Arrhytmias & cardiac toxicity

CARDIOVASCULAR SYSTEM

Porsolt has an extensive portfolio of cardiovascular procedures, ranging from standard cardiovascular telemetry studies for safety evaluation, to pathophysiological models for specific therapeutic areas. Porsolt also possesses considerable expertise with in vitro models, providing clients with a comprehensive assessment of all aspects of cardiovascular function.

Arrhytmias & cardiac toxicity

Torsades de Pointes Carlsson Model in the anesthetized rabbit

Ventricular extrasystole (VES): 1 to 4 consecutive ventricular premature beats

• Ventricular tachycardia (VT): five or more consecutive ventricular premature beats with regular amplitude

• Torsade ventricular tachycardia (TVT): Polymorphic VT

• Torsade de pointes (TdP): polymorphic VT where clear twisting of QRS complexes around the isoelectric line is seen in at least one ECG lead and QT interval is prolonged.

• Ventricular Fibrillation (VF)

• Atrio Ventricular Block (AV Block)

ECG Events

Females are more sensitive than males to arrhythmia occurrence (clofilium 100 nmol/kg/min)

Model is more sensitive with higher doses over shorter infusion time (clofilium)

Clofilium, sotalol and terfenadine consistency with previous induced arrhythmias (+/- TdP) with concomitant QTc interval prolongation