bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitization of the Cardiac Na Channel to α1-Adrenergic Stimulation by Inhalation Anesthetics
Authors: Weight Henry U. , Kowk Wai-Meng , Rehmert Georg C. , Bosnjak Zeljko J. 
Published: November 2003

Background
Alpha1-adrenergic receptor stimulation has been shown to inhibit cardiac Na+ current (INa). Furthermore, some form of synergistic interaction of alpha1-adrenergic effects on INa in combination with volatile anesthetics has been reported. In this study, the authors investigated the possible role of G proteins and protein kinase C in the effects of halothane and isoflurane in the absence and presence of alpha1-adrenergic stimulation on the cardiac INa.

Methods
The standard whole-cell configuration of the patch-clamp technique was used. INa was elicited by depolarizing test pulses from a holding potential of -80 mV in reduced Na+ solution (10 mM). The experiments were conducted on ventricular myocytes enzymatically isolated from adult guinea pig hearts.

Results
The inhibitory effect of halothane (1.2 mM) and isoflurane (1 mM) on peak INa was significantly diminished in the presence of guanosine 5'-O-[2-thiodiphosphate (GDPbetaS). In myocytes pretreated with pertussis toxin (PTX), the potency of halothane was significantly enhanced, but the isoflurane effect was unchanged. In the presence of the protein kinase C (PKC) inhibitor bisindolylmaleimide (BIS), the effect of halothane was unchanged. In contrast, the effect of isoflurane on INa in the presence of BIS was significantly enhanced. The positive interaction between methoxamine and halothane was evident in the presence of G protein and PKC inhibitors. In contrast, the effect of methoxamine with isoflurane was additive in the presence of GDPbetaS or BIS.

Conclusions
Different second messenger systems are involved in the regulation of cardiac Na+ current by volatile anesthetics. The effect of halothane involves a complex interaction with G proteins but is independent of regulation by PKC. In contrast, PKC is involved in the modulation of cardiac INa by isoflurane. In addition, non-PTX-sensitive G proteins may contribute to the effects of isoflurane. The positive interaction between methoxamine and anesthetics are independent of G proteins and PKC for halothane. In the case of isoflurane, the positive interaction with methoxamine is coupled to PTX-insensitive G proteins and PKC.
Comparison of the Effects of Treatment with Intrathecal Lidocaine Given before and after Formalin on Both Nociception and Fos Expression in the Spinal Cord Dorsal Horn
Authors: Yashpal Kiran , Mason Patrick , McKenna John E. , Sharma Sushil K. , Henry James L. , Coderre Terence J. 
Published: November 2003

Background
It has been proposed that the measure of noxious stimulus-induced Fos (the protein product of the immediate early gene c-fos) expression in the spinal cord dorsal horn of laboratory animals may provide an estimate of the potential of specific treatments to produce preemptive analgesia. The present study examined this hypothesis by comparing the effects of intrathecal lidocaine given before and after hindpaw formalin injection on persistent nociceptive responses and Fos expression in spinal cord dorsal horn of rats.

Methods
Formalin-induced nociception and Fos expression in the spinal cord, in response to a 50-microl injection of 2.5% formalin into the hind paw, were assessed in rats given an intrathecal injection of 50 microl 2% lidocaine by lumbar puncture between the L5 and L6 vertebrae, either 3 min before (pretreatment) or 5 min after (post-treatment) formalin injection.

Results
Pain behaviors (hindpaw licking, elevation, and favoring) in the second phase of the formalin test were significantly reduced by pretreatment, but were unaffected by post-treatment. The number of immunocytochemically stained Fos-positive cells and the immunoprecipitation of the Fos antibodies were reduced by pretreatment, and were also reduced, to a lesser extent, by post-treatment.

