Abstract:
UNLABELLED:Local anesthetics inhibit binding of ligands to beta2-adrenergic receptors (beta2ARs), and, as a consequence, inhibit intracellular cAMP production. We hypothesized that among homologous local anesthetics, their avidity at inhibiting binding of tritiated dihydroalprenolol (3H-DHA) to beta2ARs would increase with increasing length of alkyl substituents and would demonstrate stereospecificity. Specific binding of 3H-DHA to human beta2ARs was assayed in the presence of six different members of the 1-alkyl-2,6-pipecoloxylidide class of local anesthetics (including mepivacaine, ropivacaine, and bupivacaine), the R(+) and S(-) bupivacaine enantiomers, lidocaine, prilocaine, etidocaine, procaine, and tetracaine. Avidity of binding to beta2ARs increased with increasing length of the alkyl chain (pKi values = 2.4, 3.6, 4.3, 4.1, 4.1, 5.9 for the methyl [mepivacaine], ethyl, S(-)propyl [ropivacaine], butyl [bupivacaine], pentyl, and octyl derivatives, respectively). We found no evidence for bupivacaine stereospecificity (pKi values = 4.3 and 4.9 for the S(-) and R(+) isomers, respectively). Other amide and ester local anesthetics also showed increasing potency with increasing length of alkyl substituents (pKi values = 3.6, 3.8, and 4.3 for lidocaine, prilocaine, and etidocaine; 4.2 and 5.6 for procaine and tetracaine, respectively). The correlation between increased inhibition of beta2AR binding and alkyl chain length resembles the correlation between local anesthetic potency at nerve block and increased alkyl chain length. The lack of clear stereospecificity is consistent with the relatively low potency these agents demonstrate at inhibition of beta2AR binding. Finally, the relatively potent inhibition of beta2ARs by etidocaine, tetracaine, and bupivacaine suggests that their propensity for cardiovascular depression after accidental intravenous overdose could result from beta2AR or beta1AR blockade and inhibition of cAMP production. IMPLICATIONS:Local anesthetics demonstrate a rank order of avidity for displacing ligands from beta2-adrenergic receptors such that larger molecules displace ligands at lower concentrations than smaller local anesthetic molecules. This relationship between molecular size and receptor avidity could explain the greater propensity for cardiovascular toxicity of relatively large local anesthetics such as bupivacaine.
journal_name
Anesth Analgjournal_title
Anesthesia and analgesiaauthors
Butterworth J,James RL,Grimes Jdoi
10.1097/00000539-199708000-00017subject
Has Abstractpub_date
1997-08-01 00:00:00pages
336-42issue
2eissn
0003-2999issn
1526-7598journal_volume
85pub_type
杂志文章abstract::This investigation examined the role of myocardial adenosine triphosphate-regulated potassium (KATP) channels in isoflurane-induced enhancement of myocardial function after reversible tissue injury produced by a 15-min left anterior descending coronary artery occlusion (LAD) and reperfusion. Dogs (n = 14) were chronic...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-199607000-00006
更新日期:1996-07-01 00:00:00
abstract::Cimetidine blunts the increase in cerebral blood flow (CBF) normally observed during hypoxia. It is important, therefore, to know whether other H2-blockers also affect the cerebral circulation adaptation to hypoxia. Cerebral blood flow was measured in 24 awake dogs after an intravenous injection of either saline (cont...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/00000539-199104000-00020
更新日期:1991-04-01 00:00:00
abstract::Four patients underwent laryngoscopy and general anesthesia surgery without apparent perioperative complications. Within days of their procedure, throat and mouth pain were reported and intraoral examination in all cases revealed exposed bone in the posterior mandible. The sequestra were easily removed and healing was...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0b013e3181e0cdcd
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND:Variations in the butyrylcholinesterase (BCHE) gene can prolong neuromuscular block after the administration of the neuromuscular blocking drugs succinylcholine and mivacurium. The most frequent variations in the BCHE gene are the atypical (A) and Kalow (K) variants. We, therefore, developed a detection appr...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/01.ane.0000296455.31211.bd
更新日期:2008-01-01 00:00:00
abstract:UNLABELLED:Manufacturer's instructions recommend discarding unused portions of sodium thiopental 24 h after reconstitution. Heeding this recommendation may result in the disposal of a large proportion of prepared thiopental. Although thiopental is relatively inexpensive, the volume prepared by many anesthesia departmen...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-199801000-00040
更新日期:1998-01-01 00:00:00
abstract::Adenosine, a ubiquitous metabolic intermediate in the body, is involved in nearly every aspect of cell function, including neuromodulation and neurotransmission. Adenosine A(1) and A(2) receptors are widely distributed in the brain and spinal cord, and are a novel, non-opiate target for pain management. The potential ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章,评审
