Ex Vivo Heart Perfusion Research Articles

A whole blood–based perfusate provides superior preservation of myocardial function during ex vivo heart perfusion

Ex vivo heart perfusion (EVHP) provides the opportunity to resuscitate unused donor organs and facilitates assessments of myocardial function that are required to demonstrate organ viability before transplantation. We sought to evaluate the effect of different oxygen carriers on the preservation of myocardial function during EVHP. Twenty-seven pig hearts were perfused ex vivo in a normothermic beating state for 6 hours and transitioned into working mode for assessments after 1 (T1), 3 (T3), and 5 (T5) hours. Hearts were allocated to 4 groups according to the perfusate composition. Red blood cell concentrate (RBC, n = 6), whole blood (RBC+Plasma, n = 6), an acellular hemoglobin-based oxygen carrier (HBOC, n = 8), or HBOC plus plasma (HBOC+Plasma, n = 7) were added to STEEN Solution (XVIVO Perfusion, Goteborg, Sweden) to achieve a perfusate hemoglobin concentration of 40 g/liter. The perfusate composition affected the preservation of systolic (T5 dP/dtmax: RBC+Plasma = 903 ± 99, RBC = 771 ± 77, HBOC+Plasma = 691 ± 82, HBOC = 563 ± 52 mm Hg/sec; p = 0.047) and diastolic (T5 dP/dtmin: RBC+Plasma = -574 ± 48, RBC = -492 ± 63, HBOC+Plasma = -326 ± 32, HBOC = -268 ± 22 mm Hg/sec; p < 0.001) function, and the development of myocardial edema (weight gain: RBC+Plasma = 6.6 ± 0.9, RBC = 6.6 ± 1.2, HBOC+Plasma = 9.8 ± 1.7, HBOC = 16.3 ± 1.9 g/hour; p < 0.001) during EVHP. RBC+Plasma hearts exhibited less histologic evidence of myocyte damage (injury score: RBC+Plasma = 0.0 ± 0.0, RBC = 0.8 ± 0.3, HBOC+Plasma = 2.6 ± 0.2, HBOC = 1.75 ± 0.4; p < 0.001) and less troponin-I release (troponin-I fold-change T1-T5: RBC+Plasma = 7.0 ± 1.7, RBC = 13.1 ± 1.6, HBOC+Plasma = 20.5 ± 1.1, HBOC = 16.7 ± 5.8; p < 0.001). Oxidative stress was minimized by the addition of plasma to RBC and HBOC hearts (oxidized phosphatidylcholine compound fold-change T1-T5: RBC+Plasma = 1.83 ± 0.20 vs RBC = 2.31 ± 0.20, p < 0.001; HBOC+Plasma = 1.23 ± 0.17 vs HBOC = 2.80 ± 0.28, p < 0.001). A whole blood-based perfusate (RBC+Plasma) minimizes injury and provides superior preservation of myocardial function during EVHP. The beneficial effect of plasma on the preservation of myocardial function requires further investigation.

Assessment of Myocardial Performance During Ex Vivo Heart Perfusion.

