What is isolated heart perfusion?
- Isolated heart perfusion, commonly using the classical Langendorff preparation, maintains an excised small-animal heart by perfusion outside the body, allowing it to continue beating without neural input.
- Control of perfusate composition, flow rate and temperature allows selected aspects of circulatory conditions to be reproduced for systematic investigation of cardiac function.
The Langendorff method
- Langendorff perfusion is a classical isolated-heart method in which retrograde perfusion through the aorta sustains cardiac beating in the absence of systemic neural and humoral regulation.
- A perfusate such as Krebs-Henseleit buffer is delivered into the aorta at constant pressure or constant flow and passes through the coronary circulation to supply cardiomyocytes with oxygen and nutrients.
- The preparation provides precise control of external conditions, including drug concentration, pH and temperature, and is suitable for short-term observation of cardiac function and assessment of drug effects.
- Common applications include mechanisms of arrhythmia induction, ischemia-reperfusion injury, ion channel regulation, and drug effects on cardiac electrophysiology or mechanical function.
- Compared with in vivo models, the controlled preparation offers experimental stability and reproducibility and facilitates protocol standardization.
Why use an isolated perfused heart?
- Removing systemic metabolism and neurohormonal influences helps isolate the direct effects of a compound on the heart.
- Acute pharmacological responses, dose-response relationships and rhythm changes can be examined for early cardiac toxicity screening and cardiovascular mechanism studies.
- Perfusate can be collected to analyze changes in metabolites and factors released by the myocardium.
Available measurements
- Electrocardiography (ECG): Real-time monitoring of heart rate, rhythm, the QT interval and QRS duration supports evaluation of drug-induced arrhythmic risk.
- Left ventricular pressure: A pressure catheter records left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and positive and negative dP/dt to characterize changes in systolic and diastolic function.
- Drug challenges and interventions such as ion channel blockers can be incorporated for mechanistic validation.
