Inhaled nitric oxide attenuates apoptosis in ischemia-reperfusion injury of the rabbit lung.
BACKGROUND
Lung ischemia-reperfusion injury occurs after lung transplantation and various clinical procedures. Recently, apoptosis was reported to be induced after ischemia-reperfusion. We investigated the effects of inhaled nitric oxide (NO) on lung ischemia-reperfusion and apoptosis after ischemia-reperfusion.


METHODS
As a control group, the left pulmonary hilum of Japanese white rabbits (n = 10) was occluded for 120 minutes and reperfused for 120 minutes. In the inhaled NO group (n = 10), 20 parts per million nitric oxide was inhaled during reperfusion. The sham-operated group was ligated at the right hilum and perfused by the left lung only for 120 minutes. The mean pulmonary arterial pressures and Pao2 were measured during reperfusion. The wet-to-dry weight ratio of the left lower lobe of the lung was calculated. The number of apoptotic cells was estimated using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) technique. The TUNEL staining for a time course study was done using 15 control animals that were killed by exsanguination at 15, 30, and 60 minutes after reperfusion.


RESULTS
After 120 minutes of reperfusion, the mean pulmonary arterial pressures in the control group and in the inhaled NO group were 23.0 +/- 3.2 mm Hg and 13.6 +/- 2.4 mm Hg, respectively (p < 0.01). At the same time point, the Pao2 in the control group and in the inhaled NO group were 46.1 +/- 15.9 mm Hg and 88.1 +/- 14.7 mm Hg, respectively (p < 0.01). The wet-to-dry weight ratios in the control group and in the inhaled NO group were 0.856 +/- 0.024 and 0.808 +/- 0.006, respectively (p < 0.01). Apoptotic cells appeared in the early phase of reperfusion (after 15 minutes' reperfusion). The number of apoptotic cells was significantly lower in the inhaled group than in the control group after 120 minutes' reperfusion (1.76% versus 2.87%, p < 0.01).


CONCLUSIONS
Our results suggest that the inhaled NO prevents lung ischemia-reperfusion injury and attenuates apoptosis after reperfusion in the rabbit lung.
Yamashita
Hideki
H
Department of Translational Medical Sciences, Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
Akamine
Shinji
S
Sumida
Yorihisa
Y
Inoue
Masao
M
Sawada
Takahiro
T
Nagayasu
Takeshi
T
Oka
Tadayuki
T
D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000188:drug therapy*; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D011651:Pulmonary Artery; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy*
D009569:Nitric Oxide