A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver
Meguro, M; Katsuramaki, T; Nagayama, M; Kimura, H; Isobe, M; Kimura, Y; Matsuno, T; Nui, A; Hirata, K
| HERO ID | 1656025 |
|---|---|
| In Press | No |
| Year | 2002 |
| Title | A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver |
| Authors | Meguro, M; Katsuramaki, T; Nagayama, M; Kimura, H; Isobe, M; Kimura, Y; Matsuno, T; Nui, A; Hirata, K |
| Journal | Transplantation |
| Volume | 73 |
| Issue | 9 |
| Page Numbers | 1439-1446 |
| Abstract | <strong>BACKGROUND: </strong>Recently, a novel inhibitor of inducible nitric oxide synthase, ONO-1714, was developed. We evaluated the effect of ONO-1714 on a critical warm I/R model of the pig liver.<br /><br /><strong>METHODS: </strong>Pigs were subjected to 180 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in the serum NO2- + NO3- (NOx), the cellular distribution of endothelial and inducible nitric oxide synthase, thrombocyte-thrombi, and nitrotyrosine by immunohistochemistry. The hepatic tissue blood flow (HTBF) was measured continuously using a laser-Doppler blood flowmeter.<br /><br /><strong>RESULTS: </strong>ONO-1714 at 0.05 mg/kg improved the survival rate from 54 (control group) to 100%. The serum NOx levels in the ONO-1714 group were significantly lower than those in the control group at 1, 1.5, 2, 3, and 6 hr after reperfusion. The serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels of the ONO-1714 group were significantly lower than the control group, and the HTBF of the ONO-1714 group was significantly higher than the control group. The formation of thrombocyte-thrombi and nitrotyrosine after reperfusion was significantly lower in the ONO-1714 group.<br /><br /><strong>CONCLUSIONS: </strong>These results indicated that ONO-1714 improved the survival rates and attenuated I/R injury in a critical hepatic warm I/R model of the pig. ONO-1714 will be beneficial for hepatectomy or liver transplantation in the clinical field. |
| Pmid | 12023622 |
| Wosid | WOS:000175933100010 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |