Methods: A microdialysis probe was positioned in the pontine reticular formation of halothane-anesthetized cats. Probes were perfused with Ringer's solution (control) followed by the adenosine A1 receptor agonist SPA (0.088 or 8.8 mm). Dependent measures included acetylcholine release and a numeric assessment of recovery from anesthesia. An intensive, within-subjects design and analysis of variance evaluated SPA's main effect on acetylcholine release and anesthetic recovery. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 [mu]m) was coadministered with SPA to test for antagonist blocking of SPA's effects.
Results: SPA significantly (P < 0.0001) decreased acetylcholine release in the pontine reticular formation and significantly (P < 0.0001) delayed recovery from anesthesia. Coadministration of SPA and DPCPX caused no decrease in acetylcholine release or delay in postanesthetic recovery. Dialysis delivery of SPA into the cerebellar cortex confirmed that the SPA effects were site-specific to the pontine reticular formation. 相似文献
Methods: Rats with intrathecal catheters were anesthetized and underwent plantar incision. Spontaneous pain behavior and withdrawal threshold to punctuate stimulation were measured before and after administration of intrathecal R-phenylisopropyl-adenosine (R-PIA; A1R agonist), 2-w p-2-carbonyl-ethyl-phenylethylaminox-5X-N-ethylcarboxami-doadenosine (CGS21680; A2aR agonist), or vehicle. In separate groups of animals, the effects of pertussis toxin, forskolin, glibenclamide, 4-aminopyridine, tetraethylammonium, apamin, charybdotoxin, or margatoxin on R-PIA-induced antinociception were examined.
Results: Intrathecal administration of 5 nmol R-PIA but not 10 nmol CGS21680 decreased nonevoked spontaneous pain behavior. Furthermore, intrathecal administration of R-PIA but not of CGS21680 increased withdrawal thresholds after incision. Pretreatment with pertussis toxin and administration of forskolin, glibenclamide, 4-aminopyridine, and tetraethylammonium inhibited R-PIA-induced antinociception. In addition, intrathecal administration of apamin, charybdotoxin, or margatoxin did not modify mechanical hypoalgesia mediated by R-PIA. 相似文献
Methods: The arterial branch of the left lower lung lobe in intact-chest, spontaneously breathing cats was occluded for 2 h and reperfused for 3 h (IR group). Animals were treated with the selective A3 receptor agonist IB-MECA (300 [mu]g/kg intravenously) given 15 min before ischemia or with IB-MECA as described, with pretreatment 15 min earlier with the selective A3AR antagonist MRS-1191, the nonsulfonylurea adenosine triphosphate-sensitive potassium channel-blocking agent U-37883A, or the nitric oxide synthase inhibitor Nw-nitro-l-arginine benzyl ester.
Results: IB-MECA markedly (P < 0.01) reduced the percentage of injured alveoli (IR, 48 +/- 4%; IB-MECA, 18 +/- 2%), wet:dry weight ratio (IR, 8.2 +/- 0.4; IB-MECA, 4 +/- 2), and myeloperoxidase activity (IR, 0.52 +/- 0.06 U/g; IB-MECA, 0.17 +/- 0.04 U/g). This protective effect was completely blocked by pretreatment with the selective A3AR antagonist MRS-1191 and the adenosine triphosphate-sensitive potassium channel blocking agent U-37883A but not the nitric oxide synthase inhibitor Nw-nitro-l-arginine benzyl ester. 相似文献
Methods: In membranes from porcine striatum and guinea pig ventricle, competition binding assays to displace [3H]nitrobenzylmercaptopurine riboside ([3H]NBMPR) from nucleoside transporter were performed using alprazolam, chlorodiazepoxide, diazepam, flurazepam, and midazolam. The augmentation by the most potent benzodiazepine of A1- and A2A-adenosine receptor-mediated responses, elicited by exogenous administration of adenosine or brief periods of global hypoxia, was subsequently studied in guinea pig Langendorff-perfused hearts.
