Biomedical subjects

W X Wang

Publications and source records attributed to W X Wang.

At least 19 recordsLinked to original sources

PubMed2001

Bioaccumulation of Cd, Se, and Zn in an estuarine oyster (Crassostrea rivularis) and a coastal oyster (Saccostrea glomerata).

We compared the bioaccumulation of Cd, Se, and Zn in an estuarine oyster (Crassostrea rivularis) and a coastal oyster (Saccostrea glomerata) from both the dissolved and particulate phases. A bioenergetic-based kinetic model was used to predict the exposure pathways of metals in the oysters. The assimilation efficiencies (AEs) of metals, determined for four species of phytoplankton and natural sediment, were in the range of 30-75% for Cd, 25-75% for Se, and 30-80% for Zn, respectively, in the two oysters. There was little difference in metal AE between the two oysters and among the three metals on the same particle type. Metal uptake rate constant, determined from the log-log relationship between metal influx rate and metal concentration in the dissolved phase, was higher for Cd and Zn in the estuarine oyster C. rivularis than in the coastal oyster S. glomerata. The uptake rate constants quantified for Cd, Se, and Zn were the highest among different bivalve species studied so far. The calculated metal absorption efficiency from the dissolved phase was similar to those found in other bivalve species. The measured efflux rate constant in the estuarine oyster C. rivularis was in the range of 0.01-0.03 day(-1) for Cd, Se, and Zn, and were comparable to those found in mussels and clams. In contrast, the efflux rate constant of Cd and Zn in the coastal oyster S. glomerata was 0.003-0.004 day(-1), which may be responsible for the high Cd and Zn concentrations in the oysters. The bioenergetic-based kinetic model predicts that under most circumstances likely experienced by oysters in nature, the majority of Se and Zn in the two oysters stem from uptake from the dietary phase. Dissolved uptake contributes significantly to metal accumulation only when the metal concentration factor (CF) in the particles is in the lower portion of the range typically found in nature. Sensitivity analysis indicates that the metal CF is a critical parameter in determining the exposure pathways of metals in the oysters. Our study demonstrated that estuarine and coastal oysters differed in their strategies in accumulating a high metal concentration in their tissues.

Animals↗

PubMed2001

Metal accumulation in the green macroalga Ulva fasciata: effects of nitrate, ammonium and phosphate.

Coastal organisms are often exposed to both metal pollution and nutrient enrichment. The influences of major nutrients (nitrate, ammonium, and phosphate) on the accumulation of trace metals (Cd, Cr, Zn and Se) in Ulva fasciata were examined. The relative accumulation of metals was quantified by the kinetic measurements of accumulated metal concentration over a short exposure period (8 h). Our study demonstrated that macronutrients could markedly influence the rate of metal accumulation in the macroalgae. An increase in ambient nitrate concentration resulted in a significant increase in Cd accumulation rate, whereas the rate of accumulation of Cr and Zn was not greatly affected by the ambient nitrate level (between 10 and 100 microM). Zn uptake in nitrate-enriched macroalgae was, however, significantly higher than its uptake in N-starved macroalgae. The accumulation of Cd, Cr and Zn was not appreciably affected by the concentration of ammonium. Se accumulation was significantly inversely related to the ambient phosphate concentration, presumably due to the competitive inhibition by a high P concentration. Cr accumulation in the macroalgae increased significantly with increasing phosphate concentration. These data implied that the influences of major nutrients on cationic and anionic metal accumulation were highly metal-specific. The dependence of metal accumulation on major nutrients will appreciably affect our prediction of metal accumulation in macroalgae and the interpretation of biomonitoring data using the Ulva species.

Chlorophyta↗

PubMed2001

Neoclassical radial electric field and transport with finite orbits.

Neoclassical transport in a toroidal plasma with finite ion orbits is studied, including for the first time the self-consistent radial electric field. Using a low-noise deltaf particle simulation, we demonstrate that a deep electric-field well develops in a region with a steep density gradient, because of the self-collision-driven ion flux. We find that the electric field agrees with the standard neoclassical expression, when the toroidal rotation is zero, even for a steep density gradient. Ion thermal transport is modified by the electric-field well in a way which is consistent with the orbit squeezing effect, but smoothed by the finite orbits.

Journal Article↗

PubMed2001

Metal uptake in a coastal diatom influenced by major nutrients (N, P, and Si).

