(490) - Identification of Hypoxic Cells in Lung Grafts for Future Cell Targeted Therapy for Obliterans Bronchiolitis

Abstract

Purpose: Ex vivo heart perfusion (EVHP) has been proposed as a means improving heart preservation and expanding the donor pool. Current clinical EVHP protocols involve preservation in an unloaded and non-working state; however, the impact of this approach on the preservation of donor heart function is unknown. We sought to determine if myocardial load during EVHP impacts the preservation of donor heart function. Methods: Donor porcine hearts were perfused ex vivo in a beating state for 12 hours. Loaded hearts (N= 4) were perfused in a working mode (left atrial pressure= 6 mmHg, heart rate= 100 beats/minute) for the entire EVHP interval. Unloaded hearts (N= 4) were briefly transitioned into a working mode at hours 1 (T1), 5 (T5), and 11 (T11) for metabolic and functional assessments, but were otherwise perfused in a resting mode (left atrial pressure= 0 mmHg). Results: Myocardial function (T11 cardiac index (mL/minute/gram): loaded= 6.9±1.0 vs. unloaded= 2.0±1.2, p= 0.02) and mechanical efficiency (T11: loaded= 11±1 vs. unloaded= 2±1 %, p< 0.01) were better preserved in loaded hearts. Myocardial injury (T11 troponin I (ng/mL): loaded= 11.6±0.4 vs. unloaded= 12.1±0.3, p= 0.39) and edema formation (% weight gain: loaded= 14±8 vs. unloaded= 24±3 %, p= 0.15) did not account for these differences. Free fatty acids were rapidly depleted in both groups; however, triglycerides were continually consumed by loaded hearts and secreted by unloaded heats (Figure 1). Conclusion: EVHP in a loaded state improves the preservation of myocardial function. Uncoupling of fatty acid oxidation may contribute to the decline in myocardial function observed in unloaded hearts; however, further research is required to elucidate the mechanism underlying these observations. These results highlight the need for an EVHP device capable of preserving the donor heart in a physiologic working mode.