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[High Resolution ECG Methods and Programmed Stimulation]
H. A. Tritthard1, G. Stark, E. Hofer
1Institut für Medizinische Physik und Biophysik der Karl-Franzens-Universität A-Graz.
Abstract:
There are not many "gates to death", but one of the most important is the sudden cardiac death. Therefore the exact knowledge of drug effects on the cardiac function, especially of arhythmogenic side effects are crucial during the development of a new compound. Hitherto expensive catheter experiments in anesthetized animals (dogs, pigs or monkeys) were necessary to evaluate drug effects on the intracardiac electrophysiological activity of all parts of the cardiac conduction system. Only these intracardiac stimulation and recording methods were suitable to measure drug effects on all parameters used in clinical electrophysiology. A suitable method, to replace at least partly these catheter experiments, was developed with a new epicardiac surface and stimulation technique (SST-ECG method: Stark et al, Basic Res. Cardio. 82, 437, 1987; Stark et al, J. Pharmacol. Meth. 21, 195, 1989) which received the prize of the Austrian government for "Alternative Methods to Animal Experiment" in 1988. With this method all parameters used in clinical electrophysiology can be evaluated in one isolated heart preparation and, thus, interactions with anesthetics and of the vegetative nervous system can be excluded. Due to the high resolution of this system, the common ECG-Parameters (PQ-, QT-time and heart rate) and the low amplitude signals (such as early atrial and His-bundle signals) can be detected continuously. Additionally, the refractory periods of all parts of the conduction system can be determined. It is further possible to evaluate hemodynamic parameters such as left ventricular contraction amplitude and coronary flow. A great advantage of the SST-ECG method is the minor scattering of the values measured, due to the elimination of effects of anesthetics and of the vegetative nervous system and the lack of problems with the electrode position. In the future, the evaluation of drug effects on the cardiac electrical activity will further need laboratory animals, but the number of experiments can be significantly reduced and in vivo experiments on anesthetized dogs, pigs or monkeys can mainly be replaced by in vitro experiments using isolated heart preparations of rats or guinea-pigs.
Insights
Sudden cardiac death necessitates understanding drug effects on heart function. A new surface and stimulation technique (SST-ECG) method reduces animal testing by evaluating drug impacts on cardiac electrophysiology in isolated hearts.
Area of Science:
- Cardiology
- Pharmacology
- Animal Alternative Methods
Background:
- Sudden cardiac death is a critical concern, requiring precise knowledge of drug effects on cardiac function.
- Evaluating drug-induced arhythmogenic side effects traditionally involved invasive, expensive catheter experiments in anesthetized animals.
- Existing methods lacked the ability to isolate drug effects from anesthetic and autonomic nervous system influences.
Purpose of the Study:
- To introduce and validate a novel epicardial surface and stimulation technique (SST-ECG) as an alternative to traditional animal experiments.
- To demonstrate the SST-ECG method's capability in evaluating comprehensive cardiac electrophysiological parameters.
- To assess the SST-ECG method's potential in reducing the need for in vivo animal testing in drug development.
Main Methods:
- Development of the SST-ECG method using isolated heart preparations.
- Continuous monitoring of common ECG parameters (PQ, QT, heart rate) and low-amplitude signals (atrial, His-bundle).
- Determination of refractory periods across the cardiac conduction system and evaluation of hemodynamic parameters (left ventricular contraction, coronary flow).
Main Results:
- The SST-ECG method allows evaluation of all clinical electrophysiology parameters in a single isolated heart preparation.
- High-resolution detection of both common and low-amplitude ECG signals.
- Reduced scattering of measured values due to the exclusion of anesthetic and autonomic nervous system effects.
Conclusions:
- The SST-ECG method offers a viable alternative for assessing drug effects on cardiac electrophysiology, minimizing animal use.
- This in vitro technique provides a more controlled environment, excluding confounding factors present in in vivo studies.
- The SST-ECG method significantly reduces the number of laboratory animals needed for drug safety evaluations, replacing many in vivo experiments.