Table 2.
Vascular and Endothelial Function
| Biomarker | Model | Experimental Design | Biomarker Sampling | Outcome | Biomarker‐Outcome Correlation/Predictive Value | Correlation With Other, Potential Predictive Marker |
|---|---|---|---|---|---|---|
| Coronary vascular resistance 15 | DCD, preclinical (pig) |
Parallel, 2‐arm study, unloaded and loaded MP at 37°C and orthotopic HTx:
|
(A) At 30 min MP (B) At 3 h MP |
RVSWI at 3 h posttransplant (A and B) |
Yes: A and B (ρ=Nve, P<0.05) |
|
| Coronary flow 26 | DBD, preclinical (pig) |
Parallel, 3‐arm study, 3 h brain death period, followed by in situ WIT of:
|
At time of cardioplegic flush | Post‐HTx function (details NR) | Yes (r=NR, P=NR) | NR |
| Energetic index after cardioplegic flush | Yes (R=Pve, P<0.001) | |||||
| Coronary flow 27 | DCD, preclinical (pig) |
Parallel, 5‐arm study with in situ WIT of:
|
At time of cardioplegic flush | LVDP during MP | Yes (R=0.9, P<0.001) | NR |
| Energetic index after cardioplegic flush | Yes (R=0.84, P<0.001) | |||||
| Coronary flow 25 | DCD, preclinical (rat) |
Parallel, 5‐arm study, MP (10 min unloaded+50 min loaded) at 37°C following WIT of:
|
At 3 min MP | CO, DP, LV work, TP at 60 min MP | Yes (ρ=Pve, P<0.001 for all) |
Yes: O2C (ρ=Pve, P<0.001); LDH (ρ=Nve, P<0.001); peroxynitrite (100 kDa; ρ=Nve, P<0.05); WIT (ρ=Nve, P<0.001) |
| dP/dt max at 60 min MP | Yes (ρ=Pve, P<0.05) | |||||
| dP/dt min at 60 min MP | Yes (ρ=Nve, P<0.05) | |||||
| Coronary flow 17 | DCD, preclinical (rat) |
Parallel, 5‐arm study, MP (10 min unloaded+50 min loaded) at 37°C following WIT of:
|
At 10 min MP | CO, dP/dt max, LV work, TP at 60 min MP | Yes (ρ=Pve, P<0.01) | NR |
| dP/dt min at 60 min MP | Yes (ρ=Nve, P<0.01) | |||||
| Coronary flow 18 | DCD, preclinical (rat) |
Parallel, 3‐arm study in hearts subjected to WIT, as described below, followed by 10 min procurement reperfusion, cardioplegic flush, CSS for 3 h 120 min loaded, normothermic MP:
|
(A) At 10 min procurement reperfusion (before CSS) (B) At 10 min loaded, normothermic MP (after CSS) |
CO, DP, dP/dt max, dP/dt min, LV work at 120 min loaded, normothermic MP | Yes: A and B (ρ=NR, P<0.05 for all) | NR |
| HR at 120 min loaded, normothermic MP | Yes: B only (ρ=NR, P<0.05) | |||||
| Coronary flow 19 | DCD, preclinical (rat) |
Parallel, 4‐arm study, MP (20 min unloaded+40 min loaded) at 37°C of hearts subjected to WIT of:
|
At 10 min MP | DP, dP/dt max, LV work, PSP at 60 min MP | Yes (ρ=NR, P<0.05 for all) | NR |
| dP/dt min, CO, HR at 60 min MP | No (P=NS for all) | |||||
| Coronary flow (time to peak) 28 | DCD, preclinical (rat) | Ex vivo WIT of 5–43 min, followed by 40 min MP (n=NR) | During MP | Power output recovery at 10 min MP | Yes (R=−0.86, P=0.005) | NR |
| Edema 25 | DCD, preclinical (rat) |
Parallel, 5‐arm study, 60 min MP in hearts subjected to WIT of:
|
At 60 min MP | CO, DP, LV work, TP at 60 min MP (simultaneous with biomarker) | Yes (ρ=Nve, P<0.05) |
