bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Preemptive or Postinjury Intrathecal Local Anesthesia on Persistent Nociceptive Responses in Rats
Authors: Yashpal Kiran , Katz Joel , Coderre Terence J. 
Published: November 2003

Background
Although experimental evidence indicates that preemptive intrathecal treatment with local anesthetics reduces postinjury neuronal hyperexcitability, clinical evidence indicates that preemptive treatments do not consistently reduce postoperative pain. The current study used experimental models of postinjury nociception, in which rats received subcutaneous or intraarticular injections of the irritant formalin, to evaluate the effects of peripheral inflammation, or the use of agents supplemental to anesthesia, as possible confounding influences on the effectiveness of preinjury and postinjury intrathecal local anesthetic treatments.

Methods
In experiment 1, lumbar intrathecal lidocaine (30 microliters, 2%), given either 5 min before or 5 min after hind paw injection of 50 microliters of varying concentrations of formalin, was compared with intrathecal cerebrospinal fluid, for their effects on nociceptive responses in the late phase of the formalin test. Furthermore, the effect of hind paw injection of 50 microliters of 2.5, 3.75, or 5.0% formalin on peripheral inflammation was assessed by measuring plasma extravasation in the hind paws of rats given Evans Blue dye (50 mg/kg, intravenous). In experiment 2, rats received a deep tissue injury (100 microliters of 5.0% formalin into the knee joint) while under halothane anesthesia. In addition to halothane (3-4%), rats received either saline, pentobarbital (13 mg/kg, intraperitoneal), or pentobarbital + morphine (0.5 mg/kg, intravenous), with or without preinjury or postinjury spinal anesthesia using intrathecal bupivacaine (30 microliters, 0.75%), to assess the effects of supplemental treatments on the preemptive effects of intrathecal bupivacaine.

Results
Lumbar intrathecal lidocaine pretreatment, but not posttreatment, significantly reduced late phase nociceptive responses to hind paw injections of 2.5% formalin. The preemptive effects of lidocaine were overridden in rats that received hind paw injections of 3.75 and 5.0% formalin. Hind paw injection of 50 microliters of 3.75 or 5.0%, but not 2.5% formalin produced an increase in plasma extravasation. Either pentobarbital or pentobarbital + morphine treatment, or a pentobarbital + morphine treatment and postinjury treatment with intrathecal bupivacaine failed to produce a significant reduction in the nociceptive response to the deep tissue injury. However, rats that received pentobarbital + morphine treatments and intrathecal bupivacaine before the injury had significantly reduced nociceptive responses to deep tissue injury when compared to the saline control group, but not to the group that received pentobarbital + morphine treatment and postinjury treatment with bupivacaine.

Conclusions
The current results attest to the important effects of ongoing inputs from inflamed tissue, and the use of supplemental treatments, as important confounding factors that may influence the effectiveness of preemptive spinal anesthesia for postoperative pain.
Pentobarbital Enhances Cyclic Adenosine Monophosphate Production in the Brain by Effects on Neurons but Not Glia
Authors: Gonzales Jerry M. , Mendez-Bobe Iris 
Published: November 2003

Background
Cyclic adenosine monophosphate (cAMP) is an important regulator of neuronal excitability. The effects of barbiturates on cAMP production in intact neurons are not known. This study used cultures of cortical neurons, cultures of glia, and slices of cerebral cortex from the rat to study the effects of barbiturates on cAMP regulation in the brain.

Methods
Primary cultures of cortical neurons or glia were prepared from 17-day gestational Sprague-Dawley rat fetuses and were used after 12-16 days in culture. Cross-cut slices (300 microns) were prepared from cerebral cortex of adult rats. Cyclic AMP accumulation was determined by measuring the conversion of [3H]adenosine triphosphate (ATP) to [3H]cAMP in cells preloaded with [3H]adenine.

Results
Pentobarbital enhanced isoproterenol- and forskolin-stimulated, but not basal, cAMP accumulation in cultures of cerebral neurons. Cyclic AMP production was enhanced by pentobarbital in a dose-dependent fashion up to a concentration of 250 microM; This concentration of pentobarbital increased cAMP production by 40-50% relative to that in controls without pentobarbital. At 500 microM pentobarbital, the magnitude of the enhancement was less. Pentobarbital had no effect on isoproterenol-stimulated cAMP production in cultures containing only glia. Pentobarbital also enhanced isoproterenol-stimulated, but not basal, cAMP production in slices of cerebral cortex by approximately 30% at concentrations of 62.5-250 microM and by almost 100% at 500 microM.

