If lungs could be retrieved from non-heart-beating donors (NHBDs), the critical shortage of lungs for transplant could be alleviated. However, this strategy is hampered by ischemia-reperfsuion injury (IRI) due to unavoidable warm ischemic time. We used an isolated perfused rat lung model (IPRLM) to measure filtration coefficient (Kfc) as an index of IRI in rat lungs retrieved from NHBDs. We evaluated the effect of inhaled nitric oxide (NO) at reperfusion and during the period of warm ischemia.
48 Sprague-Dawley donor rats were sacrificed, and lungs retrieved immediately or after varying intervals following death (n=6/group). Lungs were ventilated with alveolar gas and reperfused with buffered Earle’s solution in the IPRLM. NO (40ppm) was administered during reperfusion or after death by ventilating the NHBD with 100% O2/40ppm NO combined with post-reperfusion NO administration. Outcome measures were: Kfc, wet-to-dry weight ratio (W/D), pulmonary hemodynamics, and lung tissue levels of adenine nucleotides (by HPLC) and cGMP (by ELISA).
Lungs retrieved immediately after arrest had normal Kfc (@0.3 ml/min/100gm lung weight) and W/D (@5.8). Lungs retrieved 2 hour post-mortem from NHBDs had markedly increased Kfc and W/D. Inhaled NO at reperfusion decreased Kfc and W/D significantly (p<0.01); these were further reduced when NO was administered during warm ischemia. In lungs retrieved 3 hour post-mortem from NHBDs, Kfc was not measurable due to pulmonary edema. However, when NO was administered at reperfusion, Kfc could be measured. Inhaled NO during warm ischemia and at reperfusion decreased Kfc and W/D significantly (p<0.05) compared to lungs given NO at reperfusion alone and ventilated with O2 alone during warm ischemia. NO administration was associated with increased lung cGMP levels.
Inhaled NO at reperfusion attenuates IRI in lungs retrieved from NHBDs. The benefit is enhanced when NO is given during warm ischemia.
Administration of agents to cadavers via the airway may redeuce IRI in lungs from NHBDs.
mean±SEMn=6/groupKfc ml/min/100 gm lung weightW/D2 hours post-mortemControl no vent1.67±0.1710.83±0.402 hours post-mortemNO reperf0.73±0.078.30±0.452 hours post-mortemNO isch-reperf0.52±0.087.021±0.4263 hours post-mortemControl O2 vent1.77±0.219.22±0.693 hours post-mortemNO reperf1.66±0.318.77±0.493 hours post-mortemNO isch-reperf0.87±0.237.25±0.76
S. Takashima, None.