Heterogeneous mass distribution of the rubble-pile asteroid (101955) Bennu.

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body.

Hemispherical differences in the shape and topography of asteroid (101955) Bennu.

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu's southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu's history.

Shape of (101955) Bennu indicative of a rubble pile with internal stiffness.

The shapes of asteroids reflect interplay between their interior properties and the processes responsible for their formation and evolution as they journey through the Solar System. Prior to the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) mission, Earth-based radar imaging gave an overview of (101955) Bennu's shape. Here, we construct a high-resolution shape model from OSIRIS-REx images. We find that Bennu's top-like shape, considerable macroporosity, and prominent surface boulders suggest that it is a rubble pile. High-standing, north-south ridges that extend from pole to pole, many long grooves, and surface mass wasting indicate some low levels of internal friction and/or cohesion. Our shape model indicates that, similar to other top-shaped asteroids, Bennu formed by reaccumulation and underwent past periods of fast spin leading to its current shape. Today, Bennu might follow a different evolutionary pathway, with interior stiffness permitting surface cracking and mass wasting.

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements.

The top-shape morphology of asteroid (101955) Bennu is commonly found among fast-spinning asteroids and binary asteroid primaries, and might have contributed significantly to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of OSIRIS-REx, we find a significant transition in Bennu's surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu's surface has been most recently migrating towards its equator (given Bennu's increasing spin rate), we infer that Bennu's surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior has a distribution of voids and boulders. The presence of such heterogeneity and Bennu's top-shape is consistent with spin-induced failure at some point in its past, although the manner of its failure cannot be determined yet. Future measurements by the OSIRIS-REx spacecraft will give additional insights and may resolve questions regarding the formation and evolution of Bennu's top-shape morphology and its link to the formation of binary asteroids.

Statewide assessment of local wellness policies in Pennsylvania public school districts.

With the passage of the Child Nutrition and Women, Infants, and Children Reauthorization Act of 2004, schools that sponsor school meals programs are required to establish local wellness policies to address childhood obesity. Little is known about how school districts will respond to this mandate, the nature of local wellness policies, and their compliance with this mandate. The objectives of this cross-sectional descriptive study, conducted in early 2007, were to assess local wellness policies established by Pennsylvania public school districts, compare these policies to local wellness policy mandate requirements, and provide information about local wellness policy development and implementation. Local wellness policies were collected from all Pennsylvania public school districts that sponsor school meals programs (N=499). School district representatives also completed and submitted a local wellness policy checklist, providing information about local wellness policy development and implementation. Policy goal data were abstracted and entered into a Microsoft Access database along with local wellness policy data. Frequencies were calculated. All required public school districts (N=499) submitted local wellness policies. Most school district local wellness policies (85.6%-100%) met each mandate requirement (eg, included goals for nutrition education, physical activity, etc.). The most common policy goals were general and may be difficult to measure, suggesting school staff may need assistance developing action plans and measuring policy implementation. Most respondents identified the superintendent (n=377; 75.6%) and school foodservice director (n=301; 60.3%) as responsible for ensuring local wellness policy implementation. Questions remain about feasibility of these district-level personnel to ensure policy implementation at the school level. The ability of local wellness policies to impact childhood obesity will depend on efforts at both the school and district levels to implement and enforce local wellness policies.

Addressing childhood overweight through schools.

Rates of childhood obesity in have reached alarming proportions in many countries. Sixteen percent of school-aged children and adolescents in the U.S. are overweight. Legislation implemented in 2004 in the U.S. requires local education agencies (LEAs) that sponsor school meal programs to establish local wellness policies to address childhood obesity. Project PA, a collaboration between a state agency and a university providing school-based interventions focuses on the school environment and policy changes. Interventions have targeted foodservice personnel, administrators, teachers, parents and students. In two recent projects schools assessed their school nutrition environments, developed nutrition policies, and implemented strategies to encourage healthier food selections. Schools identified weaknesses in the areas of marketing and communication of policies. Media attention on the childhood obesity facilitated policy changes. Time and cost were identified as barriers to policy development and there were concerns about weak enforcement of policies. These themes are discussed.

Factors associated with the offering and sale of competitive foods and school lunch participation.

