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Biomedical subjects

S T Li

Publications and source records attributed to S T Li.

At least 19 recordsLinked to original sources
PubMed2002

Prevalence of wheeze, bronchial hyper-responsiveness and asthma in the elderly Chinese.

BACKGROUND: Asthma is a common health problem affecting patients of all ages. Because of the ease of sampling, epidemiological studies have concentrated mainly on the paediatric and general population. OBJECTIVE: This study aimed to determine the prevalence of wheeze, bronchial hyper-responsiveness and asthma amongst our elderly population and deduce any clinical and laboratory risk factors that might identify elderly asthmatics at an earlier stage. METHODS: Two thousand and thirty-two elderly Chinese aged > or = 70 years, randomly selected from a registered list of all recipients of Old Age and Disability Allowances in Hong Kong, were administered a questionnaire on lung health. Two hundred and fifty subjects were invited to attend our laboratory for skin tests and pulmonary function tests and 179 agreed. Of these, 173 (96.6%) and 176 (98.3%) had eosinophil count and serum IgE levels measured, respectively. Two definitions of asthma were used: (1) bronchial hyper-responsiveness (BHR) plus current wheeze, and (2) history of wheezing without previous diagnostic labels of emphysema or chronic bronchitis. RESULTS: Fifteen patients (out of 179: 8.4%) reported wheezing over the past 1 year. Fifty-one patients (28.5%) demonstrated BHR on spirometry or histamine challenge tests. Seven patients had both symptoms of wheezing and evidence of BHR. The prevalence of asthma using this definition is therefore 3.9% (95% CI 1.6-7.9%). Nine patients had symptoms of wheezing without previous diagnostic labels of chronic bronchitis or emphysema and, using this definition, the prevalence is 5.0% (95% CI 2.3-9.3%). Using multiple logistic regression studies, sex, social class, age, smoking habits, serum IgE levels and eosinophil counts did not predict a diagnosis of asthma using either definition. We found no association between a positive skin test and any respiratory symptoms or illnesses including asthma. CONCLUSION: Wheeze, bronchial hyper-responsiveness and asthma are prevalent amongst our elderly population. However, there were no identifiable demographic and laboratory risk factors in this study that may help us predict a diagnosis of asthma.

Aged↗
PubMed2002

Individual allergens as risk factors for asthma and bronchial hyperresponsiveness in Chinese children.

The role of allergen sensitization in the development of asthma in the Chinese is not clear. This study aims to determine the relationship of sensitization to individual allergens, and the development of asthma and bronchial hyperresponsiveness (BHR) in schoolchildren from three Chinese cities: Hong Kong, Beijing and Guangzhou. Community-based random samples of 10-yr-old schoolchildren from three Chinese cities were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Subjects were studied by parental questionnaires (n=10,902), skin-prick tests (n=3,479), and methacholine challenge tests (n=608). The prevalence rates of wheeze in the past 12 months (Hong Kong, 5.8%; Beijing, 3.8%; Guangzhou, 3.4%) and atopy (Hong Kong, 41.2%; Beijing, 23.9%; Guangzhou, 30.8%) were highest in schoolchildren from Hong Kong. Multivariate logistic regression analyses revealed that sensitization to Dermatophagoides pteronyssinus (odds ratio (OR)=4.48; 95% confidence interval (CI): 3.02-6.66), cat (2.59; 1.67-4.03), Dermatophagoides farinae (2.41; 1.65-3.51) and mixed grass pollen (2.85; 1.24-6.50) were significantly associated with current wheeze. Atopy, defined as having > or = 1 positive skin-prick tests, was not an independent risk factor for current wheeze in children from any of the three cities. Furthermore, atopy (OR=2.53; 95% CI: 1.07-5.97), sensitization to cat (3.01; 1.39-6.52) and D. farinae (3.67; 1.93-6.97) were significantly associated with BHR. The authors confirmed that sensitization to house dust mite and cat was significantly associated with current wheeze and bronchial hyperresponsiveness in Chinese schoolchildren. However, the difference in the prevalence rate of atopic sensitization cannot explain the higher prevalence of childhood asthma in Hong Kong, when compared with those children from Beijing and Guangzhou.