Conclusions
Pentobarbital enhances stimulated cAMP accumulation in cultured preparations from brain and fresh cortical slices. Neurons are required for this effect. Because cAMP modulates neuronal excitability, this effect of pentobarbital may be an important mechanism by which this anesthetic influences brain function.
Volatile Anesthetics Selectively Inhibit the Calcium sup 2+ -transporting ATPase in Neuronal and Erythrocyte Plasma Membranes
Authors: Fomitcheva Ioulia , Kosk-Kosicka Danuta 
Published: November 2003

Background
The activity of the plasma membrane Ca(2+)-transporting adenosine triphosphatase (PMCA) is inhibited by volatile anesthetics at clinical concentrations. The goal of the current study was to determine whether the inhibition is selective as compared to other adenosine triphosphatases (ATPases) and another group of general anesthetics, barbiturates. In addition, the authors determined whether the response to anesthetics of the enzymes in neuronal membranes is similar to that in erythrocyte membranes.

Methods
The effects of halothane, isoflurane, and sodium pentobarbital on four different ATPase activities were studied at 37 degrees C in two distinct plasma membrane preparations, human red blood cells and synaptosomal membranes from rat cerebellum.

Results
Inhibition patterns of the PMCA by halothane and isoflurane at anesthetic concentrations were vary similar in red blood cells and synaptosomal membranes. The half-maximal inhibition (I50) occurred at 0.25-0.30 mM halothane and 0.30-0.32 mM isoflurane. The PMCA in both membranes was significantly more sensitive to the inhibitory action of volatile anesthetics (I50 = 0.75-1.15 minimum alveolar concentration) than were other ATPases, such as the Na+,K+-ATPase (I50 approximately 3 minimum alveolar concentration) or Mg(2+)-ATPase (I50 > or = 5 minimum alveolar concentration). In contrast, sodium pentobarbital inhibited the PMCA in both membranes only at approximately 100-200-fold above its anesthetic concentrations. The other ATPases were inhibited at similar pentobarbital concentrations (I50 = 11-22 mM).

Conclusions
The findings demonstrate analogous response of the PMCA of neuronal and erythrocyte cells to two groups of general anesthetics. The PMCA activity is selectively inhibited by volatile anesthetics at their clinical concentrations. The enzyme in vivo may then be a pharmacologic target for volatile anesthetics but not for barbiturates.
Effects of the Serotonin2Receptor Agonist DOI on Skeletal Muscle Specimens from Malignant Hyperthermia-susceptible Patients
Authors: Wappler Frank , Roewer Norbert , Kochling Andreas , Scholz Jens , Loscher Wolfgang , Steinfath Markus , Schulte am Esch Jochen 
Published: November 2003

Background
Administration of serotonin2 (5-HT2) receptor agonists in pigs triggers malignant hyperthermia (MH) and psychotic-like behavior. Both can be reduced by 5-HT2 receptor antagonists. Furthermore, an increase in the plasma concentration of 5-HT has been found during onset of halothane-induced MH in pigs. Therefore, in this study, the in vitro effects of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were investigated in muscle specimens from MH-susceptible (MHS) and -negative (MHN) patients.

Methods
After MH classification using the caffeine-halothane contracture test (CHCT), surplus muscle specimens from 23 MHS and 17 MHN patients were used to examine the effects of DOI. In the first study, DOI was added to the bath in a concentration of 0.02 mM. In a second experiment, muscles were preincubated for 60 min with 0.02 mM DOI, and subsequently, halothane was added incrementally to the organ bath (0.11-0.22-0.44 mM) for 15 min according to the CHCT protocol. The in vitro effects of DOI on contracture development and muscle twitch were measured for 120 min in both investigations.

Results
Muscle specimens form all patients developed contractures after administration of DOI, characterized by a significantly earlier development of contracture in MHS (16.8 +/- 1.7 min) than in MHN (66.3 +/- 5.8 min) muscles (P < 0.05). There was no overlap between the groups in the range of times. The onset of contracture development after DOI was prolonged by halothane in specimens from MHN patients (89.7 +/- 5.6 min) but not MHS patients. Preincubation with DOI increased the halothane-induced contractures in specimens from MHS patients compared to the results of the CHCT. The contracture development in specimens from MHS patients was larger than from MHN patients. At the end of the experiment, contractures had reached a maximum of 12.9 +/- 1.1 mN in specimens from MHS and 5.3 +/- 0.6 mN in MHN patients (P < 0.05). The additional administration of halothane led to significantly increased contractures in specimens from MHS individuals (15.9 +/- 0.9 mN) at 120 min. However, the contracture development decreased significantly to 3.1 +/- 0.4 mN in MHN muscles. Muscle twitch after DOI administration was reduced significantly in specimens from MHS and MHN patients.

