If lungs could be transplanted from non-heart-beating donors (NHBDs), the critical shortage of lungs for transplant could be abolished. Using an isolated perfused rat lung model (IPRLM) we demonstrated that reperfusion of NHBD lungs with either 10μM isoproterenol (iso) or with 0.1mg/ml nitroglycerine (NTG) attenuated ischemia-reperfusion injury (IRI). To test the hypothesis that the effects were synergistic (additive) or independent, lungs retrieved from NHBDs were reperfused with both iso and NTG (iso-NTG) in combination.
36 male Sprague-Dawley rats were sacrificed by intrahepatic pentothal injection. Lungs were retrieved immediately after death (control) or following 2 hours of ischemia; NHBDs were ventilated with oxygen (O2-vent) or not ventilated (NV). Lungs were suspended in the IPRLM and reperfused with Earle’s crystalloid solution without or with iso-NTG (n=6/group). Outcome measures were filtration co-efficient (Kfc), wet:dry weight ratio (WD), and tissue levels of cAMP and cGMP (by ELISA).
(see tablen=6/group mean±SEMKfc ml/min/cm H20/ 100 gm lungW/DControlno drug0.22±0.036.06±0.51Controliso-NTG0.27±.015.82±0.472 hr non -ventno drug1.49±0.1210.08±1.422 hr O2-ventno drug1.31±0.2410.11±0.552 hr non-ventiso-NTG0.63±.09*8.42±0.892 hr O2-ventiso-NTG1.24±0.137.8±0.88). All lungs from NHBDs after 2 hours ischemia had significantly higher Kfc than controls. Reperfusion with iso-NTG significantly reduced Kfc in lungs from 2 hour NV NHBDs compared to other 2 hour NHBD lungs but Kfc was surprisingly not reduced in O2-ventilated NHBD lungs reperfused with iso-NTG. Furthermore, while Kfc could be measured in lungs retrieved from NHBDs 3 hrs post-mortem reperfused with NTG alone, lungs retrieved from NHBDs 3 hours post-mortem and reperfused with iso-NTG developed pulmonary edema so Kfc could not be measured. Although there was a trend toward reduced WD in iso-NTG reperfused lungs after 2 hours of ischemia, this was not statistically significant.CONCLUSIONS: Reperfusion of NHBD lungs with iso-NTG did not result in synergistic effects on reduced IRI in lungs retrieved from NHBDs. Contrary to our hypothesis, our results suggest that iso and NTG may act through different and possibly competitive pathways to reduce Kfc in NHBD lungs assessed in the IPRLM.
Strategies at reperfusion may minmize IRI in lungs retrieved from NHBDs.
S.A. Schlidt, None.