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与羟乙基淀粉相比,在体外循环期间使用乳酸林格液、白蛋白和甘露醇作为预充液可减轻大鼠肺水肿。

Lactated Ringers, albumin and mannitol as priming during cardiopulmonary bypass reduces pulmonary edema in rats compared with hydroxyethyl starch.

作者信息

Beukers Anne M, van Leeuwen Anoek L I, Ibelings Roselique, Tuip-de Boer Anita M, Bulte Carolien S E, Eberl Susanne, van den Brom Charissa E

机构信息

Department of Anesthesiology, Amsterdam UMC, VU University, Amsterdam, The Netherlands.

Department of Cardiothoracic Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Intensive Care Med Exp. 2024 Sep 7;12(1):78. doi: 10.1186/s40635-024-00661-4.

Abstract

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.

CONCLUSION

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.

摘要

背景

伴有水肿形成和微循环灌注障碍的内皮功能紊乱在体外循环(CPB)心脏手术中很常见,并导致组织氧合障碍,进而引起器官功能障碍。白蛋白对内皮具有保护作用,可能是CPB预充液中一种有用的添加剂。因此,本研究旨在比较乳酸林格氏液、白蛋白和甘露醇(LR/白蛋白/甘露醇)预充CPB的大鼠与6%羟乙基淀粉(HES)预充CPB的大鼠的器官水肿和微循环灌注情况。

结果

雄性大鼠接受75分钟的CPB,预充液为LR/白蛋白/甘露醇或6% HES。通过湿/干重比测定肾和肺水肿情况。与HES预充CPB的大鼠相比,LR/白蛋白/甘露醇预充CPB的大鼠肺湿/干重比更低(4.77 [4.44 - 5.25] 对 5.33 [5.06 - 6.33],p = 0.032),而两组间肾湿/干重比无差异(4.57 [4.41 - 4.75] 对 4.51 [4.47 - 4.73],p = 0.813)。在CPB前、中、后用活体显微镜评估提睾肌微循环灌注。与基线相比,CPB立即损害微循环灌注(LR/白蛋白/甘露醇:每次记录2 [1 - 7] 条血管对14 [12 - 16] 条血管,p = 0.008;HES:每次记录4 [2 - 6] 条血管对12 [10 - 13] 条血管,p = 0.037),在脱离CPB后这种情况持续存在,两组间无差异(LR/白蛋白/甘露醇:5 [1 - 9] 对HES:1 [0 - 4],p = 0.926)。此外,LR/白蛋白/甘露醇预充CPB的大鼠达到足够流速所需液体量更少(0.5 [0.0 - 5.0] mL对9 [4.5 - 10.0],p < 0.001),去氧肾上腺素用量也更少(20 [0 - 40] μg对90 [40 - 200],p = 0.004)。通过ELISA或Luminex测定炎症(白细胞介素6和10)、黏附(ICAM - 1)、糖萼脱落(syndecan - 1)和肾损伤(NGAL)的循环标志物。与HES预充CPB的大鼠相比,LR/白蛋白/甘露醇预充CPB的大鼠循环白细胞介素 - 6(16 [13 - 25] ng/mL对33 [24 - 51] ng/mL,p = 0.006)、白细胞介素 - 10(434 [295 - 782] pg/ml对2120 [1309 - 3408] pg/ml,p < 0.0001)、syndecan - ①(5 [3 - 7] ng/mL对15 [11 - 16] ng/mL,p < 0.001)和NGAL(555 [375 - 1078] ng/mL对2200 [835 - 3671] ng/mL,p = 0.008)更低。

结论

与6% HES相比,LR、白蛋白和甘露醇预充CPB导致的肺水肿、肾损伤、炎症和糖萼降解更少。此外,与HES相比,它增强了血流动力学稳定性。需要进一步研究探索白蛋白作为CPB预充有益添加剂的具体作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4d9/11380653/f41cb46a782e/40635_2024_661_Fig1_HTML.jpg

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