bluuebunny/crossref_metadata_2025 huggingface dataset:
NITRATE UTILIZATION BY PHYTOPLANKTON IN LAKE SUPERIOR IS IMPAIRED BY LOW NUTRIENT (P, Fe) AVAILABILITY AND SEASONAL LIGHT LIMITATION — A CYANOBACTERIAL BIOREPORTER STUDY1
Authors: Ivanikova Natalia V. , McKay R. Michael L. , Bullerjahn George S. , Sterner Robert W.
Published: May 2007

We previously developed a luminescent Synechococystis sp. strain PCC 6803 cyanobacterial bioreporter that is used as a real‐time whole‐cell sensor to assess nitrate assimilatory capacity in freshwaters. Applying the bioreporter assay to Lake Superior, a system whose nitrate levels have increased 6‐fold since 1900, we investigated factors that constrain nitrate utilization in this oligotrophic system. Clean sampling methods were used to collect water from Lake Superior during spring and summer 2004, and nitrate utilization was measured by monitoring bioreporter luminescence. Bioreporter response was monitored during experiments in which the lake water was amended with nutrients and incubated under light regimes simulating integrated spring and summer mixing depths. These studies demonstrated that nitrate utilization was enhanced at most stations following addition of phosphorus (P). Moreover, at many stations, addition of iron (Fe) enhanced the P effect. Strength‐of‐effect statistical analysis provided the individual contribution of P and Fe toward stimulating bioreporter response. In general, distance from shore and season were not good predictors of nitrate assimilatory capacity. Manipulation of light flux during bioreporter experiments also showed that light intensities experienced during spring mixing are likely insufficient to saturate the rate of nitrate utilization. Overall, these data suggest that P‐limited algae are deficient in their ability to assimilate nitrate in Lake Superior. Furthermore, we suggest that a secondary limitation for Fe may occur that further constrains nitrate drawdown. Lastly, during spring, light fluxes are sufficiently low to prevent maximal nitrate utilization, even in the absence of nutrient limitation.
ANALYSES OF EXPRESSED SEQUENCE TAGS FROM SARGASSUM BINDERI (PHAEOPHYTA)1
Authors: Wong Tony Kok‐Min , Ho Chai‐Ling , Lee Weng‐Wah , Rahim Raha Abd. , Phang Siew‐Moi
Published: May 2007

Sargassum is a source for many metabolites, including alginic acid, alginates, sulfated fucoidans, pigments, oils, sterols, and mannitols. The present study is the first attempt to examine Sargassum binderi (Sonder) J. Agardh, a tropical brown seaweed, using an expressed sequence tag (EST) approach. Single‐pass 5′ sequencing of 2304 cDNA clones generated 1876 ESTs of good quality, from which 1270 tentative unique genes (TUGs) consisting of 991 singletons and 279 contigs were obtained. Approximately 39.5% of the TUGs from S. binderi showed significant matches to the existing data bases and were further divided into nine subcategories: metabolism (24.9%); transcription and translation (22.5%); cellular processes (7.2%); protein folding, sorting, and degradation (5.6%); signaling (2.8%); membrane and transport (3%); receptor (1.1%); other functions (4.2%); and unknown proteins (28.7%). The sequences were compared with ESTs from Laminaria digitata (Hudson) J. V. Lamour.
Implications of Executive Hedge Markets for Firm Value Maximization
Authors: Çelen Boǧaçhan , Özertürk Saltuk
Published: May 2007

This paper analyzes the incentive implications of executive hedge markets. The manager can promise the return from his shares to third parties in exchange for a fixed payment—swap contracts—and/or he can trade a customized security correlated with his firm‐specific risk. The customized security improves incentives by diversifying the manager's firm‐specific risk. However, unless they are exclusive, swap contracts lead to a complete unraveling of incentives. When security customization is sufficiently high, the manager only trades the customized security—but not any nonexclusive swap contracts, and incentives improve. Access to highly customized hedge securities and/or exclusive swap contracts increases the manager's pay‐performance sensitivity.
Preliminary Injunctions and Damage Rules in Patent Law
Authors: Boyce John R. , Hollis Aidan
Published: May 2007

This paper shows that preliminary injunctions may be sought in patent cases to obtain market power during the period of the injunction and are likely to be sought only where there is a small probability that the patent will be ultimately found valid. Both patentee and alleged infringer benefit from a preliminary injunction. This is an artifact of the asymmetry of current damage rules. Altering the rules so that an innovator who wins a preliminary injunction on a patent ultimately declared invalid pays both lost profits to the imitator and a fine equal to lost consumer surplus creates efficient incentives.
Price and Quantity Competition in a Differentiated Duopoly with Upstream Suppliers
Authors: Correa‐López Mónica
Published: May 2007

This paper analyzes the noncooperative game on the choice of strategic variable to set in duopoly in the presence of an upstream market for the input. For the case of labor input, the analysis shows that if the wage is the result of decentralized firm‐union bargain, a duopoly producing substitutes may choose to compete either in the quantity space or in the price space, depending upon the distribution of bargaining power in the wage negotiation and the union's relative preference over the wage. For the case of input suppliers as profit‐maximizing firms, the paper shows that a vertically differentiated duopoly may prefer to compete either in the quantity space or in a mixed strategy setting where the high‐quality firm plays price and the low‐quality firm plays quantity, depending upon the extent of substitutability, the degree of vertical product differentiation and the distribution of bargaining power in the input price negotiation.
Stroke: A Randomized Trial of Exercise or Relaxation
Authors: Mead Gillian E. , Greig Carolyn A. , Cunningham Irene , Lewis Susan J. , Dinan Susie , Saunders David H. , Fitzsimons Claire , Young Archie
Published: May 2007

OBJECTIVES: To determine the feasibility and effect of exercise training after stroke.

DESIGN: Randomized exploratory trial comparing exercise training (including progressive endurance and resistance training) with relaxation (attention control).

SETTING: Interventions were performed in a rehabilitation hospital.

PARTICIPANTS: Sixty‐six independently ambulatory patients (mean age 72, 36 men) without significant dysphasia, confusion, or medical contraindications to exercise training who had completed their usual rehabilitation and had been discharged from hospital.

INTERVENTION: Both interventions were held three times a week for 12 weeks. Up to seven patients attended each session.

MEASUREMENTS: The Functional Independence Measure; Nottingham Extended Activities of Daily Living; Rivermead Mobility Index; functional reach; sit‐to‐stand; elderly mobility score; timed up‐and‐go; Medical Outcomes Study 36‐Item Short Form Questionnaire, version 2 (SF‐36); Hospital Anxiety and Depression Score; aspects of physical fitness (comfortable walking speed, walking economy, and explosive leg extensor power) were measured at baseline, immediately after interventions (3 months), and 7 months after baseline.

RESULTS: The median number of intervention sessions attended was 36 (interquartile range (IQR) 30.00–36.75) for exercise and 36 (IQR 30.50–37.00) for relaxation. Adherence to the individual exercises ranged from 94% to 99%. At 3 months, role‐physical (an item in SF‐36), timed up‐and‐go, and walking economy were significantly better in the exercise group (analysis of covariance). At 7 months, role‐physical was the only significant difference between groups.

CONCLUSION: Exercise training for ambulatory stroke patients was feasible and led to significantly greater benefits in aspects of physical function and perceived effect of physical health on daily life.
Faculty Development for the 21st Century: Lessons from the Society of General Internal Medicine–Hartford Collaborative Centers for the Care of Older Adults
Authors: Williams Brent C. , Weber Valerie , Babbott Stewart F. , Kirk Lynne M. , Heflin Mitchell T. , O'Toole Elizabeth , Schapira Marilyn M. , Eckstrom Elizabeth , Tulsky Asher , Wolf Andrew M. , Landefeld Seth
Published: May 2007

In this review of a recent set of faculty development initiatives to promote geriatrics teaching by general internists, nontraditional strategies to promote sustained change were identified, included enrolling a limited number of “star” faculty, creating ongoing working relationships between faculty, and developing projects for clinical or education program improvement. External funding, although limited, garnered administration support and was associated with changes in individual career trajectories. Activities to enfranchise top leadership were felt essential to sustain change.

Traditional faculty development programs for clinician educators are periodic, seminar‐based interventions to enhance teaching and clinical skills. In 2003/04 the Collaborative Centers for Research and Education in the Care of Older Adults were funded by the John A. Hartford Foundation and administered by the Society of General Internal Medicine. Ten academic medical centers received individual grants of $91,000, with required cost sharing, to develop collaborations between general internists and geriatricians to create sustained change in geriatrics clinical teaching and learning. Through written and structured telephone surveys, activities designed to foster sustainability at funded sites were identified, and the activities and perceived effects of funding at the 10 funded sites were compared with those of the 11 highest‐ranking unfunded sites.

The experience of the Collaborative Centers supports the conclusion that modest, targeted funding can provide the credibility and legitimacy crucial for clinician educators to allocate time and energy in new directions. Key success factors likely include high intensity and duration, integration into career trajectories, integration into clinical programs, and activities to enfranchise institutional leadership.
Benefits of a blood donation archive repository: international survey of donor repository procedures and Scottish experiences
Authors: Franklin I.M. , Dow B.C. , Jordan A.D.
Published: May 2007

BACKGROUND: The use of a donation sample archive has been in place within the Scottish National Blood Transfusion Service for almost 35 years but the advent of human immunodeficiency virus donor testing led to this archive being kept for an indefinite period. This article describes the uses made of our archive repository.

STUDY DESIGN AND METHODS: Records of various potential transfusion transmission episodes were accessed and examined to assess the age of the archives investigated and the outcome of the investigations. Other uses of the archive repository were also investigated by reviewing the records of retrievals. The use of the archive to aid the interpretation of hepatitis C virus–indeterminate results was also conducted. Finally a global survey was performed to ascertain the temperature and length of storage used by various transfusion services.

RESULTS: A 3‐year archive would have allowed for the investigation of 45 percent of cases (including all hepatitis B virus cases), while a 10‐year archive would have allowed for 90 percent of cases. Only 34 percent of cases were shown to be transfusion‐transmitted. Of 16 donors with c22‐indeterminate bands on recombinant immunoblot assay, 2 (12%) could have been classified as confirmed‐positive on the basis of their archive samples. A considerable proportion (41%) of the most recent requests for retrieval from the archive have been associated with the need to perform new mandatory tests for tissue donations at issue. Samples older than 3 years accounted for 25 percent of all samples retrieved. The global survey showed a variety of conditions in terms of both length and temperature of storage.