The influence of major nutrient additions on trace metal uptake (Cd, Se, and Zn) in a coastal diatom Thalassiosira pseudonana was investigated. A short-term exposure (5 h) was employed to measure the concentration factor (ratio of metal concentration in the cells to metal concentration in the medium) which was used as a kinetic parameter to quantify the relative rate of metal uptake in the cells. Following an initial rapid surface sorption, a linear pattern of uptake over time was typical for Cd, Se and Zn, indicating that these metals may have been transported intracellularly during the short-term exposure period. N addition significantly increased the rates of Cd uptake in the cells. Although the concentration factor of Zn increased with N addition, statistical analysis indicated that N addition did not significantly affect the rate of Zn uptake in the cells. Se uptake in the cells was independent of N additions, but was lowered with increasing Si concentration. Si addition did not significantly affect Cd and Zn uptake. Similarly, P addition did not influence the rates of metal uptake in the cells. There was a significant correlation between the rate of uptake of Cd and Zn and the cell growth rate. This study demonstrated that water quality brought about by a change in nutrient condition could considerably influence the uptake of metals by marine phytoplankton.

Cadmium↗

PubMed2001

Influences of phosphate and silicate on Cr(VI) and Se(IV) accumulation in marine phytoplankton.

The influences of major nutrient additions (P, Si, or N) on the accumulation of chromate [Cr(VI)] and selenite [Se(IV)] in three species of marine phytoplankton, including two diatoms (Thalassiosira pseudonana, and Skeletonema costatum), and one green alga (Chlorella autotrophica) were examined. Accumulation rate was quantified by measurements of metal concentration factor in algal cells over a short 5-h exposure period. Our results suggested that Se(IV) was little bioavailable to C. autotrophica and S. costatum, but was highly bioavailable to diatom T. pseudonana. Se(IV) accumulation in both diatoms and green alga was inversely dependent on the ambient P and Si concentration. Concentration factor decreased by 2.4-8.1 and 1.5-4.6 times with the additions of 7.2 microM P or 105.6 microM Si, respectively, after 5 h of exposure. Bioconcentration factors of Se(IV) in these species determined under laboratory conditions, which generally employ high nutrient concentrations, may not be applicable to those prevailing in the field. In contrast to Se(IV), Cr(VI) accumulation in the green alga and two diatoms was not related to the ambient P concentrations, but was inversely dependent on the ambient Si concentrations. These data demonstrated that the influences of major nutrients on anionic metal accumulation were highly species-specific, both for metals and phytoplankton. Nutrient enrichments in many water bodies may potentially affect the accumulation of anionic metals, and thus their biological transport and fate in these environments.

Animals↗

PubMed2001

Effects of major nutrient additions on metal uptake in phytoplankton.

We examined the influences of major nutrients (N, P, Si) on the accumulation of three trace metals [Cd, Se(IV), and Zn] in four species of marine phytoplankton (diatom, green alga, dinoflagellate, prasinophyte). Relative metal uptake was quantified by the kinetic measurements of metal concentration factor over a short exposure period. Our study demonstrated that nutrient addition significantly influenced the metal uptake rate and the cell growth rate in all four phytoplankton species. An increase in ambient N concentration considerably enhanced metal uptake by the cells. The dry weight concentration factor increased by 2.4-14.9 times for Cd, 1.1-4.0 times for Se, and 1.1-5.4 times for Zn in all four phytoplankton species with an addition of 176.4 microM N. The effects of P or Si addition on metal uptake and cell growth were less pronounced than the effects of N addition. Under most circumstances the rate of metal uptake increased exponentially with increasing cell growth rate constant. Only Se(IV) uptake in the diatom Phaeodactylum tricornutum was not correlated with cell growth rate. Se(IV) was not accumulated by the green algae Chlorella autotrophica at a high P concentration (7.2 microM), but appreciable accumulation was documented in cells inoculated without P addition. Our study therefore demonstrated that nutrient enrichments in many coastal waters can considerably affect trace metal uptake in phytoplankton and presumably metal trophic transfer in marine food chains.

Biological Availability↗

PubMed2001

Comparative studies on the biokinetics of Cd, Cr, and Zn in the green mussel Perna viridis and the Manila clam Ruditapes philippinarum.