Results: All benzodiazepines completely displaced [3H]NBMPR in a concentration-dependent manner with Hill coefficients not significantly different from unity in both striatal and ventricular membranes. Midazolam was the most potent inhibitor of nucleoside transporter (ventricle:p Ki = 5.22 +/- 0.41, Ki = 6 [mu]M). In isolated hearts, midazolam (5, 10, 20 [mu]M) significantly augmented coronary flow in a concentration-dependent manner in the presence of adenosine (30 nM), an effect reversed by ZM 241385, a selective A2A-receptor antagonist. In contrast, midazolam did not increase the effect of adenosine (30 nM) on atrioventricular conduction. Similarly, midazolam potentiated A2A- but not A1-receptor-mediated effects of endogenous adenosine released during hypoxia. 相似文献
Methods: Human atrial trabecular muscles were superfused with oxygenated Krebs-Henseleit buffer and stimulated at 1 Hz, with recording of maximum contractile force. Fifteen minutes before a 30-min anoxic insult, muscles were pretreated for 5 min with either anoxia, the A1 agonist N6-cyclohexyladenosine, 1% halothane or 1.2% isoflurane. These treatments were also performed in the presence of either the KATP channel antagonist glibenclamide or the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Anesthetic effects were also determined on KATP currents in isolated whole cell voltage-clamped human atrial myocytes.
Results: Recovery of force (recorded 60 min after anoxia) in isoflurane-pretreated muscles was reduced from 76.6 +/- 7.5% of baseline to 43.7 +/- 7.1% by pretreatment with glibenclamide, and to 52.5 +/- 6.2% by pretreatment with DPCPX. Halothane treatment provided no cardioprotection and seemed to inhibit protection by anoxic preconditioning. Halothane decreased whole cell KATP currents in atrial myocytes, whereas isoflurane had no effects. 相似文献
Methods: A functional study was conducted to evaluate the effects of edrophonium on the concentration-response curves for the negative chronotropic effect and the bronchoconstricting effect of carbachol in spontaneously beating right atria and tracheas of guinea pigs. An electrophysiologic study was conducted to compare the effects of edrophonium on carbachol-, guanosine triphosphate (GTP)[gamma] S-, and adenosine-induced outward K+ currents in guinea pig atrial cells by whole cell voltage clamp technique. A radioligand binding study was conducted to examine the effects of edrophonium on specific [3H]N-methyl-scopolamine (NMS) binding to guinea pig atrial (M2) and submandibular gland (M3) membrane preparations, and on atropine-induced dissociation of [3H]NMS.
Results: Edrophonium shifted rightward the concentration-response curves for the negative chronotropic and bronchoconstricting effects of carbachol in a competitive manner. The pA2 values for cardiac and tracheal muscarinic receptors were 4.61 and 4.03, respectively. Edrophonium abolished the carbachol-induced outward current without affecting the GTP[gamma] S- and adenosine-induced currents in the atrial cells. Edrophonium inhibited [3H]NMS binding to M2 and M3 receptors in a concentration-dependent manner. The pseudo-Hill coefficient values and apparent dissociation constants of edrophonium for M2 and M3 receptors were 1.02 and 1.07 and 21 and 34 [mu]m, respectively. Edrophonium also changed dissociation constant values of [3H]NMS without affecting its maximum binding capacities. 相似文献
Methods: After institutional approval and informed patient consent were obtained, 23 patients scheduled to undergo supratentorial tumor surgery were randomly assigned to remifentanil or fentanyl infusion groups in a double-blinded manner. Midazolam, thiopental, and pancuronium induction was followed by equipotent narcotic loading infusions of remifentanil (1 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or fentanyl (2 [micro sign]g [middle dot] kg-1 [middle dot] min-1) for 5-10 min. Patients were ventilated with 2:1 nitrous oxide-oxygen, and opioid rates were reduced and then titrated to a stable hemodynamic effect. After dural exposure, CBF was measured by the intravenous133 xenon technique at normocapnia and hypocapnia. Reactivity of CBF to carbon dioxide was calculated as the absolute increase in CBF per millimeters of mercury increase in the partial pressure of carbon dioxide (PaCO2). Data were analyzed by repeated-measures analysis of variance, unpaired Student's t tests, or contingency analysis.
