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The mode of death in the non-heart-beating donor has an impact on lung graft quality

^a Laboratory for Experimental Thoracic Surgery, KU Leuven, Leuven, Belgium
^b Laboratory for Pneumology, KU Leuven, Leuven, Belgium
^c Department of Thoracic Surgery, UZ Leuven, Leuven, Belgium

Received 18 February 2009; received in revised form 12 May 2009; accepted 16 May 2009.

^_* Corresponding author. Address: Department of Thoracic Surgery, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Tel.: +32 16 34 68 23; fax: +32 16 34 68 24. (Email: dirk.vanraemdonck{at}uzleuven.be).

Objective: We hypothesised that the agonal phase prior to cardiac death may negatively influence the quality of the pulmonary graft recovered from non-heart-beating donors (NHBDs). Different modes of death were compared in an experimental model. Methods: Non-heparinised pigs were divided into three groups (n = 6 per group). Animals in group I [FIB] were sacrificed by ventricular fibrillation resulting in immediate circulatory arrest. In group II [EXS], animals were exsanguinated (45 ± 11 min). In group III [HYP], hypoxic cardiac arrest (13 ± 3 min) was induced by disconnecting the animal from the ventilator. Blood samples were taken pre-mortem in HYP and EXS for measurement of catecholamine levels. After 1 h of in situ warm ischaemia, unflushed lungs were explanted and stored for 3 h (4 °C). Left lung performance was then tested during 60 min in our ex vivo reperfusion model. Total protein concentration in bronchial lavage fluid was measured at the end of reperfusion. Results: Pre-mortem noradrenalin (mcg l^–1) concentration (baseline: 0.03 ± 0) increased to a higher level in HYP (50 ± 8) vs EXS (15 ± 3); p = 0.0074. PO₂ (mmHg) at 60 min of reperfusion was significantly worse in HYP compared to FIB (445 ± 64 vs 621 ± 25; p < 0.05), but not to EXS (563 ± 51). Pulmonary vascular resistance (dynes s cm^–5) was initially higher in EXS (p < 0.001) and HYP (NS) vs FIB (15824 ± 5052 and 8557 ± 4933 vs 1482 ± 61, respectively) but normalised thereafter. Wet-to-dry weight ratio was higher in HYP compared to FIB (5.2 ± 0.3 vs 4.7 ± 0.2, p = 0.041), but not to EXS (4.9 ± 0.2). Total protein (g l^–1) concentration was higher, although not significant in HYP and EXS vs FIB (18 ± 6 and 13 ± 4 vs 4.5 ± 1.3, respectively). Conclusion: Pre-mortem agonal phase in the NHBD induces a sympathetic storm leading to capillary leak with pulmonary oedema and reduced oxygenation upon reperfusion. Graft quality appears inferior in NHBD lungs when recovered in controlled (HYP) vs uncontrolled (EXS and FIB) setting.

Key Words: Lung transplantation • Non-heart-beating donor • Agonal phase