Peritoneal Oxygen Delivery For The Treatment Of Acute Respiratory Distress Syndrome
腹膜供氧治疗急性呼吸窘迫综合征
基本信息
- 批准号:10556430
- 负责人:
- 金额:$ 65.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-09 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:Acute Respiratory Distress SyndromeAffectAnimal ModelAnimalsAnticoagulantsAnticoagulationBedsBlood VesselsBrainBypassChemistryCirculationDataDiffusionDoseDrug KineticsElectrodesEndotoxinsEngineeringEstersExtracorporeal Membrane OxygenationFormulationGasesGoalsGreater sac of peritoneumHemorrhageIn VitroInhalationInjuryIntensive Care UnitsIntraperitoneal InjectionsJournalsLipidsLipopolysaccharidesLungMeasuresMechanical ventilationMedicineMembraneMethodsMicrobubblesModelingMolecular StructureMulticenter StudiesMuscleNew EnglandOrganOxygenPatientsPeripheralPeritonealPhospholipidsPropertyProteinsPublishingPulmonary SurfactantsRattusResearchResearch Project GrantsRestRiskRodent ModelSafetySerum AlbuminSmoke Inhalation InjurySourceStructure of parenchyma of lungSucroseSystemTechniquesTechnologyTestingTherapeuticTissuesTraumaTraumatic injuryVentilatorWorkbody cavitydesignhealingimprovedin vivoinnovationintraperitoneallung healthmortalitynovelphosphorescenceporcine modelrational designresponsesafety testingsmoke inhalationsugarsupplemental oxygensurfactanttrauma careventilation
项目摘要
Severe acute respiratory distress syndrome (ARDS) occurs in approximately 10% of patients entering
the intensive care unit, affecting nearly 190,000 patients per year in the US alone. The initiation of ARDS is
multifactorial but often results in an inability to oxygenate the patient using conventional ventilation methods.
Despite the use of different ventilator modes and various inhalational agents, patient proning etc., approximately
30-50% of ARDS cases end in mortality. The ultimate aim of pulmonary support is to cause the least damage to
the lung parenchyma while it heals; with this in mind, extracorporeal membrane oxygenation (ECMO) has been
used in the most severe cases, when other means have failed. Unfortunately, ECMO also has a substantial
contraindication list and risk profile, which in part is driven by the need for full anticoagulation while the patient
is on the circuit. For a large portion of patients – traumatically injured patients, in particular – full anticoagulation
carries the risk of uncontrolled hemorrhage in the brain or other organs affected by trauma. We therefore continue
to search for effective means of resting the lungs while supporting the oxygenation and ventilation needs of the
patient. Oxygen microbubbles (OMBs) have shown promise as a method of extra-pulmonary oxygenation that
is safe, versatile and does not require use of anticoagulants. Our work is innovative as it explores a novel method
for extra-pulmonary oxygenation using body cavities, such as the peritoneal cavity. This could have a significant
impact on the field of trauma care in situations where anticoagulants cannot be used, as well as in settings where
ECMO technology is not readily accessible or practical. We have shown in small-animal models of ARDS induced
by lipopolysaccharide (LPS) and smoke inhalation (SI) that an intraperitoneal injection of OMBs improves
peripheral oxygenation saturation by 10-15% to normoxic levels, as well as survival and lung health. While our
preliminary studies have shown favorable improvements in oxygenation and survival in a preliminary lipid-based
formulation, it is unclear that this chemistry is the optimal formulation for intraperitoneal delivery.
The goal of this research project is to develop, characterize and test alternative OMB formulations based
on different lipids, lung surfactant, protein and sugar shells. The first aim will determine pharmacokinetic
parameters for novel OMB formulations. We will perform a “deep dive” design analysis of four different shell
types: characterizing mass transfer properties, gas-exchange phenomena and in vivo persistence in the
peritoneal cavity. The second aim will use a novel electrode-phosphorescence method to measure OMB dose
response and effects on muscle microvascular O2 supply in local tissue. The third aim will test the new OMB
formulations in rodent and pig models of LPS-ARDS. Finally, the fourth aim will Test new OMB formulations in
rodent and pig models of SI-ARDS. Overall, this research will test safety and efficacy of peritoneal microbubble
oxygenation in small and large animal models of ARDS, as well as establish key engineering principles for
rational design of oxygen microbubbles for peritoneal oxygenation.
