Mechanisms of organ failure and abnormal oxygen metabolism during sepsis

本研究基于我们以前的发现，在兔IL-1β诱导的感染性休克模型(休克14：193-9,2000)中，在非供应的DO2范围内，出现了全身耗氧量(VO2)对全身氧输送(DO2)的异常依赖。在本系列研究中，我们确定了在脓毒症过程中导致氧代谢异常发展的器官。静脉注射1 mg/kg复制高动力性脓毒症时的血流动力学。给兔注射脂多糖。用动脉导管、Swan-Ganz导管和放置在肠系膜上静脉(SMV)上的超声探头对每只动物进行侵入性监测。此外，采用表面多普勒扫描法监测回肠粘膜血流。动物在注射脂多糖后90分钟出现低血压和代谢性酸中毒，心输出量持续或略有增加。这种血管舒张性休克在注射内毒素后持续240分钟。SMV血流量较基线值增加约50%。反之，回肠粘膜血流量在内毒素后120min较基础值下降约67%，到240min逐渐恢复至基线值。无论在一段时间内，回肠粘膜血流量的相对离散度均显著增加，以此来评价血流的不均一性。这些结果表明，肠道组织在血液动力学和氧代谢的全身性异常的发展中起着重要作用。

This study was based on our previous findings that abnormal dependency of systemic oxygen consumption (VO_2) on systemic oxygen delivery (DO_2) occurred during the supply-independent range of DO_2 in a rabbit IL-1β-induced septic shock model (SHOCK 14:193-9,2000). In the present series of study, we identified the organ responsible for the development of the abnormal oxygen metabolism during sepsis. Hemodynamics during hyperdynamic sepsis was reproduced by 1 mg/kg i.v. administration of lipopolysaccharide (LPS) to rabbits. Each animal was monitored invasively with an arterial catheter, a Swan-Ganz catheter, and an ultrasonic probe placed on the superior mesenteric vein (SMV). In addition, mucosal blood flow of the ileum was monitored by the surface Doppler scan method. The animals developed hypotension with metabolic acidosis by 90 min after the administration of LPS in the presence of the consistent or somewhat increased cardiac output. This vasomotor shock persisted by 240 min after the administration of LPS. The SMV blood flow was increased approximately by 50% from the baseline value. In contrast, mucosal blood flow of the ileum was decreased initially by 67% from the baseline value approximately by 120 min after LPS, and returned gradually to the baseline value by 240 min. The heterogeneity of the blood flow assessed by a relative dispersion of the blood flow to an area of ileal mucosa was significantly increased after LPS regardless of a period of time. These results suggest a significant role of the gut tissue in the development of systemic abnormalities in hemodyamics and oxygen metabolism.