Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the years to improve both the data quality and the well being of our animal subjects. Of particular interest for us has been the use of telemetry-based data acquisition for conducting studies on cardiovascular (CV) function.

The impact of environmental and biological factors on the resting heart rate of dogs as assessed using 20 years of data from safety pharmacology studies.

Introduction: A safety pharmacology study detects and evaluates potential side effects of a new drug on physiological function at therapeutic levels and above and, in most cases, prior to the initiation of clinical trials. The aim of this study was to investigate the effects of environmental and biological factors on resting heart rate (HR), a representative cardiac parameter in cardiovascular safety pharmacology.

Methods: Over twenty years, 143 dogs (Beagles, Labradors and mongrels) received implanted telemetry transmitters to measure aortic pressure (AP), left ventricular pressure (LVP), Electrocardiogram (ECG) and body temperature.

Multi-layer solar radiative transfer considering the vertical variation of inherent microphysical properties of clouds.

A multi-layer solar radiative transfer (RT) scheme is proposed to deal with the vertical variation of inherent microphysical properties of clouds in this study. The exponential expressions are used to represent the vertical variation of optical properties caused by inhomogeneous microphysical properties. A perturbation method, coupled with the Eddington approximation, is used to solve the RT equation.

A new telemetry-based system for assessing cardiovascular function in group-housed large animals. Taking the 3Rs to a new level with the evaluation of remote measurement via cloud data transmission.

Introduction: A newly developed total implant telemetry system for cardiovascular (CV), electrophysiological and body temperature measurement was evaluated. A cloud-based transmission of the physiological signals allowed an assessment of the quality of the physiological signals despite the physical separation between the instrumented animals and the evaluating home laboratory. The new system is intended to be used for safety pharmacological evaluations of drug candidates in various species.

Evaluation of a method to correct the contractility index LVdP/dt(max) for changes in heart rate.

Introduction: In order to differentiate heart rate (HR)-induced changes from drug-induced positive or negative inotropic effects, HR-dependent effects need to be taken into account. Left ventricular (LV)dP/dt(max), the maximal value of the first derivative of a left ventricular pressure signal, is a convenient index for LV contractile state. The objective of this study was to define the normal relationship between left ventricular LVdP/dt(max) and HR in chronically instrumented, conscious dogs, primates and minipigs in our laboratory and then to use these data as the basis for developing a LVdP/dt(max)-HR-correction formula for each species.

Aerosol size distribution and mass concentration measurements in various cities of Pakistan.

During March and April 2010 aerosol inventories from four large cities in Pakistan were assessed in terms of particle size distributions (N), mass (M) concentrations, and particulate matter (PM) concentrations. These M and PM concentrations were obtained for Karachi, Lahore, Rawalpindi, and Peshawar from N concentrations using a native algorithm based on the Grimm model 1.109 dust monitor.

Heart rate correction models to detect QT interval prolongation in novel pharmaceutical development.

Introduction: The QT interval of the electrocardiogram (ECG) reflects the duration of ventricular depolarization and repolarization. A drug-induced prolongation of ventricular repolarization, and thereby QT prolongation, is recognized to be a marker for an enhanced risk for ventricular arrhythmia. The assessment of a drug's effect on the QT interval has therefore become routine within pharmaceutical research and development.

Validation of the normal, freely moving Göttingen minipig for pharmacological safety testing.

Introduction: The objective of this study was to use a newly established cardiovascular model using freely moving minipigs to document the hemodynamic and electrocardiographic effects of known pharmacological agents. The data generated are to serve as the basis of pharmacological drug safety evaluations using this new model.

Methods: 6 Göttingen minipigs were equipped with a radiotelemetry system (ITS).

Scattering database for spheroidal particles.

We present a database containing light scattering quantities of randomly oriented dielectric spheroidal particles in the resonance region. The database has been generated by using a thoroughly tested T-matrix method implementation. The data possess a defined accuracy so that they can be used as benchmarks for electromagnetic and light scattering computations of spheroids.

Optical properties of internally mixed ammonium sulfate and soot particles--a study of individual aerosol particles and ambient aerosol populations.

