The Effect of Fk409 on Ischemia-Reperfusion Injury in Canine Lung Transplantation Models

194 Purpose: Nitric oxide (NO) has protective effects on ischemia-reperfusion injury through vasodilatory action, inhibition of leukocyte adherence to the endothelium, and platelet aggregation. The effect of FK409 (FK), which is a spontaneous NO releaser was investigated in canine lung Tx models. Material and Methods: Ten pairs of adult mongrel dogs were divided into two groups. Five pairs were assigned to the FK group, in which FK (5 μg/kg/hr) was administered in the donor from 30 min prior to ischemia until the induction of ischemia, and in the recipient from 15 min prior to reperfusion until 45 min after reperfusion. Five pairs were assigned to the control group. The donor left lung was preserved in a 4C Euro-Collins solution for 8 hr, followed by orthotopic transplantation. A 5-minute clamping test of the right pulmonary artery was performed prior to ischemia and 30 min after reperfusion. Pulmonary arterial pressure (PAP), left pulmonary vascular resistance (L-PVR), arterial O2 pressure (PaO2), and alveolar arterial O2 pressure difference (AaDO2) were measured. The lung specimens were harvested for histological study, and polymorphonuclear neutrophiles (PMNs) were counted. Pulmonary ventilation and perfusion scintigraphy (Xe-133 and Tc-99m-MAA) were performed. Results:(Table)TableHistological findings after 30 min of reperfusion revealed severe alveolar damage with interstitial edema in the control group, while they showed only slight interstitial edema in the FK group. In lung scintigrams, Xe-133 and Tc-99m-MAA were clearly accumulated into the transplanted lungs in the FK group. Conclusion: FK appears to generate a protective effect on ischemia-reperfusion injury in canine lung Tx models.