Allergens↗
PubMed2001

Flowering plant sperm contains a cytosolic soluble protein factor which can trigger calcium oscillations in mouse eggs.

There is evidence showing that the sperm-induced Ca(2+) oscillations in mammalian eggs at fertilization are triggered by a sperm-derived protein factor. It was established recently that the activity of the putative sperm protein in causing Ca(2+) oscillations in mammalian eggs is not species-specific in vertebrates (1, 16). Here we report that cytosolic soluble extracts derived from flowering plant sperms in Brassica campestris can also induce fertilization-like Ca(2+) oscillations when microinjected into mouse eggs. The factor responsible for inducing Ca(2+) oscillations in the plant sperm was sperm-specific and heat- or trypsin-labile. Eight to ten sperm equivalents of the plant sperm extracts had enough activity to trigger Ca(2+) oscillations in mouse eggs. Our study suggests that, although plant and mammal are evolutionary divergent species, the activity of the putative sperm protein factor in triggering Ca(2+) signaling in mammalian eggs is not specific to the animal kingdom.

Animals↗
PubMed2001

A high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation.

Proteins and peptides have been demonstrated to penetrate across the plasma membrane of eukaryotic cells by protein transduction domains. We show that protein transduction by 11 arginine (11R) is an efficient method of delivering proteins into the neurons of brain slices. Here, we demonstrate that PKA inhibitory peptide, fused with 11R and nuclear localization signal, delivers the peptide exclusively into the nuclear compartment of neurons in brain slices. This inhibitory peptide blocked both cAMP responsive element-binding protein phosphorylation and long-lasting long-term potentiation (LTP) induction, but not early LTP. These results highlight transduction of proteins and peptides into specific neuronal subcellular compartments in brain slices as a powerful tool for studying neuronal plasticity.

Active Transport, Cell Nucleus↗
PubMed2001

Influence of restraint stress on the expression and the serine/threonine phosphatase activity of calcineurin in the rat brain.

To investigate the role of calcineurin (CaN) in the pathogenesis of stress-related psychiatric disorders, we examined the expression of CaN A mRNA and the serine/threonine phosphatase activity of CaN in the rat brain following various restraint stress paradigms. Northern blot analysis revealed no significant changes in the levels of CaN A mRNA expression, in either the frontal cortex or the hippocampus, in response to a single restraint stress for either 15, 45, or 90 min. In addition, no significant change in the levels of CaN A mRNA was found 3 or 6 h after a single restraint stress for 90 min. In situ hybridization analysis revealed that a single restraint stress for 45 min had no influence on CaN A mRNA expression in the CA1 and CA3 pyramidal cell layers or in the dentate gyrus granule cell layer of the hippocampus. However, serine/threonine phosphatase activity was significantly increased in both regions in response to a single restraint stress for either 45 or 90 min. These results demonstrate that the single restraint stress paradigms used in this study increase the activity of CaN without any changes in the expression of CaN, suggesting that the activation of calmodulin and the increased levels of heat shock proteins in response to the restraint stress may upregulate the activity of CaN in the rat brain.

Animals↗
PubMed2001

Sex differences in cocaine-stimulated motor behavior: disparate effects of gonadectomy.

Sex differences in biological substrates of drug use and addiction are poorly understood. The present study investigated sexual dimorphisms in motor behavior following acute cocaine administration (10, 20, or 40 mg/kg, i.p.). Cocaine increased stereotypy rating, horizontal and vertical activity in both sexes, and effects were always greater in females than males. A population analysis using data from multiple experiments indicated that horizontal activity scores were normally distributed in males but not in females. Gonadectomy induced disparate effects on cocaine-stimulated motor behavior. Population analysis indicated that castrated males exhibited more horizontal activity and stereotypy than shams. Ovariectomy did not affect cocaine-stimulated stereotypy but did attenuate horizontal activity in a subset of rats that had not been vaginally lavaged. In summary, gonadectomy effects were sex and behavioral topography specific and indicate that activational effects of gonadal hormones partially mediate the robust sex differences in cocaine-stimulated open-field behavior.

