bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal Echogenic Findings Detected by Transesophageal Echocardiography and Cardiorespiratory Impairment during Total Knee Arthroplasty with Tourniquet
Authors: Kato Nobuya , Nakanishi Kazuhiro , Yoshino Shinichi , Ogawa Ryo 
Published: November 2003

Background
In patients undergoing total knee arthroplasty, intraoperative pulmonary embolic events are rare, and most occur following tourniquet deflation. This embolization can be observed using transesophageal echocardiography. However, the authors have encountered sudden decreases in arterial oxygen partial pressure while a tourniquet is still inflated. Therefore, the current investigation was designed to detect emboli during the tourniquet inflation phase and to identify the composition of the echogenic material.

Methods
Forty-six patients were randomly assigned to undergo total knee arthroplasty without (control, n = 24) or with a tourniquet (n = 22). Hemodynamic monitoring, blood gas analysis, and continuous transesophageal echocardiography were performed during the total knee arthroplasty procedure. Right jugular blood specimens were collected whenever echogenic material was seen in the atrium.

Results
In the tourniquet group, embolic events occurred in 27% of patients during femoral reaming and in 100% after tourniquet deflation. In the control group, emboli were detected in 54% of patients during femoral reaming. Most of the patients exhibited cardiopulmonary impairment after severe echogenic embolism, even while the tourniquet was inflated (two patients). None of the blood samples aspirated from the central catheters contained detectable material.

Conclusions
This prospective study showed that embolic events occurred during total knee arthroplasty, even while a tourniquet was inflated. An inflated tourniquet does not completely prevent pulmonary emboli.
Negative and Positive Inotropic Effects of Propofol via L-type Calcium Channels and the Sodium-Calcium Exchanger in Rat Cardiac Trabeculae
Authors: de Ruijter Wouter , M. Stienen Ger J. , van Klarenbosch Jan , de Lange Jacob J. 
Published: November 2003

Background
Conflicting opinions are present in the literature regarding the origin of the negative inotropic effect of propofol on the myocardium. This study aims to resolve these discrepancies by investigating the inotropic effects of propofol the L-type calcium channels and the sodium-calcium exchanger (NCX).

Methods
The effect of 20 microg/ml propofol on force development was determined in rat cardiac trabeculae at different pacing frequencies and different extracellular calcium concentrations. Postrest potentiation, sodium withdrawal during quiescence, and the NCX inhibitor KB-R7943 were used to study changes in the activity of the reverse mode of the NCX by propofol.

Results
The effect of propofol on steady state peak force depended on pacing frequency and calcium concentration. A negative inotropic effect was observed at pacing frequencies greater than 0.5 Hz, but a positive inotropic effect was observed at 0.1 Hz and low calcium, which cannot be explained by an effect on the L-type calcium channel. Propofol enhanced postrest potentiation in a calcium-dependent manner. Sodium withdrawal during quiescence and the use of the specific NCX inhibitor KB-R7943 provided evidence for an enhancement of calcium influx by propofol the reverse mode of the NCX.

Conclusions
The effects of propofol on the myocardium depend on pacing frequency and calcium concentration. The positive inotropic effect of propofol is associated with increased calcium influx the reverse mode of the NCX. The authors conclude that the net inotropic effect of propofol is the result of its counteracting influence on the functioning of the L-type calcium channel and the NCX.
Influence of Hemorrhage on Propofol Pseudo–Steady State Concentration
Authors: Kazama Tomiei , Kurita Tadayoshi , Morita Koji , Nakata Jun , Sato Shigehito 
Published: November 2003

Background
A small induction dose has been recommended in cases of hemorrhagic shock. However, the influence of hemorrhage on the amplitude of plasma propofol concentration has not yet been fully investigated during continuous propofol infusion. The authors hypothesized that the effect of hemorrhage on plasma propofol concentration is variously influenced by the different stages of shock.

Methods
After 120 min of steady state infusion of propofol at a rate of 2 mg x kg(-1) x h(-1), nine instrumented immature swine were studied using a stepwise increasing hemorrhagic model (200 ml of blood every 30 min until 1 h, then additional stepwise bleeding of 100 ml every 30 min thereafter, to the point of circulatory collapse). Hemodynamic parameters and plasma propofol concentration were recorded at every step.