A kinetic approach was employed to determine the rates of metal uptake (Cd, Cr and Zn) from the dissolved phase and the rate constants of metal depuration in the mussel Perna viridis and the clam Ruditapes philippinarum. The effects of ambient metal concentration, salinity, and body size on the metal influx rate were examined. A linear positive relationship was observed between the metal influx rate and the metal concentration in ambient seawater. There was some evidence that Zn uptake was regulated by the bivalves in response to an increase in ambient Zn concentration. The uptake rate constant was highest for Zn and lowest for Cr in both bivalves, and was higher in mussels than in clams. The metal influx rate decreased by 1.6-1.8 times for the three metals when the salinity was increased from 15 ppt to 30 ppt. However, the effect of salinity on Zn influx in mussels was not statistically significant. A negative relationship of Cd and Zn influx rates with tissue dry weight was also found in both bivalves. Cr uptake in mussels was not significantly correlated with body size, but its uptake in clams was significantly correlated with body size. Metal concentration in ambient seawater appeared to be the most determining factor on metal uptake from the dissolved phase in both bivalves. The efflux rate constants of the three metals were within the range of 0.01-0.03 d-1, and were comparable between the mussels and the clams. Using a simple bioenergetic-based kinetic model, it was shown that both dissolved uptake and food ingestion can contribute to metal accumulation in the bivalves. However, Zn accumulation in the clam R. philippinarum was dominated by uptake from food ingestion. Metal partitioning in ingested food was found to be critical in affecting the relative importance of metal uptake from the dissolved phase and food source, primarily because of the large variability of this parameter in natural environments.

Animals↗

PubMed2001

Temporal variability and ignorance in Monte Carlo contaminant bioaccumulation models: a case study with selenium in Mytilus edulis.

Although the parameters for contaminant bioaccumulation models most likely vary over time, lack of data makes it impossible to quantify this variability. As a consequence, Monte Carlo models of contaminant bioaccumulation often treat all parameters as having fixed true values that are unknown. This can lead to biased distributions of predicted contaminant concentrations. This article demonstrates this phenomenon with a case study of selenium accumulation in the mussel Mytilus edulis in San Francisco Bay. "Ignorance-only" simulations (in which phytoplankton and bioavailable selenium concentrations are constant over time, but sampled from distributions of field measurements taken at different times), which an analyst might be forced to use due to lack of data, were compared with "variability and ignorance" simulations (sampling phytoplankton and bioavailable selenium concentrations each month). It was found that ignorance-only simulations may underestimate or overestimate the median predicted contaminant concentration at any time, relative to variability and ignorance simulations. However, over a long enough time period (such as the complete seasonal cycle in a seasonal model), treating temporal variability as if it were ignorance at least gave a range of predicted concentrations that enclosed the range predicted by explicit treatment of temporal variability. Comparing the temporal variability in field data with that predicted by simulations may indicate whether the right amount of temporal variability is being included in input variables. Sensitivity analysis combined with biological knowledge suggests which parameters might make important contributions to temporal variability. Temporal variability is potentially more complicated to deal with than other types of stochastic variability, because of the range of time scales over which parameters may vary.

Animals↗

PubMed2001

Influences of metal concentration in phytoplankton and seawater on metal assimilation and elimination in marine copepods.

Radiotracer experiments were conducted to examine the influence of the concentration of Cd, Se, and Zn in ingested phytoplankton (dinoflagellate Prorocentrum minimum and diatom Thalassiosira weissflogii) and in ambient seawater on metal assimilation and elimination efficiencies of three marine copepods, Acartia spinicauda, Paracalanus aculeatus, and Calanus sinicus. The assimilation efficiencies (AEs) decreased by 1.7 to 2.0 times, 1.4 to 4.1 times, and 1.3 to 2.2 times in the copepods with an increase in metal concentration in ingested algae by 16 to 84 times, 14 times, and 45 to 153 times, for Cd, Se, and Zn, respectively. However, the physiologic turnover rate constant was relatively independent of the metal concentration in copepods. No evidence was found of any interaction between Cd and Zn in their assimilation by copepods. Assimilation efficiencies of Cd were higher in copepods feeding on the dinoflagellate P. minimum, whereas the AEs of Zn were higher in copepods feeding on the diatom T. weissflogii. Differences in metal distribution in algal cytoplasm at different ambient metal concentrations may be partially responsible for the observed influence of metal concentration in algal cells on metal assimilation in copepods. However, metal desorption within the gut of the copepod may have little influence on metal assimilation, as a result of the short gut residence time of food particles and the neutral gut pH. Our study also indicated that the ingestion rate of copepods was reduced by a higher concentration of Cd and Se, but was not affected by Zn concentration in the food particles. Consequently, partial regulation of metal trophic transfer in response to increasing metal contamination may be achieved by a change in metal assimilation efficiency and the ingestion activity of the copepod, but not by changes in metal turnover rates from the animals.

