Optimal coronary flow rates for preservation of function during normothermic ex situ heart perfusion.

Alexander, Wyeth D; Nakashima, Takahiro; Chakrabortty, Vikramjit; Urrea, Kristopher A; King, Sarah D; Raza, S Sikandar; Daman, Martin G; Ling, Carol et al. · J Thorac Cardiovasc Surg · 2026

basic_science · Level V

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Abstract

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. 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. 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. 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.