Inhaled nitric oxide attenuates reperfusion injury in non-heartbeating-donor lung transplantation. Paris-Sud University Lung Transplantation Group.
BACKGROUND
Non-heartbeating-donor (NHBD) lung transplantation could help reduce the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung transplantation.


METHODS
The effect of inhaled NO on PMNs was studied by measuring in vivo PMN lung sequestration (myeloperoxidase activity) and adhesion of recipient circulating PMNs to cultured pulmonary artery endothelial cells (PAECs) in vitro. Pigs were randomly assigned to an NO or a control group (n=9 each). In the NO group, cadavers and recipients were ventilated with oxygen and 30 parts per million of NO. After 3 hr of postmortem in situ warm ischemia and 2 hr of cold ischemia, left allotransplantation was performed. The right pulmonary artery was ligated, and hemodynamic and gas exchange data were recorded hourly for 9 hr. Recipient PMN adherence to tumor necrosis factor-alpha- and calcium ionophore-stimulated PAECs was measured before and after reperfusion, and lung PMN sequestration was determined after death.


RESULTS
NO-treated animals exhibited lowered pulmonary vascular resistance (P<0.01), as well as improved oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAECs was inhibited in the NO group before (P<0.001) and after reperfusion (P<0.0001). Lung PMN sequestration was reduced by NO (P<0.05).


CONCLUSIONS
Inhaled NO attenuates I-R injury after NHBD lung transplantation. This is likely due to the prevention of I-R-induced pulmonary vasoconstriction and to the direct effect on peripheral blood PMN adhesion to endothelium, which results in reduced sequestration and tissue injury.
Bacha
E A
EA
Department of Thoracic and Vascular Surgery, and Heart-Lung Transplantation, Centre Chirurgical Marie-Lannelongue, Paris-Sud University, Le Plessis Robinson, France.
Sellak
H
H
Murakami
S
S
Mazmanian
G M
GM
Détruit
H
H
de Montpreville
V
V
Chapelier
A R
AR
Libert
J M
JM
Dartevelle
P G
PG
Hervé
P
P
D000280:Administration, Inhalation; D000818:Animals; D001998:Bronchopulmonary Sequestration / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000502:physiology; D016040:Lung Transplantation / Q000009:adverse effects* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013552:Swine; D014019:Tissue Donors
D009569:Nitric Oxide; D009195:Peroxidase