title: 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.
authors.affiliation: Mediport Biotechnik GmbH, D-Berlin, Germany. ast@mediport.net
authors.forename: Inga
authors.initials: I
authors.lastname: Ast
authors.forename: Dagmar
authors.initials: D
authors.lastname: Heydeck
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mothes
authors.forename: Bruno
authors.initials: B
authors.lastname: Christ
mesh_terms: D000818:Animals; D004562:Electrocardiography; D004594:Electrophysiology / Q000379:methods*; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D066298:In Vitro Techniques; D010477:Perfusion; D013552:Swine