Isolated Heart (Langendorff)

The potential to prolong the QT interval has a major impact on drug development programs. The isolated heart preparation by Langendorff provides rapid, inexpensive, reproducible and sensitive predictions of QT-prolonging potential. Moreover, the Langendorff preparation allows the assessment of the effects of a drug on electrophysiological (ECG, MAP) and mechanical (left ventricular tension, coronary pressure and flow rate) parameters, yielding a variety of safety or toxicity indicators in a single study. Common disease phenotypes are easily reproduced using this complex ex vivo model.

Method

Retrograde heart perfusion (Langendorff) with monitoring of ECGs, left ventricular pressure and Monophasic Action Potential (MAP).

• Number of hearts exposed to the test article: 5 hearts (Screens: 3)
• Number of concentrations of test article tested: 4 or more (Screens: 3)
• The model can be surgically altered to reproduce disease characteristics of interest
• Stimulation : variable frequencies of stimulation or spontaneously beating hearts
• A study includes positive, negative, and vehicle controls

• A simultaneous assessment of cardiac electrophysiological and mechanical parameters
• Dissection and compilation of RR, PR, QRS, QT, QTc, intervals and LVP, dLVP/dt
• Continuous monophasic action potential (MAP), coronary pressure and flow monitoring
• Clinical cardiology interpretation of the ECG signal, describing events and tendencies
• FDA-ready hard copy and e-report for electronic IND submission
• Holistic interpretation of a positive signal, considering all other data generated

Pre-IND (GLP-compliant) or exploratory designs (screen = non-GLP).

Species

Rat, guinea-pig, rabbit, dog hearts