Effect of atrial natriuretic peptide on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model.
OBJECTIVE
To evaluate the effect of ANP on warm I/R injury in a porcine THVE model.


METHODS
Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 mug/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-alpha. Hepatic tissue blood flow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study. Those results were compared between the two groups.


RESULTS
The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were significantly different between the two groups (60 min: 568.7 +/- 113.3 vs 321.6 +/- 60.1, P = 0.038 < 0.05, 120 min: 673.6 +/- 148.2 vs 281.1 +/- 44.8, P = 0.004 < 0.01). No significant difference was observed in the TNF-alpha levels between the two groups. HTBF was higher in the ANP group, but the difference was not significant. A significantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the control group (0 min: 2.92 +/- 1.1 vs 6.38 +/- 1.1, P = 0.011 < 0.05). Histological tissue damage was milder in the ANP group than in the control group.


CONCLUSIONS
Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8511, Japan.
Katsumi
K
Kobayashi
Kiyohiro
K
Oshima
Masato
M
Muraoka
Takahiko
T
Akao
Osamu
O
Totsuka
Hisashi
H
Shimizu
Hiroaki
H
Sato
Kazumi
K
Tanaka
Kenjiro
K
Konno
Koshi
K
Matsumoto
Izumi
I
Takeyoshi
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D005260:Female; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply*; D008297:Male; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D009320:Atrial Natriuretic Factor; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D048051:p38 Mitogen-Activated Protein Kinases