Animals↗
PubMed2001

Dr. Gary J. Becker young investigator award: comparison of small-diameter type 1 collagen stent-grafts and PTFE stent-grafts in a canine model--work in progress.

PURPOSE: To report an in-progress experiment in a canine model in which two types of small-diameter stent-grafts-one constructed of polytetrafluoroethylene (PTFE) and the other of a new, type 1 collagen material-were compared regarding vessel patency, intimal hyperplasia formation, and tissue reaction. MATERIALS AND METHODS: Six mongrel dogs weighing 30-35 kg were used. Stent-grafts of 4-mm diameter and 20-mm length were constructed with use of balloon-expandable stainless-steel stents wrapped with either PTFE or a new type 1 collagen graft. Stent-grafts were placed in deep femoral arteries bilaterally (PTFE on one side, collagen on the other). Animals were followed for 2 weeks (n = 2), 6 weeks (n = 2), or 12 weeks (n = 2). Percent stenosis based on angiographic findings as well as thickness and area of neointimal hyperplasia were compared at each time point and compared with use of the Student t test. RESULTS: All devices were patent in the immediate postimplantation period. Five of six collagen stent-grafts and five of six PTFE implants were patent at follow-up. In-stent stenosis was undetectable angiographically in all five patent collagen stent-grafts. All five patent PTFE stent-grafts showed demonstrable in-stent stenosis (10%-60%), indicating a trend toward improved patency in collagen stent-grafts versus PTFE stent-grafts (P = .07). Neointimal hyperplasia was absent at 2 weeks in the collagen stent-grafts. Neointimal thickness increased to a maximum of 360 microm at 12 weeks in the collagen stent-grafts. For PTFE stent-grafts, neointimal hyperplasia was present in all samples and reached a maximum of 770 microm at 12 weeks (P = .03). CONCLUSIONS: Even in small-diameter vessels, type 1 collagen stent-grafts demonstrate excellent patency rates and favorable histologic findings. The type 1 collagen stent-graft technology merits further developmental efforts in preclinical models.

Animals↗
PubMed2001

Temporal relationship between air pollution and hospital admissions for asthmatic children in Hong Kong.

BACKGROUND: Many epidemiological studies have shown positive association between respiratory health and current levels of outdoor air pollution in Europe and America. OBJECTIVE: The aim of this study was to investigate the association between air pollution and the number of childhood admissions for asthma in Hong Kong. METHODS: Daily counts of childhood admission for asthma to a large teaching Hospital were obtained from the computerized database for the period 1993-1994. A Poisson regression allowing for seasonal patterns and meteorological conditions was used to assess the associations between the number of Hospital admissions and the three pollutants: nitrogen dioxide, sulphur dioxide and inhalable particles (measured as PM10, particles < 10 microm in aerodynamic diameter). RESULTS: A total of 1217 children under 15 years of age were admitted for asthma during the study period. The calculated annual hospitalization rates were 283 and 178 per 100 000 for boys and girls, respectively. The mean PM10, NO2 and SO2 levels were 44.1 microg/m3, 43.3 microg/m3, and 12.2 microg/m3, respectively. Daily admission for asthma increased significantly with increasing ambient level of nitrogen dioxide (relative risk (RR) = 1.08 per 10 microg/m3 increase), sulphur dioxide (RR = 1.06) and inhalable particles (RR = 1.03). No association was found between hospital admission and humidity, temperature or atmospheric pressure. CONCLUSION: This is the first daily time series study of childhood admissions for asthma and air pollution in Hong Kong. The results support that current levels of air pollution contribute to the respiratory morbidity in asthmatic children in Hong Kong.

Adolescent↗
PubMed2001

Effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents of the dorsal horn neurons in newborn rats.

