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Computer simulation of systemic circulation and clot lysis dynamics during thrombolytic therapy that accounts for inner clot transport and reaction.

BACKGROUND: We developed a computer model to predict lysis rates of thrombi for intravenous thrombolytic regimens based on the convective/diffusive penetration of reacting and adsorbing fibrinolytic species from the circulation into the proximal face of a dissolving clot. METHODS AND RESULTS: Solution of a one-compartment plasma model provided the dynamic concentrations of fibrinolytic species that served as inlet conditions for stimulation of the one-dimensional spatiodynamics within a dissolving fibrin clot of defined composition. The model predicted the circulating levels of tissue plasminogen activator (TPA) and plasminogen levels found in clinical trials for various intravenous therapies. To test the model predictions under in vitro conditions, plasma clots were perfused with TPA (0.1 mumol/L) and plasminogen (1.0 mumol/L) delivered at constant permeation velocity of 0.1 or 0.2 mm/min. The model provided an accurate prediction of the measured lysis front movement. For TPA administration regimens used clinically, simulations predicted clot dissolution rates that were consistent with observed reperfusion times. For unidirectional permeation, the continual accumulation of adsorbing species at the moving lysis front due to prior rounds of solubilization and rebinding was predicted to provide for a marked concentration of TPA and plasmin and the eventual depletion of antiplasmin and macroglobulin in an advancing (approximately 0.25 mm thick) lysis zone. CONCLUSIONS: Pressure-driven permeation greatly enhances and is a primary determinant of the overall rate of clot lysis and creates a complex local reaction environment at the plasma/clot interface. With simulation of reaction and transport, it becomes possible to quantitatively link the administration regimen, plasminogena activator properties, and thrombolytic outcome.

Clot Retraction↗

Computer simulation of after-inhibition in crayfish slowly adapting stretch receptor neuron.

A theoretical model is described which is able to mimic the responses of slowly adapting stretch receptor neurons of crayfish to applied currents. Its principal feature is postspike inhibition, in which each nerve impulses produces a small inhibitory current that decays with a simple exponential time-course that is long compared with normal interspike intervals. The model was simulated with both an analogue and a digital computer. Parameters for particular model neurons were determined both by an analysis of experimental data obtained from adaptation to constant injected currents, and by matching computer output to the data. Parameter values estimated by the two techniques agreed within +/-10%. Model parameters determined from adaptation data successfully predicted the magnitude and time-course of posttetanic hyperpolarization (PTH) in the stretch receptor neuron. In addition, model neurons were able to reproduce posttetanic depression (PTD) as seen in stretch receptor cells.

Animals↗

Development of a computer simulation for laboratory planning.

OBJECTIVE: This study presents a description of a laboratory simulation model and how it can be used to aid in making management decisions for meeting laboratory personnel and instrumentation needs to provide the quality of health care desired. DESIGN: Observations were made and data recorded about resources from the appropriate areas in the laboratory. The computer model was developed using a simulation application program. The simulation was then run in three different configurations to obtain data on how changes in the laboratory may affect resource usage. SETTING: A 600-bed hospital laboratory was used as the model to collect initial data. MAIN OUTCOME MEASURES: Measurements were obtained for the effects of three different employee/instrument mixes to determine the effects of instrument utilization, employee workload, and specimen turn around time. RESULTS: The outcomes measured showed varying degrees of resource utilization versus processing times of specimens. CONCLUSION: Simulation can be an effective means of providing information to aid the laboratory manager in making decisions about resource needs in the clinical laboratory.

Chemistry, Clinical↗

Possible mechanism of ECG features in patients with idiopathic ventricular fibrillation studied by heart model and computer simulation.