Results: In the remifentanil group (n = 10), CBF decreased from 36 +/- 11 to 27 +/- 8 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 33 +/- 5 to 25 +/- 2 mmHg. In the fentanyl group (n = 8), CBF decreased from 37 +/- 11 to 25 +/- 6 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 34 +/- 3 to 25 +/- 3 mmHg. Absolute carbon dioxide reactivity was preserved with both agents: 1 +/- 1.2 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for remifentanil and 1.5 +/- 0.5 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for fentanyl (P = 0.318). 相似文献
Methods: Forty-two parturients undergoing elective cesarean delivery with use of combined spinal-epidural anesthesia received intrathecal hyperbaric bupivacaine in doses of 6, 7, 8, 9, 10, 11, or 12 mg in equal volumes with an added 10 [mu]g intrathecal fentanyl and 200 [mu]g intrathecal morphine. Sensory levels (pinprick) were evaluated every 2 min until a T6 level was achieved. The dose was a success(induction) if a bilateral T6 block occurred in 10 min; otherwise, it was a failure(induction). In addition to being a success(induction), the dose was a success(operation) if no intraoperative epidural supplement was required; otherwise, it was a failure(operation). ED50 and ED95 for both success(induction) and success(operation) were determined with use of a logistic regression model.
Results: ED50 for success(induction) and success(operation) were 6.7 and 7.6 mg, respectively, whereas the ED95 for success(induction) and success(operation) were 11.0 and 11.2 mg. Speed of onset correlated inversely with dose. Although no clear advantage for low doses could be demonstrated (hypotension, nausea, vomiting, pruritus, or maternal satisfaction), this study was underpowered to detect significance in these variables. 相似文献
Methods: Male rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. Two weeks later, a lumbar intrathecal catheter and intrathecal space microdialysis catheter were inserted. Adenosine, 20 [mu]g, was injected intrathecally in these and in normal rats, and microdialysates of the intrathecal space were obtained. Radioligand binding studies of adenosine A1 receptors were determined in spinal cord tissue from other normal and spinal nerve-ligated rats.
Results: Adenosine disappeared from rat cerebrospinal fluid within 30 min after intrathecal injection, with no difference between normal and spinal nerve-ligated animals. A1 adenosine receptor binding sites in the spinal cord were increased after spinal nerve ligation. This increase disappeared when adenosine deaminase was added to the membrane homogenates, suggestive of decreased endogenous adenosine in the membranes of nerve-ligated animals. 相似文献
Methods: After institutional review board approval and written informed consent were obtained, 48 parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this double-blind, randomized, dose-ranging study. Patients received a 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-mg intrathecal isobaric bupivacaine dose with 10 [mu]g fentanyl and 200 [mu]g morphine. Overall anesthetic success was recorded when no intraoperative epidural supplement was required during the cesarean delivery. ED50 and ED95 values for overall anesthetic success were determined using a logistic regression model.
Results: ED50 and ED95 values for overall anesthetic success were 7.25 and 13.0 mg, respectively. No advantages for low doses could be demonstrated with regard to hypotension, nausea, vomiting, pruritus, or maternal satisfaction, although this study was underpowered to detect significant differences in secondary outcome variables. 相似文献
Methods: The PGE2 concentrations in the dorsal horn of the spinal cord were measured after formalin was injected into the hind paw of rats. The effect of antinociceptive doses of acetaminophen (100, 200, and 300 mg/kg given intraperitoneally) on PGE2 levels and flinching behavior was monitored. Spinal PGE2 and acetaminophen concentrations were obtained by microdialysis using a probe that was implanted transversely through the dorsal horn of the spinal cord at L4. Furthermore, the effects of acetaminophen on urinary prostaglandin excretion were determined.