Animals↗

PubMed2001

Comparison of metal uptake rate and absorption efficiency in marine bivalves.

Recent studies have quantified extensively metal assimilation efficiency from ingested food sources in aquatic invertebrates. Metal absorption efficiency (alpha) from the dissolved phase is analogous to metal assimilation efficiency, but it remains poorly defined and quantified. In this study, the alpha of four trace metals [Cd, Cr(VI), Se(IV), and Zn] was determined in three species of marine bivalves (green mussel [Perna viridis], black mussel [Septifer virgatus], and clam [Ruditapes philippinarum]). Individual bivalves were first measured for their clearance rates, followed by measurements of the metal influx rate, after which the metal alpha and the uptake rate constant (Ku) were then computed. Among the four metals considered, the highest Ku and alpha were found for Zn, followed by Cd > Cr(VI) > Se(IV). The Ku values were comparable between the two mussels but were 1.8- to 3.3-fold lower in the clams. Interspecific difference in metal Ku was strongly related to, but intraspecific difference in Ku was not affected by, the bivalve's clearance rate. Interspecific difference in metal alpha was smaller than the metal Ku and was independent of the clearance rate, whereas the intraspecific difference in metal alpha correlated with the individual variations of the clearance rate. Within each bivalve species, a significant negative correlation was found between the metal alpha and the clearance rate, implying that an individual pumping a greater amount of water was coupled to a lower alpha. Significant correlation between the alpha of four metals was also documented in all three species of bivalves. Thus, metal bioavailability from the aqueous phase was directly related to the physiological conditions of the animals. Both the aqueous chemistry and the physiology of the animals can be important in affecting metal bioavailability from the dissolved phase.

Absorption↗

PubMed2001

Sediment geochemical controls on CD, CR, and ZN assmilation by the clam Ruditapes philippinarum.

Several important sediment geochemical factors (particle size, contact time, artificial sediment composition, acid volatile sulfide, and pure inorganic particles coated or uncoated with humic acid) were examined for their influences on the assimilation of Cd, Cr, and Zn in the marine clam Ruditapes philippinarum. Metal desorption and phase speciation were concurrently measured for these particles. Differences in particle size did not significantly affect metal assimilation. Increasing contact time with sediments decreased assimilation by the clams of Cr and Zn, but not of Cd. A significant positive relationship was found between the metal assimilation efficiency (AE) and the metal partitioning in the exchangeable fraction of sediments for Cd and Zn. The assimilation of metals was negatively dependent on the metal distribution in the reducible (Fe oxide) fraction, indicating that Fe oxide reduced metal bioavailability to the clams. Metal AEs measured with artificially prepared sediments were comparable to those measured with natural sediments. The AEs were significantly higher in artificial sediment without Fe oxide. Humic acid coating appeared to have no major and consistent influence on metal assimilation by the clams. The AEs measured for pure inorganic particles were much higher than those measured for sediments or artificially prepared sediments, except for the Fe oxide particles, indicating that digestion may behave differently for pure particles. Metals bound to artificially synthesized acid volatile sulfide were much less bioavailable to the clams. The AEs were as low as 4% for Cd and 7% for Zn, whereas the AE for Cr was somewhat similar to those measured for other types of particles. When all particle types (natural sediments, artificial sediment, and pure particles) were considered, a significant relationship was found between Cd AE and its desorption in seawater. This study has demonstrated that several geochemical fractions of the sediments, particularly the exchangeable, Fe oxide, and sulfide fractions, are important in determining metal bioavailability from sediments to clams.

Adsorption↗

PubMed2000

Mechanism of cardiotoxicity of halofantrine.