The possible contribution of localized conduction delay and abnormal action potentials to ventricular fibrillation (VF) was studied by applying an anisotropic cardiac computer model to clinical cases of the Brugada-type electrocardiogram (ECG), which shows right bundle branch block (RBBB), a normal QT interval, ST-segment elevation, and late r' in leads V1 and V2. The anisotropic heart model was composed of 50,000 discrete units with a spatial resolution of 1.5 mm and was mounted in a human torso model. The longitudinal/transverse conduction velocity ratio was 3:1. For the normal ECG, a conduction velocity of 0.75 m/s was required. In the abnormal area of the right anterior epicardial wall, the conduction velocity was set at 0.2 m/s, with decreasing action potential amplitude and 10% prolonged action potential duration. The ECG features of ST-segment elevation and Brugada-type right bundle branch block pattern were simulated. The action potential duration was able to change dynamically with coupling interval of stimulation, with a ratio of 9% for normal ventricular muscle and 50% for Purkinje fibers. Five successive stimuli were applied to the left lateral epicardium 300 ms after the first sinus excitation, and sustained VF was induced with the transmural conduction delay at the right anterior ventricle as a block increasing the vulnerability. At the initiation of VF, reentry circuits were shown around the border zone of the right epicardium and were very heterogeneous around the conduction delayed area and septal area. In an area with the characteristics of nontransmural conduction delay, sustained VF was prevented, and the pattern of transient right bundle branch block appeared on the simulated ECG and body surface potential maps. The late r' wave was calculated in the precordial leads and right anterior site on the body surface potential maps. These results suggest that increased multipolarity in the border zone between the Purkinje fibers and delayed conduction area in the right ventricle might play an important role as a functional block for the persistence of VF.

Action Potentials↗

Computer simulations help determine safe vertical boom speeds for roof bolting in underground coal mines.

PROBLEM: Incident investigation reports do not usually contain enough information to aid in studying boom arm vertical speed for roof bolting machines to determine the impact that appendage speed had on an operator's risk of experiencing a contact. Laboratory experiments with human subjects are also not feasible because of safety and ethical issues. METHOD: Researchers successfully developed a three-dimensional computer model that uses virtual human simulation software as the primary means to gather contact data when the boom arm touches the operator's hand, arm, head, or leg. RESULTS: Data analysis of roof bolter simulations shows that the speed of the boom arm is the most important factor in determining the risk of an operator making contact. Regardless of other variables, contact incidents were always greater when the bolter arm was moving up, greater on the hand, and greater for the boom arm part of the machine. The reason why the subject experiences more contacts when the boom arm is moving up rather than down is that more risky behaviors occur during drilling and bolting when the boom arm is ascending. Based on the data collected, boom speeds greater than 13 in/sec result in a substantial increase in risk to the roof bolter operator of making contact. Speeds less than or equal to 13 in/sec are associated with a more modest relative risk of making contact, which represents a decrease in potential hazard. IMPACT ON INDUSTRY: The use of such information can be quite helpful in making recommendations to machine design and task procedures to reduce the likelihood that roof bolter operators will experience injury due to contact with a moving roof bolting machine's boom arm.

Accidents, Occupational↗

Evolutionary games and computer simulations.

The Prisoner's Dilemma has long been considered the paradigm for studying the emergence of cooperation among selfish individuals. Because of its importance, it has been studied through computer experiments as well as in the laboratory and by analytical means. However, there are important differences between the way a system composed of many interacting elements is simulated by a digital machine and the manner in which it behaves when studied in real experiments. In some instances, these disparities can be marked enough so as to cast doubt on the implications of cellular automata-type simulations for the study of cooperation in social systems. In particular, if such a simulation imposes space-time granularity, then its ability to describe the real world may be compromised. Indeed, we show that the results of digital simulations regarding territoriality and cooperation differ greatly when time is discrete as opposed to continuous.

Animals↗

Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients.

The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering.

Algorithms↗

A computer simulation of the electrophoretic separation and detection of the isozymes of creatine kinase.

A program is described, written in BASIC for the Apple II + Computer, which allows for the simulation of a typical experiment in electrophoresis. The subject of the simulation is the separation and detection of the isozymes of creatine kinase, which are important in the diagnosis of several disorders, including myocardial infarction. The program allows the user to investigate the effects of several variables on electrophoretic mobility and includes simulations of isozyme patterns characteristic of specific pathological conditions.

Animals↗

Computer simulation study on the swelling of a model polymer network by a chainlike solvent.

A molecular-dynamics-particle-transfer method was used to study the swelling of a model polymer network by a short chain solvent. The solvent chains were transferred depending on the difference between the solvent chemical potentials in the coupled simulation boxes, containing pure solvent and gel, respectively. The chemical potentials were computed via the Rosenbluth sampling method. The simulated swelling ratio of the network under subcritical and supercritical conditions is compared with the prediction of a modified Flory-Huggins theory. In addition, the chains exhibit markedly different structural and dynamic properties in the corresponding phases due to the constraint imposed by the network, which are discussed in detail.

Journal Article↗