Conclusions
The finding that persistent nociceptive behaviors and Fos expression were suppressed by intrathecal lidocaine pretreatment suggests that nociception in the second phase of the formalin test depends on increases in central hyperexcitability generated during the first phase. On the other hand, the finding that the intrathecal injection of lidocaine after formalin treatment reduced Fos expression but not nociceptive responses indicates an uncoupling of the behavioral and Fos protein responses to formalin and suggests that changes in Fos expression may not be a good predictor of the ability of agents to produce preemptive analgesia.
Comparison of the Effects of Pancuronium and Vecuronium in Canine Coronary and Renal Arteries
Authors: Sai Yoshikazu , Ayajiki Kazuhide , Okamura Tomio , Nosaka Shuichi , Toda Noboru 
Published: November 2003

Background
Pancuronium has sympathomimetic actions but does not change or lowers systemic blood pressure in some studies of anesthetized humans and dogs. The present study was done to determine the actions and mechanisms of action of pancuronium on coronary and renal arteries other than those as a sympathomimetic agent.

Methods
Helical strips of coronary and renal arteries from mongrel dogs were suspended in oxygenated, warmed Ringer-Locke solution, and changes in the isometric tension were recorded. In some strips, transmural electrical stimulation (5 Hz for 40 s) was applied to activate perivascular adrenergic nerves.

Results
Pancuronium (10[-7] to 10[-5] M) caused dose-dependent relaxation in coronary and renal arteries contracted with prostaglandin (PG) F2alpha, whereas no significant response was induced with vecuronium. The relaxation was endothelium independent and abolished by indomethacin or tranylcypromine, a PGI2 synthase inhibitor. Transmural electrical stimulation caused coronary arterial relaxation, which was augmented by pancuronium and vecuronium. Desipramine also increased the response, and additional potentiation of the response was not elicited by pancuronium and vecuronium. In renal arteries, electrical stimulation caused contraction, which was also augmented by pancuronium and vecuronium. With desipramine treatment, these muscle relaxants did not potentiate the response. Endothelium-dependent coronary arterial relaxation caused by bradykinin was not affected by pancuronium.

Conclusions
Pancuronium-induced relaxations in canine coronary and renal arteries appear to be mediated by PGI2 released from subendothelial tissues. Potentiations by pancuronium and vecuronium of the response to adrenergic nerve stimulation are expected to be due to an inhibition of the norepinephrine uptake but not to facilitated release of the amine.
Modulation of Recombination Human γ-Aminobutyric Acid-A Receptors by Isoflurane
Authors: Lees George , Edwards Michelle D. 
Published: November 2003

Background
The gamma-aminobutyric acid (GABA)A receptor/chloride channel has a broad-spectrum anesthetic sensitivity and is a key regulator of arousal. Each receptor/channel complex is an assembly of five protein subunits. Six subunit classes have been identified, each containing one to six members; many combinations are expressed throughout the brain. Benzodiazepines and intravenous anesthetic agents are clearly subunit dependent, but the literature to date suggests that volatile anesthetics are not. The physiological role of the delta subunit remains enigmatic, and it has not been examined as a determinant of anesthetic sensitivity.

Methods
Combinations of GABA(A) receptor subunit cDNAs were injected into Xenopus laevis oocytes: alpha1beta1, alpha1beta1gamma2L, alpha1beta1delta, and alpha1beta1gamma2Ldelta. Expression of functional ion channels with distinct signalling and pharmacologic properties was demonstrated within 1-4 days by established electrophysiological methods.

Results
Co-expression of the delta subunit produced changes in receptor affinity; current density; and the modulatory efficacy of diazepam, zinc, and lanthanum; it also produced subtle changes in the rate of desensitization in response to GABA. Isoflurane enhanced GABA-induced responses from all combinations: alphabeta delta (>10-fold) > alphabeta > alphabeta gamma > or = alphabeta gammadelta (approximately 5-fold). Dose-response plots were bell shaped. Compared with alphabeta gamma receptors (EC50 = 225 microM), both alphabeta delta (EC50 = 372 microM) and alphabeta gammadelta (EC50 = 399 microM) had a reduced affinity for isoflurane. Isoflurane (at a concentration close to the EC50 for each subunit) increased the affinity of GABA for its receptor but depressed the maximal response (alphabeta gamma and alphabeta gammadelta). In contrast, the small currents through alphabeta delta receptors were enhanced, even at saturating agonist concentrations.