OBJECTIVE: The objective of this study was to identify factors that predict offering and sale of competitive foods, as well as factors that predict average daily participation in school lunch. DESIGN: Surveys were distributed to 271 school foodservice directors in a random sample of high schools in Pennsylvania that were selected to be representative of the entire population of high schools in Pennsylvania based on chosen demographic characteristics. SUBJECTS: Two hundred twenty-eight school foodservice directors (84%) returned surveys. STATISTICAL ANALYSES: Descriptive and multiple regression analyses were done using SPSS version 11.5 (2002, SPSS Inc, Chicago, IL). RESULTS: Percentage of students eligible for free or reduced-price meals and timing of lunch were significant predictors of a la carte sales. Enrollment was negatively associated with number of vending machines per student. The number of less nutritious food items offered in vending machines and existence of soft drink machines owned by soft drink companies, for which the school receives a percent of sales, both predicted number of vending machines per student. Enrollment was inversely related to average daily participation in school lunch. The percentage of students eligible for free/reduced-price meals and enforcement of a policy prohibiting parents or students from bringing food into the cafeteria from local fast-food establishments positively predicted average daily participation in school lunch. CONCLUSIONS: These findings may be useful to school wellness councils in developing wellness policies as mandated by the Child Nutrition and WIC Reauthorization Act of 2004, as well as in structuring school environments to promote more healthful food choices by students.

School competitive food policies: perceptions of Pennsylvania public high school foodservice directors and principals.

The objectives of this study were to describe the extent, nature, and enforcement of school competitive food policies in Pennsylvania public high schools and to determine if there are differences between school foodservice directors' and principals' perceptions of the existence and enforcement of these policies. A survey was distributed to 271 school foodservice directors and 100 principals in a representative, random sample of high schools. Two hundred twenty-eight school foodservice directors (84%) and 79 principals (79%) returned surveys. Descriptive statistics, chi2 analyses, and a proportions test were done using SPSS statistical software (SPSS base 11.5 for Windows, 2002, SPSS Inc, Chicago, IL). Few nutrition policies were reported related to setting nutritional standards for competitive foods (0.5% to 15.0%). Respondents' reporting of existence of policies not always enforced ranged from 0% to 12.8%. School foodservice directors reported uncertainty about existence of several policies outside their direct domain, but with potential effect on school meals participation. Differences were found between school foodservice directors' and principals' reporting of policies, with principals more often reporting policy existence and enforcement. These findings suggest the need for communication, both about existence of policies and chain of command in enforcement of policies. Given the local wellness policy provision of the Child Nutrition and WIC Reauthorization Act of 2004, opportunities exist for nutrition professionals to contribute to development of policies that influence the nutritional quality of school foods.

Existence and predictors of soft drink advertisements in Pennsylvania high schools.

The objective of this study was to describe the extent and locations of soft drink advertisements on high school campuses in Pennsylvania and identify factors related to extent of these advertisements. Surveys were distributed to 271 school foodservice directors in a random sample of high schools in Pennsylvania. These high schools were selected to be representative of the entire population of high schools in Pennsylvania based on chosen demographic characteristics. A three-phase survey strategy was used, involving distribution of a postcard reminder 1 to 2 weeks after the initial survey distribution, and mailing of a second survey to nonrespondents 1 to 2 weeks after mailing of the postcard. Two hundred twenty-eight school foodservice directors (84%) returned surveys. Linear multiple regression analyses were done using SPSS (version 11.5.1, 2002, SPSS Inc, Chicago, IL). Approximately two thirds (66.5%) of respondents indicated soft drink advertisements exist in at least one location in their school, with the most prevalent locations being on vending machines (62%) and school grounds, such as playing fields (27%). Slightly more than 10% of respondents indicated soft drink advertisements displayed in the cafeteria. Extent of soft drink advertisement locations was positively related to existence of a pouring-rights contract, subscription to Channel One, and receipt of incentives from soft drink bottlers based on sales, but negatively related to average daily participation in school lunch. These findings suggest that commercialization and sales incentives might interact to contribute to school environments that are not "nutrition-friendly." Schools' efforts to establish wellness policies as mandated by the Child Nutrition and WIC Reauthorization Act of 2004 provide ideal opportunities to examine school environments for advertising that might conflict with the healthful environments they are aiming to establish, and perhaps to develop policies to address these practices.