Objective: Ex vivo heart perfusion (EVHP) may facilitate resuscitation of non-utilized donor hearts and expand the donor pool. However, a reliable means of demonstrating organ viability prior to transplantation is required. We sought to identify metabolic and functional parameters that correlated with myocardial performance during EVHP. Methods: Six normal pig hearts and 8 donation after circulatory death hearts (238±10 grams) were procured and perfused ex vivo with a donor blood-STEEN solution (hemoglobin concentration of 45 g/L). Myocardial performance was determined by measuring the cardiac output indexed to heart weight (left atrial pressure = 8mmHg, diastolic pressure = 40mmHg). Myocardial function was assessed using a conductance catheter placed in the left ventricle (LV). Metabolic function was assessed by measuring myocardial oxygen consumption (MVO2) and lactate metabolism. Cardiac efficiency was calculated by the ratio of cardiac work and MVO2. Linear regression with stepwise selection analysis was used to determine which parameters best correlated with myocardial performance. Results: The minimum rate of pressure change in the LV (dP/dtmin; R2=0.92) was the best functional correlate of myocardial performance, while the isovolumic relaxation time (Tau; R2=0.78), maximum rate of pressure change (dP/dtmax; R2=0.62), preload recruitable stroke work (PRSW; R2=0.57), cardiac efficiency (R2=0.53), end-diastolic pressure volume relationship (EDPVR; R2=0.23), and end-systolic pressure volume relationship (ESPVR; R2=0.14) correlated to lesser degrees.Myocardial oxygen consumption (R2=0.75) was the best metabolic predictor of myocardial performance, while lactate metabolism failed to demonstrate any correlation (R2=0.004). The combination of the dP/dtmin and MVO2 was the most reliable predictor of myocardial performance (R2=0.94). Conclusions:Measurement of lactate metabolism is an insufficient means of determining organ viability during EVHP, while the combined evaluation of dP/dtmin and MVO2 produced the most reliable assessment of myocardial performance. Further studies are required to determine thresholds of these parameters that predict successful transplantation.

A Donor Whole Blood-Based Perfusate Provides Superior Preservation of Myocardial Function During Ex Vivo Heart Perfusion

Discarded hearts from brain-dead donors and donors after circulatory death may represent unutilized sources of organs for transplantation; however, demonstration of adequate myocardial function prior to transplantation is necessary. Ex vivo heart perfusion (EVHP) provides an opportunity for such functional assessment. The optimal method of oxygen delivery to meet the metabolic demands of a heart in working mode during EVHP has not been established. We sought to determine the impact of different oxygen carriers on the preservation of myocardial function during EVHP.

A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death

Ex vivo heart perfusion (EVHP) has been proposed as a means to facilitate the resuscitation of donor hearts after cardiocirculatory death (DCD) and increase the donor pool. However, the current approach to clinical EVHP may exacerbate myocardial injury and impair function after transplant. Therefore, we sought to determine if a cardioprotective EVHP strategy that eliminates myocardial exposure to hypothermic hyperkalemia cardioplegia and minimizes cold ischemia could facilitate successful DCD heart transplantation. Anesthetized pigs sustained a hypoxic cardiac arrest and a 15-minute warm ischemic standoff period. Strategy 1 hearts (S1, n = 9) underwent initial reperfusion with a cold hyperkalemic cardioplegia, normothermic EVHP, and transplantation after a cold hyperkalemic cardioplegic arrest (current EVHP strategy). Strategy 2 hearts (S2, n = 8) underwent initial reperfusion with a tepid adenosine-lidocaine cardioplegia, normothermic EVHP, and transplantation with continuous myocardial perfusion (cardioprotective EVHP strategy). At completion of EVHP, S2 hearts exhibited less weight gain (9.7 ± 6.7 [S2] vs 21.2 ± 6.7 [S1] g/hour, p = 0.008) and less troponin-I release into the coronary sinus effluent (4.2 ± 1.3 [S2] vs 6.3 ± 1.5 [S1] ng/ml; p = 0.014). Mass spectrometry analysis of oxidized pleural in post-transplant myocardium revealed less oxidative stress in S2 hearts. At 30 minutes after wean from cardiopulmonary bypass, post-transplant systolic (pre-load recruitable stroke work: 33.5 ± 1.3 [S2] vs 19.7 ± 10.9 [S1], p = 0.043) and diastolic (isovolumic relaxation constant: 42.9 ± 6.7 [S2] vs 65.2 ± 21.1 [S1], p = 0.020) function were superior in S2 hearts. In this experimental model of DCD, an EVHP strategy using initial reperfusion with a tepid adenosine-lidocaine cardioplegia and continuous myocardial perfusion minimizes myocardial injury and improves short-term post-transplant function compared with the current EVHP strategy using cold hyperkalemic cardioplegia before organ procurement and transplantation.