Results: Intraperitoneal administration of acetaminophen resulted in a significant decrease in spinal PGE2 release that was associated with a significant reduction in the flinching behavior in the formalin test. Acetaminophen was distributed rapidly into the spinal cord with maximum dialysate concentrations 45-60 min after intraperitoneal administration. Urinary excretion of prostanoids (PGE2, PGF2 [Greek small letter alpha], and 6-keto-PGF1 [Greek small letter alpha]) was not significantly altered after acetaminophen administration. 相似文献
Methods: Recombinant GABAARs composed of [alpha]1[beta]2 or [alpha]1[beta]2[gamma]2L subunit mixtures were studied electrophysiologically in whole Xenopus oocytes in the voltage clamp configuration. Currents elicited by GABA (0.03 [mu]m to 1 mm) were measured in the absence and presence of isoflurane or halothane. Anesthetic effects on GABA concentration responses were evaluated for individual oocytes.
Results: In wild-type [alpha]1[beta]2[gamma]2L GABAA, anesthetics at approximately 2 minimum alveolar concentration (MAC) shifted GABA concentration response curves to the left approximately threefold, decreased the Hill coefficient, and enhanced currents at all GABA concentrations. The [alpha]1(S270I) mutation itself rendered the GABAAR more sensitive to GABA and reduced the Hill coefficient. At low GABA concentrations (EC5), anesthetic enhancement of peak current was much smaller in [alpha]1(S270I)[beta]2[gamma]2Lversus wild-type channels. Paradoxically, the leftward shift of the whole GABA concentration-response relation by anesthetics was the same in both mutant and wild-type channels. At high GABA concentrations, volatile anesthetics reduced currents in [alpha]1(S270I)[beta]2[gamma]2L GABAARs. In parallel studies on [alpha]1[beta]2 ([gamma]-less) GABAARs, anesthetic-induced leftward shifts in wild-type receptors were more than eightfold at 2 MAC, and the [alpha]1(S270I) mutation nearly eliminated anesthetic-induced leftward shift. 相似文献
Methods: Using a double-blind, crossover design, 14 healthy volunteers completed the protocol and were randomized to receive one dose of loratadine (20 mg), ranitidine (300 mg), or placebo on each of three separate testing sessions. Continuous electrocardiogram and BP recordings were obtained before and 3 h after administration of study drug. Effects on cardiac autonomic control were quantified using power spectral analysis of heart rate variability and calculation of spontaneous baroreflex sensitivity.
Results: Neither placebo nor loratadine significantly altered indices of autonomic cardiovascular control. Conversely, H2 antagonism with ranitidine resulted in a 23.3% decrease in baroreflex sensitivity (P < 0.05) and a corresponding 25.0% decrease in the ratio of high frequency to total power of heart rate variability, both indices of parasympathetic modulation (P < 0.01). Furthermore, ranitidine evoked a concomitant 103.8% increase in the ratio of low to high frequency power of heart rate variability, an index of sympathetic control (P < 0.01). 相似文献
Methods: Sixteen adult sheep were operatively instrumented for chronic study. The injured intervention group was treated with the selective thromboxane A2 synthase inhibitor OKY-046, whereas the injured control group received only the vehicle (n = 8 each).