Competitive foods available in Pennsylvania public high schools.

OBJECTIVE: This study examined the types and extent of competitive foods available in public high schools in Pennsylvania. DESIGN: We developed, pilot tested, and distributed surveys to school foodservice directors in a random sample of 271 high schools in Pennsylvania. SUBJECTS: Two hundred twenty-eight surveys were returned, for a response rate of 84%. Statistical analyses were performed: Descriptive statistics were used to examine the extent of competitive food sales in Pennsylvania public high schools. The survey data were analyzed using SPSS software version 11.5.1 (2002, SPSS base 11.0 for Windows, SPSS Inc, Chicago, IL). RESULTS: A la carte sales provide almost dollar 700/day to school foodservice programs, almost 85% of which receive no financial support from their school districts. The top-selling a la carte items are "hamburgers, pizza, and sandwiches." Ninety-four percent of respondents indicated that vending machines are accessible to students. The item most commonly offered in vending machines is bottled water (71.5%). While food items are less often available through school stores and club fund-raisers, candy is the item most commonly offered through these sources. CONCLUSIONS: Competitive foods are widely available in high schools. Although many of the items available are low in nutritional value, we found several of the top-selling a la carte options to be nutritious and bottled water the item most often identified as available through vending machines.

Lunar formation. Dating the Moon-forming impact event with asteroidal meteorites.

The inner solar system's biggest and most recent known collision was the Moon-forming giant impact between a large protoplanet and proto-Earth. Not only did it create a disk near Earth that formed the Moon, it also ejected several percent of an Earth mass out of the Earth-Moon system. Here, we argue that numerous kilometer-sized ejecta fragments from that event struck main-belt asteroids at velocities exceeding 10 kilometers per second, enough to heat and degas target rock. Such impacts produce ~1000 times more highly heated material by volume than do typical main belt collisions at ~5 kilometers per second. By modeling their temporal evolution, and fitting the results to ancient impact heating signatures in stony meteorites, we infer that the Moon formed ~4.47 billion years ago, which is in agreement with previous estimates.

Ca(2+) entry into primary cultured pig coronary smooth muscle cells after previous store depletion by repetitive P2Y purinoceptor stimulation.

Store-operated Ca(2+) entry, stimulated by depletion of intracellular Ca(2+) pools, has not been fully elucidated in vascular smooth muscle cells of pig coronary arteries. Therefore, [Ca(2+)](i) was measured in cultured cells derived from extramural pig coronary arteries using the Fura-2/AM fluorometry. Divalent cation entry was visualized with the Fura-2 Mn(2+)-quenching technique. Ca(2+) stores were depleted either by repetitive stimulation of P2Y purinoceptors with ATP (10 micromol/L), or by the sarcoendoplasmic Ca(2+)-ATPase inhibitor 2,5-Di-(tert-butyl)-1,4-benzohydroquinone (BHQ; 1 micromol/L) in Ca(2+)-free medium (EGTA 1 mmol/L). Addition of Ca(2+)(1 mmol/L) induced refilling of ATP-sensitive Ca(2+) stores and an increase in [Ca(2+)](i) in the presence of BHQ. Both could be significantly diminished by Ni(2+)(5 and 1mmol/L), La(3+)(10 micromol/L), Gd(3+)(10 micromol/L), and Mg(2+)(5.1 mmol/L). In contrast to the BHQ-mediated rise in [Ca(2+)](i), refilling of ATP-depleted stores was affected by neither flufenamate (0.1 mmol/L), nor by nitrendipine, nifedipine, and nisoldipine (each 1 micromol/L). The data suggest that after store depletion in pig coronary smooth muscle cells ATP and BHQ may converge on a common, Ni(2+)-, La(3+)-, Gd(3+)-, and Mg(2+)- sensitive Ca(2+) entry pathway, i.e. on a store-operated Ca(2+) entry. An additional contribution of the Na(+)/Ca(2+) exchanger cannot be excluded. Flufenamate-sensitive non-selective cation channels and dihydropyridine-sensitive L-type Ca(2+) channels are not involved in refilling of Ca(2+) stores after previous depletion by repetitive P2Y purinoceptor stimulation. The store-operated Ca(2+) entry in-between repetitive purinoceptor stimulation, i.e. in the absence of the agonist, may be responsible for the maintenance of agonist-induced rhythmic Ca(2+) responses.