Conclusions
A functional or structural altered serotonin system might be involved in the development of MH in humans.
Normothemic Continuous Blood Cardioplegia Improves Electrophysiologic Recovery after Open Heart Surgery
Authors: Gozal Yaacov , Glantz Lucio , Luria Myron H. , Milgalter Eli , Shimon Dov , Drenger Benjamin 
Published: November 2003

Background
Myocardial protection during open heart surgery is based on administration of oxygenated blood cardioplegia, the preferred temperature of which is still under debate. The current randomized study was designed to prospectively evaluate the quality of myocardial protection and the functional recovery of the heart with either normothermic (group N) or hypothermic (group H) oxygenated blood cardioplegia.

Methods
Under continuous electrocardiographic Holter monitoring, 42 patients were randomly scheduled to receive either normothermic (33.5 degrees C) or hypothermic (10 degrees C) cardioplegia solutions during coronary bypass grafting surgery. Blood samples for creatinine phosphokinase, creatinine phosphokinase-MB, lactate, epinephrine, and norepinephrine were withdrawn during cardiopulmonary bypass via a coronary sinus cannula.

Results
Active cooling in group H on initiation of cardiopulmonary bypass was characterized by transition through ventricular fibrillation in 75% of patients, whereas in group N atrial fibrillation occurred in 65% of patients. On myocardial reperfusion, sinus rhythm spontaneously resumed in 95% of group N patients compared to 25% in group H (P = 0.0003). In the latter, 75% of patients developed ventricular fibrillation often followed by complete atrioventricular block, which necessitated temporary pacing for a mean duration of 168 +/- 32 min. Both groups showed a similar incidence of intraventricular block and ST segment changes. However, the incidence of ventricular premature beats in the first 16 h after cardiopulmonary bypass was significantly greater in group H (P < 0.05), 20 +/- 26/h, compared to 3 +/- 5/h in group N. Blood concentrations of lactate, creatinine phosphokinase, epinephrine, and norepinephrine increased gradually during the operation, but the differences between the groups were not significant.

Conclusions
The current prospective human study suggests that the increased susceptibility for ventricular fibrillation and dysrhythmia, and the delayed recovery of the conduction system after hypothermic myocardial protection, are related to temperature-induced changes in vital cellular functions of the conduction tissue in the postischemic period. Both cardioplegic methods provide adequate myocardial protection but normothermic oxygenated blood cardioplegia may accelerate recovery of the heart after cardiopulmonary bypass.
Prospective Study of the Incidence of Transient Radicular Irritation in Patients Undergoing Spinal Anesthesia
Authors: Pollock Julia E. , Neal Joseph M. , Stephenson Carol A. , Wiley Carol E. 
Published: November 2003

Background
There is considerable controversy regarding the role of subarachnoid 5% hyperbaric lidocaine in the syndrome transient radicular irritation (TRI). This randomized, double-blinded, prospective study was designed to determine the incidence of TRI and identify factors possibly contributing to its development.

Methods
One hundred fifty-nine ASA physical status 1 or 2 patients undergoing outpatient knee arthroscopy or unilateral inguinal hernia repair were prospectively randomized to receive spinal anesthesia with 5% hyperbaric lidocaine with epinephrine (60 mg with 0.2 mg epinephrine for arthroscopy or 75 mg with 0.2 mg epinephrine for hernia repair), 2% isobaric lidocaine without epinephrine (60 mg for arthroscopy or 75 mg for hernia repair), or 0.75% hyperbaric bupivacaine without epinephrine (7.5 mg for arthroscopy or 9.0 mg for hernia repair) in a double-blinded fashion. On the 3rd postoperative day, patients were contacted by a blinded investigator and questioned regarding the incidence of postoperative complications including TRI, defined as back pain with radiation down one or both buttocks or legs occurring within 24 h after surgery. Postoperatively, time from injection to block resolution, ambulation, voiding, and ready for discharge were recorded by a postanesthesia care unit nurse blinded to the group assignment.

