Beneficial effects of novel nitric oxide donor (FK409) on pulmonary ischemia-reperfusion injury in rats.

Takeyoshi I, Otani Y, Yoshinari D, Kawashima Y, Ohwada S, Matsumoto K, Morishita Y

Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.

J Heart Lung Transplant. 2000 Feb;19(2):185-92. doi: 10.1016/s1053-2498(99)00113-8.

BACKGROUND

Nitric oxide (NO) seems to play an important role in tissue injury during reperfusion of the lung. FK409 is the first spontaneous NO donor that increases plasma guanosine 3':5'-cyclic monophosphate. It is reported that FK409 prevented myocardial infarction following occlusion and reperfusion in rat coronary arteries. In this study, we evaluated the effects of FK409 on pulmonary ischemia-reperfusion injury in an in situ warm ischemia model of rats.

METHODS

Animals were divided into 2 groups: the FK409 study group that was administered FK409 (0.4 mg/kg) before reperfusion and the control group, administered a saline vehicle only. Following a thoracotomy, the bronchus, pulmonary artery and vein were separately clamped for 1 hour. Arterial oxygen tension (PaO2), arterial oxygen saturation (SaO2), and endothelin-I (ET-I) were measured after 2 hours of reperfusion. Histologic and immunohistochemical studies were performed; polymorphonuclear neutrophils (PMNs) were counted after 2 hours of reperfusion.

RESULTS

PaO2, SaO2, ET-I after 2 hours of reperfusion and the 7-day survival rate were significantly (p < 0.05) better in the FK409 group than the control group. Histologic damage was reduced in the FK409 group compared with the control group. PMN infiltration was also significantly (p < 0.05) lower in the FK409 group than in the control group.

CONCLUSION

FK409 seems to protect against ischemia-reperfusion injury of the lung. This effect may be related to a homeostatic effect on pulmonary vascular beds and prevention of PMN sequestration.