Modelling frequency- and voltage-dependent effects of a class I antiarrhythmic drug (nicainoprol) on Vmax of the cardiac action potential from guinea-pig papillary muscle.

Frequency- and voltage-dependent effects of a class I antiarrhythmic agent (nicainoprol) on the maximal upstroke velocity (Vmax) of the action potential of guinea-pig papillary muscle are compared with the effects predicted by a kinetic model of frequency- and voltage-dependent block of fast sodium channels. The model is based on the guarded-receptor hypothesis, which assumes a constant affinity binding site with the drug access to and egress from the binding site being controlled by the channel conformational state. At normal resting membrane potential (RMP approximately -86 mV) nicainoprol (3.3 x 10(-6) mol/l and 10(-5) mol/l) causes no Vmax-reduction after a resting period (i.e. no resting block) but a frequency-dependent decrease of Vmax (frequency-dependent block), which saturates at above 2.0 Hz. Both, resting and frequency-dependent block strongly depend on the RMP in a way that the frequency-dependent block decreases with depolarizing RMP while the resting block increases. Development of and recovery from frequency-dependent block is faster at depolarized RMP. These results can be interpreted in terms of the guarded-receptor hypothesis with nicainoprol preferentially binding to inactivated sodium channels. All its effects on Vmax can be fully described by only three model parameters: a binding rate coefficient (kB = 8.49 x 10(3) mol-1.1.s-1), an unbinding rate coefficient (k-B = 6.24 x 10(-2).S-1), and a parameter with the meaning of an electrical location of the binding site (about 35% on the way through the membrane field from the extracellular surface).

Argyrophil and beta-endorphin immunoreactive cells in focal islet-cell adenomatosis and insulin-producing islet-cell adenomata.

Pancreatic tissue from 3 cases of hyperinsulinemic hypoglycemia was examined using histochemical and immunoperoxidase staining techniques. The insular lesions present were adenomatosis and insulin-producing islet-cell adenomata. The great majority of the islet parenchymal cells in these lesions were reactive with antibodies to pro-insulin, C-peptide, and insulin. A variable number of islet cells was found to react with beta-endorphin antiserum in all 3 cases, while the reaction with antiserum against the neural tissue marker antigen, S-100, was restricted to the cases with islet-cell adenoma. Argyrophil parenchymal cells were present in focal adenomatosis but almost absent in insulomata. These results suggest that various lesions of the endocrine pancreas causing hypoglycemia can be distinguished by means of specific histo- and immunocytochemical methods because of differences in the distribution of characteristic cellular antigens.

Frequency-dependent action of antiarrhythmic drugs: the useful concept of periodical ligand binding.

The action of most antiarrhythmic drugs which block cardiac ionic channels depends on heart rate, which is established as use- or frequency-dependence. This property is consistent with periodical drug (ligand) binding to channel binding sites which are transiently available during the excitation sequence of cardiac tissue. Antiarrhythmic drugs differ with respect to their binding and unbinding kinetics, i.e., with respect to their blocking and unblocking kinetics. This gives rise to different block-frequency relations and onset-kinetics of frequency-dependent ion channel blockade. Antiarrhythmic drugs have never been systematically compared with regard to their block-frequency relations. However, both the onset-kinetics as well as the block-frequency relation are essential in characterizing the frequency-dependent drug action, since both may be predictors of the anti- and pro-arrhythmic potential of antiarrhythmic drugs.

[New aspects of frequency-dependent effect of class 1 anti-arrhythmia drugs. A critical analysis of useful subclassification]. / Neue Aspekte zur frequenzabhängigen Wirkung von Klasse-1-Antiarrhythmika. Eine kritische Analyse der gebräuchlichen Subklassifikation.