Results
The incidence of TRI was greater in patients receiving lidocaine than in those receiving bupivacaine (16% vs. 0%; P = 0.003). There was no difference in the incidence of TRI between the patients receiving 5% hyperbaric lidocaine with epinephrine and those receiving 2% isobaric lidocaine without epinephrine (16% vs. 16%; P = 0.98). The incidence of TRI was greater in patients undergoing arthroscopy than in those undergoing hernia repair (13% vs. 5%; P = 0.04). There was no difference in discharge times in patients receiving bupivacaine versus those receiving hyperbaric lidocaine with epinephrine (292 vs. 322 min; P = 0.61).

Conclusions
The incidence of TRI is greater with lidocaine than bupivacaine, decreasing the lidocaine concentration to 2% does not prevent TRI, and surgical position may be an important contributing factor. Discharge times at our institution are not different when equipotent doses of 0.75% hyperbaric bupivacaine or 5% hyperbaric lidocaine with 0.2 mg epinephrine are used in ambulatory patients undergoing spinal anesthesia.
Dantrolene Sodium Can Increase or Attenuate Activity of Skeletal Muscle Ryanodine Receptor Calcium Release Channel
Authors: Nelson Thomas E. , Lin Marina , Zapata-Sudo Gisele , Sudo Roberto Takashi 
Published: November 2003

Background
Dantrolene sodium (DS) is a direct-acting skeletal muscle relaxant whose only known action is to block calcium release from intracellular storage sites. The exact site of action for DS is unknown, but its efficacy in treating and preventing anesthetic-induced malignant hyperthermia (MH) is well established.

Methods
Single ryanodine (Ry1) receptor calcium release channels were incorporated into a planar lipid bilayer for electrophysiologic recording and for subsequent analysis of the channel's gating and conductance properties. The cellular effects of low DS concentrations were investigated by isometric contracture tension responses in biopsied MH human and dog muscle fascicles and in normal, single fibers from human vastus lateralis muscle.

Results
Two concentration-dependent DS effects on the isolated Ry1 receptor were discovered, suggesting at least two different binding sites. At nanomolar concentrations, DS activated the channel by causing three-to fivefold increases in open-state probability and dwell times. At micromolar concentrations, DS first increased then reduced activity in the channels; with the dominant effect being reduced activity. A 20 nm concentration of DS produced significant contracture tension in human muscle from one MH subject and caused potentiation of twitch in muscle from another MH patient. Halothane contracture in MH dog muscle was followed by an additional increase in tension when treated with 20 nm DS. Other investigations on chemically skinned, human fibers showed that calcium loaded in the sarcoplasmic reticulum was partially released by nM DS.

Conclusions
The study results suggest that at least two binding sites for DS exist on the Ry1 receptor calcium channel. A low-affinity (microM) site is associated with reduced channel gating and open-state dwell time and may relate to the established pharmacologic muscle relaxant effect of DS. The proposed high-affinity (nM) DS binding site activates the channel, producing Ca2+ release to the myoplasm, which, under environmentally adverse conditions, could damage genetically predisposed MH muscle. Such a phenomenon, if it occurs in DS treated MH patients, could generate a recrudescence of the syndrome.
Chlorocresol, an Additive to Commercial Succinylcholine, Induces Contracture of Human Malignant Hyperthermia-susceptible Muscles Via Activation of the Ryanodine Receptor Calcium sup 2+ Channel
Authors: Tegazzin Vincenzo , Scutari Erica , Treves Susan , Zorzato Francesco 
Published: November 2003

Background
A defect in the ryanodine (Ry1) receptor Ca2+ channel has been implicated as one of the possible underlying causes of malignant hyperthermia (MH), a pharmacogenetic disorder characterized by sustained muscle contracture. The disease is triggered by common halogenated anesthetics and skeletal muscle relaxants, such as succinylcholine. This study tested whether the functional properties of the Ry1 receptor Ca2+ channel are affected by chlorocresol, a preservative added to a commercial preparation of succinylcholine (Midarine) and other parenteral compounds.

Methods
In vitro contracture testing was carried out on muscle biopsies from malignant hyperthermia-susceptible (MHS) and -negative (MHN) individual according to the protocol of the European MH group. Ca2+ flux studies on isolated rabbit sarcoplasmic reticulum fractions were measured spectrophotometrically by following the A710-790 of the Ca2+ indicator antipyrylazo III.

