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Intravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation and reduces ventilation-induced lung injury in a respiratory distress model
bioRxiv - Physiology Pub Date : 2020-11-14 , DOI: 10.1101/2020.04.08.031435
You Wu , Tam L. Ngyuen , Carrie E. Perlman

In the neonatal (NRDS) and acute (ARDS) respiratory distress syndromes, mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI) that contributes to high mortality. Further, surface tension, T, should be elevated and VILI is proportional to T. Surfactant therapy is effective in NRDS but not ARDS. Sulforhodamine B (SRB) is a potential alternative T-lowering therapeutic. In anesthetized male rats, we injure the lungs with 15 min of 42 ml/kg tidal volume, VT, and zero end-expiratory pressure ventilation. Then, over 4 hrs, we support the rats with protective ventilation - VT of 6 ml/kg with positive end-expiratory pressure. At the start of the support period, we administer intravenous non-T-altering fluorescein (targeting 27 μM in plasma) without or with therapeutic SRB (10 nM). Throughout the support period, we increase inspired oxygen fraction, as necessary, to maintain >90% arterial oxygen saturation. At the end of the support period we sacrifice the rat; sample systemic venous blood for injury marker ELISAs; excise the lungs; combine confocal microscopy and servo-nulling pressure measurement to determine T in situ in the lungs; image fluorescein in alveolar liquid to assess local permeability; and determine lavage protein content and wet-to-dry ratio (W/D), both to assess global permeability. Lungs exhibit focal injury. Surface tension is elevated 72% throughout control lungs and in uninjured regions of SRB-treated lungs, but normal in injured regions of treated lungs. Sulforhodamine B administration improves oxygenation, reduces W/D and reduces plasma injury markers. Intravenous SRB holds promise as a therapy for respiratory distress.

中文翻译:

在呼吸窘迫模型中,静脉给予磺基若丹明B可以降低肺泡表面张力,改善氧合作用并减少通气引起的肺损伤

在新生儿(NRDS)和急性(ARDS)呼吸窘迫综合征中,机械通气支持气体交换,但会引起通气诱发的肺损伤(VILI),导致高死亡率。此外,应该提高表面张力T,并且VILI与T成正比。表面活性剂疗法对NRDS有效,但对ARDS无效。磺胺丁丹B(SRB)是潜在的降低T的替代疗法。在麻醉的雄性大鼠中,我们用15分钟的42 ml / kg潮气量V T和零呼气末通气来伤害肺。然后,在4小时内,我们为大鼠提供保护性通气-V T呼气末正压为6 ml / kg。在支持期开始时,我们在不使用或使用治疗性SRB(10 nM)的情况下,静脉注射非T改变的荧光素(血浆中目标浓度为27μM)。在整个支持期间,我们会根据需要增加吸入的氧气分数,以保持> 90%的动脉血氧饱和度。在支持期结束时,我们牺牲了老鼠。用于损伤标记ELISA的全身静脉血样品; 切除肺部;结合共焦显微镜和伺服零压力测量来确定T肺内原位;对肺泡液中的荧光素进行成像,以评估局部渗透性;并确定灌洗蛋白含量和干湿比(W / D),以评估总体通透性​​。肺部表现出局灶性损伤。在整个对照肺中以及在SRB处理过的肺的未受伤区域中,表面张力均升高了72%,但在治疗过的肺部受伤区域中,表面张力正常。磺胺丁丹B的使用可改善氧合,降低W / D并减少血浆损伤标志物。静脉SRB有望作为呼吸窘迫的治疗方法。
更新日期:2020-11-15
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