Standardised in vitro Electrophysiologic Measurements Using Isolated Perfused Porcine Hearts - Assessment of QT Interval Alterations

Abstract

During the last decade there have been many clinical case reports on severe arrhythmias following drug administration. These potentially fatal heart rhythm disturbances are often associated with a QT interval prolongation in the ECG. The aim of the present study was to evaluate, whether isolated hemoperfused porcine hearts from slaughter pigs are suitable to detect a drug effect on the ECG. In the absence of test substances heart rate, QT or QRS interval remained fairly constant during 4 hours of perfusion. In contrast, after application of the positive control sotalol a reproducible, concentration-dependent QT interval prolongation as well as adverse effects such as described in clinical case reports were observed. Lidocaine, which served as a negative control, did not change QT interval duration. As a complex model the isolated hemoperfused porcine heart is a versatile system for monitoring drug effects on heart electrophysiology. Therefore, the model might reduce or even replace certain in vivo dog experiments in heart toxicology and safety pharmacology.