Results
Chlorocresol causes muscle contracture in MHS muscles at a concentration of 25-50 microM and potentiates the caffeine contracture response in human MHS muscles. Sub-threshold (20 microM) concentrations of chlorocresol increase both the Kd and the Vmax of caffeine-induced Ca2+ release from isolated rabbit terminal cisternae.

Conclusions
These data suggest that, in muscle from MHS individuals, the enhanced Ca2+ released from the sarcoplasmic reticulum may not be due to the effect of succinylcholine alone but rather to the action of the preservative chlorocresol added to the drug.
Acute Lung Injury after Instillation of Human Breast Milk or Infant Formula into Rabbits' Lungs
Authors: O'Hare Brendan , Lerman Jerrold , Endo Junko , Cutz Ernest 
Published: November 2003

Background
Recent interest in shortening the fasting interval after ingestion of milk products demonstrated large volumes of breast milk in the stomach 2 h after breastfeeding. Although aspiration is a rare event, if it were to occur with human breast milk, it is important to understand the extent of the lung injury that might occur. Therefore, the response to instillation of acidified breast milk and infant formula in the lungs of adult rabbits was studied.

Methods
In 18 anesthetized adult rabbits, 1 of 3 fluids (in a volume of 0.8 ml.kg-1 and pH level of 1.8, acidified with hydrochloric acid); saline, breast milk, or infant formula (SMA, Wyeth, Windsor, Ontario), was instilled into the lungs via a tracheotomy. The lungs were ventilated for 4 h after instillation. Alveolar-to-arterial oxygen gradient and dynamic compliance were measured before and at hourly intervals after instillation. After 4 h, the rabbits were killed and the lungs were excised. Neutrophil infiltration was quantitated by a pathologist blinded to the instilled fluid. A histologic control group of four rabbits was ventilated under study conditions without any intratracheal fluid instillation.

Results
Alveolar-to-arterial oxygen gradient increased and dynamic compliance decreased significantly during the 4 h after instillation of both breast milk and infant formula compared with baseline measurements and with saline controls (P < 0.05). The neutrophil counts in the lungs from the saline, breast milk, and formula rabbits were significantly greater than those in the control group.

Conclusions
Instillation of acidified breast milk or infant formula (in a volume of 0.8 ml.kg-1 and pH level of 1.8) into rabbits' lungs induces acute lung injury of similar intensity that lasts at least 4 h.
Synaptic Mechanisms of Thiopental-induced Alterations in Synchronized Cortical Activity
Authors: Lukatch Heath S. , MacIver Bruce M. 
Published: November 2003

Background
Anesthetic depth after barbiturate administration has been correlated with distinct electroencephalogram (EEG) patterns. The current study used a rat neocortical brain slice micro-EEG preparation to investigate synaptic mechanisms underlying thiopental-induced transitions in synchronized neuronal activity.

Methods
Concentration-dependent cellular actions of thiopental were investigated in brain slices using specific pharmacologic probes, whole cell patch clamps, and extracellular field recordings. Theta-Like micro-EEG oscillations were elicited in neocortical slices by mimicking subcortical cholinergic and gamma-aminobutyric acid (GABA) afferent input with carbachol (100 microM), a cholinergic agonist, and bicuculline (10 microM) a GABAA antagonist.

Results
In the presence of 20 microM thiopental, micro-EEG slowing from theta (7.3 +/- 0.9 Hz, mean +/- SD, n = 19) to delta frequencies (2.5 +/- 0.5 Hz, n = 11) was associated with a threefold prolongation of inhibitory currents. Burst suppression activity occurred at 50 microM thiopental, and appeared to result from direct activation of GABAA-gated chloride currents, observed with voltage clamp recordings, and mimicked with a direct acting GABAA agonist, muscimol (1 microM). Isoelectric activity occurred at 100 microM thiopental, and likely resulted from reduced glutamatergic transmission, evidenced by depressed excitatory postsynaptic potentials. Glutamatergic excitation was required for burst suppression activity, because glutamate receptor antagonists blocked thiopental-induced bursts; forcing a transition to isoelectric activity.

Conclusions
Thiopental produced a continuum of EEG-like states in brain slices similar to those observed in vivo. The progression of thiopental-induced effects appear to have resulted from specific cellular actions that were recruited in a concentration-dependent manner. Progressive enhancement of synaptic inhibition followed by depression of excitatory transmission led to micro-EEG frequency slowing, burst suppression, and isoelectric activity.