Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria.
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Shock. 2018 May;49(5):564-571. doi: 10.1097/SHK.0000000000000944.
Hemorrhagic shock (HS) followed by resuscitation is often associated with sympathoadrenal activation (SAA) and endothelial damage (ED).
We aimed to evaluate the impact of HS alone on the magnitude of SAA and consecutive ED, and to characterize potential targets for a standardized and reproducible model of HS-induced endotheliopathy in rats.
Rats were subjected either to a volume-controlled HS (40% of total blood volume: v-HS group) or to a laboratory-guided HS (l-HS) targeting base deficit (BD) more than 5.5 mmol/L and/or lactate more than 2.2 mmol/L using a pressure-controlled volume loss.
At the end of shock, mean arterial pressure was significantly higher in the v-HS than the l-HS group (36 ± 5.6 vs. 30 ± 3.0 mmHg; P < 0.01). Base deficit and lactate were higher in l-HS than the v-HS group (BD: 9.5 ± 2.5 vs. 3.0 ± 1.0 mmol/L; P < 0.001; lactate: 4.1 ± 1.3 vs. 1.6 ± 0.6 mmol/L; P < 0.001). sVEGFR-1 and syndecan-1 were approximately 50% higher in the l-HS than the v-HS group (% changes vs. baseline: 160 ± 10 vs. 116 ± 36; P < 0.01; 170 ± 37 vs. 113 ± 27; P < 0.001). Adrenaline was 2-fold higher in l-HS than the v-HS group (1964 ± 961% vs. 855 ± 451%; P < 0.02, respectively). Moreover, linear regression analysis revealed an independent association of shock severity BD with syndecan-1 (rho = 0.55, P = 0.0005), sVEGFR1 (rho = 0.25, P < 0.05), and adrenaline (rho = 0.31, P = 0.021).
Our findings indicate that ED has already occurred during HS without reperfusion; intensity is strongly related to the severity of HS and consecutive SAA; and severity may appropriately be targeted and standardized in a HS model controlled by biological endpoints such as BD and/or lactate.
出血性休克（HS）复苏后常伴有交感肾上腺激活（SAA）和内皮损伤（ED）。
本研究旨在评估单纯 HS 对 SAA 和随后 ED 的影响，并确定大鼠 HS 诱导内皮病变标准化和可重现模型的潜在靶点。
大鼠分别接受容量控制 HS（40%总血容量：v-HS 组）或实验室引导 HS（l-HS），使用压力控制容量损失使基础缺陷（BD）超过 5.5mmol/L 和/或乳酸超过 2.2mmol/L。
休克结束时，v-HS 组的平均动脉压明显高于 l-HS 组（36±5.6 vs. 30±3.0mmHg；P<0.01）。l-HS 组的 BD 和乳酸均高于 v-HS 组（BD：9.5±2.5 vs. 3.0±1.0mmol/L；P<0.001；乳酸：4.1±1.3 vs. 1.6±0.6mmol/L；P<0.001）。与 v-HS 组相比，l-HS 组 sVEGFR-1 和 syndecan-1 分别升高约 50%（与基线相比的百分比变化：160±10 vs. 116±36；P<0.01；170±37 vs. 113±27；P<0.001）。l-HS 组肾上腺素是 v-HS 组的 2 倍（1964±961% vs. 855±451%；P<0.02，分别）。此外，线性回归分析显示，休克严重程度 BD 与 syndecan-1（rho=0.55，P=0.0005）、sVEGFR1（rho=0.25，P<0.05）和肾上腺素（rho=0.31，P=0.021）呈独立相关。
本研究结果表明，在无再灌注的 HS 期间已经发生 ED；强度与 HS 的严重程度和随后的 SAA 强烈相关；严重程度可以通过生物终点（如 BD 和/或乳酸）控制的 HS 模型进行适当靶向和标准化。
