Hemodynamic and Functional Analysis of Human DCD Hearts Undergoing Normothermic Ex Vivo Perfusion

Background: Heart donation after cardiac death may represent a new pool of donor organs to be used for transplantation. We conducted a pre-clinical study utilizing human DCD hearts to assess their functional and hemodynamic parameters.

Methods: Five human donors (age range 28–51yrs) underwent heart procurement after circulatory death (DCD, Maastricht III). After cold cardioplegia, normothermic ex vivo perfusion was initiated using the Organ Care System (Transmedics®). Lactate trends were monitored and hemodynamic assessments were performed using a Langendorff balloon placed in the left ventricle. Left ventricular end-diastolic pressure (LVEDP) and systolic left ventricular pressure (sLVP) were recorded. Perfusate for analysis of cardiac enzymes as well as cytokines were collected and analyzed.

Results: Time between withdrawal of life support and declaration of death varied between 17–44 minutes and time between declaration of death and cold cardioplegia ranged between 5–10 minutes. Total median warm ischemic time was 28 (IQR 26–43) minutes. Normothermic perfusion was performed for a median of 338 (IQR 299–367) minutes. Decreasing lactate trends were seen in 2 hearts whereas 3 donor hearts showed increasing lactate trends. Lactate trends correlated with the macroscopic appearance of the myocardium, increasing lactate showing decreased contractility, as well as with the hemodynamic assessment. The most physiologic increase in LVEDP (maximum 16.3 mm Hg), as well as the highest sLVP,(maximum 133.7mmHg) were seen in the donor heart that exhibited decreasing lactate levels, whereas hearts with increasing lactate levels showed an unphysiologic pattern in LVEDP increase and reduced mean sLVP values. After normothermic perfusion, Troponine-I(68.8vs.34.8 ng/l) as well as NT-proBNP(2381.8vs.859.3 pg/ml) showed higher concentrations in the perfusate of hearts with uptrending lactate levels as compared with hearts with downtrending lactate levels. TNF-α(138.2vs.42.2 pg/ml), IL-1β(5 vs 2.4 pg/ml) as well as IL-6(3614.7vs.1391.9 pg/ml) showed higher trends in hearts with an uptrending lactate course as compared with hearts with a downtrending lactate course in the perfusate.

Conclusion: Cardiac markers as well as cytokines in the perfusate of DCD hearts during normothermic perfusion correlate with lactate trends and hemodynamic assessment in human grafts, and may be useful in assessing the overall transplantability of these marginal donor organs.