[High Resolution ECG Methods and Programmed Stimulation]

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.