doi:10.1213/01.ane.0000267260.00384.d9
更新日期:2007-08-01 00:00:00
abstract::To determine the incidence of atrioventricular (A-V) block, 86 patients, aged 58.9 +/- 10.4 yr, undergoing elective coronary artery bypass grafting (CABG) during aortic cross-clamping (ACC) and cold potassium cardioplegia were investigated. The incidence and duration of complete A-V block after release of the aortic c...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-199501000-00009
更新日期:1995-01-01 00:00:00
abstract::The purpose of this study was to measure cardiac sympathetic nerve activity (CSNA) and atrioventricular (AV) conduction and to test the effects of dobutamine (DOB) and phenylephrine (PHE) on AV conduction during combined use of halothane and thoracic epidural lidocaine. Cats were anesthetized with 1 % halothane and an...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-199603000-00022
更新日期:1996-03-01 00:00:00
abstract:UNLABELLED:Clinical and basic science studies suggest that spinal alpha-2-adrenergic receptor agonists and local anesthetics produce analgesia, but interaction between alpha-2-adrenergic receptor agonists and local anesthetics in the persistent pain model has not been examined. In the present study, using isobolographi...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200103000-00034
更新日期:2001-03-01 00:00:00
abstract:UNLABELLED:Clonidine decreases the stress-induced sympathoadrenal responses to painful stimuli and improves hemodynamic stability during general anesthesia. Because acute hypertensive responses are often observed immediately after electroconvulsive therapy (ECT), we designed a prospective, randomized, placebo-controlle...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00000539-199805000-00042
更新日期:1998-05-01 00:00:00
abstract::Lidocaine and MgSO4 are often coadministered to patients with pregnancy-induced hypertension. This study examined whether MgSO4 alters the lidocaine-seizure threshold in the rat and, if so, whether systemic MgSO4 administration is as effective as intracerebroventricular MgSO4 infusion. In Experiment 1, rats were admin...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-199612000-00016
更新日期:1996-12-01 00:00:00
abstract:BACKGROUND:Among the various factors influencing the success rate, onset time, and duration of peripheral nerve blocks, the role of local anesthetics concentration remains uncertain. In this prospective, randomized, single-blinded study, we evaluated whether varying the dilution of a fixed dose of mepivacaine solution ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章,随机对照试验
doi:10.1213/ANE.0000000000000293
更新日期:2014-08-01 00:00:00
abstract:UNLABELLED:In this study, we examined the effectiveness of caudal blocks and correlated it with the laxity of the patients' anal sphincter before emergence from anesthesia in 178 children undergoing inguinal and/or penile surgery. Bupivacaine 0.25% in a volume of 0.6-1.25 mL/kg was used in all patients. The presence of...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200205000-00019
更新日期:2002-05-01 00:00:00
abstract::The effects of midazolam on atrial rate and contractile force in the isolated canine atrium perfused with donor blood were investigated. When midazolam in a dose range of 100-1000 micrograms was injected directly into the sinus node artery of the isolated atrium, biphasic (negative followed by positive) chronotropic a...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::The value of family-centered care in general and subspecialty pediatrics has been well documented in the literature. Translation of these principles into perioperative medicine has its logistical challenges; however, there are theoretical benefits. Specifically, pediatric patients with psychiatric diagnoses or special...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0b013e31827ab89c
更新日期:2013-06-01 00:00:00
abstract::The Brandt tube system can limit excessive cuff pressure during nitrous oxide (N(2)O) anesthesia, but there is a lack of data assessing whether the Brandt tube system avoids cuff deflation after cessation of N(2)O administration. In this study, we recorded air-filled cuff pressures of the Mallinckrodt Brandt or Hi-Con...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00000539-200302000-00055
更新日期:2003-02-01 00:00:00
abstract::The effects of nitrous oxide-oxygen plus small doses of fentanyl with (N = 7) and without (N = 15) naloxone and the effects of nitrous oxide-oxygen plus halothane (N = 13) on plasma concentration of arginine vasopressin (AVP) and cortisol were studied in normal patients before and during gynecologic laparotomies. Pati...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Respiratory variations in arterial pulse pressure (DeltaPP) are accurate predictors of fluid responsiveness in mechanically ventilated patients. The aim of our study was to assess the ability of a novel algorithm for automatic estimation of stroke volume variation (SVV) to predict fluid responsiveness in mec...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ane.0b013e318192a36b