Results
Before total circulatory collapse, it was possible to drain 976 +/- 166 ml (mean +/- SD) of blood. Hemorrhage of less than 600 ml (19 ml/kg) was not accompanied by a significant change in plasma propofol concentration. At individual peak systemic vascular resistance, when cardiac output and mean arterial pressure decreased by 31% and 14%, respectively, plasma propofol concentration increased by 19% of its prehemorrhagic value. At maximum heart rate, when cardiac output and mean arterial pressure decreased by 46% and 28%, respectively, plasma propofol concentration increased by 38%. In uncompensated shock, it increased to 3.75 times its prehemorrhagic value.

Conclusions
During continuous propofol infusion, plasma propofol concentration increased by less than 20% during compensated shock. However, it increased 3.75 times its prehemorrhagic concentration during uncompensated shock.
Bupivacaine Attenuates Contractility by Decreasing Sensitivity of Myofilaments to Ca2+,in Rat Ventricular Muscle
Authors: Mio Yasushi , Fukuda Norio , Kusakari Yoichiro , Tanifuji Yasumasa , Kurihara Satoshi 
Published: November 2003

Background
Bupivacaine exhibits a cardiodepressant effect, the molecular mechanism(s) of which have yet to be fully understood. Bupivacaine may directly act on contractile proteins and thereby decrease myofibrillar Ca2+ sensitivity.

Methods
Rat ventricular muscle was used. First, the effect of bupivacaine was examined on tetanic contractions in isolated intact myocytes. Next, Triton X-100-treated ventricular trabeculae were used to investigate the effect of bupivacaine on the pCa (= -log [Ca2+ ])-tension relation as well as on maximal Ca2+ -activated tension. Furthermore, to test whether bupivacaine inhibits the pathway downstream from Ca2+ binding to troponin C, tension was elicited in the skinned preparations by lowering the Mg-adenosine triphosphate (MgATP) concentration in the absence of Ca2+. The effect of bupivacaine on the pMgATP (= -log [MgATP])-tension relation was examined.

Results
In myocytes, 3 microm bupivacaine significantly (P < 0.01) increased intracellular Ca2+ concentration required for 5% cell shortening from the resting cell length. In skinned preparations, bupivacaine shifted the pCa-tension relation to the lower pCa side; the midpoint of the pCa curve (pCa50) was significantly (P < 0.05) changed by 10 and 100 microm bupivacaine. A highly correlated linear relation (R = 0.81; P< 0.0005) was present between pCa50 and maximal Ca2+ -activated tension. Bupivacaine (10 and 100 microm) significantly (P < 0.05) shifted the midpoint of the pMgATP-tension relation to the higher pMgATP side.

Conclusions
Bupivacaine decreases myofibrillar Ca2+ sensitivity in ventricular muscle, and this is coupled with the compound's inhibitory effect on the pathway beyond Ca2+ binding to troponin C, possibly on the actomyosin interaction. The current results may partly explain the overall cardiodepressant effect of bupivacaine in vivo.
Transmission through the Dorsal Spinocerebellar and Spinoreticular Tracts
Authors: Soja Peter J. , Taepavarapruk Niwat , Pang Walton , Cairns Brian E. , McErlane Shelly A. , Fragoso Miguel C. 
Published: November 2003

Background
Most of what is known regarding the actions of injectable barbiturate anesthetics on the activity of lumbar sensory neurons arises from experiments performed in acute animal preparations that are exposed to invasive surgery and neural depression caused by coadministered inhalational anesthetics. Other parameters such as cortical synchronization and motor ouflow are typically not monitored, and, therefore, anesthetic actions on multiple cellular systems have not been quantitatively compared.

Methods
The activities of antidromically identified dorsal spinocerebellar and spinoreticular tract neurons, neck motoneurons, and cortical neurons were monitored extracellularly before, during, and following recovery from the anesthetic state induced by thiopental in intact, chronically instrumented animal preparations.

