bluuebunny/crossref_metadata_2025_split huggingface dataset:
Halothane and Isoflurane Augment Depolarization-induced Cytosolic CA2+Transients and Attenuate Carbachol-stimulated CA2+Transients
Authors: Xu Fang , Zhang Jin , Recio-Pinto Esperanza , Blanck Thomas J. J. 
Published: November 2003

Background
Neuronal excitability is in part determined by Ca2+ availability that is controlled by regulatory mechanisms of cytosolic Ca2+ ([Ca2+]cyt). Alteration of any of those mechanisms by volatile anesthetics (VAs) may lead to a change in presynaptic transmission and postsynaptic excitability. Using a human neuroblastoma cell line, the effects of halothane and isoflurane on cytosolic Ca2+ concentration ([Ca2+]cyt) in response to K+ and carbachol stimulation were investigated.

Methods
Volatile anesthetic (0.05-1 mm) action on stimulated [Ca2+]cyt transients were monitored in suspensions of SH-SY5Y cells loaded with fura-2. Potassium chloride (KCl; 100 mm) was used to depolarize and activate Ca2+ entry through voltage-dependent calcium channels; 1 mm carbachol was used to activate muscarinic receptor-mediated inositol triphosphate (IP3)-dependent intracellular Ca2+ release. Sequential stimulations, KCl followed by carbachol and vice versa, were used to investigate interactions between intracellular Ca2+ stores.

Results
Halothane and isoflurane in clinically relevant concentrations enhanced the K+-evoked [Ca2+]cyt transient whether intracellular Ca2+ stores were full or partially depleted. In contrast, halothane and isoflurane reduced the carbachol-evoked [Ca2+]cyt transient when the intracellular Ca2+ stores were full but had no effect when the Ca2+ stores were partially depleted by KCl stimulation.

Conclusions
Volatile anesthetics acted on sites that differently affect the K+- and carbachol-evoked [Ca2+]cyt transients. These data suggest the involvement of an intracellular Ca2+ translocation from the caffeine-sensitive Ca2+ store to the inositol triphosphate-sensitive Ca2+ store that was altered by halothane and isoflurane.
Isoflurane Alters the Recirculatory Pharmacokinetics of Physiologic Markers
Authors: Avram Michael J. , Krejcie Tom C. , Niemann Claus U. , Enders-Klein Cheri , Shanks Colin A. , Henthorn Thomas K. 
Published: November 2003

Background
Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution.

Methods
The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition.

Results
Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered.

Conclusions
The isoflurane-induced changes in marker disposition were different than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia. These data provide further evidence that not only cardiac output but also its peripheral distribution affect early drug concentration history after rapid intravenous administration.
Pentobarbital, but not Propofol, Suppresses Vasopressin-stimulated Heat Shock Protein 27 Induction in Aortic Smooth Muscle Cells
Authors: Kozawa Osamu , Tanabe Kumiko , Matsuno Hiroyuki , Niwa Masayuki , Yamamoto Takuji , Akamatsu Shigeru , Kato Kanefusa , Dohi Shuji , Uematsu Toshihiko 
Published: November 2003

Background
Although it is known that systemic blood pressure decreases after the administration of pentobarbital or propofol, the mechanisms underlying the cardiovascular effects of these anesthetics are still poorly understood. The authors previously showed that vasopressin stimulates the induction of heat shock protein (HSP) 27, a low-molecular-weight HSP, by a protein kinase C-dependent manner in aortic smooth muscle A10 cells. It is recognized that HSP27 may act as a chaperone like high-molecular-weight HSPs such as HSP70. HSP27 is reportedly associated with agonist-induced contraction of vascular smooth muscle cells. The authors examined the effects of pentobarbital and propofol on the vasopressin-stimulated HSP27 induction in A10 cells.

Methods
Cultured A10 cells were pretreated with pentobarbital or propofol and then stimulated by vasopressin or 12-o-tetradecanoylphorbol 13-acetate (TPA). The effect of vasopressin on HSP70 was evaluated by Western blot analysis and compared with its effect on HSP27. The concentrations of HSP27 were determined by a specific immunoassay. The effect of pentobarbital on the expression levels of mRNA for HSP27 by vasopressin was evaluated by Northern blot analysis.