OBJECTIVES AND METHODS: To further evaluate the scope and mechanism of potential cardiotoxicity associated with the antimalarial drug halofantrine, case reports submitted to the US Food and Drug Administration Spontaneous Reporting System were examined. Because halofantrine was associated with electrocardiographic prolongation of the QT interval and ventricular arrhythmias, in vitro cardiac electrophysiologic studies (isolated perfused cardiac model and isolated ventricular myocytes) were conducted to test the hypothesis that halofantrine or its metabolite is responsible for cardiotoxicity. RESULTS: Although it is difficult to ascertain causality and to estimate overall incidence, a significant number of adverse events related to the cardiovascular system were reported, including QT interval prolongation, life-threatening arrhythmias, and sudden death. The effect of halofantrine and its active metabolite (N-desbutylhalofantrine) on repolarization were examined in an isolated perfused heart model. Results indicate that halofantrine was able to prolong the QT interval, whereas N-desbutylhalofantrine had minimal effect on the QT interval relative to baseline. In an attempt to further elucidate the mechanism of QT interval prolongation, the effects of racemic halofantrine, its stereoisomers, and N-desbutylhalofantrine on repolarizing currents in isolated ventricular myocytes were studied with use of patch-clamp techniques. Halofantrine produced a stereoselective block of the delayed rectifier potassium channel in isolated feline myocytes. CONCLUSIONS: These results indicate that halofantrine is similar to quinidine and class III antiarrhythmics in its ability to prolong repolarization. We conclude that high plasma concentrations of halofantrine should be avoided, especially in women, and that N-desbutylhalofantrine may have potential as a safer antimalarial drug.

Adolescent↗

PubMed2000

[Expression of single-chain Fv antibody for anti-beet necrotic yellow vein virus in Escherichia coli].

The heavy chains variable region gene (VH) of monoclonal antibody against beet necrotic yellow vein virus (BNYVV) was amplified from total DNA extracted from anti-BNYVV hybridoma cells by PCR. Sequencing showed that the VH belongs to mouse subgroup II(A) and contains 360 bp, which code one hundred and twenty amino acids. The VH and VL genes were inserted into a plasmid which contains a linker sequence for constructing scFv gene. The new vector named pTC scFv. The scFv was produced in Escherichia coli and appeared binding activity with BNYVV antigen by ELISA method.

Amino Acid Sequence↗

PubMed2000

[Effect of haidonghua powder(HDHP) on hypothalamic obesity in rats].

OBJECTIVE: To study the effect of HDHP including Laminaria japonica Aresch. and Benincasa hispida(Thunb.) Cogn. etc. on antiobesity in rats with hypothalamic obesity. METHOD: A rat model of hypothalamic obesity induced by MSG was used and the relative indexes was observed. RESULT: HDHP(2.5 g.kg-1) could significantly reduce the Lee's index as well as the size of fat cells. HDHP did not influence the serum levels of T3 and T4, insulin and aldosterone, did not inhibited appetite not led to diarrhea. CONCLUSION: HDHP has the effect of anti-obesity, Without any influencing on the function of thyroid gland and metabolism of water and salt. The mechanism is related to the reduction of fat cell size and the accumulation of fat.

Animals↗

PubMed1999

Comparison of tegaserod (HTF 919) and its main human metabolite with cisapride and erythromycin on cardiac repolarization in the isolated rabbit heart.

Tegaserod (HTF 919) is a new drug being developed for gastrointestinal motility disorders. Because other gastrointestinal prokinetic agents, such as cisapride and erythromycin, cause slowing of cardiac repolarization and have been implicated in the development of the potentially fatal ventricular arrhythmia, torsades de pointes, a study was initiated to determine whether tegaserod and its main human metabolite adversely influence cardiac repolarization. By using isolated Langendorff-perfused rabbit hearts, we show that QT intervals remain unchanged at concentrations of tegaserod from 0.5 to 10 microM. It was not until the tegaserod concentration was increased to 50 microM (roughly 500-5,000 times more concentrated than those typically found in human plasma after administration of recommended clinical dosages), that a small, but significant increase in the QT interval (12+/-4%; p < 0.05; n = 4) was observed. No significant changes in QT occurred in the presence of the tegaserod metabolite at any of the concentrations tested (0.5-50 microM). In contrast, cisapride caused QT lengthening at concentrations as low as 0.1 microM, with significant QT increases occurring when 5-50 microM cisapride was used (22+/-4% to >70%, respectively; p < 0.01; n = 4). Erythromycin also caused significant lengthening of QT intervals (11+/-2%; p < 0.001; n = 4), although 100 microM concentrations of this drug were required to achieve this effect. These results demonstrate that both cisapride and erythromycin can slow cardiac repolarization at therapeutic doses and that tegaserod's lack of QT prolongation at therapeutic doses suggests that it has the potential to be a safer alternative to cisapride as a gastrointestinal prokinetic agent.

Animals↗

PubMed1998

Cardiac actions of erythromycin: influence of female sex.

