Inhaled nitric oxide reduces ischemia-reperfusion injury in rat lungs from non-heart-beating donors.
OBJECTIVE
If lungs could be retrieved from non-heart-beating donors, the critical shortage of lungs for transplantation could be alleviated. However, lungs subjected to warm ischemia develop edema when reperfused. We hypothesized that ventilation of rat lungs from non-heart-beating donors with nitric oxide during the period of warm ischemia alone, with reperfusion, or both might reduce ischemia-reperfusion injury.


METHODS
An isolated perfused rat lung model measured the filtration coefficient and accumulation of lung water by the wet/dry weight ratio. Donor rats were euthanized, and then lungs were retrieved immediately after death or 2 or 3 hours postmortem. Lungs retrieved postmortem were either not ventilated or ventilated with 100% oxygen alone or 40 ppm nitric oxide in oxygen. In the circuit, lungs were ventilated with alveolar gas with or without 40 ppm nitric oxide.


RESULTS
Nitric oxide administration to the non-heart-beating donor or in the perfusion circuit reduced filtration coefficient and wet/dry weight ratio. Lungs retrieved 2 hours postmortem ventilated with nitric oxide or treated with nitric oxide on reperfusion had filtration coefficients and wet/dry weight ratios similar to those of lungs retrieved immediately after death. Nitric oxide was most beneficial when administered both during warm ischemia and at reperfusion in lungs retrieved 3 hours postmortem. Nitric oxide administration in the circuit was associated with increased lung levels of lung cyclic guanosine monophosphate, determined by enzyme-linked immunosorbent assay.


CONCLUSIONS
Administration of nitric oxide to non-heart-beating donors during warm ischemia and with reperfusion might facilitate transplantation of lungs from non-heart-beating donors by reducing ischemia-reperfusion injury and capillary leak.
Takashima
Seiki
S
Department of Cancer and Thoracic Surgery (Surgery II), Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Koukoulis
Giovanna
G
Inokawa
Hidetoshi
H
Sevala
Mayura
M
Egan
Thomas M
TM
D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D016040:Lung Transplantation; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D014655:Vascular Resistance / Q000187:drug effects
D000227:Adenine Nucleotides; D009569:Nitric Oxide; D006152:Cyclic GMP