Results
Vasopressin induced HSP27 but had little effect on HSP70. At concentrations used clinically, pentobarbital inhibited the accumulation of HSP27 by vasopressin or TPA. Pentobarbital reduced the levels of mRNA for HSP27 induced by vasopressin. In contrast, propofol affected neither the vasopressin- nor TPA-induced HSP27 accumulation.

Conclusions
These results suggest that pentobarbital suppresses the vasopressin-stimulated HSP27 induction in vascular smooth muscle cells. This inhibitory effect is probably exerted at a point downstream from protein kinase C.
Pulsus Alternans during General Anesthesia with Halothane
Authors: Saghaei Mahmood , Mortazavian Mojtaba 
Published: November 2003

Background
Pulsus alternans is a classic type of abnormal pulse. It can be defined as a regular alternation of pulse amplitude in which runs of weak and strong beats follow each other alternatively without any change in cycle length. It may be a sign of severe decompensated congestive heart failure. The authors infrequently encountered some cases of pulsus alternans during halothane anesthesia with spontaneous respiration in otherwise normal subjects in association with high levels of end-tidal carbon dioxide. This study was conducted to determine if there is any relation between this phenomena and hypercapnia.

Methods
One hundred twenty patients undergoing elective lower extremity surgery were selected. Halothane was used for maintenance of anesthesia, and the patients were allowed to breath spontaneously. The occurrence of pulsus alternans was determined by plethysmographic display of pulse wave and then confirmed by palpation of the radial artery.

Results
Ten patients (8.3%) developed pulsus alternans together with elevated levels of end-tidal carbon dioxide (57 +/- 4 mmHg vs. 41 +/- 4 mmHg in patients without pulsus alternans [mean +/- SD]). The pulsus alternans disappeared after switching to controlled ventilation and 15-20% reduction in end-tidal carbon dioxide. During the period of pulsus alternans, vital signs and electrocardiography remained within normal limits.

Conclusions
There may be some relation between occurrence of pulsus alternans and hypercapnia during halothane anesthesia. Pulsus alternans occurs in a small fraction of spontaneously breathing, halothane-anesthetized patients. Although hypercapnia is clearly a factor, the mechanism of this phenomenon is unknown.
Differences in Cardiovascular Response to Airway Stimulation at Different Sites and Blockade of the Responses by Lidocaine
Authors: Hamaya Yoshihiro , Dohi Shuji 
Published: November 2003

Background
Mechanical stimulation of the airways elicits abrupt cardiovascular responses (CVR) in anesthetized humans. We examined a potential difference in such responses by comparing changes in heart rate (HR) and arterial blood pressure (AP) responses to mechanical stimulation of three different parts of the airways, as well as the effects of localized airway anesthesia with lidocaine on these responses.

Methods
After induction of general anesthesia, the larynx under laryngeal mask insertion (L, n = 20), the trachea-carina under tracheal intubation (T, n = 20), or the bronchus under bronchial intubation (B, N = 20) of each patient was mechanically stimulated in a similar manner. The same stimulation was repeated in 15 patients in each group after 5 ml of 4% lidocaine had been sprayed onto the part of the airway being stimulated. To test the systemic effect, intravenous lidocaine 1 mg/kg was given to five patients in each group, followed by the same airway stimulation. Consequent changes in HR and AP were continuously recorded and analyzed.

Results
Significant increases in HR and AP in response to airway tactile stimulation differed in magnitude according to the stimulated sites (L > T > or = B). These responses were completely blocked by topical application of lidocaine and partially blocked by intravenous lidocaine.

Conclusions
We found that CVRs to tactile stimulation differ in their magnitude at three different sites within the airways, and localized anesthesia with lidocaine can abolish these responses in humans. The inhibition of lidocaine could be mainly due to direct blockade of the mechanoreceptors of the airways and partly to its systemic effect.
Anesthesiologist Direction and Patient Outcomes
Authors: Silber Jeffrey H. , Kennedy Sean K. , Even-Shoshan Orit , Chen Wei , Koziol Laurie F. , Showan Ann M. , Longnecker David E. 
Published: November 2003

Background
Anesthesia services for surgical procedures may or may not be personally performed or medically directed by anesthesiologists. This study compares the outcomes of surgical patients whose anesthesia care was personally performed or medically directed by an anesthesiologist with the outcomes of patients whose anesthesia care was not personally performed or medically directed by an anesthesiologist.