BACKGROUND: Local anesthetics, such as bupivacaine, have been reported to block calcium currents in primary sensory neurons and to interfere with the release of neurotransmitters in central nervous system neurons. However, it is unknown whether local anesthetics affect the calcium current activity of central nervous system neurons. METHODS: Using a traditional whole cell voltage clamp technique, effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents (HVA-Ic(a)) were investigated in enzymatically dissociated dorsal horn neurons of neonatal rats. Calcium currents were evoked by testing pulses from a holding potential of -90 to 0 mV. RESULTS: Bupivacaine significantly reduced HVA-Ic(a) in a dose-dependent manner. The peak HVA-Ic(a) decreased by 24.5+/-2.5, 32.0+/-6.8, 59.4+/-6.2, 88.3+/-1.5, and 91.6+/-1.1% in response to 10, 30, 50, 100 and 200 microM bupivacaine, respectively. Unlike bupivacaine, ropivacaine markedly increased HVA-Ic(a) at lower concentrations (< 50 microM) but decreased HVA-Ic(a) at higher concentrations (> or = 50 microM). The percent increases in peak HVA-Ic(a) induced by 10 and 30 microM ropivacaine were 95+/-19.1 and 41.6+/-8.3%, respectively. The percent decreases in response to 50, 100, and 200 microM ropivacaine were 21.1+/-2.1, 63.2+/-6.0 and 79.1+/-7.6%, respectively. Results indicate that the inhibitory potency of ropivacaine on HVA-Ic(a) was significantly lower than that of bupivacaine at the same concentrations. CONCLUSIONS: The current study showed that bupivacaine inhibited HVA-Ic(a) recorded from dorsal horn neurons and that ropivacaine increased HVA-Ic(a) at lower concentrations but decreased HVA-Ic(a) at higher concentrations. The inhibitory potency of ropivacaine was lower than that of bupivacaine. Inhibition of calcium currents of central nervous system neurons may be related to the systemic neurotoxic effects of local anesthetics (e.g., convulsions, seizures).

Amides↗
PubMed2001

Sex, steroids, and stimulant sensitivity.

The current study investigated ovarian modulation of the locomotor response to cocaine in rats. Ovariectomy in females lowered the response to cocaine (10 mg/kg i.p.), whereas castration did not change that of males. The locomotor responses of prepubertal males and females to cocaine were similar. However, the postpubertal sex difference resulted from a fall in cocaine-stimulated locomotion in males rather than a rise in females. Neonatal testosterone treatment of female rat pups decreased the response to cocaine in adulthood. These findings suggest that both the activational and organizational effects of gonadal steroids contribute to the greater response of females to cocaine.

Animals↗
PubMed2001

6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma.

The diagnosis and treatment of pheochromocytoma depend critically on effective means to localize the tumor. Computed tomography and magnetic resonance imaging have good sensitivity but poor specificity for detecting pheochromocytoma, and nuclear imaging approaches such as (131)I-metaiodobenzylguanidine scintigraphy have limited sensitivity. Here we report initial results using 6-[(18)F]fluorodopamine positron emission tomography (PET) scanning in the diagnostic localization of pheochromocytoma. Twenty-eight patients with known or clinically suspected pheochromocytoma underwent PET scanning after intravenous injection of 6-[(18)F]fluorodopamine. Of the 28 patients, 9 had surgical confirmation of the tumor, 8 had previously diagnosed metastatic pheochromocytoma, and 11 had plasma levels of metanephrines that were within normal limits. All 9 patients with surgically proven pheochromocytoma had abnormal 6-[(18)F]fluorodopamine PET scans that identified the tumors. All 8 patients with metastatic pheochromocytoma had extra-adrenal sites of 6-[(18)F]fluorodopamine-derived activity. Of the 11 patients with normal plasma levels of metanephrines, 9 had negative 6-[(18)F]fluorodopamine PET scans, 1 had extra-adrenal foci of 6-[(18)F]fluorodopamine-derived activity, and 1 had symmetric uptake of 6-[(18)F]fluorodopamine in the region of the adrenal glands. In patients with known disease, 6-[(18)F]fluorodopamine PET scanning can detect and localize pheochromocytomas with high sensitivity. In patients in whom the diagnosis of pheochromocytoma is considered but excluded because of negative plasma metanephrine results, 6-[(18)F]fluorodopamine PET scans are consistently negative. These findings justify a clinical trial of 6-[(18)F]fluorodopamine PET scanning as a diagnostic tool.

Adrenal Gland Neoplasms↗
PubMed2001

Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes.