更新日期:2009-02-01 00:00:00
abstract:UNLABELLED:In this study, we evaluated the reliability of a newly developed method for pain assessment, which is based on perceptual matching by Pain Matcher, Cefar Medical AB, Lund, Sweden, during minor gynecological surgery. In addition, the responsiveness to two different anesthetic methods-electro-acupuncture or a ...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00000539-200207000-00027
更新日期:2002-07-01 00:00:00
abstract::A pharmacokinetic evaluation of bupivacaine was carried out after intercostal nerve blocks performed on 28 occasions in 27 children varying in age from 3 months to 16 yr. Bupivacaine HCl, 0.5%, with epinephrine 1:200,000 was employed. Doses of 2 mg/kg, 3 mg/kg, and 4 mg/kg resulted in peak whole blood arterial bupivac...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::To compare the dose-response of remifentanil for tracheal intubation in infants and children, 32 healthy full-term infants and 32 children were anesthetized with 10 mug/kg glycopyrrolate and 4.0 mg/kg propofol and administered 1 of 4 doses of remifentanil (1.25, 1.50, 1.75, or 2.00 microg/kg) to facilitate tracheal in...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1213/01.ANE.0000150940.57369.B5
更新日期:2005-06-01 00:00:00
abstract:UNLABELLED:The effects of heparinization and the reversal of heparin activity on platelet function after cardiopulmonary bypass have not been well defined. Flow cytometry has become a convenient and powerful technique for characterizing platelets. We examined the expression of a secretion marker (P-selectin) and an agg...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200004000-00007
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND:Although local anesthetics (LAs) are generally accepted as being safe, incidental neuronal damage has been reported for all LAs in humans. Therefore, in this study, we compared the dose corresponding to 50% cell lethality (LD50) of articaine, lidocaine, mepivacaine, bupivacaine, prilocaine, and ropivacaine i...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0000000000000562
更新日期:2015-03-01 00:00:00
abstract::The effects of continuous epidural anesthesia and of general anesthesia on the incidence of thromboembolism following total hip replacement were studied. Sixty patients were randomly allotted to one of two groups receiving either epidural or general anesthesia. Epidural anesthesia (N = 30) consisted of 0.5% bupivacain...
journal_title:Anesthesia and analgesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1983-02-01 00:00:00
abstract::The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/00000539-198902000-00006
更新日期:1989-02-01 00:00:00
abstract:IMPLICATIONS:Manipulating the density of local anesthetic solutions by using a simple formula may be clinically useful in producing optimal density solutions for spinal anesthesia under a variety of clinical conditions. ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200206000-00048
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND:Incomplete reversal with a recommended 5-g dose of idarucizumab has been reported in patients with excessively high dabigatran concentrations. A timely detection of reversal failure after idarucizumab using whole blood (WB) coagulation testing is clinically useful. The aims of this study were to determine re...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0000000000004419
更新日期:2020-02-01 00:00:00
abstract::Spontaneous or evoked electrical brain activity is increasingly used to monitor general anesthesia. Previous studies investigated the variables from spontaneous electroencephalogram (EEG), acoustic (AEP), or somatosensory evoked potentials (SSEP). But, by monitoring them separately, the available information from simu...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章,多中心研究
doi:10.1213/01.ane.0000237231.73261.92
更新日期:2006-10-01 00:00:00
abstract:UNLABELLED:As the surgical population ages, the number of patients presenting with coronary artery disease and age-related loss of pulmonary recoil will increase. Although their influence on gas exchange in this population remains unknown, sevoflurane and isoflurane are used for an increasing variety of surgical proced...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1097/00000539-200205000-00009
更新日期:2002-05-01 00:00:00
abstract:BACKGROUND:Modifications in physician billing patterns have been shown to occur in response to payer incentives, but the phenomenon remains largely unexplored in billing for anesthesia services. Within the field of anesthesiology, Medicare's policy not to provide additional reimbursement for higher ASA physical status ...
journal_title:Anesthesia and analgesia
pub_type: 杂志文章
doi:10.1213/ANE.0000000000000917
更新日期:2016-01-01 00:00:00