Impact of Topical Cooling Solution and Prediction of Pulmonary Graft Viability From Non–heart-beating Donors

Abstract

Functional assessment of the potentially damaged graft from a non-heart-beating donor (NHBD) is mandatory for successful outcome after transplantation. We investigated the impact of the topical cooling solution on graft preservation and whether inflammatory markers in bronchoalveolar lavage (BAL) can predict pulmonary graft viability in a pig ex vivo lung perfusion model. Pigs were euthanized and left untouched for 1 (SAL-1, PER-1) or 3 (SAL-3, PER-3) hours. Topical cooling was done with saline or low-potassium dextran solution (Perfadex) for 1 or 3 hours. In the heart-beating donor control group, the lungs were flushed, explanted and stored for 4 hours. BAL samples were taken from right lungs after explantation and assessed for nitrite, interleukin-8 (IL-8) and protein levels. Left lungs were prepared for ex vivo evaluation. Hemodynamic and oxygenation parameters were measured. Pulmonary vascular resistance (PVR), oxygenation index and Pao(2)/Fio(2) ratio differed significantly between the SAL-3 (42.2 +/- 6.0, 15.9 +/- 3.2 and 148 +/- 14.6 Wood units, respectively) and PER-3 (23.9 +/- 2.7, 6.4 +/- 0.8 and 221.7 +/- 15.06 Wood units, respectively) groups (p < 0.05). BAL IL-8 levels were higher in the SAL-3 group compared with the PER-3 group. BAL nitrite and protein levels were statistically higher in the SAL-3 group (0.98 +/- 0.17 micromol/liter, 728.3 +/- 75.7 microg/ml) than in the PER-3 (0.22 +/- 0.09 micromol/liter, 393.3 +/- 51.1 microg/ml) group (p < 0.05) and correlated with an increase in PVR (r = 0.623, p = 0.001; r = 0.530, p = 0.006, respectively). After 3 hours of warm ischemia topical cooling with Perfadex resulted in better graft function. Nitrite and protein levels in BAL correlated well with PVR and may therefore be used as a non-invasive marker to predict graft function for NHBDs.