CONCLUSION: The use of a donation archive has been shown to be extremely useful in the investigation of potential transfusion‐transmitted infections with most (66%) having no evidence of transfusion transmission. Although 90 percent of our cases could have been fully investigated with only a 10‐year archive, perhaps the future retention period of hospital records should be considered when determining the length of storage of current donation archive samples.
Unconditional Intergovernmental Transfers to Finance Decentralization in Albania
Authors: SCHROEDER LARRY
Published: May 2007

The Government of Albania embarked on a comprehensive program to decentralize decision‐making powers with the passage of the Law on Organization and Functioning of Local Governments in 2000. A centerpiece of the policies undertaken to implement that legislation was an unconditional transfer program which, using a formula‐based allocation mechanism, transferred substantial financial resources to the local communes and municipalities beginning in 2002. This paper describes that system and its evolution. It illustrates how the transfer was designed to take into account the transition from a centralized system to a decentralized arrangement for provision of local public services and how the formula has undergone some “fine‐tuning” while retaining its simplicity. Analysis of the outcomes reveals how it has achieved its mandated objective of equalizing resources across local governments; however, it does so while running the risk of substantially discouraging local governments from mobilizing resources of their own.
Clinic Overbooking to Improve Patient Access and Increase Provider Productivity*
Authors: LaGanga Linda R. , Lawrence Stephen R.
Published: May 2007

The problem of patientno‐shows(patients who do not arrive for scheduled appointments) is significant in many health care settings, where no‐show rates can vary widely. No‐shows reduce provider productivity and clinic efficiency, increase health care costs, and limit the ability of a clinic to serve its client population by reducing its effective capacity. In this article, we examine the problem of no‐shows and propose appointment overbooking as one means of reducing the negative impact of no‐shows. We find that patient access and provider productivity are significantly improved with overbooking, but that overbooking causes increases in both patient wait times and provider overtime. We develop a new clinic utility function to capture the trade‐offs between these benefits and costs, and we show that the relative values that a clinic assigns to serving additional patients, minimizing patient waiting times, and minimizing clinic overtime will determine whether overbooking is warranted. From the results of a series of simulation experiments, we determine that overbooking provides greater utility when clinics serve larger numbers of patients, no‐show rates are higher, and service variability is lower. Even with highly variable service times, many clinics will achieve positive net results with overbooking. Our analysis provides valuable guidance to clinic administrators about the use of appointment overbooking to improve patient access, provider productivity, and overall clinic performance.
Improving Revenue Management Decision Making for Airlines by Evaluating Analyst‐Adjusted Passenger Demand Forecasts*
Authors: Mukhopadhyay Somnath , Samaddar Subhashish , Colville Glenn
Published: May 2007

To maximize revenue, airline revenue management analysts (RMAs) attempt to protect the right number of seats for late‐booking, high‐revenue‐generating passengers from low‐valued leisure passengers. Simulation results in the past showed that a major airline can generate approximately $500 million per year through efficient RM operations. Accurate passenger demand forecasts are required, because reduced forecast error significantly improves revenue. RMAs often adjust the system forecasts to improve revenue opportunity. Analysis of system forecast performance and analyst adjustment is complex, because one must account for all unseen demands throughout the life of a flight. This article proposes a method to account for unseen demand and evaluate forecast performance (adjusted or unadjusted) through a forecast monitoring system. Initial results from one major airline's origin‐destination market data justify the value of RMA forecasting adjustments.
Why Do Firms Become Widely Held? An Analysis of the Dynamics of Corporate Ownership
Authors: HELWEGE JEAN , PIRINSKY CHRISTO , STULZ RENÉ M.
Published: May 2007

We examine the evolution of insider ownership of IPO firms from 1970 to 2001 to understand how U.S. firms become widely held. A majority of these firms has insider ownership below 20% after 10 years. Stock market performance and liquidity play an extremely important role in ownership dynamics. Firms with stocks that are highly valued, are liquid, and have performed well experience large decreases in insider ownership and become widely held. Ownership also falls for low cash flow and high capital expenditures firms. Surprisingly, variables proxying for agency costs have limited success in explaining the evolution of insider ownership.
Reputation Effects in Trading on the New York Stock Exchange
Authors: BATTALIO ROBERT , ELLUL ANDREW , JENNINGS ROBERT
Published: May 2007

Theory suggests that reputations allow nonanonymous markets to attenuate adverse selection in trading. We identify instances in which New York Stock Exchange (NYSE) stocks experience trading floor relocations. Although specialists follow the stocks to their new locations, most brokers do not. We find a discernable increase in liquidity costs around a stock's relocation that is larger for stocks with higher adverse selection and greater broker turnover. We also find that floor brokers relocating with the stock obtain lower trading costs than brokers not moving and brokers beginning trading post‐move. Our results suggest that reputation plays an important role in the NYSE's liquidity provision process.
Participation Costs and the Sensitivity of Fund Flows to Past Performance
Authors: HUANG JENNIFER , WEI KELSEY D. , YAN HONG
Published: May 2007

We present a simple rational model to highlight the effect of investors' participation costs on the response of mutual fund flows to past fund performance. By incorporating participation costs into a model in which investors learn about managers' ability from past returns, we show that mutual funds with lower participation costs have a higher flow sensitivity to medium performance and a lower flow sensitivity to high performance than their higher‐cost peers. Using various fund characteristics as proxies for the reduction in participation costs, we provide empirical evidence supporting the model's implications for the asymmetric flow‐performance relationship.
Optimal Debt and Equity Values in the Presence of Chapter 7 and Chapter 11
Authors: BROADIE MARK , CHERNOV MIKHAIL , SUNDARESAN SURESH
Published: May 2007

Explicit presence of reorganization in addition to liquidation leads to conflicts of interest between borrowers and lenders. In the first–best outcome, reorganization adds value to both parties via higher debt capacity, lower credit spreads, and improved overall firm value. If control of the ex ante reorganization timing and the ex post decision to liquidate is given to borrowers, most of the benefits are appropriated by borrowers ex post. Lenders can restore the first–best outcome by seizing this control or by the ex post transfer of control rights. Reorganization is more likely and liquidation is less likely relative to the benchmark case with liquidation only.
The Value of Corporate Risk Management
Authors: MACKAY PETER , MOELLER SARA B.
Published: May 2007

We model and estimate the value of corporate risk management. We show how risk management can add value when revenues and costs are nonlinearly related to prices and estimate the model by regressing quarterly firm sales and costs on the second and higher moments of output and input prices. For a sample of 34 oil refiners, we find that hedging concave revenues and leaving concave costs exposed each represent between 2% and 3% of firm value. We validate our approach by regressing Tobin's q on the estimated value and level of risk management and find results consistent with the model.
Mechanism‐Specific Therapy of Ventricular Tachycardia
Authors: KADISH ALAN , MORADY FRED
Published: May 2007

Arrhythmia Mechanisms and Therapy. An understanding of the mechanisms responsible for experimental and clinical arrhythmias has led to the development of mechanism‐specific therapies for ventricular tachycardia. These include: (1) beta blockade for catecholamine‐sensitive ventricular tachycardia; (2) verapamil for ventricular tachycardia possibly due to triggered activity; (3) pacing, isoproterenol and magnesium therapy for torsade de pointes possibly due to early afterdepolarizations; (4) catheter ablation of the right bundle for bundle branch reentry tachycardia; and (5) catheter ablation of the zone of slow conduction for ventricular tachycardia due to reentry. Hopefully, further progress will be made in removing some of the empiricism from antiarrhythmic therapy.
Supraventricular Tachycardia Due to Multiple Atrial Ectopic Foci: A Relatively Common Problem
Authors: GARSON ARTHUR , GILLETTE PAUL C. , MOAK JEFFREY P. , PERRY JAMES C. , OTT DAVID A. , COOLEY DENTON A.
Published: May 2007

Multiple Atrial Ectopic Foci. Atrial ectopic focus is a common mechanism for chronic incessant supraventricular tachycardia in children. The majority of patients require treatment because of symptoms or tachycardia‐induced cardiomyopathy. Management with traditional drugs fails to restore sinus rhythm and surgery has heen thought to be curative. We have had 54 patients with atrial ectopic focus tachycardia; 40 right atrial (36 with normal P waves simulating sinus tachycardia), and 14 left atrial. Surgical treatment of tachycardia was performed in 28 patients; all 28 had a single abnormal P wave axis before surgery, had mapping in the electrophysiology lab, and were thought to have a single focus. However, in 14/28 (50%) after surgical removal of this focus, additional foci became apparent. In 11/14, the next focus appeared during surgery; between 3–15 additional foci were identifled and surgically treated. This resulted in cure in 9/11, but 2/11 despite almost total atrial disconnection, continued to have atrial ectopic focus tachycardia. The other three patients with multiple foci had atrial ectopic focus tachycardia recur with a diflPerent P wave axis from 1 week to 2 months postoperatively. Since the overall initial success rate for multiple foci was different from single foci, patients with multiple foci and single foci were compared to try to predict multiple foci. Patients with multiple foci had: (1) the same incidence of cardiomyopathy (78%); (2) faster maximum atrial rate on Holter (89% of multiple foci had a rate faster than 160/min vs 43% of single foci, (P < 0.05); (3) faster minimum atrial rate on Holter (89% of multiple foci had a minimum rate faster than 70/min vs 0% single foci, (P < 0.05); and (4) different preoperative electrocardiogram (0% multiple foci had left atrial P waves vs 44% of single foci, (P < 0.025). In conclusion: (1) approximately half the patients with atrial ectopic tachycardia had multiple foci; (2) surgical treatment of multiple foci was less successful than single foci, although with improvement in surgical techniques, even multiple foci were successfully eliminated by surgery, and surgery was successful in 100% of the last 10 cases; (3) multiple foci were unlikely with left atrial P waves and slower atrial rates. We speculate that atrial ectopic focus tachycardia may have different etiologies: multiple foci may be due to extensive atrial disease such as that found in primary cardiomyopathy or after myocarditis, whereas single foci may be a developmental aberration. (J Cardiovasc Electrophysiol, Vol. J, pp. 132–138, April 1990)
Nodoventricular Accessory Connections: A Misnomer or a Structural Functional Spectrum
Authors: BENDITT DAVID G. , MILSTEIN SIMÖN , Burchell(1986) —H.B.
Published: May 2007

