Barbiturate Induction for the Prevention of Emergence Agitation after Pediatric Sevoflurane Anesthesia.

OBJECTIVES: Emergence agitation (EA) is a common and troublesome problem in pediatric patients recovering from general anesthesia. The incidence of EA is reportedly higher after general anesthesia maintained with sevoflurane, a popular inhalational anesthetic agent for pediatric patients. We conducted this prospective, randomized, double-blind study to test the effect of an intravenous ultra-short-acting barbiturate, thiamylal, administered during induction of general anesthesia on the incidence and severity of EA in pediatric patients recovering from Sevoflurane anesthesia. METHODS: Fifty-four pediatric patients (1 to 6 years of age) undergoing subumbilical surgeries were randomized into 2 groups. Patients received either intravenous thiamylal 5mg/kg (Group T) or inhalational Sevoflurane 5% (Group S) as an anesthetic induction agent. Following induction, general anesthesia was maintained with Sevoflurane and nitrous oxide (N2O) in both groups. To control the intra- and post-operative pain, caudal block or ilioinguinal/iliohypogastric block was performed. The incidence and severity of EA were evaluated by using the Modified Objective Pain Scale (MOPS: 0 to 6) at 15 and 30 min after arrival in the post-anesthesia care unit (PACU). RESULTS: Fifteen minutes after arrival in the PACU, the incidence of EA in Group T (28%) was significantly lower than in Group S (64%; p = 0.023) and the MOPS in Group T (median 0, range 0 to 6) was significantly lower than in Group S (median 4, range 0 to 6; p = 0.005). The interval from discontinuation of Sevoflurane to emergence from anesthesia was not significantly different between the 2 groups. CONCLUSIONS: Thiamylal induction reduced the incidence and severity of EA in pediatric patients immediately after Sevoflurane anesthesia.

Succinylcholine potentiates acetylcholine-induced contractile and phosphatidylinositol responses of rat trachea.

PURPOSE: Although succinylcholine (SCh) is often used as a muscle relaxant in electroconvulsive therapy, its influence on airway reactivity has not been fully investigated. We examined the effects of SCh on acetylcholine (ACh)-, carbachol (CCh)-, and electrical field stimulation (EFS)-induced contractions, and on the ACh-induced phosphatidylinositol (PI) response of rat trachea. METHODS: Thirty-two male Wistar rats weighing 250-350 g were used. The trachea was rapidly isolated and cut into 3-mm-wide rings. The resting tension was adjusted periodically to 1.0 g during the equilibration period. ACh, 1 microM; carbachol (CCh), 0.05 microM; or neither of them, was added, and SCh was then added at 1-300 microM final concentrations, and ring tension was examined. Contractions were elicited by EFS in the presence or absence of 100 microM SCh. Tracheal slices were incubated with [3H] myo-inositol, 1 microM ACh, and various concentrations of SCh. The accumulation of [3H] inositol monophosphate (IP1) was measured. RESULTS: SCh did not affect the tension by itself without ACh, or with CCh, but SCh potentiated the ACh-induced contraction of rat trachea at concentrations of 10 microM or more (50% effective concentration [EC50]; 43.6 microM). SCh produced a significant increase in the amplitude and duration of EFS-induced contractions. SCh, at concentrations of 10 microM and 100 microM, potentiated ACh-induced IP1 accumulation. CONCLUSION: SCh potentiated ACh-induced, but not CCh-induced, contractile and PI responses, and enhanced EFS-induced contraction of rat trachea, suggesting that competition for butyrylcholinesterase (BChE) in airway smooth muscle could be involved in the potentiation by SCh of ACh-induced airway smooth muscle contraction.

Effects of propofol and ketamine on ATP-induced contraction of the rat trachea.