Results
Intravenous administration of 15 mg/kg, but not 5 mg/kg, of thiopental to awake cats induced general anesthesia that was characterized by 5-10 min of cortical synchronization, reflected as large-amplitude slow-wave events and neck muscle atonia. However, even though the animal behaviorally began to reemerge from the anesthetic state after this 5-10-min period, neck muscle (neck motoneuron) activity recovered more slowly and remained significantly suppressed for up to 23 min after thiopental administration. The spontaneous activity of both dorsal spinocerebellar and spinoreticular tract neurons was maximally suppressed 5 min after administration but remained significantly attenuated for up to 17 min after injection. Peripheral nerve and glutamate-evoked responses of dorsal spinocerebellar and spinoreticular tract neurons were particularly sensitive to thiopental administration and remained suppressed for up to 20 min after injection.

Conclusions
These results demonstrate that thiopental administration is associated with a prolonged blockade of motoneuron output and sensory transmission through the dorsal spinocerebellar and spinoreticular tracts that exceeds the duration of general anesthesia. Further, the blockade of glutamate-evoked neuronal responses indicates that these effects are due, in part, to a local action of the drug in the spinal cord. The authors suggest that this combination of lumbar sensory and motoneuron inhibition underlies the prolonged impairment of reflex coordination observed when thiopental is used clinically.
Protein Tyrosine Kinase-Dependent Modulation of Isoflurane Effects on Cardiac Sarcolemmal KATPChannel
Authors: Stadnicka Anna , Kwok Wai-Meng , Warltier David C. , Bosnjak Zeljko J 
Published: November 2003

Background
Cardiac adenosine triphosphate-sensitive potassium (K(ATP)) channels and protein tyrosine kinases (PTKs) are mediators of ischemic preconditioning, but the interaction of both and a role in myocardial protection afforded by volatile anesthetics have not been defined.

Methods
Whole cell and single channel patch clamp techniques were used to investigate the effects of isoflurane and the PTK inhibitor genistein on the cardiac sarcolemmal K(ATP) channel in acutely dissociated guinea pig ventricular myocytes.

Results
At 0.5 mm internal ATP, genistein (50 microm) elicited whole cell K(ATP) current (22.5 +/- 7.9 pA/pF). Genistein effects were concentration-dependent, with an EC50 of 32.3 +/- 1.4 microm. Another PTK inhibitor, tyrphostin B42, had a similar effect. The inactive analog of genistein, daidzein (50 microm), did not elicit K(ATP) current. Isoflurane (0.5 mm) increased genistein (35 microm)-activated whole cell K(ATP) current from 14.5 +/- 3.1 to 32.5 +/- 6.6 pA/pF. Stimulation of receptor PTKs with epidermal growth factor, nerve growth factor, or insulin attenuated genistein and isoflurane effects, and the protein tyrosine phosphatase inhibitor orthovanadate (1 mm) prevented their actions on K(ATP) current. In excised inside-out membrane patches, and at fixed 0.2 mm internal ATP, genistein (50 microm) increased channel open probability from 0.053 +/- 0.016 to 0.183 +/- 0.039, but isoflurane failed to further increase open probability (0.162 +/- 0.051) of genistein-activated channels. However, applied in the presence of genistein and protein tyrosine phosphatase 1B (1 microg/ml), isoflurane significantly increased open probability to 0.473 +/- 0.114.

Conclusions
These results suggest that the PTK-protein tyrosine phosphatase signaling pathway may be one of the regulators of cardiac sarcolemmal K(ATP) channel and may play a role in modulating its responsiveness to isoflurane. Relative importance of this modulation for cardioprotection by volatile anesthetics remains to be established.
What Is the Minimum Training Required for Successful Cricothyroidotomy?
Authors: Wong David T. , Prabhu Atul J. , Coloma Margarita , Imasogie Ngozi , Chung Frances F. 
Published: November 2003

Background
A correctly performed cricothyroidotomy may be lifesaving in a cannot-ventilate, cannot-intubate situation. However, many practicing anesthesiologists do not have experience with cricothyroidotomy. The purpose of this study was to determine the minimum training required to perform cricothyroidotomy in 40 s or less in mannequins.

Methods
After informed consent, participants were shown a demonstration video and asked to perform 10 consecutive cricothyroidotomy procedures on a mannequin using a preassembled percutaneous dilational cricothyroidotomy set. Each attempt was timed from skin palpation to lung insufflation. Cricothyroidotomy was considered successful if it was performed in 40 s or less, and the cricothyroidotomy time was considered to have plateaued when there were no significant reductions in cricothyroidotomy times in three consecutive attempts.

Results
One hundred two anesthesiologists participated in the study. There was a significant reduction of cricothyroidotomy times over the 10 attempts (P < 0.0001) and between three consecutive attempts until the fourth attempt (P < 0.03). The cricothyroidotomy times plateaued by the fourth attempt, while the success rate plateaued at the fifth attempt (94, 96, 96, and 96% at the fourth, fifth, sixth, and seventh attempts, respectively).

Conclusion
Practice on mannequins leads to reductions in cricothyroidotomy times and improvement in success rates. By the fifth attempt, 96% of participants were able to successfully perform the cricothyroidotomy in 40 s or less. While clinical correlates are not known, the authors recommend that providers of emergency airway management be trained on mannequins for at least five attempts or until their cricothyroidotomy time is 40 s or less. The most appropriate retraining intervals have yet to be determined for optimal cricothyroidotomy skill retention.
Effects of Isoflurane and Propofol on Glutamate and GABA Transporters in Isolated Cortical Nerve Terminals
Authors: Westphalen Robert I. , Hemmings Hugh C. 
Published: November 2003

Background
Depression of glutamate-mediated excitatory transmission and potentiation of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission appear to be primary mechanisms by which general anesthetics produce anesthesia. Since effects on transmitter transport have been implicated in anesthetic actions, the authors examined the sensitivity of presynaptic glutamate and GABA transporters to the effects of a representative volatile (isoflurane) and a representative intravenous (propofol) anesthetic.

Methods
A dual-isotope (l-[3H]glutamate and [14C]GABA) approach allowed simultaneous comparisons of anesthetic effects on three independent assays of glutamate and GABA transporters in adult rat cerebral cortex: transmitter uptake into isolated nerve terminals (synaptosomes), transmitter binding to lysed and washed synaptosomes (synaptic membranes), and carrier-mediated release (reverse transport) of transmitter from preloaded synaptosomes using a modified superfusion system.

Results
Isoflurane produced small but statistically significant inhibition of l-[3H]glutamate and [14C]GABA uptake, while propofol had no effect. Inhibition of uptake by isoflurane was noncompetitive, an outcome that was mimicked by indirectly affecting transporter function through synaptosomal depolarization. Neither isoflurane nor propofol affected l-[3H]glutamate or [14C]GABA binding to synaptic membranes or Ca(2+)-independent carrier-mediated l-[3H]glutamate or [14C]GABA release (reverse transport).

Conclusions
These findings suggest that isoflurane and propofol at clinical concentrations do not affect excitatory glutamatergic transmission or inhibitory GABAergic transmission directly effects on their presynaptic neuronal transporters.
Isoflurane Decreases ATP Sensitivity of Guinea Pig Cardiac Sarcolemmal KATPChannel at Reduced Intracellular pH
Authors: Stadnicka Anna , Bosnjak Zeljko J. 
Published: November 2003

Background
Volatile anesthetics can protect the myocardium against ischemic injury by opening the adenosine triphosphate (ATP)-sensitive potassium (K(atp)) channels. However, direct evidence for anesthetic-channel interaction is still limited, and little is known about the role K(atp) channel modulators play in this effect. Because pH is one of the regulators of K(atp) channels, the authors tested the hypothesis that intracellular pH (pHi) modulates the direct interaction of isoflurane with the cardiac K(atp) channel.

Methods
The effects of isoflurane on sarcolemmal K(atp) channels were investigated at pHi 7.4 and pHi 6.8 in excised inside-out membrane patches from ventricular myocytes of guinea pig hearts.

Results
At pHi 7.4, intracellular ATP (1-1,000 microm) inhibited K(atp) channels and decreased channel open probability (Po) in a concentration-dependent manner with an IC(50) of 8 +/- 1.5 microm, and isoflurane (0.5 mm) either had no effect or decreased channel activity. Lowering pHi from 7.4 to 6.8 enhanced channel opening by increasing Po and reduced channel sensitivity to ATP, with IC shifting from 8 +/- 1.2 to 45 +/- 5.6 microm. When applied to the channels activated at pHi 6.8, isoflurane (0.5 mm) increased Po and further reduced ATP sensitivity, shifting IC(50) to 110 +/- 10.0 microm.

Conclusions
Changes in pHi appear to modulate isoflurane interaction with the cardiac K(atp) channel. At pHi 6.8, which itself facilitates channel opening, isoflurane enhances channel activity by increasing Po and reduces sensitivity to inhibition by ATP without changing the unitary amplitude of single channel current or the conductance. These results support the hypothesis of direct isoflurane-K(atp) channel interaction that may play a role in cardioprotection by volatile anesthetics.
Interaction of Isoflurane with the Dopamine Transporter
Authors: Votaw John , Byas-Smith Michael , Hua Jian , Voll Ronald , Martarello Laurent , Levey Allan I. , Bowman F. DuBois , Goodman Mark 
Published: November 2003

Background
Isoflurane administration is known to increase extracellular dopamine (DA) concentration. Because the dopamine transporter (DAT) is a key regulator of DA, it is likely affected by isoflurane. This study investigates the hypothesis that isoflurane inhibits DA reuptake by causing DAT to be trafficked into the cell.

Methods
Rhesus monkeys were scanned with positron emission tomography (PET) using [18F]FECNT (a highly specific DAT ligand) while anesthetized with 1% isoflurane. The isoflurane was increased to 2%, and the animals were rescanned. Uptake was analyzed with the tissue reference method using the cerebellum as the reference tissue to determine the binding potential in the putamen. Immunohistochemistry and Western blot analyses were performed in rats to determine if isoflurane administration would change the total amount of DAT. Rats breathed air plus 2% isoflurane for 30 min, and then striatal DAT assays were rapidly performed. immunocytochemistry experiments were performed using human embryonic kidney (HEK) cells stably transfected with human DAT. The cells were exposed to 4% isoflurane for 1 h while the location of DAT was observed with fluorescent confocal microscopy.

Results
The [18F]FECNT binding potential in rhesus monkeys decreased by 63 +/- 6% (SEM, n = 5) when isoflurane was increased from 1 to 2% as compared with no significant change (0.7 +/- 2.5%; SEM, n = 5) when the isoflurane concentration was not changed (P < 0.001). No difference in DAT staining between isoflurane-treated and control rats was apparent from visual inspection, and quantitative Western blot analyses showed no significant change in total DAT protein. After isoflurane treatment, focal puncta of intense fluorescence was visible inside the HEK cells.

Conclusions
The experiments indicate that DAT is trafficked into the cell by isoflurane without changing the total amount of DAT in the striatum. The PET data are consistent with this finding, provided that intracellular DAT acquires a conformation that has low affinity for [18F]FECNT. Thus, [18F]FECNT appears to be an excellent agent for measuring plasma membrane-expressed DAT and evaluating DAT trafficking.
Supraspinal Antinociceptive Effects of μ and δ Agonists Involve Modulation of Adenosine Uptake
Authors: Pham Thao , Carrega Louis , Sauze Nicole , Fund-Saunier Odile , Devaux Christiane , Peragut Jean-Claude , Saadjian Alain , Guieu Régis 
Published: November 2003

Background
The modulation of extracellular adenosine concentration by opioids provides evidence that the antinociceptive effects of these compounds involve endogenous adenosine. The aim of this study was to determine whether there is a relation between the inhibition of brain synaptosome adenosine uptake by opioid agonists and the analgesic effects of these compounds.

Methods
The authors used the hot plate and tail-pinch tests to evaluate in mice (C57BL/6 females; weight, 25-30 g) the effects of caffeine, a nonspecific adenosine receptor antagonist, on the antinociceptive effect induced by the intracerebroventricular administration of oxymorphone as a mu agonist, SNC80 as a delta agonist, or U69593 as a kappa agonist. They also investigated the effect of these opioid receptor agonists on the uptake of adenosine by whole brain synaptosomes.

Results
Caffeine decreased the analgesic effects induced by oxymorphone or SNC80 but not those induced by U69593. Oxymorphone and SNC80 inhibited adenosine uptake by brain cells, but U69593 did not.

Conclusion
The antinociceptive effects obtained with mu or delta (but not kappa) agonists administered supraspinally were indicative of the involvement of modulation of adenosine uptake.