Optical parameters of simulated ambient individual ammonium sulfate and soot-mixed particles were calculated using the discrete-dipole approximation method with different model geometries. Knowledge of the mixing state and the approximation by a suited idealized geometry reduces the errors of the optical properties by +/-50% to +/-10%. The influence of the soot content and the mixing state on the optical properties of the total aerosol was estimated.

Evaluation of cardiovascular and ECG parameters in the normal, freely moving Göttingen Minipig.

Introduction: The objective of this study was to evaluate the normal cardiovascular and ECG parameters in freely moving minipigs and to use these data as the basis of pharmacological drug safety evaluation.

Methods: 7 Göttingen Minipigs were equipped with radiotelemetry transmitters (ITS). Aortic pressure (AP), left ventricular pressure (LVP), lead II of the ECG and body temperature were continuously monitored.

The value added by measuring myocardial contractility 'in vivo' in safety pharmacological profiling of drug candidates.

Introduction: The objective of this study was to define the normal LVdP/dt (an index of myocardial contractility)-heart rate relationship in telemetered conscious dogs, primates and mini-pigs in our laboratory and to use these data as the basis for an additional parameter useful in drug safety evaluation.

Methods: Trained dogs, Rhesus monkeys, Cynomolgus monkeys and mini-pigs (Goettinger) were equipped with radiotelemetry transmitters (ITS). Aortic pressure (AP), left ventricular pressure (LVP), a lead II ECG and body temperature could be continuously monitored.

Optimizing the experimental environment for dog telemetry studies.

Introduction: The objective of this study was to test the influence of housing conditions on hemodynamics during cardiovascular general pharmacological studies. Our goal was to optimize both the quality of the data through an optimization of the physiological conditions, as well as to ensure the dog's well-being in general pharmacological studies.

Methods: Two groups of four dogs were equipped with radiotelemetry transmitters and continuously monitored in two different housing models.

Positron Emission Tomography for pretreatment staging and posttreatment evaluation in cancer of the anal canal.

Purpose: In recent years, combined modality therapy (CMT) with chemotherapy and radiation has replaced surgery as the preferred treatment for cancer of the anal canal. Clinical staging with computed tomography (CT) scan alone may underestimate the extent of disease. We investigated the utility of positron emission tomography (PET) with 2-deoxy-2[F-18]fluoro-D-glucose (FDG) in the staging and determination of response to CMT.

Airborne system for fast measurements of upwelling and downwelling spectral actinic flux densities.

An airborne system for fast measurements of spectral actinic flux densities in the wavelength range 305-700 nm is introduced. The system is called the Actinic Flux Density Meter (AFDM). The AFDM utilizes the diode array technique and measures downwelling and upwelling spectral actinic flux densities separately with a time resolution of less than 1 s.

Modeling of the signals of an optical particle counter for real nonspherical particles.

An optical particle counter (OPC) was exposed to atmospheric particles of diameters of 200, 300, and 400 nm. The OPC data were combined with the results of single-particle analysis with a transmission electron microscope (TEM) on samples taken in parallel with the OPC measurements. With a T-matrix-based optical model the measured OPC spectra of scattered light pulses could be approximated with good precision.

A novel propellant-free inhalation drug delivery system for cardiovascular drug safety evaluation in conscious dogs.

Introduction: Estimation of possible cardiovascular side effects belongs to the safety assessment of every drug candidate. This paper describes a new strategy for treating conscious labrador dogs with drugs by inhalation using a specially designed mask and a novel inhaler device.

Methods: Labrador dogs (male or female) were used that had transducers implanted for the measurement of left ventricular and descending aortic blood pressures and an ECG for use together with a telemetry system.

Noncritically phase-matched second-harmonic generation in cesium lithium borate.

Efficient generation of 236-nm light was demonstrated by use of noncritically phase-matched second-harmonic generation in cesium lithium borate. Noncritical phase matching provided approximately 20x the nonlinear drive for second-harmonic generation than beta-barium borate for 236-nm generation. The 236-nm wavelength is the fourth harmonic of a 946-nm Nd:YAG laser.