PURPOSE: ATP causes airway smooth-muscle contraction in patients with asthma and chronic obstructive pulmonary disease. Propofol and ketamine attenuate the airway smooth-muscle contraction induced by histamine and acetylcholine. However, it is not clear whether propofol and ketamine affect the ATP-induced airway smooth-muscle contraction. METHODS: We examined the effects of propofol and ketamine on the ATP-induced contraction and ATP-P(2)-purinoceptor binding. RESULTS: Propofol attenuated the ATP-induced contraction in a dose-dependent manner, with a 50% inhibitory concentration of 54 +/- 22 microM. Ketamine at 300 microM attenuated the ATP-induced contraction. In the binding study, propofol attenuated the binding of the P(2)-purinoceptor with [(3)H]-ATP in a dose-dependent manner, while ketamine did not attenuate this binding. CONCLUSION: Propofol attenuates ATP-induced contraction through the inhibition of ATP-P(2)-purinoceptor binding.

Anticholinesterase drugs stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.

We performed this study to determine the effects of Rho-kinase inhibitors, Y-27632 and fasudil, on the anticholinesterase (anti-ChE)-induced contractile and phosphatidylinositol responses of the rat trachea. In vitro measurements of isometric tension and [3H] inositol monophosphate (IP1) that was formed were conducted by using rat tracheal rings or slices. Neostigmine- and pyridostigmine-induced contractions were almost completely inhibited by Y-27632 and fasudil at 30 microM each, whereas acetylcholine-induced contraction was inhibited incompletely, i.e., by 56% by Y-27632 and by 51% by fasudil, at 100 microM for each, respectively. The inhibitory effects of fasudil on neostigmine- and acetylcholine-induced contractions were completely reversed by calyculin-A, a myosin phosphatase inhibitor. Neostigmine-induced IP1 accumulation was attenuated by fasudil at 100 microM. The results suggest that anti-ChEs cause airway smooth muscle contraction, in part, through activation of the Rho-kinase pathway.

Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea.

Selegiline is widely used for Parkinson's disease and sometimes for Alzheimer's disease. It is reported to affect intracellular Ca(2+) concentration. Since intracellular Ca(2+) is partly regulated by phosphatidylinositol (PI) response and is important for smooth muscle contraction, selegiline may affect airway smooth muscle tension. We examined the effects of selegiline on acetylcholine (ACh)- and KCl-induced contractile and PI responses in rat trachea. The trachea was cut into 3-mm-wide ring segments or 1-mm-wide slices. ACh (3 microM, 50% effective dose) or KCl (40 mM) was added, and ring relaxation was induced by the addition of selegiline. Tracheal slices were incubated with [(3)H]myo-inositol and 3 microM ACh in the presence of selegiline, and [(3)H]inositol monophosphate (IP(1)) was measured. Selegiline dose-dependently attenuated ACh- and KCl-induced tracheal ring contractions. Fifty-percent inhibitory doses (ID50) of selegiline against ACh- and KCl-induced contraction were 120 +/- 30 microM and 80 +/- 20 microM, respectively. Basal and ACh-induced IP(1) accumulation were 2.20 +/- 0.20 Bq and 7.88 +/- 0.23 Bq, respectively, and selegiline at a dose of 1000 microM attenuated ACh-induced IP(1) accumulation (5.44 +/- 0.30 Bq). These results suggest that selegiline inhibits contractile responses through the inhibition of voltage-operated Ca(2+) channels and the PI response.

Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M3 receptor in the rat trachea.

