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. 2021 Jan 30;10(4):e018966. doi: 10.1161/JAHA.120.018966

Table 5.

HEP Metabolites

Biomarker Model Experimental Design Biomarker Sampling Outcome Biomarker‐Outcome Correlation/Predictive Value
MRS score (PCr/Pi+pH−7) 36 DBD, clinical Retrospective, parallel, 3‐arm study Graft during static storage (MRS)

Heart allocation to

  1. Successfully transplanted hearts (n=14)

  2. Transplanted hearts with EGF (n=3)

  3. Grafts not suitable for transplantation (n=9)

Supported:

MRS score progressively decreased from group 1 to group 2 and group 3 (differences among groups statistically significant; P=0.0001)
PCr/ATP ratio 37 DBD, clinical Prospective, single‐arm study (n=25) Graft during static storage (MRS) Cardiac index 1 wk after HTx Yes (r=0.45, P=0.02)
ATP 38 DBD, preclinical (pig)

Parallel, 4‐arm study:

  1. 8 h CSS (n=6)

  2. 8 h reperfusion storage (32°C–34°C; n=6)

  3. 8 h CSS followed by orthotopic HTx (n=12)

  4. 8 h reperfusion storage (32°C–34°C) followed by orthotopic HTx (n=12)

 Tissue samples after 8 h storage Myocardial function 2 h after HTx Supported: ↑ ATP in group 2 vs 1 (P<0.05) with ↑ LVSP and cardiac index (P=0.00 for all) and ↑ cardiac output (P=0.001) in group 4 vs 3
ATP 39 DBD, preclinical (dog)

Parallel, 2‐arm study with graft storage conditions, as described below, followed by 1 h unloaded, normothermic MP:

  1. 6 h CSS (n=9)

  2. 6 h reperfusion (25°C for first 30 min, 4°C–6°C for the remaining time; n=9)

 Tissue samples after 6 h storage dP/dt max after 1 h normothermic MP Yes (R=0.41, P=0.049)
ATP after 1 h normothermic MP

Not supported:

unchanged ATP (biomarker) after 6 h storage between groups, but ↑ ATP (outcome; P=0.003) in group 2 vs 1
ATP/Pi and PCr/Pi ratios 40 DBD, preclinical (dog)

Parallel, 4‐arm study:

  1. 24 h CSS (n=6)

  2. 24 h cold reperfusion (n=6)

  3. 24 h CSS followed by HTx (n=6)

  4. 24 h cold reperfusion followed by HTx (n=6)

 Tissue samples after 24 h storage (MRS) Myocardial function after HTx Not supported: ↑ ATP/Pi and PCr/Pi ratios (P<0.05 for both) in group 2 vs 1 with unchanged recovery of CO (P=NR), LVP (P=NS), dP/dt max (P=NR), and dP/dt min (P=NS) in group 4 vs 3
ATP and EC (ATP+0.5×ADP)/(ATP+ADP+AMP) 41 DBD, preclinical (rat)

Parallel, 6‐arm study with graft storage conditions, as described below, followed by 2 h normothermic MP:

Groups 1–4: 200 min CSS (n=10)

Groups 5–6: 200 min cold reperfusion (n=10)

 Tissue samples after storage period Myocardial function after 2 h normothermic MP Not supported: ↑ ATP and EC (biomarkers) in groups 5–6 vs groups 1–4 with unchanged RPP
EC (ATP+0.5×ADP)/(ATP+ADP+AMP), PCr×100/PCr+creatine and AMP/ATP ratio 32 DCD, preclinical (pig)

Parallel, 2‐arm study with 8–44 min WIT, followed by storage conditions described below, and 1 h unloaded, normothermic MP:

  1. 4 h cold CSS (n=8)

  2. 4 h cold reperfusion (n=8)

 Tissue samples after 4 h storage Myocardial function after 1 h normothermic MP

Supported:

↑ EC (P<0.01), PCr×100/PCr+creatine (P<0.05) and ↓ AMP/ATP (P<0.01) with ↑ heart rate (P<0.05), Pmax (P<0.05), dP/dt max (P<0.05), RPP (P<0.01), and contractility index (P<0.05), ↓ dP/dt min (P<0.05) in group 2 (reperfusion) vs 1 (CSS)
EC and AMP/ATP after 1 h normothermic MP Supported: in parallel with biomarker changes (above), ↑ EC and ↓ AMP/ATP as outcomes (P<0.001 for both) in group 2 (reperfusion) vs 1 (CSS)
ATP 42 DCD, preclinical (rat)

Parallel, 7‐arm study (6 relevant arms) with 25 min global, warm ischemia, followed by storage conditions, as described below, and 1 h unloaded, normothermic MP:

Group 1: 4 h CSS (n=14)

Groups 2–6: 1 h reperfusion at 20°C, 25°C, 30°C, 33°C, or 37°C, respectively, and 4 h CCS (n=14)

 Tissue samples after storage period Myocardial function after 1 h normothermic MP Supported: ↑ ATP (P<0.0001 for all) with ↑ heart rate (P<0.0001 for all) and mean dP/dt (P=0.0125 for all) in groups 2–6 vs 1
ATP after 1 h normothermic MP Not supported: in parallel with biomarker changes (above), unchanged ATP (P=NR) as outcome in groups 2–6 vs 1
ATP 43 DCD, preclinical (rat)

Parallel, 3‐arm study (2 relevant arms) with 25 min WIT followed by storage conditions, as described below, and 1 h, unloaded, normothermic MP:

  1. 4 h CSS (n=11)

  2. 1 h normothermic reperfusion and 4 h CSS (n=11)

 Tissue samples after storage period Myocardial function after 1 h normothermic MP

Mixed results Supported: ↑ ATP (biomarker; P<0.05) with ↑ heart rate (P=0.024) and mean dP/dt (P=0.042) in group 2 vs 1

Not supported: in parallel with biomarker changes (above), unchanged contractile index
ATP after 1 h normothermic MP Supported: in parallel with biomarker changes (above) ↑ ATP (outcome; P<0.05) in group 2 vs 1

CO indicates cardiac output; CSS, cold static storage; DBD, donation after brain death; DCD, donation after cardiac death; dP/dt, first derivative of left ventricular pressure; dP/dt max, maximal dP/dt; dP/dt min, minimal dP/dt; EC, energy charge; EGF, early graft failure; HEP, high‐energy phosphate; HTx, heart transplantation; LVP, left ventricular pressure; LVSP, left ventricular systolic pressure; MP, machine perfusion; MRS, magnetic resonance spectroscopy; NR, not reported; NS, not significant; Pmax, maximal developed pressure; PCr, creatine phosphate; Pi, inorganic phosphate; r, correlation coefficent for linear regression; R, Pearson correlation; RPP, rate‐pressure product (heart rate×peak systolic pressure); and WIT, warm ischemia time.