Gennaro M, Mohan C, Ascer E
Division of Vascular Surgery, Maimonides Medical Center, SUNY Health Science Center at Brooklyn 11219, USA.
Cardiovasc Surg. 1996 Jun;4(3):399-404. doi: 10.1016/0967-2109(95)00060-7.
Eicosanoids play an important role in mediating deleterious effects following skeletal muscle ischemia-reperfusion injury. It has previously been shown that oxygenated perfluorocarbon emulsion (O2 Fluosol-DA 20%) decreases the amount of muscle necrosis and neutrophil sequestration when given during the reperfusion phase following skeletal muscle ischemia. As thromboxane is known to alter the endothelial cytoskeleton, thereby favoring diapedesis of neutrophils, the effects of O2 Fluosol-DA 20% on thromboxane release in a canine gracilis muscle model were investigated. The gracilis muscle on one randomly selected side of 14 adult mongrel dogs (body-weight 22-26 kg) was subjected to 6 h of normothermic ischemia followed by 48 h of normothermic reperfusion. The control group (n = 7) underwent ischemia-reperfusion, but without any pharmacological intervention. The Fluosol group (n = 7) were infused with O2 Fluosol-DA 20% (4.3(0.2) ml O2/100 ml) at 12 ml/min for 40 min via the gracilis artery following the ischemic period. Thromboxane B2 levels were measured from blood samples obtained at pre-ischemia, and at 1 h and 48 h of reperfusion. The gracilis muscles were harvested at the end of the experiment and extent of muscle necrosis quantitated by serial transections, nitroblue tetrazolium staining and computed planimetry. The mean(s.e.m.) muscle necrosis in the control group (59(6)%) was significantly higher than in the Fluosol group (22(5)%, P < 0.05, t-test). Thromboxane levels (pg/ml) in the control group at 1 h of reperfusion were significantly higher than the pre-ischemic and 48-h reperfusion levels (7286(1383) versus 1336(592) and 2314(1297), P < 0.05 by ANOVA and Student-Newman-Keuls test). The thromboxane level in the Fluosol group at 1 h reperfusion was significantly lower than the control group (2700(556) and 7286(1383) pg/ml, respectively; P < 0.05, t-test). In contrast, there was no statistically significant difference between thromboxane levels in the Fluosol group at 1 h reperfusion compared with levels at pre-ischemia and 48 h reperfusion (2700(556) versus 1336(592) and 1400(474). Thus, perfluorocarbons are effective in decreasing skeletal muscle necrosis, probably by maintaining the endothelial integrity and preventing vasospasm, secondary to their inhibitory effect on thromboxane release. Perfluorocarbons may also minimize some of the deleterious pulmonary effects known to be caused by increased levels of eicosanoids during reperfusion.
类二十烷酸在介导骨骼肌缺血再灌注损伤后的有害影响中起重要作用。先前的研究表明，在骨骼肌缺血后的再灌注阶段给予含氧全氟碳乳剂（O2 Fluosol - DA 20%）可减少肌肉坏死量和中性粒细胞滞留。由于已知血栓素会改变内皮细胞骨架，从而有利于中性粒细胞的渗出，因此在犬股薄肌模型中研究了O2 Fluosol - DA 20%对血栓素释放的影响。对14只成年杂种犬（体重22 - 26 kg）随机选择的一侧股薄肌进行6小时的常温缺血，然后进行48小时的常温再灌注。对照组（n = 7）进行缺血再灌注，但未进行任何药物干预。氟碳组（n = 7）在缺血期后通过股薄肌动脉以12 ml/分钟的速度输注O2 Fluosol - DA 20%（4.3(0.2) ml O2/100 ml），持续40分钟。在缺血前、再灌注1小时和48小时采集血样，测量血栓素B2水平。实验结束时收获股薄肌，通过连续切片、硝基蓝四氮唑染色和计算机平面测量法定量肌肉坏死程度。对照组的平均（标准误）肌肉坏死率（59(6)%）显著高于氟碳组（22(5)%，P < 0.05，t检验）。对照组再灌注1小时时的血栓素水平（pg/ml）显著高于缺血前和再灌注48小时时的水平（7286(1383) 对 1336(592) 和 2314(1297)，方差分析和Student - Newman - Keuls检验，P < 0.05）。氟碳组再灌注1小时时的血栓素水平显著低于对照组（分别为2700(556) 和 7286(1383) pg/ml；P < 0.05，t检验）。相比之下，氟碳组再灌注1小时时的血栓素水平与缺血前和再灌注48小时时的水平之间无统计学显著差异（2700(556) 对 1336(592) 和 1400(474)）。因此，全氟碳化合物可有效减少骨骼肌坏死，可能是通过维持内皮完整性和预防血管痉挛，这继发于它们对血栓素释放的抑制作用。全氟碳化合物还可能使一些已知由再灌注期间类二十烷酸水平升高引起的有害肺部影响最小化。