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients. Thus, mutation-dependent differences in the expression of genes controlling catecholamine synthesis represent molecular mechanisms linking the underlying mutation to differences in clinical presentation of pheochromocytoma in patients with MEN 2 and the VHL syndrome.

Adolescent↗
PubMed2001

Improving effects of SSF on memory deficits and pathological changes of neural and immunological systems in senescent mice.

AIM: To study the effects of SSF, an effective part isolated from Scutellaria baicalensis George, on memory impairments and the pathological changes of neural and immunological systems in senescent mice induced by chronic galactose. METHODS: Senescent performance in mice was induced by consecutive administration of D-galactose (120 mg/kg, ip) for 47 d. The behavioral tests of mice used water maze task. The neural and immunological changes were assessed by alterations of cerebral cortex morphology and immune tissue index. The improving effects of SSF (50, 100, and 200 mg/kg, ig, 47 d) on above changes in the senescent mice were detected. Piracetam (PIR) was as reference drug. RESULTS: D-Galactose (120 mg/kg, ip, 47 d) resulted in an increase in the latencies to find the terminal platform and the number of errors entering non-exits in water maze, neuropathological changes and immune tissue index (spleen index) deducted in mice as compared with saline treated group. Both PIR (200 mg/kg, ig, 47 d) and SSF (50, 100, and 200 mg/kg, ig, 47 d) could significantly reverse the increased latencies and number of errors and improve the pathological alterations of neural and immunological systems. CONCLUSION: SSF could ameliorate the cognitive deficits and pathological alterations of neuron and immune systems in senescent mice induced by chronic galactose.

Aging↗
PubMed2000

Cardiac sympathetic denervation in Parkinson disease.

BACKGROUND: In Parkinson disease, orthostatic hypotension can result from L-dopa treatment or from sympathetic neurocirculatory failure. The latter is detected by abnormal blood pressure responses to the Valsalva maneuver and can be associated with loss of functional cardiac sympathetic nerve terminals. OBJECTIVE: To determine the frequency of cardiac sympathetic denervation in Parkinson disease, with or without sympathetic neurocirculatory failure, and its association with disease duration, severity, and L-dopa treatment DESIGN: Intergroup comparisons in resting patients. SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PATIENTS: 29 patients with Parkinson disease (9 with sympathetic neurocirculatory failure, 10 who had stopped receiving or had never been treated with L-dopa), 24 patients with multiple-system atrophy (17 with sympathetic neurocirculatory failure, 8 receiving L-dopa), 7 patients with pure autonomic failure, 33 controls with episodic or persistent orthostatic intolerance without sympathetic neurocirculatory failure, and 19 normal volunteers. MEASUREMENTS: Beat-to-beat blood pressure responses to the Valsalva maneuver, interventricular septal 6-[18F]fluorodopamine-derived radioactivity, cardiac extraction fraction of [3H]norepinephrine, appearance rate of norepinephrine in coronary sinus plasma (cardiac norepinephrine spillover) and venous-arterial differences in levels of dihydroxyphenylglycol (DHPG) and endogenous L-dopa. RESULTS: Of the 29 patients with Parkinson disease, 9 with sympathetic neurocirculatory failure and 11 without had low septal 6-[18F]fluorodopamine-derived radioactivity (2861 +/- 453 Bq/mL per MBq/kg and 5217 +/- 525 Bq/mL per MBq/kg, respectively). All 6 patients with Parkinson disease and decreased 6-[18F]fluorodopamine-derived radioactivity who underwent right-heart catheterization had a decreased cardiac extraction fraction of [3H]norepinephrine and virtually no cardiac norepinephrine spillover or venous-arterial increments in plasma levels of DHPG and L-dopa. Sympathetic neurocirculatory failure and decreased 6-[18F]fluorodopamine-derived radioactivity were unrelated to disease duration, disease severity, or L-dopa treatment CONCLUSIONS: Many patients with Parkinson disease-including all those with sympathetic neurocirculatory failure-have evidence of cardiac sympathetic denervation. This suggests that loss of catecholamine innervation in Parkinson disease occurs in the nigrostriatal system in the brain and in the sympathetic nervous system in the heart

Adult↗
PubMed2000

High Ca(2+)/low Mg(2+) solution induces long-term depression in rat CA1 pyramidal neurons.

