacy of μ- but Not κ-Opioid Agonist Inhibition in Response to Uterine Cervical Distension
Authors: Sandner-Kiesling Andreas , Eisenach James C. 
Published: November 2003

Background
Although the uterine cervix is a common source of acute and chronic visceral pain in women, there is practically no neurobiological investigation of nociception from this visceral organ. With use of a novel model of uterine cervical distension nociception in rats, the estrogen dependency of opioid agonist-induced inhibition was investigated.

Methods
Sprague Dawley rats were anesthetized with halothane and bilateral ovariectomy was performed, after which placebo or estrogen treatment was administered for 1 week. Animals were reanesthetized and fine metal rods were inserted into the uterine cervix for manual distension. Reflex contraction of the rectus abdominis in response to distension was recorded before and after cumulative dosing with the mu-opioid agonist morphine and the kappa-opioid agonist (-)U50488.

Results
Uterine cervical distension increased reflex abdominal muscle contraction with a threshold of 75 g, regardless of estrogen treatment. Morphine and (-)U50488 reduced the reflex response to cervical distension in a dose-dependent manner. Estrogen reduced the inhibitory effect of morphine but not that of (-)U50488.

Conclusions
It has been suggested that mu-opioid agonists are less potent in females than males, whereas kappa-opioid agonists are more potent in females than males. These data suggest that estrogen may influence the action of opioids, at least against visceral pain, which may explain this sex difference. In addition, these data suggest that kappa-opioid agonists may be effective in the treatment of pain originating from the uterine cervix, regardless of estrogen status.