Sepsis impairs microvascular autoregulation and delays capillary response within hypoxic capillaries
Sepsis impairs microvascular autoregulation and delays capillary response within hypoxic capillaries
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DOI：
10.1186/s13054-015-1102-7
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发表时间：
2015-11-05
期刊：
影响因子：
15.1
通讯作者：
Ellis, Christopher G.
中科院分区：
文献类型：
--
作者：
Bateman, Ryon M.;Sharpe, Michael D.;Ellis, Christopher G.
简介：微循环为所有细胞提供氧气（O-2）和营养物质，红细胞（RBC）既是O-2的输送者，也是O-2的传感器。在脓毒症（一种伴有微血管并发症的促炎性疾病）中，小血管改变与多器官功能障碍和脓毒症患者预后不良相关。我们假设，微血管自身调节存在于三个层面：整个毛细血管网络，毛细血管内和红细胞内，在败血症发作期间受损。本研究有三个目标：1）测量缺氧毛细血管内的毛细血管反应时间，2）测试的零假设，红细胞O-2依赖性三磷酸腺苷（ATP）流出不改变败血症和3）开发一个框架的病理生理学model.Methods：这是一个动物研究，比较败血症与对照组，设置在一所大学的实验室。采用盲肠结扎穿孔术（CLP）研究急性化脓性脓毒症，终点为6小时。测定大鼠后肢骨骼肌微循环，定量测定毛细血管红细胞供应率（SR = RBC/s）、红细胞血红蛋白氧饱和度（SO2）和氧供应率（qO（2）= pLO（2）/s）。分别用一氧化氮（NO）分析仪和气体交换器测定动脉NOx（亚硝酸盐+硝酸盐）和红细胞O-2依赖性ATP流出量。结果：脓毒症增加毛细血管停流（p = 0.001）和增加血浆乳酸（p < 0.001）。血浆NOx增加（p < 0.001）与毛细血管RBC供应率增加（p = 0.027）相关。对30秒SR-SO2-qO（2）曲线的分析显示，某些毛细血管中的O-2供应率出现下降（p < 0.05）的转变。此外，我们检测到缺氧毛细血管内毛细血管反应时间增加了三到四倍（p < 0.05）（毛细血管流动状态，RBC SO2 <20%）。此外，脓毒症降低了红细胞对缺氧环境的反应能力，红细胞O-2依赖性ATP流出减少了62.5%（p < 0.001）。结论：脓毒症在毛细血管和红细胞水平上都损害了微血管的自动调节，似乎使作为“O-2传感器”的红细胞与微血管的自动调节脱钩。微血管自身调节功能受损表现为毛细血管停流增加、缺氧毛细血管内毛细血管反应时间增加、毛细血管O-2供应速率降低和RBC O-2依赖性ATP流出减少。这种局部微血管控制的丧失部分地被增加的毛细血管RBC供应速率抵消，这与增加的血浆NOx相关。
Introduction: The microcirculation supplies oxygen (O-2) and nutrients to all cells with the red blood cell (RBC) acting as both a deliverer and sensor of O-2. In sepsis, a proinflammatory disease with microvascular complications, small blood vessel alterations are associated with multi-organ dysfunction and poor septic patient outcome. We hypothesized that microvascular autoregulation-existing at three levels: over the entire capillary network, within a capillary and within the erythrocyte-was impaired during onset of sepsis. This study had three objectives: 1) measure capillary response time within hypoxic capillaries, 2) test the null hypothesis that RBC O-2-dependent adenosine triphosphate (ATP) efflux was not altered by sepsis and 3) develop a framework of a pathophysiological model.Methods: This was an animal study, comparing sepsis with control, set in a university laboratory. Acute hypotensive sepsis was studied using cecal ligation and perforation (CLP) with a 6-hour end-point. Rat hindlimb skeletal muscle microcirculation was imaged, and capillary RBC supply rate (SR = RBC/s), RBC hemoglobin O-2 saturation (SO2) and O-2 supply rate (qO(2) = pLO(2)/s) were quantified. Arterial NOx (nitrite + nitrate) and RBC O-2-dependent ATP efflux were measured using a nitric oxide (NO) analyzer and gas exchanger, respectively.Results: Sepsis increased capillary stopped-flow (p = 0.001) and increased plasma lactate (p < 0.001). Increased plasma NOx (p < 0.001) was related to increased capillary RBC supply rate (p = 0.027). Analysis of 30-second SR-SO2-qO(2) profiles revealed a shift towards decreased (p < 0.05) O-2 supply rates in some capillaries. Moreover, we detected a three-to fourfold increase (p < 0.05) in capillary response time within hypoxic capillaries (capillary flow states where RBC SO2 < 20 %). Additionally, sepsis decreased the erythrocyte's ability to respond to hypoxic environments, as normalized RBC O-2-dependent ATP efflux decreased by 62.5 % (p < 0.001).Conclusions: Sepsis impaired microvascular autoregulation at both the individual capillary and erythrocyte level, seemingly uncoupling the RBC acting as an "O-2 sensor" from microvascular autoregulation. Impaired microvascular autoregulation was manifested by increased capillary stopped-flow, increased capillary response time within hypoxic capillaries, decreased capillary O-2 supply rate and decreased RBC O-2-dependent ATP efflux. This loss of local microvascular control was partially off-set by increased capillary RBC supply rate, which correlated with increased plasma NOx.