Methods
Cases were defined as being either "directed" or "undirected," depending on the type of involvement of the anesthesiologist, as determined by Health Care Financing Administration billing records. Outcome rates were adjusted to account for severity of disease and other provider characteristics using logistic regression models that included 64 patient and 42 procedure covariates, plus an additional 11 hospital characteristics often associated with quality of care. Medicare claims records were analyzed for all elderly patients in Pennsylvania who underwent general surgical or orthopedic procedures between 1991-1994. The study involved 194,430 directed and 23,010 undirected patients among 245 hospitals. Outcomes studied included death rate within 30 days of admission, in-hospital complication rate, and the failure-to-rescue rate (defined as the rate of death after complications).

Results
Adjusted odds ratios for death and failure-to-rescue were greater when care was not directed by anesthesiologists (odds ratio for death = 1.08, P < 0.04; odds ratio for failure-to-rescue = 1.10, P < 0.01), whereas complications were not increased (odds ratio for complication = 1.00, P < 0.79). This corresponds to 2.5 excess deaths/1,000 patients and 6.9 excess failures-to-rescue (deaths) per 1,000 patients with complications.

Conclusions
Both 30-day mortality rate and mortality rate after complications (failure-to-rescue) were lower when anesthesiologists directed anesthesia care. These results suggest that surgical outcomes in Medicare patients are associated with anesthesiologist direction, and may provide insight regarding potential approaches for improving surgical outcomes. (Key words: Anesthesiologists; anesthesia care team; quality of care; mortality; failure-to-rescue; complication; Medicare; general surgery; orthopedics.)
Preliminary Report on the Association of Apolipoprotein E Polymorphisms, with Postoperative Peak Serum Creatinine Concentrations in Cardiac Surgical Patients
Authors: Chew Sophia T. H. , Newman Mark F. , White William D. , Conlon Peter J. , Saunders Ann M. , Strittmatter Warren J. , Landolfo Kevin , Grocott Hilary P. , Stafford-Smith Mark 
Published: November 2003

Background
Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery.

Methods
The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values.

Results
The epsilon4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2). There was no difference in baseline creatinine among allele groups.

Conclusions
Inheritance of the apolipoprotein epsilon4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon3 or epsilon2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.
β-Adrenergic Desensitization after Burn Excision Not Affected by the Use of Epinephrine to Limit Blood Loss
Authors: McQuitty Christopher K. , Berman Jeffrey , Cortiella Joaquin , Herndon David , Mathru Mali 
Published: November 2003

Background
Burn patients have impaired myocardial function and decreased beta-adrenergic responsiveness. Further beta-adrenergic dysfunction from systemic absorption of topically administered epinephrine that is given to limit blood loss during burn excision could affect perioperative management. The authors evaluated the effect of topical epinephrine administration to patients during burn excision on the lymphocytic beta-adrenergic response.

Methods
Fifty-five patients (age, 2-18 yr) with 20-90% body surface area burns received a standardized anesthetic for a burn excision procedure. Lymphocyte samples were taken at baseline and 1 and 3 h after the initial use of epinephrine (n = 43) or thrombin (controls, n = 12). Plasma epinephrine levels were measured by high-performance liquid chromatography. Lymphocyte beta-adrenergic responsiveness was assessed by measuring production of cyclic adenosine monophosphate (cAMP) after stimulation with isoproterenol, prostaglandin E1 (PGE1), and forskolin. beta-adrenergic receptor binding assays using iodopindolol and CGP12177 yielded beta-adrenergic receptor density.

Results
Epinephrine levels were elevated at 1 h (P < 0.01) and 3 h (P < 0.01) after epinephrine use but not in control patients. Production of cAMP in lymphocytes 1 h after epinephrine was greater in patients receiving epinephrine than in control patients on stimulation with isoproterenol (P < 0.05) and PGE1 (P < 0.05). Three hours after epinephrine administration, production of cAMP decreased when compared with baseline in both control patients and those receiving epinephrine after stimulation with isoproterenol (P < 0. 05), PGE1(P < 0.05), and forskolin (P < 0.05). Lymphocytic beta-adrenergic receptor content was not changed.

