背景:在体外循环(CPB)的心脏手术中,伴有水肿形成和微循环灌注障碍的内皮疾病很常见,并导致组织氧合紊乱,导致器官功能障碍。白蛋白对内皮具有保护作用,并且可能是CPB回路引发的有用添加剂。因此,这项研究的目的是比较大鼠的器官水肿和微循环灌注在CPB引发乳酸林格,白蛋白和甘露醇(LR/白蛋白/甘露醇)与6%羟乙基淀粉(HES)相比。
结果:雄性大鼠经受用LR/白蛋白/甘露醇或6%HES引发的CPB的75分钟。通过湿/干重比确定肾脏和肺水肿。与HES相比,用LR/白蛋白/甘露醇引发的CPB大鼠的肺湿/干重比更低(4.77[4.44-5.25]与5.33[5.06-6.33],p=0.032),而肾脏湿/干重比在组间没有差异(4.57[4.41-4.75]vs.4.51[4.47-4.73],p=0.813)。之前评估了Cremaster微循环灌注,在CPB期间和之后进行活体显微镜检查。与基线相比,CPB立即损害微循环灌注(LR/白蛋白/甘露醇:2[1-7]vs.每次记录14[12-16]个容器,p=0.008;HES:4[2-6]vs.每个记录12[10-13]个容器,p=0.037),从CPB断奶后持续存在,组间无差异(LR/白蛋白/甘露醇:5[1-9]vs.HES:1[0-4],p=0.926)。此外,用LR/白蛋白/甘露醇引发的CPB大鼠需要较少的液体才能达到足够的流速(0.5[0.0-5.0]mL与9[4.5-10.0],p<0.001)和去氧肾上腺素(20[0-40]µgvs.90[40-200],p=0.004)。炎症循环标志物(白细胞介素6和10),附着力(ICAM-1),通过ELISA或Luminex确定糖萼脱落(syndecan-1)和肾损伤(NGAL)。循环白细胞介素-6(16[13-25]vs.33[24-51]ng/mL,p=0.006),白细胞介素-10(434[295-782]vs.2120[1309-3408]pg/ml,p<0.0001),syndecan-1(5[3-7]vs.15[11-16]ng/mL,p<0.001)和NGAL(555[375–1078]vs.2200[835-3671]ng/mL,与HES相比,用LR/白蛋白/甘露醇引发的CPB大鼠的p=0.008)较低。
结论:CPB启动LR,白蛋白和甘露醇导致肺水肿减少,肾损伤,与6%HES相比,炎症和糖萼降解。此外,与HES相比,它增强了血液动力学稳定性。需要进一步的研究来探索白蛋白作为CPB引发的有益添加剂的具体作用。
BACKGROUND: Endothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES).
RESULTS: Male rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44-5.25] vs. 5.33 [5.06-6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41-4.75] vs. 4.51 [4.47-4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1-7] vs. 14 [12-16] vessels per recording, p = 0.008; HES: 4 [2-6] vs. 12 [10-13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1-9] vs. HES: 1 [0-4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0-5.0] mL vs. 9 [4.5-10.0], p < 0.001) and phenylephrine (20 [0-40] µg vs. 90 [40-200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1),
glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13-25] vs. 33 [24-51] ng/mL, p = 0.006), interleukin-10 (434 [295-782] vs. 2120 [1309-3408] pg/ml, p < 0.0001), syndecan-1 (5 [3-7] vs. 15 [11-16] ng/mL, p < 0.001) and NGAL (555 [375-1078] vs. 2200 [835-3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES.
CONCLUSIONS: CPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and
glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming.