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

Abstract

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.

• Authors: I Takeyoshi, Y Otani, D Yoshinari, Y Kawashima, S Ohwada, K Matsumoto, Y Morishita
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 19 Issue 2 Pg. 185-92 (Feb 2000) ISSN: 1053-2498 [Print] United States
• PMID: 10703696 (Publication Type: Journal Article)

Chemical References

• Endothelin-1
• Nitric Oxide Donors
• Nitro Compounds
• FK 409
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos2 protein, rat
• Nos3 protein, rat
• Oxygen

Topics

• Animals
• Endothelin-1 (analysis)
• Immunohistochemistry
• Lung (blood supply, pathology)
• Lung Transplantation (pathology)
• Male
• Nitric Oxide Donors (therapeutic use)
• Nitric Oxide Synthase (analysis)
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nitro Compounds (therapeutic use)
• Oxygen (blood)
• Pulmonary Edema (pathology, prevention & control)
• Rats
• Rats, Wistar
• Reperfusion Injury (prevention & control)