UNLABELLED: Although metoclopramide, often used as an antiemetic, is reported to have an anticholinesterase action, the effect on airway smooth muscle remains unclear. We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M(3) receptors in rat trachea preparations. Male Wistar rats were anesthetized and their tracheas excised and chopped into 3-mm-wide rings, 1-mm-wide slices, or frozen 10- microm-thick sections. Contraction was induced with 0.55 microM carbachol (CCh) and, 30 min later, metoclopramide (10 microM to 1 mM) was added. The slices were incubated with (3)[H]myo-inositol, 0.55 microM CCh, and metoclopramide, and the formation of (3)[H] inositol monophosphate was measured. A radioligand binding study was conducted to examine the effects of metoclopramide using [(3)H] 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), a muscarinic M(3) receptor antagonist, in sections of the trachea. Metoclopramide concentration dependently attenuated CCh-induced contraction and inositol monophosphate accumulation, and also attenuated the binding affinity of 4-DAMP to muscarinic M(3) receptors. The 50% inhibitory concentration of metoclopramide against the binding affinity of 4-DAMP to muscarinic M(3) receptors of rat trachea was 24 micro M. These findings suggest that the attenuation by metoclopramide of CCh-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M(3) receptors. IMPLICATIONS: We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M(3) receptors in rat trachea preparations. Our findings suggest that the attenuation by metoclopramide of carbachol-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M(3) receptors.

Interactions of edrophonium with neostigmine in the rat trachea.

UNLABELLED: The muscarinic M(3) receptor of airway smooth muscle has both an orthosteric binding site and an allosteric binding site. Edrophonium may bind to the allosteric site, resulting in the inhibition of the action of the orthosteric site. Therefore, we examined the effects of edrophonium on neostigmine-induced contractile and phosphatidylinositol responses of rat trachea. Neostigmine (100 micro M in final concentration) was added, and ring tension was examined by the addition of edrophonium. After the completion of the experiment, Krebs-Henseleit (K-H) solution containing both edrophonium and neostigmine was changed three times with fresh K-H solution, and the tension was recorded. Tracheal slices were incubated with [(3)H]myo-inositol and 100 micro M neostigmine in the presence or absence of edrophonium. The [(3)H]inositol monophosphate (IP(1)) was measured. Data were expressed as mean +/- SE. Statistical significance (P < 0.05) was determined with analysis of variance. Neostigmine-induced tension and IP(1) accumulation were attenuated by edrophonium at concentrations of 100 micro M or more. This attenuation was reversed to more than 80% of control levels by washing with fresh K-H solution. The results suggest that edrophonium would bind to the allosteric site, resulting in the inhibition of the action of the orthosteric site of muscarinic M(3) receptors of rat trachea. IMPLICATIONS: We examined the effects of edrophonium on neostigmine-induced contractile and phosphatidylinositol responses of rat trachea. Neostigmine-induced tension and inositol monophosphate accumulation were attenuated by edrophonium. This attenuation was reversed by washing. The results suggest that edrophonium would bind to the allosteric site.

Effects of vasopressors on contractile and phosphatidylinositol responses of rat trachea.

PURPOSE: Vasopressors, such as dopamine (DA), norepinephrine (NE), and phenylephrine (Phe), are commonly used during anesthesia to increase blood pressure through alpha(1)-adrenoceptors. The present study was designed to examine the effects of DA, NE, and Phe on the contractile and phosphatidylinositol (PI) responses of the rat trachea induced by a muscarinic agonist, carbachol (CCh). METHODS: A rat tracheal ring was suspended between two stainless-steel hooks in Krebs-Henseleit (K-H) solution. Contraction was induced with 0.55 microM CCh, and 30 min later DA, NE, or Phe was added. The tracheal slices were incubated in K-H solution containing LiCl, (3)[H] myo-inositol, and CCh in the presence or absence of DA, NE, or Phe. The (3)[H]inositol monophosphate (IP(1)) formed was measured. RESULTS: CCh caused tracheal ring contraction. NE attenuated CCh-induced contraction at a dose of 1 microM or greater and had a maximal effect at 3 microM. DA and Phe did not affect CCh-induced contraction. CCh-induced IP(1) accumulation was potentiated significantly by NE and Phe, but not by DA. CONCLUSION: Although NE and Phe potentiated CCh-induced IP(1) accumulation, they could not potentiate CCh-induced contraction, suggesting that in clinical settings, vasopressors such as NE, DA, and Phe might be safely used in patients with asthma.