CONTEXT: Erythromycin is a widely used antibiotic that infrequently causes QT-prolongation and torsades de pointes cardiac arrhythmias. For antiarrhythmic drugs, women are at a higher risk for these cardiac arrhythmias, but few other classes of drugs have been studied. OBJECTIVES: To determine whether female sex is a risk factor for cardiac arrhythmias associated with erythromycin, and if this can be correlated with in vitro measurements of the QT-response to erythromycin in male and female rabbit hearts. DESIGN: Food and Drug Administration (FDA) MEDWATCH database analysis and in vitro experiment. MAIN OUTCOME MEASURES: Cardiac arrhythmia reports associated with erythromycin from 1970 until 1996 classified by patient sex and age, and effect of female sex on erythromycin-induced QT-prolongation in isolated perfused rabbit hearts. RESULTS: We observed a sex difference in cardiac arrhythmias associated with administration of erythromycin. A total of 346 cases were found in the FDA database: 201 females (58%), 110 males (32%), and 35 unspecified (10%). Forty-nine were life-threatening ventricular arrhythmias and deaths directly related to intravenous erythromycin lactobionate: 33 women (67%) and 16 men (33%) (P=.03). During the same period, no sex imbalance was present in the prescription pattern for intravenous erythromycin lacobionate (men 47%, women 49%, unspecified 4%). Perfusion with erythromycin caused significantly greater QT-prolongation in female rabbit hearts (mean [SD], 11.8% [2.3%]) than in male hearts (6.9% [2.1%]; P = .03). CONCLUSIONS: As has been shown in reports of antiarrhythmic drugs, we found a female predominance in the FDA reports of erythromycin-associated cardiac arrhythmias. Based on in vitro experiments, a sex difference in cardiac repolarization response to erythromycin is a potential contributing factor.

Animals↗

PubMed1998

Trace element trophic transfer in aquatic organisms: a critique of the kinetic model approach.

The bioaccumulation of trace elements in aquatic organisms can be described with a kinetic model that includes linear expressions for uptake and elimination from dissolved and dietary sources. Within this model, trace element trophic transfer is described by four parameters: the weight-specific ingestion rate (IR); the assimilation efficiency (AE); the physiological loss rate constant (ke); and the weight-specific growth rate (g). These four parameters define the trace element trophic transfer potential (TTP = IR.AE/[ke + g]) which is equal to the ratio of the steady-state trace element concentration in a consumer due to trophic accumulation to that in its prey. Recent work devoted to the quantification of AE and ke for a variety of trace elements in aquatic invertebrates has provided the data needed for comparative studies of trace element trophic transfer among different species and trophic levels and, in at least one group of aquatic consumers (marine bivalves), sensitivity analyses and field tests of kinetic bioaccumulation models. Analysis of the trophic transfer potentials of trace elements for which data are available in zooplankton, bivalves, and fish, suggests that slight variations in assimilation efficiency or elimination rate constant may determine whether or not some trace elements (Cd, Se, and Zn) are biomagnified. A linear, single-compartment model may not be appropriate for fish which, unlike many aquatic invertebrates, have a large mass of tissue in which the concentrations of most trace elements are subject to feedback regulation.

Animals↗

PubMed1998

Prolongation of QT interval in isolated feline hearts by antipsychotic drugs.

Some antipsychotic drugs have been found to prolong the QT interval on electrocardiographic (ECG) recordings, a phenomenon which, when severe, may facilitate the occurrence of complex ventricular arrhythmias such as torsade de pointes. However, the effects of these drugs on the cardiac repolarization process have not been evaluated extensively. This study was designed to examine the potency of five antipsychotic drugs in lengthening the QT interval of the perfused feline heart: haloperidol, risperidone, sertindole, clozapine, and olanzapine. The hearts were infused with increasing concentrations of drugs (0.1-20 micromol/L) for 40-minute intervals at each concentration. ECG recordings were made, with signals amplified and data recorded on a strip chart recorder. Four representative beats from each set of three signal recordings were chosen for QT interval measurement. Our data indicated that all tested drugs prolonged the QT interval in a concentration-dependent manner (p < 0.01). Haloperidol and risperidone were significantly more potent than sertindole, clozapine, and olanzapine (p < 0.001). At a concentration of 0.5 micromol/L over a 40-minute infusion interval, haloperidol lengthened the interval by 26.2+/-0.7%, risperidone by 19.4+/-2.2%, and sertindole by 8.9+/-3.5% (p < 0.05 compared with baseline); clozapine and olanzapine were less potent. Although species differences may limit extrapolation of our findings to humans, the cardiac potassium channels of felines clearly resemble those of humans. This model may serve as the basis for further studies of drug-induced prolongation of the QT interval and precipitation of ventricular arrhythmias.

Analysis of Variance↗