The primary action of class-1-antiarrhythmic drugs is due to blockade of cardiac sodium channels and shows drug-specific frequency dependence, i.e., increasing blockade with increasing stimulation frequency. However, this increasing blockade saturates at higher rates. This behavior can be explained by a periodical binding and unbinding reaction of drug molecules with channel binding sites (periodical ligand binding). The analysis of the saturation behavior of frequency-dependent block of 12 class-1-antiarrhythmic drugs clusters into three groups (I-III), which do not coincide with the commonly used subclassification (1a-1c). However, from the saturation behavior of block and its onset-kinetics (rate of increase of block upon increasing the frequency) found with these groups, three different profiles of antiarrhythmic and proarrhythmic efficacy can be deduced. Thus, saturation in the frequency range above 120/min combined with slow onset-kinetics may create a higher risk of exercise-induced proarrhythmic effects, if agents with such characteristics are given at a concentration sufficiently high to suppress extrasystoles. Therefore, a subdivision of class-1-antiarrhythmic drugs according to the saturation behavior of frequency-dependent block and its onset-kinetics is proposed.

Evaluation and interpretation of voltage- and frequency-dependent electrophysiologic effects of a new class I antiarrhythmic agent (nicainoprol) on guinea pig papillary muscle and isolated heart.

Frequency- and voltage-dependent electrophysiologic effects of a chemically novel compound, nicainoprol, were evaluated by recording transmembrane action potentials (APs) from papillary muscles and electrograms (EGs) from isolated perfused hearts of guinea pigs. At 0.2 Hz stimulation, nicainoprol (3.3 x 10(-6) M and 10(-5) M) significantly reduces the maximal upstroke velocity (Vmax) of APs without significant change in resting membrane potential (RMP), functional refractory period (FRP), and action potential duration. Nicainoprol prolongs the spread of excitation but has little effect on the duration of the ventricular EG. The Vmax depression is frequency dependent in the range of 0.02-2.5 Hz, showing saturation at higher frequencies. Under resting conditions, nicainoprol (3.3 x 10(-6) M and 10(-5) M) has no effect on Vmax. The onset of frequency-dependent Vmax reduction follows monoexponential time courses with rate constants of 0.053 +/- 0.007 AP-1 (3.3 x 10(-6) M) and of 0.066 +/- 0.005 AP-1 (10(-5) M) at 1 Hz. Vmax recovers from frequency-dependent depression with time constants of 45.4 +/- 3.2 s (3.3 x 10(-6) M) and 48.4 +/- 3.5 s (10(-5) M). Nicainoprol significantly shifts the Vmax-RMP relation in hyperpolarizing direction by 2.6 +/- 1.1 mV (3.3 x 10(-6) M) and 5.4 +/- 1.3 mV (10(-5) M) at membrane potentials where Vmax is half maximal. It is concluded that nicainoprol can be classified as a class 1C drug and does preferentially bind to inactivated sodium channels with a dissociation constant of about 10(-5) M.

Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic efficacy.

The frequency-dependent block of cardiac sodium channels by class 1 antiarrhythmic drugs can be described by a periodical ligand binding process between drug molecules and channel binding sites. This predicts a linear relation between onset-rate constant of frequency-dependent block and diastolic interval as well as saturation of block with high stimulation rates. From both relationships, the binding kinetics (time constant, tau on) and saturation level of block (bdinf) can be estimated. This is exemplified for the frequency-dependent block (reduction of the maximal upstroke velocity of action potentials) induced by prajmaline (10(-6) M). In the same way, the frequency-dependent effects of 11 other class 1 drugs reported in the literature were analyzed and compared with each other. When the drugs are ranked with respect to their binding kinetics (tau on), there is a close relationship to the subclasses (1a, 1b, 1c), with 1b drugs exhibiting the fastest and 1c drugs the slowest kinetics. However, differences also exist in the saturation behavior of frequency-dependent block even within the same subclasses (1a and 1c). Thus, the class 1 drugs can also be subdivided in three other groups exhibiting clearly separated bands of block-frequency relations, with half-maximal saturation occurring at different stimulation rates. Our findings may have differential implications for the antiarrhythmic and proarrhythmic efficacy of class 1 drugs.

[New aspects of the electrophysiologic effect of antiarrhythmic agents]. / Neue Aspekte der electrophysiologischen Wirkung von Antiarrhythmika.

