Olprinone, a Phosphodiesterase III Inhibitor, Reduces Gut Mucosal Injury and Portal Endotoxin Level during Acute Hypoxia in Rabbits
Olprinone, a Phosphodiesterase III Inhibitor, Reduces Gut Mucosal Injury and Portal Endotoxin Level during Acute Hypoxia in Rabbits
复制标题
Olprinone 是一种磷酸二酯酶 III 抑制剂，可减少兔子急性缺氧期间的肠道粘膜损伤和门静脉内毒素水平
作者：
T. Satoh;H. Morisaki;K. Ai;Shizuko Kosugi;Michiko Yamamoto;R. Serita;Y. Kotake;J. Takeda
背景 保持肠道完整性已成为避免重症患者细菌移位的治疗目标。作者检查了磷酸二酯酶 III 抑制剂奥普利酮是否可以保护肠粘膜的功能和结构完整性，防止急性进行性缺氧。方法 32只动物在预备手术后随机分为对照组（n = 12）、低剂量组（0.2 µg·kg−1·min−1 olprinone；n = 10）和高剂量组（0.6 µg · kg−1 · min−1 olprinone；n = 10）。在常氧和三个进行性缺氧阶段（吸入氧分数= 0.17、0.13和0.10）测量升主动脉和门静脉血流量、回肠壁内pH值和门静脉内毒素水平。结果 在含氧量正常时，高剂量组的升主动脉流量比对照组和低剂量组高约 20%。在进行性缺氧期间，对照组的升主动脉和门脉血流均受到抑制，而奥普利酮输注减弱了这种变化，并以剂量依赖性方式将血液重新分配到内脏区域。相反，在急性缺氧期间，低剂量组和高剂量组中对照组观察到的回肠壁内pH值降低和门静脉内毒素水平升高均显着最小化，程度相似。奥普立农输注剂量无关地最大程度地减少了对照组中观察到的肠粘膜组织病理学改变，同时动物死亡率也降低了。结论 在急性缺氧情况下，奥普醌通过流量依赖性和非依赖性机制减缓肠粘膜酸中毒和肠道屏障功能障碍的进展，同时保留微观结构。奥普里酮的这种特性可能有助于保护遭受侮辱的宿主。
Background Preservation of gut integrity has become a therapeutic goal to obviate bacterial translocation in the critically ill. The authors examined whether olprinone, a phosphodiesterase III inhibitor, protected functional and structural integrity of gut mucosa against acute progressive hypoxia. Methods Thirty-two animals were randomly allocated to a control group (n = 12), a low-dose group (0.2 &mgr;g · kg−1 · min−1 olprinone; n = 10), or a high-dose group (0.6 &mgr;g · kg−1 · min−1 olprinone; n = 10) after preparatory surgery. Ascending aortic and portal blood flow, intramural pH of the ileum, and portal endotoxin levels were measured at normoxia and through three stages of progressive hypoxia (fraction of inspired oxygen = 0.17, 0.13, and 0.10). Results At normoxia, ascending aortic flow in the high-dose group was approximately 20% higher than in the control and low-dose groups. During progressive hypoxia, both ascending aortic and portal flow in the control group were depressed, whereas olprinone infusion attenuated such alterations and redistributed blood to the splanchnic area in a dose-dependent manner. On the contrary, the reduction of intramural pH of the ileum and the elevation of portal endotoxin levels observed in the control group were significantly minimized in both the low- and high-dose groups to a similar extent during acute hypoxia. Histopathologic alterations of gut mucosa observed in the control group were minimized by olprinone infusion dose-independently, accompanied by reduction of mortality rate of the animals. Conclusions Olprinone slows progression of intestinal mucosal acidosis and gut barrier dysfunction, concurrently with preservation of microscopic structures, through both flow-dependent and -independent mechanisms under acute hypoxia. Such properties of olprinone may serve to protect the host under insult.
影响因子：
8.8
作者：
DEITCH, EA;MORRISON, J;SPECIAN, RD
通讯作者：
SPECIAN, RD
钙和磷脂酶 A2 似乎参与失血性休克引起的粘膜损伤和细菌移位的发病机制。
影响因子：
8.8
作者：
Xu,D;Lu,Q;Deitch,EA
通讯作者：
Deitch,EA
影响因子：
--
作者：
OGAWA, S;KOGA, S;STERN, D
通讯作者：
STERN, D