“The study of preexcitation and associated arrhythmias mirrors the ages‐old fascination with the relation between structure and function. Discoveries pertaining to the mechanisms. may either have their genesis in a study of structure or the observation of function. However, there has always been the compulsion to construct a structural model for any observed function; conversely, given the structure, there is a compulsion to determine the nature, if any, of its function”
Histamine Activates the Chloride Current in Cardiac Ventricular Myocytes
Authors: HARVEY ROBERT D. , HUME JOSEPH R.
Published: May 2007

Histamine Activation of ICl. Exposure of enzymatically dispersed guinea pig ventricular myocytes to histamine evoked a time‐independent background current that was measured using the whole cell patch‐clamp technique. This current was observed when Na+ currents were inactivated by membrane potential, and Ca2+ and K+ currents were blocked by channel antagonists and impermeant ions. Alterations of the CI− gradient caused a shift of the reversal potential of the histamine‐induced current expected for a CI− current. The histamine‐induced CI− current was attenuated by concurrent exposure of cells to acetylcholine, the H2 receptor antagonist cimetidine, and adenosine. In current‐clamp experiments, histamine‐induced changes in the action potential and resting membrane potential were dependent upon the CI− gradient across the membrane. The characteristics of the histamine‐induced CI− current resemble those of the CI− current, ICl elicited by isoproterenol, forskolin, adenosine 3′,5′‐cyclic monophosphate (cAMP), and cAMP‐dependent protein kinase in this preparation. It is concluded that histamine activates a similar CI− conductance in guinea pig ventricular myocytes through a cAMP‐dependent pathway. (J Cardiovasc Electrophysiol, Vol 1, pp. 309–317, 1990)
The Electrical Thresholds of Ventricular Myocardium
Authors: WINFREE A.T.
Published: May 2007

The Electrical Thresholds of Ventricular Myocardium. According to the basic principles of electrophysiology, an action potential cannot propagate three‐dimensionally if its front is too sharply curved. The critical radius of curvature is estimated for ventricular myocardium as 1/3 mm and checked against experimental determinations of the pacing threshold. An implication of the agreement found is that pacemaker electrodes can be improved by optimizing their tip curvatures. The same basic principles imply that there should exist a vortex‐like action potential, which has in fact heen found in both two‐ and three‐dimensional settings. It rotates in 120 msec and has a 2/3‐cm diameter. This diameter can he used to derive the electrical threshold for fibrillation in normal ventricular myocardium: ahout 16 mA, depending on electrode geometry. This compares favorably with ohservations. As theory suggests, the ratio of this threshold to the pacing threshold seems independent of pulse duration and depends on electrode geometry: the minimum ratio is about five for large electrodes. Electrical defihrillation in normal myocardium should require local potential gradients of about 6 V/cm or current densities near 20 mA/cm2, roughly as observed, but much more uniform deHhrillating fields are needed to achieve this theoretical minimum throughout the myocardium. It is suggested that in normal myocardium, the transition from monomorphic tachycardia or ventricular flutter to fibrillation in some cases may be a consequence of the three‐dimensional geometry of vortex‐like action potentials; the transition should take a long time in two‐dimensional preparations unless they are pervaded hy discontinuities or other nonuniformities. (J Cardiovasc Electrophysiol, Vol. 1, pp. 393–410, October 1990)
Propagation Delays Across Cardiac Gap Junctions and their Reflection in Extracellular Potentials: A Simulation Study
Authors: RUDY YORAM , QUAN WEILUN
Published: May 2007

Propagation Delays and Extracellular Potentials. There is increasing evidence that the complex microscopic structure of the myocardium (distribution of cell‐to‐cell connections) plays an important role in determining propagation of excitation in cardiac muscle. To study this phenomenon, extracellular potentials must be measured with microscopic spatial resolution in cardiac tissue. In this article, the relationships between propagation delays across cardiac gap junctions and extracellular potential waveforms are analyzed using a one‐dimensional model of a propagating action potential, for different degrees of cellular coupling. The central question addressed by this study is whether propagation discontinuities at the cellular level can be detected by microscopic resolution extracellular potential measurements, and whether the discrete junctional propagation delay can be measured by extracellular electrodes. Results demonstrate that the discontinuous nature of propagation at the cellular level is reflected as nonuniformities in the local (microscopic) conduction velocity measured by extracellular electrodes with microscopic resolution (interelectrode distance of 50 μm); the degree of nonuniformities in the microscopic velocity is amplified as a result of decreased cellular coupling. These observations are in agreement with recent experimental findings. Propagation time between the middle regions of adjacent cells can be estimated accurately from extracellular potentials at these sites. In contrast, two extracellular electrodes positioned at opposite ends of the gap junction (electrode spacing of 5 μm) cannot detect or measure the propagation delay across the junction. This limitation results from the fact that extracellular potentials do not reflect only the localized underlying electrical sources on such a microscopic scale. As cells become less coupled, irregularities appear in the unipolar extracellular potential waveforms. The simulations relate these irregularities to depolarization of individual cells in the fiber. Under the condition of reduced cellular coupling, the depolarization events of neighboring cells are sufficiently separated in time to appear as separate events in the extracellular waveforms.
Intrinsic Cardiac Neurons
Authors: ARMOUR J. ANDREW
Published: May 2007

Intrinsic Cardiac Neurons. Physiological evidence indicates that afferent neurons, local circuit neurons, as well as efferent sympathetic and efferent parasympathetic neurons, are located in the mammalian intrinsic cardiac nervous system. Complex interneuronal interactions can occur between these neurons, as well as between such neurons and other intrathoracic and central nervous system neurons. A variety of neurochemicals have been proposed to be involved in such interneuronal interactions. Thus the electrophysiologic properties and synaptology of intrinsic cardiac neurons may be more varied than has been appreciated accounting, at least in part, for the variety of neuronal responses that in situ intrinsic cardiac neurons are capable of displaying. The various interactions that occur between intrinsic cardiac neurons and other intrathoracic neurons, as well as between neurons in all intrathoracic ganglia and the central nervous system, will have to be characterized in order to clarify the role of the autonomic nervous system regulating the heart throughout each cardiac cycle.
Prolongation of Ventricular Refractoriness by Defibrillation Shocks May be Due to Additional Depolarization of the Action Potential
Authors: DILLON STEPHEN M. , MEHRA RAHUL
Published: May 2007

Shock‐Induced Refractoriness Prolongation in Canines. Introduction: A comparison of the effects of shock timing and strength on the effective refractory periods (ERPs) of open chest canine hearts to the duration of depolarization in optically recorded action potentials from the rabbit heart was conducted in order to investigate the mechanism of ERP prolongation in the canine.

Methods and Results: Studies were conducted in four open chest canines hearts and three isolated, perfused rabbit hearts. Shocks were applied during ventricular pacing and the strength and timing were varied. The shock voltage gradient was measured at the stimulating site used to assess the ERP in the canine and at the optical recording site in the rabbit. Shock voltage gradients ranged from 7.5 to 53 V/cm in the canine and 2 to 25 V/cm in the rabbit. Shock coupling intervals (CIs) were varied over a range of 15% to 105% of the control ERP (canine) and 10% to 115% of the control action potential duration (APD) (rabbit). Shocks prolonged the ERP in the canine and they caused an additional period of depolarization that prolonged the action potential in the rabbit. ERP and APD prolongation showed similar dependencies on the shock strength and CI: both increased with increasing shock strength and CI.

Conclusion: ERP prolongation in the canine may be due to the same type of responses seen on the optically recorded action potentials in the rabbit. ERP prolongation by low‐strength shocks at long CIs in the canine may be due to graded responses and premature action potentials. ERP prolongation by high‐strength shocks over a range of CIs may be due to the additional depolarization time response that prolongs the action potential in rabbits. (J Cardiovasc Electrophysiol, Vol. 3, pp. 442–456. October 1992)
Activation of Guinea Pig Atrial Muscarinic K+ Channels by Nucleoside Triphosphates in the Absence of Acetylcholine
Authors: HEIDBÜCHEL HEIN , CALLEWAERT GEERT , VEREECKE JOHAN , CARMELIET EDWARD
Published: May 2007

Atrial Muscarinic K+ Channel Activation. Introduction: We studied the possible association of a nucieoside diphosphate kinase (NDPK) to the atrial muscarinic receptor‐G proten‐K+ channel triad and its functional importance in the activation of muscarinic K channels under basal conditions, i.e., in the absence of acetylcholine (ACh).

Methods and Results: We performed cell‐attached and inside‐out patch clamp experiments in single atrial cells isolated from guinea pig hearts. Muscarinic K+ channels in inside‐out patches can be fully activated in the absence of ACh and guanosine triphosphate (GTP), provided that adenosine triphosphate (ATP)‐Mg2 + is present at the intracellular side of the membrane. The K 50 for ATP and Mg2 + are 224 μM and 105 μ respectively. The activation by ATP‐ Mg2+ is the result of a phosphorylating reaction. Other nucleoside triphosphates (NTPs) such as ITP, GTP, UTP, and CTP can substitute for ATP, but their efficiency is lower than that of ATP. The NTP‐dependent activation can be explained by a membrane‐bound NDPK that directly phosphorylates GDP that is bound to the G protein, GK. This NDPK‐catalyzed transsphosphory lation to activate GK is distinct from the classical agonist‐induced GDP‐to‐GTP exchange. The ATP‐dependent activation can be blocked as a result of competition between different intracellular nucleotides for the binding sites on NDPK.

Conclusion: Under physiological conditions and in the absence of ACh, tbe block by G nucleotides and ADP will prevent full activation of the channels by intracellular ATP (present in millimolar concentrations). However, sporadic transphosphorylation of G K‐bound GDP may contribute to tbe basal activity of the channels and hence to the basal K* conductance of atrial cells. (J Cardiovasc Electrophysiol, Vol. 3, pp. 457–473, October 1992)
Implantable Cardioverter Defibrillator:
Authors: FAIN ERIC S. , WINKLE ROGER A.
Published: May 2007

Implantable Cardioverter Defibrillator. The Ventritex® Cadence® Model V‐100 Tiered Therapy Defibrillator is a third generation antitachyarrhythmia device currently completing clinical trials in the United States. The implantable pulse generator is capable of high energy detibrillation, low energy cardioversion, as well as antitachycardia and bradycardia pacing. In addition, this microprocessor controlled device can deliver monophasic or biphasic defibrillation/cardioversion shocks, is noncommitted to deliver shock therapy after initiating charging for defibrillation or cardioversion therapy, and can store electrograms of spontaneous tachyarrhythmia episodes. These expanded device capabilities should improve therapy efficacy and patient management, and represent a major advance in the treatment of patients with ventricular tachyarrhythmias, (J Cardiovasc Electrophysiol, Vol. 4, pp. 211–223, April 1993)
Mechanisms in Simulated Torsade de Pointes
Authors: ABILDSKOV J. A. , LUX ROBERT L.
Published: May 2007

Torsade de Pointes. A mechanism of torsade de pointes consisting of moving sites of reentrant excitation has been proposed on the basis of findings with a computer model. Substantialadditions to that mechanism are now proposed based on further studies with the same model.The model simulated propagation, cycle length‐dependent recovery of excitability, and slowpropagation during incomplete recovery. Regions of relatively short and long recovery wereassigned because of evidence of regional prolongation of recovery in long QT syndromes inwhich torsade dc pointes is frequent. As previously reported, premature excitation in the shortrecovery region initially propagated independently, then entered the long recovery region andreentered the short recovery region distal to the site of origin. Reentrant excitation initiated asimilar series of events, and serial reentry at systematically changing locations resulted inchanging patterns of excitation compatible with the changing QRS waveform in torsade depointes. Episodes terminated when reentrant excitation reached the end of unclosed shortrecovery paths, collided in closed paths, or encountered refractoriness in the presence ofnonuniform short recovery. In this study, it was shown that excitation preceding reentry hadimportant effects on the mechanism. These included reversal of the direction of serial reentry, bidirectional serial reentry, reentry at multiple sites from the same parent conditions, andoccurrence of reentry without the requirement of slow propagation. Evidence for a Dopplershift of cycle lengths in regions from which serial reentry was receding or approaching wasobtained. Sustained serial reentry was also demonstrated and is a possible mechanism for polymorphic ventricular tachycardia. Findings further define a possible mechanism of torsade depointes.
Electrotonic Inhibition and Active Facilitation of Excitability in Ventricular Muscle
Authors: DAVIDENKO JORGE M. , DELMAR MARIO , BEAUMONT JACQUES , MICHAELS DONALD C. , LORENTE PACO , JALIFE JOSÉ
Published: May 2007

Inhibition and Facilitation in Cardiac Muscle. Introduction: The effects of subthreshold electrical pulses on the response to subsequent stimulation have been described previously in experimental animal studies as well as in the human heart. In addition, previous studies in cardiac Purkinje fibers have shown that diastolic excitability may decrease after activity (active inhibition) and, to a lesser extent, following subthreshold responses (electrotonic inhibition). However, such dynamic changes in excitability have not been explored in isolated ventricular muscle, and it is uncertain whether similar phenomena may play any role in the activation pal‐terns associated with propagation abnormalities in the myocardium.

Methods and Results: Experiments were performed in isolated sheep Purkinje fibers and papillary muscles, and in enzymatically dissociated guinea pig ventricular myocytes. In all types of preparations introduction of a conditioning subthreshold pulse between two subthreshold pulses was followed by a transient decay in excitability (electrotonic inhibition). The degree of inhibition was directly related to the amplitude and duration of the conditioning pulse and inversely related to the postconditioning interval. Yet, inhibition could be demonstrated long after (> 1 sec) the end of the conditioning pulse. Electrotonic inhibition was found at all diastolic intervals and did not depend on the presence of a previous action potential. In Purkinje fibers, conditioning action potentials led to active inhibition of subsequent responses. In contrast, in muscle cells, such action potentials had a facilitating effect (active facilitation). Electrotonic inhibition and active facilitation were observed in both sheep ventricular muscle and guinea pig ventricular myocytes. Accordingly, during repetitive stimulation with pulses of barely threshold intensity, we observed: (1) bistability (i.e., with the same stimulating parameters, stimulus: response patterns were either 1:1 or 1:0, depending on previous history), and (2) abrupt transitions between 1:1 and 1:0 (absence of intermediate wenckebach‐like patterns). Simulations utilizing an ionic model of cardiac myocytes support the hypothesis that electrotonic inhibition in well‐polarized ventricular muscle is the result of partial activation of Ik following subthreshold pulses. On the other hand, active facilitation may be the result of an activity‐induced decrease in the conductance of IK1.

Conclusion: Diastolic excitability of well‐polarized ventricular myocardium may be transiently depressed following local responses and transiently enhanced following action potentials. On the other hand, diastolic excitability decreases during quiescence. Active facilitation and electrotonic inhibition may have an important role in determining the dynamics of excitation of the myocardium in the presence of propagation abnormalities.
Characterization of an E4031‐Sensitive Potassium Current in Quiescent AT‐1 Cells
Authors: LIU YANING , TAFFET STEVEN M. , ANUMONWO JUSTUS M.B. , DELMAR MARIO
Published: May 2007

IKr in Quiescent AT‐1 Cells. Introduction; A cardiac culture cell line (AT‐1) recently has been generated from transgenic mice. Initial studies have yielded opposing results as to the nature of the major repolarizing current(s) in these cells. The present study describes the ion selectivity, voltage dependence, and E4031 sensitivity of the major time‐dependent outward current present in AT‐1 cells. In addition, we have determined whether an outward current with the characteristics we observed could be capable of modulating action potential duration in a frequency‐dependent manner (for stimulation cycle lengths between 250 and 1000 msec).

