optimizing langendorff perfusion parameters for enhanced cardiac graft function and durability

通过改良 Langendorff 灌注加强 CVD 研究

The field of cardiovascular research has seen important advancements in the diagnosis and treatment of cardiovascular diseases (CVDs). However, despite the general decrease in incidence and mortality rates, CVDs remain the leading cause of death globally1,2. This alarming fact highlights the need for increased research and scientific advancement, which is undoubtedly dependent on the accuracy and predictability of the available research tools. As a result, there is a constant need for innovation, improvement and/or repurposing of the research toolset. For instance, retrograde or Langendorff heart perfusion, a technique available to the field for over a century, can be easily modified to cover a larger scope of scientific needs and achieve a broader range of applications.
The isolation of the cardiac graft from the rest of the organism during Langendorff perfusion provides an important degree of control over a wide array of experimental parameters, including temperature, circulating solution, coronary perfusion pressures, etc.3,4,5,6,7. The manipulation of these parameters facilitates the simulation of a large number of cardiac scenarios that can be leveraged to further scientific advancements5,8,9,10. Among these parameters, perfusion pressure is likely the most overlooked experimental setting11.
During Langendorff, perfusion pressures exhibit a direct correlation with heart rate, peak systolic/diastolic pressures, and oxygen consumption11. This correlation provides direct and precise control over the amount of work produced by the cardiac grafts, which can be adjusted to meet individual experimental needs. Despite this valuable control capability, the field has historically gravitated towards the use of higher perfusion pressures (60-80 mmHg), subjecting all cardiac grafts to high work demand irrespective of experimental needs8,12,13,14,15. The consequences of this unnecessarily high demand for work arise from the overarching principle that overwork tends to result in premature failure. This seems to be particularly true for cardiac grafts perfused via Langendorff, as the non-physiological nature of this method and the lack of recovery support present in vivo seem to exacerbate graft failure. This premature loss of graft function limits perfusion and experimental times significantly. In effect, in circumstances where longer perfusion times are more relevant to the experimental needs (i.e., drug treatments, immunological response analysis, gene editing, graft preservation, etc.), lower cardiac work can be afforded in exchange for increased graft durability.
This protocol demonstrates the feasibility of utilizing lower perfusion pressures (30-35 mmHg) during Langendorff, as well as the significant effect these pose for cardiac graft function over time when compared to higher perfusion pressures (60-80 mmHg). Furthermore, the findings in this manuscript highlight the importance of prioritizing the customization of the wide array of perfusion parameters to better meet experimental needs.

作者聚焦：推进心血管研究 - 量身定制的 Langendorff 灌注技术以改善实验结果

改良 Langendorff 灌注延长啮齿动物心脏移植物的灌注时间

优化 Langendorff 灌注参数以增强心脏移植物的功能和耐用性 

optimizing-langendorff-perfusion-parameters-for-enhanced-cardiac

Research

JoVE Journal

Bioengineering

Optimizing Langendorff Perfusion Parameters for Enhanced Cardiac Graft Function and Durability

241 次观看. 首先，将蠕动泵的流量设置为 1.0 毫升/分钟。在将它们连接到系统之前，称量分离大鼠的心脏和套管。将套管连接到系统的连接器并启动计时器。一旦心脏收缩，在监测压力的同时以每分钟 0.2 毫升的增量完全增加流量，当达到所需压力或达到每分钟 3.5 毫升的最小流量时，停止增加流量。4 种压力，介于 30 到 35 毫米汞柱之间。将流速设置为每?...

视频: 优化 Langendorff 灌注参数以增强心脏移植物的功能和耐用性 

Modified Langendorff Perfusion for Extended Perfusion Times of Rodent Cardiac Grafts

Despite important advancements in the diagnosis and treatment of cardiovascular diseases (CVDs), the field is in urgent need of increased research and scientific advancement. As a result, innovation, improvement and/or repurposing of the available research toolset can provide improved testbeds for research advancement. Langendorff perfusion is an extremely valuable research technique for the field of CVD research that can be modified to accommodate a wide array of experimental needs. This tailoring can be achieved by personalizing a large number of perfusion parameters, including perfusion pressure, flow, perfusate, temperature, etc. This protocol demonstrates the versatility of Langendorff perfusion and the feasibility of achieving longer perfusion times (4 h) without graft function loss by utilizing lower perfusion pressures (30-35 mmHg). Achieving extended perfusion times without graft damage and/or function loss caused by the technique itself has the potential to eliminate confounding elements from experimental results. In effect, in scientific circumstances where longer perfusion times are relevant to the experimental needs (i.e., drug treatments, immunological response analysis, gene editing, graft preservation, etc.), lower perfusion pressures can be key for scientific success.

This article demonstrates the feasibility of achieving longer perfusion times (4 h) of murine cardiac grafts without function loss by employing lower (30-35 mmHg) than physiological (60-80 mmHg) perfusion pressures during Langendorff.

Despite important advancements in the diagnosis and treatment of cardiovascular diseases (CVDs), the field is in urgent need of increased research and ...