Role of Cyclohexanone Toxicity in Mediating Congenital Cardiac Surgery Outcomes
环己酮毒性在调节先天性心脏手术结果中的作用
基本信息
- 批准号:10444513
- 负责人:
- 金额:$ 72.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:5 year oldAdrenal Cortex HormonesAdverse effectsAnimal ModelAnimalsAttentionAttention deficit hyperactivity disorderBiological AssayBlood - brain barrier anatomyBlood BanksBrainBrain InjuriesCardiacCardiac Surgery proceduresCardiopulmonary BypassCardiovascular systemCell DeathCessation of lifeChemicalsChildChildhoodClinicalClinical assessmentsCongenital AbnormalityCongenital Heart DefectsCyclohexanonesDataDevelopmentEnvironmentExcisionExposure toGoalsHealthcareHeart DiseasesHumanHyperactivityIV FluidIn VitroIndustrializationInfantInfusion proceduresIntravenous infusion proceduresLearningLength of StayMagnetic Resonance ImagingMapsMeasuresMediatingMedicalMedical DeviceMemoryMetabolismMethodsMethylprednisoloneMichiganMolecularMorbidity - disease rateMotorMulticenter TrialsNational Heart, Lung, and Blood InstituteNeonatalNeuronsOperative Surgical ProceduresOrganic solvent productOutcomePatientsPerioperativePharmacologyPhenotypePlacebosPlasticsPostoperative PeriodPrevention strategyRandomizedRattusRodent ModelRoleSamplingSerumSliceSolventsSourceStructureSurvivorsTechniquesTestingThrombosisToxic effectToxicologyUniversitiesValidationVentilatorZeolitesage relatedcardiac intensive care unitcardiovascular effectscell typecohortcongenital heart disorderdisabilityexecutive functionimprovedimproved outcomein vivoin vivo Modelinnovationmolecular sievingmortalitymotor deficitneonatal brainneonateneurodevelopmentneurodevelopmental effectnovelperioperative morbidityrelating to nervous systemsuccesssurgery outcomewhite matter injury
项目摘要
Congenital heart defects (CHD) are the leading cause of birth defect-associated illness and death.
Neurodevelopmental delays and disabilities are the most frequent and significant consequence for CHD
survivors. Efforts to reduce morbidity and improve outcomes have primarily focused on surgical techniques,
cardiopulmonary bypass (CPB) strategies and pharmacologic therapies without much success. Exposure to
industrial chemicals in the health care environment are increasingly being recognized as harmful, and maybe a
mechanism for these poor outcomes in CHD. Cyclohexanone, is a hazardous organic industrial solvent used
principally in health care as a joining compound in the fabrication of plastic medical devices. Cyclohexanone has
been shown to leach from IV infusion sets and the CPB circuit and in animal studies, with significant
cardiovascular effects. Therefore, our hypothesis is that cyclohexanone derived from medical plastics is
associated with adverse cardiovascular and neurodevelopmental outcomes in congenital cardiac surgery. We
now have significant and compelling pilot data in neonates undergoing cardiac surgery that there is a) substantial
cyclohexanone exposure from IV infusions and CPB and b) with adjusted analysis, cyclohexanone levels were
significantly associated with adverse post-operative cardiovascular outcomes, and worse 12 month
neurodevelopmental outcomes, thus supporting our hypothesis. Our long-term goal is to develop new prevention
strategies and more precise treatments to improve outcomes for neonates undergoing surgery with CPB. We
will approach this hypothesis using samples and outcomes from the discovery cohort: the completed NHLBI
multicenter Trial NCT01579513, entitled “Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary
Bypass (MP trial)”, Eric Graham, PI (n=190, randomized to MP (methylprednisolone) therapy or placebo) and
the completed external validation cohort the University of Toronto, “Clinical Assessment of Thrombosis in
Children After Heart Surgery: The CATCH Study” (NCT01435473), Brian McCrindle and Cedric Manlhiot (PIs)
(N=327, <5 years old) and a neonatal cardiac surgery from the University of Michigan (N=59), Mark Russell, PI.
With the following Specific Aims we propose to: Aim 1) Determine if serum perioperative cyclohexanone levels
are associated with perioperative morbidity, mortality, and neurodevelopmental outcomes. Aim 2) Determine
cyclohexanone exposure sources and removal using zeolite molecular sieves. Finally, Aim 3) Determine
cyclohexanone neural toxicity, blood brain barrier and learning/memory effects. These Aims describe a paradigm
shift in the mechanism of reduced neonatal heart surgery outcomes. Innovation includes discovery of the novel
role of the industrial organic solvent contaminant cyclohexanone from medical plastic fabrication on neonatal
cardiac surgery clinical outcomes and methods for removal. Reduction of organic solvent exposure from medical
plastics offers an immediate and actionable means to improve neonatal cardiac surgical outcomes.
先天性心脏缺陷(CHD)是导致出生缺陷相关疾病和死亡的主要原因。
项目成果
期刊论文数量(0)
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ALLEN D EVERETT其他文献
COMPARISON BETWEEN PULMONARY ARTERIAL HYPERTENSION (PAH) RISK ASSESSMENT METHODS, INCLUDING PULMONARY HYPERTENSION OUTCOME RISKS ASSESSMENT (PHORA)
- DOI:
10.1016/j.chest.2022.08.2013 - 发表时间:
2022-10-01 - 期刊:
- 影响因子:
- 作者:
CHARLES FAUVEL;ZILU LIU;SHILI LIN;PRISCILLA CORREA-JAQUE;AMY WEBB;REBECCA R VANDERPOOL;MANREET KANWAR;JIDAPA KRAISANGKA;PUNEET MATHUR;ADAM PERER;ALLEN D EVERETT;RAYMOND L BENZA - 通讯作者:
RAYMOND L BENZA
ALLEN D EVERETT的其他文献
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{{ truncateString('ALLEN D EVERETT', 18)}}的其他基金
Role of Cyclohexanone Toxicity in Mediating Congenital Cardiac Surgery Outcomes
环己酮毒性在调节先天性心脏手术结果中的作用
- 批准号:
10627951 - 财政年份:2022
- 资助金额:
$ 72.92万 - 项目类别:
Advanced therapeutic hypothermia efficacy network modeling in neonatal HIE
新生儿 HIE 的先进低温治疗功效网络模型
- 批准号:
10696194 - 财政年份:2022
- 资助金额:
$ 72.92万 - 项目类别:
Advanced therapeutic hypothermia efficacy network modeling in neonatal HIE
新生儿 HIE 的先进低温治疗功效网络模型
- 批准号:
10538972 - 财政年份:2022
- 资助金额:
$ 72.92万 - 项目类别:
Clinical and mechanistic role of HDGF in pulmonary hypertension
HDGF 在肺动脉高压中的临床和机制作用
- 批准号:
9772631 - 财政年份:2017
- 资助金额:
$ 72.92万 - 项目类别:
Adult Biomarkers in Neonatal Brain Injury and Development
新生儿脑损伤和发育中的成人生物标志物
- 批准号:
9761549 - 财政年份:2016
- 资助金额:
$ 72.92万 - 项目类别:
Adult Biomarkers in Neonatal Brain Injury and Development
新生儿脑损伤和发育中的成人生物标志物
- 批准号:
9549109 - 财政年份:2016
- 资助金额:
$ 72.92万 - 项目类别:
Adult Biomarkers in Neonatal Brain Injury and Development
新生儿脑损伤和发育中的成人生物标志物
- 批准号:
10006591 - 财政年份:2016
- 资助金额:
$ 72.92万 - 项目类别: