The Langendorff perfusion technique is a foundational method in cardiac research that allows scientists to study the heart outside of a living organism (ex vivo). This preparation involves surgically isolating a mammalian heart and maintaining its function by providing a continuous supply of oxygen and nutrients. Developed in the late 19th century, this model provides a stable, controlled environment to observe the heart’s physiology without the complicating factors of the nervous system or circulating hormones found in the whole body. The technique allows researchers to precisely control the heart’s environment, enabling fundamental discoveries about myocardial function.
The Core Principle of Retrograde Perfusion
The Langendorff technique centers on “retrograde perfusion,” a flow direction opposite to the heart’s natural circulation. When the heart is isolated, the aorta is cannulated and connected to the perfusion apparatus. The nutrient-rich solution is pumped into the aorta, and the pressure forces the aortic valves to close, preventing the fluid from entering the left ventricle.
Instead, the solution is shunted into the coronary ostia—the openings of the coronary arteries located just above the aortic valve—which then perfuse the heart muscle. This reverse flow ensures the cardiac muscle cells receive oxygen and energy substrates. The perfusion fluid drains from the coronary veins into the right atrium and then exits the heart through the severed pulmonary artery. This configuration maintains the heart’s viability and automatic beating while eliminating the mechanical work of pumping blood, making it a “non-working” preparation.
The Essential Experimental Setup
Maintaining the isolated heart requires a specialized apparatus to precisely control the perfusion environment. The heart is mounted on an aortic cannula connected to a perfusate reservoir. This reservoir is positioned above the heart to create a constant hydrostatic pressure, typically 60 to 100 mmHg, which drives fluid flow through the coronary arteries.
Temperature control is achieved through water-jacketed components, where warm water circulates to maintain the perfusate and the heart chamber at a physiological temperature, usually 37°C. A pressure transducer monitors the perfusion pressure. Contractile force can be recorded using a fluid-filled balloon inserted into the left ventricle.
The perfusate is commonly a modified Krebs-Henseleit buffer solution, an artificial plasma substitute. This buffer contains a carefully balanced mixture of salts, including sodium chloride, potassium chloride, and calcium chloride, necessary to maintain the correct ion concentration and a physiological pH of 7.4. The solution also contains glucose as a primary energy substrate and is continuously oxygenated with a gas mixture of 95% oxygen and 5% carbon dioxide. This composition mimics the nutritional and electrolytic environment of blood plasma, allowing the heart to continue beating for several hours.
Key Applications in Cardiac Research
The Langendorff model provides a stable, interference-free environment, making it suitable for several forms of cardiac investigation.
Pharmacology and Drug Testing
A primary application is in pharmacology and drug testing. Researchers introduce new compounds directly into the perfusate and immediately observe their effects on heart rate, contractility, and electrical activity. By eliminating the influence of systemic factors, such as hormonal or nervous system responses, scientists can determine the drug’s direct action on the heart muscle.
Ischemia and Reperfusion Injury
The technique is extensively used to model ischemia and reperfusion injury, which occurs when blood flow is blocked and then restored. Researchers easily induce ischemia by temporarily stopping the flow of oxygenated perfusate and then restarting it to simulate reperfusion. This controlled injury allows for the study of cellular damage mechanisms and the testing of protective therapies, such as preconditioning strategies.
Metabolic Studies
The setup is valuable for metabolic studies, enabling the precise analysis of how the heart uses different energy sources. By modifying the perfusate composition to include or exclude specific substrates like fatty acids or lactate alongside glucose, researchers can investigate the heart’s fuel preference. This controlled environment is relevant for understanding cardiac conditions like diabetic cardiomyopathy, where substrate utilization is altered.
Bridging the Gap to In Vivo Conditions
Despite its advantages in control and simplicity, the Langendorff heart has a limitation: it is a non-working heart that performs no mechanical output, only contracting isovolumetrically or unloaded. In the body (in vivo), the heart performs pressure-volume work, pumping blood against resistance, which determines its energy consumption and overall function. The absence of this mechanical load means the standard Langendorff model cannot fully reflect the heart’s natural physiological state.
To address this, the “Working Heart Model,” also known as the Neely model, was developed in the 1960s to allow the heart to perform pressure-volume work. This adaptation involves cannulating both the aorta and the left atrium. This enables the perfusate to enter the left atrium, fill the ventricle, and be ejected through the aorta in the correct physiological direction. By allowing the heart to pump against a controlled afterload pressure, the Working Heart Model provides a more physiologically relevant setting to measure parameters like cardiac output and stroke volume.