大约 10% 的入院患者出现严重急性呼吸窘迫综合征 (ARDS)
仅在美国,重症监护病房每年就有近 190,000 名患者受到影响。
其原因是多因素的,但通常会导致无法使用传统通气方法为患者供氧。
尽管使用不同的呼吸机模式和各种吸入剂、患者俯卧等,大约
30-50% 的 ARDS 病例最终死亡。肺支持的最终目的是尽量减少对患者的伤害。
考虑到这一点,体外膜肺氧合 (ECMO) 已在肺实质愈合过程中发挥作用。
不幸的是,ECMO 也有很大的作用。
禁忌症清单和风险状况,部分原因是患者在治疗期间需要全面抗凝
对于大部分患者(尤其是外伤患者)来说,需要进行全面抗凝治疗。
存在大脑或其他受外伤影响的器官失控出血的风险,因此我们继续进行。
寻找让肺部休息的有效方法,同时支持肺部的氧合和通气需求
氧气微泡(OMB)已显示出作为一种肺外氧合方法的前景。
安全、通用且不需要使用抗凝剂我们的工作具有创新性,因为它探索了一种新颖的方法。
使用体腔(例如腹膜腔)进行肺外氧合,这可能具有显着的效果。
在无法使用抗凝剂的情况下以及在无法使用抗凝剂的情况下对创伤护理领域的影响
ECMO 技术并不容易获得或实用,我们已经在 ARDS 的小动物模型中证明了这一点。
通过脂多糖 (LPS) 和烟雾吸入 (SI) 腹腔注射 OMB 可以改善
外周氧合饱和度提高 10-15% 至含氧量正常水平,同时我们的生存和肺部健康也得到改善。
初步研究表明,基于脂质的初步研究可显着改善氧合和存活率。
制剂,目前尚不清楚该化学物质是用于腹膜内递送的制剂。
该研究项目的目标是开发、表征和测试基于 OMB 的替代配方
第一个目标是确定药代动力学。
我们将对四种不同的外壳进行“深入”设计分析。
类型:表征传质特性、气体交换现象和体内持久性
第二个目标是使用一种新型电极磷光方法来测量 OMB 剂量。
对局部组织中肌肉微血管 O2 供应的反应和影响 第三个目标将测试新的 OMB。
最后,第四个目标是在 LPS-ARDS 的啮齿动物和猪模型中测试新的 OMB 配方。
总体而言,这项研究将测试腹膜微泡的安全性和有效性。
ARDS 的小型和大型动物模型中的氧合,以及建立关键的工程原理
合理设计用于腹膜氧合的氧气微泡。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Effect of Thermal History and Hydrocarbon Core Size on Perfluorocarbon Endoskeletal Droplet Vaporization.
- DOI:10.1021/acs.langmuir.1c03350
- 发表时间:2022-02
- 期刊:
- 影响因子:0
- 作者:Gazendra Shakya;A. K. Fajrial;Xiaoyun Ding;Mark A Borden
- 通讯作者:Gazendra Shakya;A. K. Fajrial;Xiaoyun Ding;Mark A Borden
Acoustically manipulating internal structure of disk-in-sphere endoskeletal droplets.
- DOI:10.1038/s41467-022-28574-4
- 发表时间:2022-02-21
- 期刊:
- 影响因子:16.6
- 作者:Shakya G;Yang T;Gao Y;Fajrial AK;Li B;Ruzzene M;Borden MA;Ding X
- 通讯作者:Ding X
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Mark Andrew Borden其他文献
Mark Andrew Borden的其他文献
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{{ truncateString('Mark Andrew Borden', 18)}}的其他基金
Endoskeletal nanodrops for x-ray acoustic dosimetry
用于 X 射线声剂量测定的内骨骼纳米滴
- 批准号:
10429759 - 财政年份:2022
- 资助金额:
$ 65.2万 - 项目类别:
Endoskeletal nanodrops for x-ray acoustic dosimetry
用于 X 射线声剂量测定的内骨骼纳米滴
- 批准号:
10660977 - 财政年份:2022
- 资助金额:
$ 65.2万 - 项目类别:
Microbubble Dose Optimization for Image-Guided Drug Delivery
图像引导药物输送的微泡剂量优化
- 批准号:
10190853 - 财政年份:2019
- 资助金额:
$ 65.2万 - 项目类别:
Microbubble Dose Optimization for Image-Guided Drug Delivery
图像引导药物输送的微泡剂量优化
- 批准号:
9973211 - 财政年份:2019
- 资助金额:
$ 65.2万 - 项目类别:
Microbubble Dose Optimization for Image-Guided Drug Delivery
图像引导药物输送的微泡剂量优化
- 批准号:
10438770 - 财政年份:2019
- 资助金额:
$ 65.2万 - 项目类别:
Microbubble Dose Optimization for Image-Guided Drug Delivery
图像引导药物输送的微泡剂量优化
- 批准号:
10652332 - 财政年份:2019
- 资助金额:
$ 65.2万 - 项目类别:
Ultrasound Molecular Imaging to Assess Therapeutic Response
超声分子成像评估治疗反应
- 批准号:
9053460 - 财政年份:2015
- 资助金额:
$ 65.2万 - 项目类别:
Ultrasound Molecular Imaging to Assess Therapeutic Response
超声分子成像评估治疗反应
- 批准号:
9274263 - 财政年份:2015
- 资助金额:
$ 65.2万 - 项目类别:
Ultrasound Molecular Imaging to Assess Therapeutic Response
超声分子成像评估治疗反应
- 批准号:
9440982 - 财政年份:2015
- 资助金额:
$ 65.2万 - 项目类别:
Targeted Microbubbles for Noninvasive Measurement of Tumor VEGF Levels
用于无创测量肿瘤 VEGF 水平的靶向微泡
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8702492 - 财政年份:2014
- 资助金额:
$ 65.2万 - 项目类别:
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