BASIC ACTIONS: According to Vaughan Williams antiarrhythmic agents are divided into four classes of action (Table 1). A given agent may display actions of several classes. In general, except for class II drugs there is no causal relationship between the class of action and the mechanism precipitating the arrhythmia. MECHANISM OF ACTION OF CLASS I DRUGS: The effect of class I antiarrhythmic drugs is primarily based on prolongation of the refractory period. It is assumed that the sodium channel can be in one of at least three functional conditions (Figure 1), resting, activated or inactivated. Conductance is achieved only in the state of activation, during the initial phase of the action potential which is caused by rapid sodium influx. The transition from inactivation to resting condition, which is prerequisite for renewed activation, takes place during repolarization and is responsible for the refractory period of the action potential (Figure 1). Class I antiarrhythmic drugs block the sodium channels such that they remain in a nonconductive state. As a function of the number of inoperative sodium channels, sodium influx is reduced and the rate of rise of the action potential is diminished. In order to enable sufficient sodium channels to make the transition from inactivated to resting condition, repolarization of the action potential has to continue and, concomitantly, the absolute refractory period is increased. Since the attenuation of the rapid sodium influx also causes a decrease in the conduction velocity in myocardium and in the intraventricular conduction system, reentry arrhythmias can be precipitated. DIFFERENCES IN THE ACTION OF CLASS I DRUGS: Due to different rate-dependency of the various class I drugs and the effect on the duration of the action potential as well as on specified ECG parameters, subclasses a, b and c were designated (Table 2). Access of the drug to the sodium channel receptor is facilitated during activation and inactivation but not in the resting condition. Accordingly, the effect increases in proportion to the frequency with which the sodium channel is opened. With the beginning of the cardiac cycle, there is an exponential increase in the number of blocked sodium channels and, with transition to the resting condition, an exponential decrease (Figure 2). The velocity of the increase or decrease is dependent on the properties of the given agent. Substance with rapid binding kinetics, that is time constants of 0.2 to 2.0 s are assigned to group Ib, those with time constants of 8 to 14 s to group Ic (Table 3). Group Ia is intermediate. A similar grouping is yielded on assignment according to the temporal course of deblocking. EXPLANATION FOR THE DIFFERENCES IN EFFECTS: With antiarrhythmic agents of class Ib, due to their rapid binding kinetics, at a rate of approximately 1 Hz (60/min) steady-state is achieved with no accumulation of block. Each incoming impulse with a normal interval can activate the unblocked membrane (Figure 2). Premature impulses occurring with shorter intervals are inhibited more the earlier their incidence. Consequently, class Ib antiarrhythmic drugs are particularly effective for premature beats and frequent tachycardias while, during normal sinus rhythm, in some instances, no effect such as PQ or QRS prolongation can be observed (Table 2).(ABSTRACT TRUNCATED AT 400 WORDS)

[Current classification of anti-arrhythmia agents]. / Aktuelle Einteilung antiarrhythmisch wirksamer Substanzen.

Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV) according to defined electrophysiological effects on the myocardium. Thus, the Vaughan Williams classification also coincides with the main myocardial targets of the antiarrhythmics, i.e., myocardial sodium-, potassium-, and calcium-channels or beta-adrenergic receptors. A more detailed characterization which is also based on the myocardial targets of a drug is given by the "Sicilian Gambit" approach of classification. Nevertheless, the appropriate drug for the management of a given clinical arrhythmia has to be chosen according to the electrophysiological effects of the respective drug. A main determinant of the antiarrhythmic or proarrhythmic properties of a drug is the frequency dependence of its electrophysiological effects. The sodium-channel blockade induced by class-I substances is enhanced with increasing heart rates. Thus, class-I antiarrhythmics can be subclassified as substances showing a more exponential, an approximately linear, or rather saturated block-frequency relation. Class-III antiarrhythmics (potassium-channel blockade) can be further differentiated according to the component of the delayed rectifier potassium current (IK) which is inhibited by a drug. Class-III drugs inhibiting selectively the rapidly activating and deactivating IKr component exhibit a marked reverse rate dependence, i.e., the drug induced prolongation of the cardiac action potential is minimized at high rates. On the other hand, during bradycardia the pronounced action potential prolongation may cause early afterdepolarizations and triggered activity leading to torsades de pointes arrhythmias (acquired QT syndrome). Class-III substances inhibiting the slowly activating IKs component are currently under investigation and are expected to show a direct rate dependence. Experimental data available so far point to an action potential prolonging effect at least independent of rate. However, it is uncertain whether proarrhythmic effects can be thus avoided, especially in light of the fact that one form of congenital QT syndrome (LQT1) seems to be linked to dysfunction of the IKs-channel.