失血性休克的特征是胃肠微循环紊乱。用硝酸甘油或伊洛前列素局部治疗可改善胃组织氧合,但不能改善局部灌注,可能是由于毛细血管前肾上腺素能神经支配。因此,本研究旨在研究在失血性休克期间,单纯使用拟副交感神经药卡巴胆碱以及联合使用硝酸甘油或伊洛前列素对胃和口腔微循环的局部作用。
■在交叉设计中,将五只雌性猎犬反复随机分为六个实验组。卡巴胆碱,或卡巴胆碱与硝酸甘油或伊洛前列素的组合局部应用于口腔和胃粘膜。盐水,硝化甘油,或单独应用伊洛前列素作为对照组。然后,休克1h后,动脉抽血后再输血可引起固定体积出血。使用反射分光光度法和激光多普勒血流仪测定胃和口腔微循环。用视频显微镜观察口腔微循环。统计学:用于重复测量和Bonferroni事后分析的双向ANOVA(平均值±SEM;p<0.05)。
■诱导出血导致胃和口腔组织氧合降低,通过在胃粘膜上局部应用卡巴胆碱和硝酸甘油可以改善这种情况。仅使用局部伊洛前列素并不能改善胃组织的氧合,但可以通过局部卡巴胆碱治疗来补充。向硝酸甘油中添加卡巴胆碱不会进一步增加胃组织的氧合。所有实验组的胃微血管血流量保持不变。口腔微血管血流量,休克期间微血管血流指数和总血管密度降低。局部卡巴胆碱供应改善了休克期间的口腔血管密度和出血后期的口腔微血管血流指数。
■通过局部卡巴胆碱治疗改变自主平衡对微循环变量的具体影响在胃肠道各部分之间有所不同。与我们的期望相反,通过局部应用卡巴胆碱或硝酸甘油改善胃组织氧合与增加微血管灌注无关.当卡巴胆碱与局部血管扩张剂联合使用时,对胃组织氧合的额外影响取决于特定的药物组合。因此,组织耗氧量的调制,应研究线粒体功能或局部血流分布的改变.
Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic
carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock.
In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups.
Carbachol, or
carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05).
The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding
carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local
carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage.
The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When
carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.