Conclusions
Topical epinephrine to limit blood loss during burn excision resulted in significant systemic absorption and increased plasma epinephrine levels. Acute sensitization of the lymphocytic beta-adrenergic cascade was induced by the administration of epinephrine reflected by increased cAMP production after stimulation with isoproterenol and PGE1. The lymphocytic beta-adrenergic cascade exhibited homologous and heterologous desensitization 3 h after the use of epinephrine or thrombin, indicating that epinephrine administration was not a causative factor.
Epidural Infusion of Ropivacaine for Postoperative Analgesia after Major Orthopedic Surgery
Authors: Burm Anton G. L. , Stienstra Rudolf , Brouwer Rolf P. , Emanuelsson Britt-Marie , van Kleef Jack W. 
Published: November 2003

Background
Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia.

Methods
Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured.

Results
Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values.

Conclusions
Postoperative increases in plasma alpha1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.
Absence of Bronchodilation during Desflurane Anesthesia
Authors: Goff Mitchell J. , Arain Shahbaz R. , Ficke David J. , Uhrich Toni D. , Ebert Thomas J. 
Published: November 2003

Background
Bronchospasm is a potential complication in anyone undergoing general anesthesia. Because volatile anesthetics relax bronchial smooth muscle, the effects of two newer volatile anesthetics, desflurane and sevoflurane, on respiratory resistance were evaluated. The authors hypothesized that desflurane would have greater bronchodilating effects because of its ability to increase sympathetic nervous system activity.

Methods
Informed consent was obtained from patients undergoing elective surgery with general anesthesia. We recorded airway flow and pressure after thiopental induction and tracheal intubation (baseline) and for 10 min after beginning volatile anesthesia ( approximately 1 minimum alveolar concentration inspired). Respiratory system resistance was determined using the isovolume technique.

Results
Fifty subjects were randomized to receive sevoflurane (n = 20), desflurane (n = 20), or thiopental infusion (n = 10, 0.25 mg. kg-1. h-1). There were no differences between groups for age, height, weight, smoking history, and American Society of Anesthesiologists physical class. On average, sevoflurane reduced respiratory resistance 15% below baseline, whereas both desflurane (+5%) and thiopental (+10%) did not decrease respiratory resistance. The respiratory resistance changes did not differ in patients with and without a history of smoking during sevoflurane or thiopental. In contrast, administration of desflurane to smokers resulted in the greatest increase in respiratory resistance.

Conclusions
Sevoflurane causes moderate bronchodilation that is not observed with desflurane or sodium thiopental. The bronchoconstriction produced by desflurane was primarily noted in patients who currently smoked. (Key words: Bronchospasm; respiratory resistance; volatile anesthetics.)
Cholinesterase Inhibition by Potato Glycoalkaloids Slows Mivacurium Metabolism
Authors: McGehee Daniel S. , Krasowski Matthew D. , Fung Dennis L. , Wilson Barry , Gronert Gerald A. , Moss Jonathan 
Published: November 2003

Background
The duration of action for many pharmaceutical agents is dependent on their breakdown by endogenous hydrolytic enzymes. Dietary factors that interact with these enzyme systems may alter drug efficacy and time course. Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine, heroin, esmolol, local ester anesthetics, and neuromuscular blocking drugs. Natural glycoalkaloid toxins produced by plants of the family Solanaceae, which includes potatoes and tomatoes, inhibit both AChE and BuChE. Here the authors assess the extent to which two solanaceous glycoalkaloids (SGAs), alpha-solanine and alpha-chaconine, can alter the effects of neuromuscular blocking drugs and cholinesterase inhibitors in vivo and in vitro.

Methods
Inhibition of purified human AChE and BuChE by SGAs, neuromuscular blocking drugs, and cholinesterase inhibitors was assessed by an in vitro colorimetric cholinesterase assay. In vivo experiments were carried out using anesthetized rabbits to test whether SGAs affect recovery from mivacurium-induced paralysis.

Results
SGAs inhibited human BuChE at concentrations similar to those found in serum of individuals who have eaten a standard serving of potatoes. Coapplication of SGAs (30-100 nm) with neuromuscular blocking drugs and cholinesterase inhibitors produced additive cholinesterase inhibition. SGA administration to anesthetized rabbits inhibited serum cholinesterase activity and mivacurium hydrolysis. In addition, SGA prolonged the time needed for recovery from mivacurium-induced paralysis (149 +/- 12% of control; n = 12).

Conclusions
These findings support the hypothesis that inhibition of endogenous enzyme systems by dietary factors can influence anesthetic drug metabolism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individuals.