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Updated: May 12, 2025
Author Spotlight: Advancing Cardiovascular Research — Tailored Langendorff Perfusion Techniques for Improved Experimental Outcomes
Published on: June 14, 2024
Enhancing outcomes in Langendorff-perfused rodent hearts through perfusion parameter optimization
Maya Bolger-Chen1, Manuela Lopera Higuita1, Casie A Pendexter1
1Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Children's Boston, Boston, MA, USA.
Insights
Ex vivo heart perfusion offers a biologically accurate model for cardiovascular research. Optimizing perfusion pressure and perfusate choice is crucial for experimental success and understanding heart function.
Area of Science:
- Cardiovascular Physiology
- Translational Research Models
Background:
- Cardiovascular diseases (CVDs) show a concerning lack of progress, with increasing mortality in certain groups due to aging and obesity.
- Current research models like cell lines lack biological accuracy, while animal models present excessive complexity.
- Ex vivo perfusion of isolated rodent hearts offers a balance, providing biological accuracy with reduced complexity.
Purpose of the Study:
- To demonstrate the versatility of ex vivo heart perfusion protocols for diverse experimental needs.
- To evaluate the impact of varying perfusion parameters on isolated heart function and homeostasis.
- To assess the efficacy of different perfusate compositions and pressures in maintaining cardiac health.
Main Methods:
- Utilizing ex vivo perfusion of isolated rodent hearts.
- Manipulating perfusion parameters including perfusate composition, flow rate, and coronary pressures.
- Assessing cardiac function through left ventricular (LV) pressures and evaluating organ damage and inflammation.
Main Results:
- Physiological perfusion pressures increased LV pressures but led to functional decline, suitable for organ assessment.
- Lower perfusion pressures maintained function over longer periods, ideal for extended experiments.
- Adenosine reduced edema and inflammation, while packed red blood cells induced inflammation and damage, especially at low pressures.
Conclusions:
- Ex vivo heart perfusion is a valuable tool for studying direct cardiac responses to stimuli.
- Perfusion pressure selection should be tailored to experimental duration and objectives.
- Perfusate choice significantly impacts cardiac outcomes, with adenosine showing protective effects and red blood cells causing adverse effects.
Abstract:
Despite important advancements in addressing cardiovascular diseases (CVDs), there has been an overall lack of progress in the field, leading to a slower decline in the rate of CVDs related deaths, and even an increase for some risk groups (e.g. increase in stroke mortality) exacerbated by an aging and obese population. While a multi-faceted problem, this deceleration may be influenced by the preferred model systems utilized in translation research. Cardiac cell lines, although easier to handle, lack biological accuracy due to the unnatural modifications required for successful culture and may not recapitulate complex 3-dimensional structural and environmental factors. At the same time, whole animal experimentation provides unwanted complexity during initial scientific development. Alternatively, ex vivo perfusion of isolated rodent hearts provides the needed biological accuracy with decreased organismal complexity. This platform facilitates the evaluation of the isolated heart, without neuro-reflexes and/or humoral contributions, unveiling the direct effects of stimuli in heart function/homeostasis. This manuscript leverages the wide array of perfusion parameters (i.e. perfusate, flow rate, coronary pressures), to demonstrate the capability of ex vivo heart perfusion protocols to accommodate a large range of experimental needs. Through this work, it was determined that the use of physiological perfusion pressures leads to increased left ventricular (LV) pressures but results in a loss of function over time, making it ideal conditions for organ assessment. Conversely, lower-than-physiological perfusion pressures lead to decreased LV pressures but prevent loss of function over time, which is preferable when longer perfusion times are relevant to experimental needs. Similarly, the use of adenosine as a pharmacological intervention was found to decrease both edema formation and inflammatory responses. In contrast, the use of packed red blood cells as oxygen carriers appears to induce a pro-inflammatory response and cause greater cardiac damage, particularly when combined with low perfusion pressures.