Results: The progressive increase in thromboxane B2 lung lymph concentrations in control animals was associated with increased transvascular fluid flux, augmented resistances in the pulmonary and systemic circulation, and a reciprocal decrease in cardiac output. In addition, end-systolic pressure-diameter relation and maximum +dp/dt were markedly depressed as compared with baseline (24 h: 14.3 +/- 0.9 vs. 8.9 +/- 0.5 mmHg/mm and 2,120 +/- 50 vs. 1,915 +/- 40 mmHg/s, respectively; each P < 0.05). Infusion of OKY-046 significantly inhibited pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary vascular resistance, and blocked the increase in systemic vascular resistance. In addition, OKY-046 blunted and delayed the decrease in cardiac output and maintained end-systolic pressure-diameter relation, +dp/dt, and lung lymph flow at baseline values. 相似文献
Methods: GTP hydrolysis by G[alpha]i-3 and the G[alpha]i-3[beta]1[gamma]2HF heterotrimer expressed in Spodoptera frugiperda cells was measured using a phosphohydrolase assay with [[gamma]32Pi]-labeled GTP. Anesthetic binding to G[alpha]i-3 was measured by saturation transfer difference nuclear magnetic resonance spectroscopy. G[alpha]i-3 nucleotide exchange was measured in crude membranes prepared from COS-7 cells transiently coexpressing the M2 muscarinic receptor and G[alpha]i-3. A radioactive analog of GTP, [35S]GTP[gamma]S, was used as a reporter for G[alpha]i-3 nucleotide exchange.
Results: Although spectroscopy demonstrated halothane binding to G[alpha]i-3, this binding had no effect on [[gamma]32Pi]-labeled GTP hydrolysis by the G[alpha]i-3[beta]1[gamma]2HF heterotrimer expressed in Spodoptera frugiperda cells, nor basal G[alpha]i-3 nucleotide exchange measured in crude membranes when the muscarinic receptor agonist acetylcholine was omitted from the assay. Conversely, halothane caused a concentration-dependent inhibition of G[alpha]i-3 nucleotide exchange with acetylcholine included in the assay. 相似文献
Methods: After selective lesioning of noradrenergic nuclei by intracerebroventricular application of the mitochondrial toxin saporin coupled to the antibody directed against dopamine [beta] hydroxylase (D[beta]H-saporin), the antinociceptive action of isoflurane was determined. Antagonists for the [alpha]1 and [alpha]2 adrenoceptors were injected at spinal and supraspinal sites in intact and spinally transected rats to identify the noradrenergic pathways mediating isoflurane antinociception. Null mice for each of the three [alpha]2-adrenoceptor subtypes ([alpha]2A, [alpha]2B, and [alpha]2C) and their wild-type cohorts were tested for their antinociceptive response to isoflurane.
Results: Both D[beta]H-saporin treatment and chronic spinal transection enhanced the antinociceptive effects of isoflurane. The [alpha]1-adrenoceptor antagonist prazosin also enhanced isoflurane antinociception at a supraspinal site of action. The [alpha]2-adrenoceptor antagonist yohimbine inhibited isoflurane antinociception, and this effect was mediated by spinal [alpha]2 adrenoceptors. Null mice for the [alpha]2A-adrenoceptor subtype showed a reduced antinociceptive response to isoflurane. 相似文献
Methods: G[alpha]q guanosine nucleotide exchange was measured in crude membranes prepared from COS-7 cells transiently coexpressing the human M3 muscarinic receptor and human G[alpha]q. A radioactive, nonhydrolyzable analog of guanosine-5'-triphosphate, [35S]GTP[gamma]S, was used as a reporter for nucleotide exchange at G[alpha]q.
Results: Acetylcholine caused a concentration-dependent increase in G[alpha]q [35S]GTP[gamma]S-GDP exchange. Neither anesthetic affected constitutive G[alpha]q [35S]GTP[gamma]S-GDP exchange in the absence of acetylcholine. Conversely, each anesthetic caused a concentration-dependent and reversible inhibition of G[alpha]q [35S]GTP[gamma]S-GDP exchange when promoted by acetylcholine. At concentrations of 3 MAC or less, the effect of halothane and sevoflurane were significantly greater than that of isoflurane, with only a minimal inhibition by isoflurane observed at 2 MAC. 相似文献
Methods: After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 [mu]g/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated.
Results: At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone). 相似文献