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Updated: Mar 2, 2026
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after
Petra Niederberger1, Emilie Farine1, Maria Arnold1
1Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Insights
Acute high-fat exposure before ischemia significantly impairs heart recovery after circulatory death. This suggests strategies for organ donation after circulatory death (DCD) must consider pre-ischemic fat levels to improve cardiac graft outcomes.
Area of Science:
- Cardiology
- Transplantation Biology
- Metabolic Research
Background:
- Donation after circulatory death (DCD) offers potential for increased cardiac graft availability.
- Optimization strategies for cardiac graft recovery in DCD are needed, considering pre-procurement conditions like high circulatory fat exposure.
Purpose of the Study:
- To investigate the impact of acute high-fat exposure prior to warm, global ischemia on cardiac graft recovery in a rat model.
- To determine if pre-ischemic high-fat diet affects hemodynamic and metabolic recovery post-ischemia in DCD hearts.
Main Methods:
- Isolated rat hearts underwent perfusion with either high-fat (palmitate) or no-fat solution.
- Hearts were subjected to 27 minutes of global warm ischemia.
- Post-ischemic recovery was assessed over 60 minutes of reperfusion, measuring hemodynamic function and metabolic parameters.
Main Results:
- High-fat exposure significantly reduced hemodynamic recovery by 50% compared to no-fat controls.
- Early reperfusion showed reduced glycolysis, glucose oxidation, and pyruvate dehydrogenase activity in high-fat hearts.
- High-fat hearts exhibited significantly greater lactate release during reperfusion.
Conclusions:
- Acute pre-ischemic high-fat exposure impairs cardiac recovery after ischemia in a DCD model.
- Findings suggest rapid restoration of fatty acid oxidation exacerbates ischemia-reperfusion injury.
- Pre-ischemic nutritional status, specifically fat levels, is a critical factor for optimizing cardiac graft recovery in DCD.
Rationale:
Donation after circulatory death (DCD) could improve cardiac graft availability. However, strategies to optimize cardiac graft recovery remain to be established in DCD; these hearts would be expected to be exposed to high levels of circulatory fat immediately prior to the inevitable period of ischemia prior to procurement.
Objective:
We investigated whether acute exposure to high fat prior to warm, global ischemia affects subsequent hemodynamic and metabolic recovery in an isolated rat heart model of DCD.
Methods And Results:
Hearts of male Wistar rats underwent 20min baseline perfusion with glucose (11mM) and either high fat (1.2mM palmitate; HF) or no fat (NF), 27min global ischemia (37°C), and 60min reperfusion with glucose only (n=7-8 per group). Hemodynamic recovery was 50% lower in HF vs. NF hearts (34±30% vs. 78±8% (60min reperfusion value of peak systolic pressure*heart rate as percentage of mean baseline); p<0.01). During early reperfusion, glycolysis (0.3±0.3 vs. 0.7±0.3μmol*min-1*g dry-1, p<0.05), glucose oxidation (0.1±0.03 vs. 0.4±0.2μmol*min-1*g dry-1, p<0.01) and pyruvate dehydrogenase activity (1.8±0.6 vs. 3.6±0.5U*g protein-1, p<0.01) were significantly reduced in HF vs. NF groups, respectively, while lactate release was significantly greater (1.8±0.9 vs. 0.6±0.2μmol*g wet-1*min-1; p<0.05).
Conclusions:
Acute, pre-ischemic exposure to high fat significantly lowers post-ischemic cardiac recovery vs. no fat despite identical reperfusion conditions. These findings support the concept that oxidation of residual fatty acids is rapidly restored upon reperfusion and exacerbates ischemia-reperfusion (IR) injury. Strategies to optimize post-ischemic cardiac recovery should take pre-ischemic fat levels into consideration.