Inducing long-term depression (LTD), one type of synaptic plasticity, typically requires electrical stimulation. Using rat hippocampal slices, we show that increasing the Ca(2+) of the extracellular solution to 4 mM and decreasing the Mg(2+) to 0.1 mM induced LTD in the CA1 region in the absence of electrical stimulation. The ionically-induced-LTD occluded electrical stimulation-induced LTD and was not blocked by application of 50 microM D-2-amino-5-phosphonopentanoic acid (an N-methyl-D-aspartate receptor antagonist) or by 1 mM (RS)-alpha-methyl-4-carboxyphenylglycine (a metabotropic glutamate receptor antagonist) alone. However, LTD was not ionically induced in the presence of both inhibitors. Our findings suggest that altering tissue excitability by changing the ionic environment mimics electrical stimulation in the induction of LTD.

2-Amino-5-phosphonovalerate↗
PubMed2000

Myocardial perfusion and sympathetic innervation in patients with hypertrophic cardiomyopathy.

OBJECTIVES: This study assessed left ventricular myocardial perfusion and sympathetic innervation and function in hypertrophied and nonhypertrophied myocardial regions of patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Patients with HCM often have clinical findings consistent with increased cardiac sympathetic outflow. Little is known about the status of sympathetic innervation specifically in hypertrophic regions. METHODS: We conducted positron emission tomographic (PET) scanning using the perfusion imaging agent 13N-ammonia (13NH3) and the sympathoneuronal imaging agent 6-[18F]-fluorodopamine (18F-FDA) in 8 patients with HCM and 15 normal volunteers. Positron emission tomographic data corrected for attenuation and the partial volume effect were analyzed using the region-of-interest technique. RESULTS: Myocardial 13NH3-derived radioactivity was similar in hypertrophied and nonhypertrophied regions of patients with HCM and in normal volunteers. At all time points, the 18F:13N ratio was lower in hypertrophied than in nonhypertrophied regions of HCM patients and in the septum of normal volunteers (p = 0.001). Trends in 18F-FDA-derived radioactivity over time were normal in both hypertrophied and nonhypertrophied myocardium. CONCLUSIONS: The results are consistent with decreased neuronal uptake of catecholamines in hypertrophied but not in nonhypertrophied myocardium of patients with HCM. Other aspects of cardiac sympathoneural function seem normal. Decreased neuronal uptake could reflect local relative hypoinnervation, decreased numbers of neuronal uptake sites, or metabolic limitations on cell membrane transport. By enhancing norepinephrine delivery to adrenoceptors for a given amount of sympathetic nerve traffic, decreased neuronal uptake can explain major clinical features of HCM.

Adult↗
PubMed2000

The effects of ropivacaine on sodium currents in dorsal horn neurons of neonatal rats.

We used a whole cell patch clamp technique to study the effects of ropivacaine on rat dorsal horn neurons. Under voltage clamp, ropivacaine (10-400 microM) produced a dose-dependent inhibition of sodium current. From a holding potential (V(h)) of -80 mV, sodium currents evoked by test pulses to 0 mV were inhibited by ropivacaine with a mean drug concentration required to produce 50% current inhibition (IC(50)) value of 117.3 microM, which was more than the value of the bupivacaine (IC(50) 53.7 microM). The inhibition effect of ropivacaine was also voltage-dependent. Current evoked from a V(h) of -60 mV was inhibited by ropivacaine with a mean IC(50) value of 74.3 microM, which was less than that obtained at the V(h) of -80 mV. The inhibition effect of ropivacaine on sodium current was use dependent. Repeated activation by a train of depolarizing pulses (5 Hz, 20 ms) increased the inhibitory effects of ropivacaine. The ratio amplitudes of the 20th to the first pulse were 91.2% and 71.1%, respectively, in the absence and presence of ropivacaine (50 microM). Ropivacaine also produced a significant hyperpolarizing shift of 11 mV in the steady-state inactivation curve of sodium current. The inhibition of ropivacaine on the sodium channel may contribute to the mechanism of action of local anesthetics during epidural and spinal anesthesia.

Amides↗