Methods and Results: Action potentials and membrane currents were recorded from nonconffuent cultures of quiescent AT‐1 cells using the “perforated patch” technique. AT‐1 cells showed a round appearance 1 or 2 days after plating. An E4031‐insensitive transient outward current seemed to be absent in these cells. The main time‐dependent outward current was a rapidly activating and rectifying potassium current with properties similar to those of IKr. Most of the potassium current was sensitive to the benzenesulfonamide E4031 (5 μM). The same concentration of E4031 led to a 38% increase in action potential duration. Action potential parameters were independent of the stimulation cycle length within the range of 250 to 1000 msec, thus suggesting that the membrane currents involved in the action potential of AT‐1 cells are completely reset within a diastolic interval of approximately 150 msec.

Conclusion: AT‐1 cells present a unique electrophysiologic phenotype, which is clearly different from that reported for freshly dissociated adult atrial or ventricular myocytes from other species. AT‐1 cells may be a good model to study IKr, since there seems to be minimal contamination by other outward conductances (such as ik). In addition, the feasibility of culturing AT‐1 cells provides us with a system where electrophysiologic experiments on IKr currents could be combined with biochemical or molecular biological studies requiring significant periods of incubation in a cell culture system.
Reversibility of Electrophysiologic Abnormalities of Subendocardial Purkinje Fibers Induced by Ischemia
Authors: REN XIAO‐LI , HOFFMAN BRIAN F.
Published: May 2007

Subendocardial Purkinje Fibers. Introduction: During the subacute phase of infarction in the canine heart, the Subendocardial Purkinje fibers subtended by the infarct show depolarization greater than can be accounted for by the decrease in (K), and generate abnormal action potentials and spontaneous rhythms due to abnormal automaticity. We have used pinacidil to hyperpolarize these fibers and evaluate the extent to which an increase in resting potential can normalize action potential generation.

Methods and Results: Twenty‐four hours after two‐stage ligation of the canine left anterior descending coronary artery, preparations of Subendocardial Purkinje fibers were studied in vitro by recording transmembrane potentials through standard microelectrodes and exposing the preparation to pinacidil and increases in (K+)0. Pinacidil increased resting potential to the estimated value of EK, abolished the abnormal automaticity, and restored action potentials of normal amplitude with normal values of Vmax. This effect often persisted after washout of pinucidil. Elevation of (K+), from 4.0 to 20.0 mM slightly increased maximum diastolic potential, suggesting (hat the excess (over the change in EK) depolarization was caused by a decrease in gKl.

Conclusion: The ventricular arrhythmias seen during the subacute stage of infarction probably are caused by abnormal automaticity. Our findings support the conclusion that this abnormal automaticity arises in partially depolarized suhendocardial Purkinje fibers. This loss of resting potential is due in large part to a decrease in gK1. Restoration of resting potential to the value of Ek permits the Purkinje fibers to develop essentially normal action potentials. An agent capable of reversing the partial block of 1K1, thus might be an effective drug for some types of arrhythmias.
Failure of Impulse Propagation in a Mathematically Simulated Ischemic Border Zone: Influence of Direction of Propagation and Cell‐to‐Cell Electrical Coupling
Authors: MULLER‐BORER BARBARA J. , JOHNSON TIMOTHY A. , GETTES LEONARD S. , CASCIO WAYNE E.
Published: May 2007

Propagation in a Modeled Ischemic Border Zone. Introduction: It is suggested that heterogeneous extracellular potassium concentration, cell‐to‐cell coupling, and geometric nonuniformities of the ischemic border zone contribute to the incidence of unidirectional block and subsequent development of lethal ventricular arrhythmias.

Method and Results: A discrete electrical network was used to model a single cardiac fiber with a [K+]e gradient characteristic of an ischemic border zone. Directional differences in propagation were evaluated by creating discrete regions with increased gap junctional resistance within the [K+]e gradient. Furthermore, the effect of homogeneity/heterogeneity of cell length on impulse propagation through the [K+]e gradient in the presence of increased gap junctional resistance was evaluated. The results indicate that failure of impulse propagation occurs at the junction between partially uncoupled and normally coupled cells. Furthermore, propagation failure was more likely to occur as the impulse propagated from a region of high [K+]e to low [K+]e. Heterogeneity in cell length contributes to the variability in the occurrence of unidirectional and bidirectional block.

Conclusions: The onset of cellular uncoupling in an ischemic border zone may interact with the inherent [K+]e gradient leading to unidirectional conduction block. This mechanism may be important for the generation of reentrant arrhythmias at the ischemic border zone.
Reentry: Insights From Theoretical Simulations in a Fixed Pathway
Authors: RUDY YORAM
Published: May 2007

Reentrant Activity in Cardiac Tissue. This review article summarizes theoretical insights into the principles and mechanisms associated with reentrant activity in cardiac tissue. A mathematical ring model is used in computer simulations to investigate, at the cellular level, mechanistic aspects of initiation, perpetuation, and termination of reentry. Taking advantage of the ability to compute membrane processes in this model, we relate dynamic properties of the reentrant action potential (e.g., beat‐to‐beat alternans) to the underlying kinetics of membrane ionic channels. Effects on reentry of inhomogeneities in refractoriness, excitability, cellular coupling at gap junctions, and fiber cross‐section are also studied.