Yes: WIT (ρ=Pve, P<0.05); LDH (ρ=Pve, P<0.05); ‐ peroxynitrite (60 kDa; ρ=Pve, P<0.05) |
| dP/dt min at 60 min MP (simultaneous with biomarker) | Yes (ρ=Pve, P<0.05) | |||||
| dP/dt max at 60 min MP (simultaneous with biomarker) | No (P=NS) | |||||
| Peroxynitrite tissue levels 25 | DCD, preclinical (rat) |
Parallel, 5‐arm study, 60 min MP in hearts subjected to WIT of:
(n=4–6 per group) |
Peroxynitrite (100 kDa) at 60 min MP | CO, LV work at 60 min MP (simultaneous with biomarker) | Yes (ρ=Nve, P<0.05 for both) | Yes: WIT (ρ=Pve, P<0.001); LDH (ρ=Pve, P<0.05); peroxynitrite (75 kDa; ρ=Pve, P<0.05); peroxynitrite (60 kDa; ρ=Pve, P<0.001) |
| DP, dP/dt max, dP/dt min, TP at 60 min MP (simultaneous with biomarker) | No (P=NS) | |||||
| Peroxynitrite (60 kDa) at 60 min MP | DP, LV work at 60 min MP (simultaneous with biomarker) | Yes (ρ=Nve, P<0.05) |
Yes: WIT (ρ=Pve, P<0.05); LDH (ρ=Pve, P<0.05); O2E (ρ=Nve, P<0.05); edema (ρ=Pve, P<0.05); peroxynitrite (100 kDa; ρ=Pve, P<0.001) |
|||
| CO, dP/dt max, dP/dt min, TP at 60 min MP (simultaneous with biomarker) | No (P=NS) | |||||
| Vascular function 25 | DCD, preclinical (rat) |
Parallel, 3‐arm study, 30 min MP in hearts subjected to WIT of:
(n=6 per group) |
Endothelial‐dependent vasodilation (bradykinin,10−8 mol/L) at 30 min MP | Surrogates (DP, dP/dt max, CO, TP at 20 min MP)* | Yes (ρ=Pve, P<0.05 for all) | Yes: WIT (ρ=Nve, P<0.05) |
| Surrogates (dP/dt min at 20 min MP)* | Yes (ρ=Nve, P<0.001) | |||||
| Surrogates (LV work at 20 min MP)* | No (P=NS) | |||||
| Endothelial‐independent vasodilati (3×10−5 mol/L SNP) at 30 min MP | Surrogates (dP/dt min at 20 min MP)* | Yes (ρ=Nve, P<0.05) | Yes: WIT (ρ=Nve, P<0.05) | |||
| Surrogates (CO, DP, dP/dt max, LV work, TP at 20 min MP)* | No (P=NS for all) |
Energetic index calculated as (ATP+0.5×ADP)/(ATP+ADP+AMP). Power output recovery expressed as ratio of reperfusion value/preischemic value for aortic flow rate×afterload pressure. ρ indicates Spearman ρ; CO, cardiac output; CSS, cold static storage; DBD, donation after brain death; DCD, donation after circulatory death; dP/dt max, maximal first derivative of left ventricular pressure; dP/dt min, minimal first derivative of left ventricular pressure; DP, developed pressure; HR, heart rate; HTx, heart transplantation; LDH, lactate dehydrogenase; LV work, left ventricular work (heart rate×DP); LVDP, left ventricular developed pressure; MP, machine perfusion; NR, not reported; NS, not significant; Nve, negative correlation; O2C, oxygen consumption; O2E, oxygen efficiency; PSP, peak systolic pressure; Pve, positive correlation; R, Pearson correlation; RVSWI, right ventricular stroke work index; SNP, sodium nitroprusside; TP, triple product (HR−DP−dP/dt max product); and WIT, warm ischemia time.
Surrogates (measured at 20 minutes MP) as indicators of LV work at 60 minutes MP.