Conclusions
Delta subunit expression alters GABA(A) receptor function but is not an absolute determinant of anesthetic sensitivity.
Partial Liquid Ventilation with Perfluorocarbon in the Treatment of Rats with Lethal Pneumococcal Pneumonia
Authors: Dickson Eric W. , Heard Stephen O. , Chu Benson , Fraire Armando , Brueggemann Angela B. , Doern Gary V. 
Published: November 2003

Background
Partial liquid ventilation with perfluorocarbon is a new therapeutic strategy to treat various lung disorders. The current study was undertaken to determine the efficacy of partial liquid ventilation with a perfluorocarbon (FC-77) in the treatment of pneumococcal pneumonia in rats.

Methods
Male Wistar rats (weight, 275-300 g; n, 75) were infected via direct intratracheal inoculation with ca 10(9) colony-forming units of viable Streptococcus pneumoniae, serotype 3, and 24 h after infection were placed into one of five groups, each containing 15 rats. The groups were (1) no treatment, (2) one intramuscular injection of penicillin G benzathine (200,000 U), (3) partial liquid ventilation with FC-77, (4) partial liquid ventilation with FC-77 and a single intramuscular dose of penicillin G benzathine (200,000 U), and (5) gas ventilation. Animals were observed every 24 h for survival.

Results
All untreated or gas-ventilated animals or animals that received only partial liquid ventilation were dead by 7 days. Those receiving only partial liquid ventilation survived longer than untreated controls, but ultimately all succumbed by day 7. Survival was 40% for penicillin-treated rats compared with controls (P < 0.05) and 80% for animals treated with both partial liquid ventilation and penicillin versus antibiotic alone (P < 0.05).

Conclusions
These observations suggest that partial liquid ventilation with perfluorocarbon in combination with antibiotic administration may be an effective therapeutic modality in pneumococcal pneumonia.
Effect of Prolonged Nerve Block on Inflammatory Hyperalgesia in Rats
Authors: Kissin Igor , Lee Sandra S. , Bradley Edwin L. 
Published: November 2003

Background
Recent evidence suggests that the duration of the nociceptive block may be an important factor in determining the effect of the block on injury-induced hyperalgesia after block resolution. The authors examined whether a tonicaine nerve block lasting for 12 to 16 h could prevent late inflammatory hyperalgesia.

Methods
Inflammatory hyperalgesia was induced by injection of carrageenan into the rat paw. A threshold of motor response to increasing pressure was determined for the injected paw, contralateral paw, and tail The development of edema of the paw and an increase in paw temperature also were determined. The block was achieved by simultaneous percutaneous injections of tonicaine (a new long-acting anesthetic agent) or lidocaine at the sciatic nerve (greater trochanter level) and the saphenous nerve (midthigh level).

Results
Carrageenan without nerve block caused a profound primary (injected paw) and secondary (contralateral paw and tail) hyperalgesia that lasted for 3-5 days. Tonicaine nerve block administered before carrageenan completely prevented primary and secondary hyperalgesia. Tonicaine block administered 5 h after carrageenan injection reversed secondary hyperalgesia and prevented the development of late (> or = 24 h) primary and secondary hyperalgesia. Edema and temperature of the paw were not significantly affected by the nerve block administered before or after carrageenan.

Conclusions
A prolonged nerve block (12-16 h) can prevent the development of long-lasting (3-5 days) inflammatory hyperalgesia. Prevention of late hyperalgesia can be provided not only by the preinjury block but also by the postinjury block administered when hyperalgesia is already well established.
Effects of Intravenous Anesthetics on Normal and Passively Sensitized Human Isolated Airway Smooth Muscle
Authors: Ouedraogo Nazinigouba , Roux Etienne , Forestier Francois , Rossetti Max , Savineau Jean-Pierre , Marthan Roger 
Published: November 2003

Background
General anesthetics may modify airway responsiveness. The authors investigated the effect of thiopental, propofol, and etomidate on airway smooth muscle.

Methods
Contraction experiments were done in human airway rings that were either normal or passively sensitized with asthmatic serum. The effect of propofol and etomidate was also studied on both [Ca2+]i increase measured by microspectrofluorimetry in isolated myocytes and isometric contraction in the rat trachea.

Results
In human bronchi, thiopental (10[-7] to 10[-4] M) induced a concentration-dependent contraction. Neither propofol nor etomidate altered baseline tone, but both anesthetics reduced histamine-induced contraction. In human immunologically sensitized isolated bronchi, propofol (3 x 10[-4] M) reduced histamine reactivity (deltaFmax in %) to a greater degree than in nonsensitized tissues (64.4 +/- 15.7% and 16.4 +/- 8.5%, respectively; n = 6, P < 0.05), whereas the effect of etomidate (10[-4] M) was similar in both types of tissue (24.1 +/- 6% and 22.3 +/- 15%, respectively, n = 6). In rat isolated tracheal myocytes, propofol (3 x 10[-4] M) and etomidate (10[-4] M) altered the [Ca2+]i signal in response to the depolarizing agent potassium chloride and the muscarinic agonist acetylcholine. Accordingly, the two anesthetics also reduced the mechanical response of rat tracheal rings to these agonists.

Conclusions
Whereas thiopental contracts human isolated bronchi, propofol and etomidate reduce histamine-induced contraction in human isolated airway smooth muscle that were either not sensitized or passively sensitized with asthmatic serum. This effect involves inhibition of both electro- and pharmacomechanical coupling.
Cerebral Swelling after Normothermic Cardiopulmonary Bypass
Authors: Harris David N. F. , Oatridge Angela , Dob Darryl , Smith Peter L. C. , Taylor Kenneth M. , Bydder Graeme M. 
Published: November 2003

Background
Marked cerebral swelling visible on magnetic resonance images has been found immediately after hypothermic (28 degrees C) cardiopulmonary bypass. The mechanism is unknown, but indices of cerebral ischemia are seen during rewarming from hypothermic bypass that are not present with normothermic bypass (37 degrees C).

Methods
T1-weighted and fluid-attenuated inversion recovery magnetic resonance images were taken of seven patients undergoing routine coronary artery bypass surgery before, 1 h, and 7 days after the operation using normothermic bypass.

Results
Marked cerebral swelling was seen in fluid-attenuated inversion recovery images in five of seven patients 1 h after bypass. Scans in four patients taken 7 days after bypass showed that the cerebral swelling had returned to normal. There was no change in cerebral ventricular size, and all patients had uncomplicated postoperative courses.

Conclusions
Normothermic bypass is followed by acute postoperative cerebral swelling. However, the amount of swelling was similar to that found in a previous study after hypothermic bypass. The mechanism of swelling is still obscure, and its relation to neurologic outcome is unknown.
The Response of Patients with Duchenne's Muscular Dystrophy to Neuromuscular Blockade with Vecuronium
Authors: Ririe Douglas G. , Shapiro Frederic , Sethna Navil F. 
Published: November 2003

Background
The authors hypothesized that patients with Duchenne's muscular dystrophy (DMD) are more sensitive to nondepolarizing muscle relaxants.

Methods
Eight children with DMD and eight healthy children having orthopedic procedures were studied. Anesthesia consisted of thiopental, 60% nitrous oxide in 40% oxygen, and intravenous fentanyl and midazolam. Using electromyography, the ulnar nerve was stimulated and the electromyographic train-of-four ratio (TOFr) of the first dorsal interosseous muscle was recorded every 60 s. After baseline TOFr recording, all patients received 50 microg/kg vecuronium and the TOFr at 3 min was compared. Vecuronium (10 microg/kg) was then administered every minute until TOFr was < or =0.1. The TOFr was followed until TOFr was > or =0.01. Then 10 microg/kg of vecuronium were administered to maintain TOFr < or = 0.1. At the conclusion of the procedure, TOFr was allowed to recover to 0.25, and then neostigmine and glycopyrrolate were administered. Data are presented as medians and ranges.

Results
The initial dose of vecuronium resulted in greater TOFr depression in patients with DMD than in controls (0.14 vs. 0.86). Less vecuronium was needed to produce TOFr < or = 0.1 in the patients with DMD than in the control patients (55 microg/kg vs. 95 microg/kg). Recovery time for the TOFr to > or =0.1 after the initial dose was longer in the patients with DMD than in the controls (28 vs. 20 min; P = 0.03), and the maintenance dose of vecuronium was less in patients with DMD (0.6 vs. 1.3 microg x kg[-1] min[-1]; P < 0.01). The time for TOFr recovery from 0.1 to 0.25 was 36 min in the patients with DMD and 6 min in the controls (P < 0.01). After neostigmine, the TOFr was 1.0 in the controls and 0.91 (P = 0.03) in the patients with DMD.

Conclusion
There is increased sensitivity to vecuronium from neuromuscular blockade in patients with DMD.
The Dose-Response Relation of Intrathecal Fentanyl for Labor Analgesia
Authors: Palmer Craig M. , Cork Randall C. , Hays Richard , Van Maren Gretchen , Alves Diane 
Published: November 2003

Background
This study determined the dose-response relation of intrathecal fentanyl for labor analgesia and described the onset, duration, and quality of analgesia when used as the sole analgesic.

Methods
Eighty-four parturients in active labor who requested analgesia were randomized to one of seven treatment groups. They received 5-45 microg intrathecal fentanyl as part of a combined spinal-epidural technique. Visual analog pain scores were recorded before and at intervals after injection patients requested additional analgesia. The occurrence and severity of pruritus, nausea, and vomiting were also recorded. Maternal blood pressure was recorded before injection and at intervals after injection. Fetal heart rate was recorded before and 30 min after injection.

Results
By 5 min after injection, pain scores were significantly different among groups (P < 0.001). Mean duration of analgesia increased to 89 min as the dose increased to 25 microg. Maternal diastolic blood pressure was significantly lower 10 and 30 min after injection. There was no difference among groups in the incidence of pruritus; nausea and vomiting were uncommon. Fetal heart rates did not change after injection. A dose-response curve indicates that the median effective dose of intrathecal fentanyl for labor analgesia is 14 microg (95% confidence interval, 13-15 microg).

Conclusions
Intrathecal fentanyl produces rapid, profound labor analgesia with minimal side effects. These data indicate that there is little benefit to increasing the dose beyond 25 microg when it is used as the sole agent for intrathecal labor analgesia.
Influence of Volatile Anesthetics on Thromboxane A2Signaling
Authors: Honemann Christian W. , Nietgen Gregor W. , Podranski Tobias , Chan Carrie K. , Durieux Marcel E. 
Published: November 2003

Background
Thromboxane A2 (TXA2) is a member of the prostaglandin family; activation of its receptor induces several important effects, including platelet aggregation and smooth muscle contraction. Because volatile anesthetics interfere with aggregation and contraction, the authors investigated effects of halothane, isoflurane, and sevoflurane on TXA2 signaling in an isolated receptor model.

Methods
mRNA encoding TXA2 receptors was prepared in vitro and expressed in Xenopus oocytes. The effects of halothane, isoflurane, and sevoflurane on Ca2+-activated Cl- currents induced by the TXA2 agonist U-46619 and on those induced by intracellular injection of inositol 1-4-5 trisphosphate or guanosine 5'-O-(2-thiodiphosphate) were measured using the voltage-clamp technique.

Results
Expressed TXA2 receptors were functional (half maximal effect concentration [EC50], 3.2 x 10(-7) +/- 1.1 x 10(-7) M; Hill coefficient (h), 0.8 +/- 0.2). Halothane and isoflurane inhibition of TXA2 signaling was reversible and concentration dependent (halothane half maximal inhibitory concentration [IC50], 0.46 +/- 0.04 mM; h, 1.6 +/- 0.21; isoflurane IC50, 0.69 +/- 0.12 mM; h, 1.3 +/- 0.27). 0.56 mM halothane (1%) right-shifted the U-46619 concentration-response relationship by two orders of magnitude (EC50, 1 x 10[-5] M). That h and maximal effect (Emax) were unchanged indicates that halothane acts in a competitive manner. In contrast, isoflurane acted noncompetitively, decreasing Emax by 30% (h and EC50 were unchanged). Both halothane and isoflurane had no effect on intracellular signaling pathways. Sevoflurane (0-1.3 mM) did not affect TXA2 signaling.

Conclusions
Both halothane and isoflurane inhibit TXA2 signaling at the membrane receptor, but by different mechanisms. This suggests that the effects of these anesthetics on TXA2 signaling are evoked at different locations of the receptor protein: halothane probably acts at the ligand binding site and isoflurane at an allosteric site.
Absence of Biochemical Evidence for Renal and Hepatic Dysfunction after 8 Hours of 1.25 Minimum Alveolar Concentration Sevoflurane Anesthesia in Volunteers
Authors: Ebert Thomas J. , Frink Edward J. , Kharasch Evan D. 
Published: November 2003

Background
Sevoflurane is degraded by carbon dioxide absorbents to a difluorovinyl ether (compound A) that can cause renal and hepatic injury in rats. The present study applied sensitive markers of renal and hepatic function to determine the safety of prolonged (8 h), high concentration (3% end-tidal) sevoflurane anesthesia in human volunteers.

Methods
Thirteen healthy male volunteers provided informed consent to undergo 8 h of 1.25 minimum alveolar concentration sevoflurane anesthesia delivered with a fresh gas flow of 2 l/min. Glucose, protein, albumin, N-acetyl-beta-D-glucosaminidase (NAG), and alpha- and pi-glutathione-S-transferase (GST) levels were analyzed in urine collected at 24 h before and for 3 days after sevoflurane anesthesia. Daily blood samples were analyzed for creatinine, blood urea nitrogen (BUN), alanine aminotransferase, alkaline phosphatase, and bilirubin concentrations. Circuit compound A and plasma fluoride concentrations were measured.

Results
During anesthesia, average and maximum inspired compound A concentrations were 27 +/- 7 and 34 +/- 6 (mean +/- SD) and median mean blood pressure, esophageal temperature, and end-tidal carbon dioxide levels were 63 mmHg, 36.8 degrees C, and 32 mmHg, respectively. The average serum inorganic fluoride concentration 2 h after anesthesia was 66.2 +/- 14.7 microM. Results of tests of hepatic function and renal function (BUN, creatinine concentration) were unchanged after anesthesia. Glucose, protein, albumin, and NAG excretion were not significantly increased after anesthesia. Urine concentrations of alpha-GST and pi-GST were increased on day 1 after anesthesia and alpha-GST was increased on day 2 after anesthesia but returned to normal afterward.

Conclusions
Prolonged (8 h), high concentration (3%) sevoflurane anesthesia administered to volunteers in a fresh gas flow of 2 l/min does not result in clinically significant changes in biochemical markers of renal or hepatic dysfunction.