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Updated: May 22, 2026
Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism
Published on: January 12, 2019
Optimal coronary flow rates for preservation of function during normothermic ex situ heart perfusion
Wyeth D Alexander1, Takahiro Nakashima2, Vikramjit Chakrabortty2
1Department of Surgery, University of Michigan, Ann Arbor, Mich; Department of Surgery, University of California, San Diego, San Diego, Calif.
Insights
Optimizing donor heart preservation during normothermic ex situ heart perfusion (NEHP) requires adjusting coronary flow rates. Medium flow (0.75cc/g/min) best preserved heart function and minimized injury compared to high or low flow rates.
Area of Science:
- Cardiology
- Transplantation Medicine
- Organ Preservation
Background:
- Current clinical normothermic ex situ heart perfusion (NEHP) flow rates are approximately 1.5cc/gram of cardiac tissue/min (cc/g/min).
- These rates were established based on lactate trends, which may not be sufficient for optimizing myocardial preservation.
- Optimizing coronary flow is crucial for improving donor heart function post-transplantation.
Purpose of the Study:
- To identify optimal coronary flow rates for donor heart preservation during NEHP.
- To evaluate the efficacy of multiple assays in determining myocardial preservation.
- To compare the effects of different perfusion rates on heart function and injury markers.
Main Methods:
- Porcine donor hearts were maintained in a 24-hour NEHP model.
- Hearts were randomized to high flow (HF) 1.5cc/g/min, medium flow (MF) 0.75cc/g/min, or low flow (LF) 0.25cc/g/min.
- Data included biomarkers, immunohistochemistry, and echocardiography.
Main Results:
- Medium flow (MF) exhibited the least secondary aortic regurgitation and preserved Troponin-I staining.
- High flow (HF) led to increased interventricular septum dimension (IVSd) due to edema and elevated myocardial injury markers (fatty acid binding proteins, sST2).
- Low flow (LF) showed initial increases in von Willebrand factor (vWf), indicating endothelial ischemia, and histopathological signs of autolysis and myofiber degeneration.
Conclusions:
- Coronary flow rates of 0.75cc/g/min during NEHP optimize donor heart function and minimize myocardial injury.
- This optimized flow rate is significantly lower than current clinical practice.
- Reducing coronary flow during NEHP may enhance donor heart preservation and improve outcomes after transplantation.
Objective:
Current clinical normothermic ex situ heart perfusion (NEHP) flow rates, approximately 1.5 cc/g cardiac tissue per minute, are based on lactate level trends. Lactate level alone may not be sufficient for optimizing flow. We sought to identify optimal coronary flow using multiple assays of myocardial preservation.
Methods:
Consecutive porcine donor hearts were maintained in our 24-hour NEHP model. Hearts were randomized to 1 of 3 perfusion rates: high flow (HF) 1.5 cc/g/minute, medium flow (MF) 0.75 cc/g/minute, and low flow (LF) 0.25 cc/g/minute (n = 5 each). Data collection included biomarkers, immunohistochemistry, and echocardiography.
Results:
MF had the least secondary aortic regurgitation (LF 14.0% ± 16.3% vs MF 7.9% ± 3.4% [P < .001] and MF vs HF 14.0% ± 16.3% [P = .023]). HF interventricular septal dimension in diastole increased due to edema (LF 91% ± 8% vs HF 129% ± 11% [P = .024] and MF 84% ± 9% vs HF [P = .013]). HF fatty acid binding proteins and soluble suppression of tumorigenicity-2 levels increased, indicating myocardial injury (LF 0.426 ± 0.13 ng/mL vs HF 1.41 ± 0.70 ng/mL [P = .016], MF 0.021 ± 0.03 ng/mL vs HF [P < .001], and MF 1.06 ± 0.10 ng/mL vs HF 9.53 ± 7.8 ng/mL [P = .013]). Initial LF von Willebrand factor increases indicated endothelial ischemia (LF 11.2 ± 0.9 ng/mL, MF 6.2 ± 1.3 ng/mL, and HF 6.9 ± 0.6 ng/mL; LF vs MF P = .013, LF vs HF P = .026). Histopathology demonstrated autolysis and myofiber degeneration in LF, focal hemorrhage in MF, and extensive hemorrhage, myofiber degeneration, and endothelial damage in HF. Troponin-I immunohistochemistry staining was preserved in MF and markedly diminished in LF and HF.
Conclusions:
NEHP coronary flow rates of 0.75 cc/g/minute optimized donor heart function while minimizing injury. This coronary flow rate is substantially less than current clinical practice. Reducing coronary flow during NEHP may improve donor heart preservation and function following transplantation.
