Post-ischemic infusion of atrial natriuretic peptide attenuates warm ischemia-reperfusion injury in rat lung.
BACKGROUND
The serious shortage of organs for transplantation, especially lungs, has drawn increasing attention to donation after cardiac death and protection of organs against warm ischemic injury. Atrial natriuretic peptide (ANP) activates guanylate cyclase receptors and increases cyclic guanosine monophosphate (cGMP) levels, which decrease in the lung during ischemia. In this study we investigated the effect on lung ischemia-reperfusion injury of administering synthetic ANP (carperitide) at the onset of reperfusion after warm ischemia.


METHODS
An isolated rat lung perfusion model was used. The rats were allocated into three groups: the control group; the ANP group; and the sham group. In the control and ANP groups, the heart-lung block was exposed to 60 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. At the onset of reperfusion, either saline or ANP was added to the perfusate. In the sham group, lungs were continuously perfused without ischemia and only saline was added to the perfusate.


RESULTS
ANP significantly reduced pulmonary vascular resistance and pulmonary edema, and improved oxygenation. It also significantly increased cGMP levels in reperfused lungs. Histologically, lungs in the ANP group showed significantly fewer signs of injury and fewer cells demonstrated apoptotic changes or single-stranded DNA than lungs in the control group.


CONCLUSIONS
Our results indicate that ANP administered at the onset of reperfusion increases cGMP in lung tissue and attenuates warm ischemia-reperfusion injury in isolated perfused rat lung.
Aoyama
Akihiro
A
Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Chen
Fengshi
F
Fujinaga
Takuji
T
Sato
Atsuyasu
A
Tsuruyama
Tatsuaki
T
Zhang
Jitian
J
Shoji
Tsuyoshi
T
Sakai
Hiroaki
H
Nakamura
Takayuki
T
Date
Hiroshi
H
Wada
Hiromi
H
Bando
Toru
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D023421:Models, Animal; D010477:Perfusion; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D052096:Warm Ischemia / Q000009:adverse effects*
C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP