Personalized Anesthetic Pharmacology Across the Lifespan
整个生命周期的个性化麻醉药理学
基本信息
- 批准号:10684036
- 负责人:
- 金额:$ 50.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-21 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAffectAgeAge MonthsAgingAnesthesia proceduresAnesthesiologyAnestheticsAnimalsArousalAttentionCharacteristicsClinicalCognitionConsciousControl AnimalDataDeliriumDependenceDependovirusDevelopmentDoseDrug resistanceDrug usageElderlyEnterobacteria phage P1 Cre recombinaseExhibitsExposure toGeneticHuman VolunteersImpaired cognitionImpairmentInbred MouseIndividualIndividual DifferencesInvestigationIsofluraneLinkLongevityLongitudinal StudiesMeasuresMediatingMethodologyMusNeurobiologyNeuronsOperative Surgical ProceduresPathway interactionsPatientsPerformancePharmaceutical PreparationsPharmacologyPharmacology StudyPopulationPopulation StudyPostoperative ComplicationsPublishingRecording of previous eventsRecoveryReflex actionReproducibilityResistanceRoleSleepSpeedTestingTimeTransfectionTransgenic MiceWakefulnessagedbehavior testcognitive functioncognitive performancecognitive recoverycognitive testingcohortcostdesigner receptors exclusively activated by designer drugsdrug sensitivitydrug standardhuman old age (65+)hypocretinimprovedinattentioninnovationinter-individual variationnovelolder patientpatient populationpersonalized medicinepopulation basedpostoperative deliriumprecision drugspromoterresponserestorationselective expressionsustained attentionvirtual
项目摘要
Abstract.
Decisions concerning anesthetic dosing typically rely on population-based measures of drug potency.
However, similar anesthetic doses have markedly different effects on distinct individuals. While some patients
recover from anesthesia uneventfully, in others, recovery is complicated by postoperative delirium and
cognitive dysfunction. Such complications are disproportionally prevalent in the elderly. It is presently unclear
why some elderly patients exhibit these debilitating and costly complications. To answer this question,
individual-based rather than population-based measures of drug effects must be developed. We create such
measures for anesthetics in mice. Preliminary data indicate that standard population-based measures of
anesthetic potency, such as half-maximal effective concentration (EC50), are insufficient to explain anesthetic
responses in each individual. This is because at a fixed anesthetic concentration, the level of consciousness in
each individual fluctuates. While fluctuations in the state of arousal occur spontaneously, there is an inertial
tendency in each animal to resist state transitions. Hence, the response in each individual depends not just
upon the anesthetic concentration, but also upon the individual’s previous state of arousal. Standard drug
potency measures fail to account for this history-dependence. Thus, to adequately quantify individual-based
responses to anesthetics, we develop two independent measures: personalized drug sensitivity and resistance
to state transitions. We hypothesize that resistance to state transitions contributes to delayed restoration of
cognitive function after anesthesia. We investigate age-dependence of resistance to state transitions in a first
of a kind longitudinal study (Aim 1). To investigate a neurobiological basis of resistance to state transitions, we
selectively decrease resistance to state transitions using chemogenetic activation of orexinergic neurons that
are critically involved in stabilization of sleep and wakefulness (Aim 2). To determine whether resistance to
state transitions is causally linked to restoration of cognition, we use a behavioral test of sustained attention
(SA) performed immediately upon recovery after anesthesia. Our published results indicate that SA is
dramatically disrupted after recovery from anesthesia in human volunteers. We determine if increased
resistance to state transitions is associated with greater impairment on SA performance after emergence in
mice. We attempt to restore normal SA performance by modulating resistance to state transitions using
chemogenetic activation of orexinergic neurons (Aim 3). In summary, we develop a qualitatively novel measure
of personalized, rather than population-based anesthetic responses: resistance to state transitions. We
determine the neurobiological underpinnings of resistance to state transitions, and investigate its relationship to
subsequent cognitive recovery. Thus, we offer a critical first step towards developing truly personalized
anesthesia and delineate factors underlying delayed restoration of consciousness.
摘要。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Max Kelz其他文献
Max Kelz的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Max Kelz', 18)}}的其他基金
Personalized Anesthetic Pharmacology Across the Lifespan
整个生命周期的个性化麻醉药理学
- 批准号:
10339719 - 财政年份:2021
- 资助金额:
$ 50.67万 - 项目类别:
Physician Postdoctoral Research Training in Perioperative Medicine (PPRTPM)
围手术期医学医师博士后研究培训 (PPRTPM)
- 批准号:
10206170 - 财政年份:2015
- 资助金额:
$ 50.67万 - 项目类别:
Physician Postdoctoral Research Training in Perioperative Medicine (PPRTPM)
围手术期医学医师博士后研究培训 (PPRTPM)
- 批准号:
10405486 - 财政年份:2015
- 资助金额:
$ 50.67万 - 项目类别:
Physician Postdoctoral Research Training in Perioperative Medicine (PPRTPM)
围手术期医学医师博士后研究培训 (PPRTPM)
- 批准号:
10693326 - 财政年份:2015
- 资助金额:
$ 50.67万 - 项目类别:
NEURONAL BASIS UNDERLYING VOLATILE ANESTHETIC INDUCED HYPNOSIS
挥发性麻醉剂诱导催眠的神经基础
- 批准号:
8061958 - 财政年份:2010
- 资助金额:
$ 50.67万 - 项目类别:
NEURONAL BASIS UNDERLYING VOLATILE ANESTHETIC INDUCED HYPNOSIS
挥发性麻醉剂诱导催眠的神经基础
- 批准号:
8245764 - 财政年份:2010
- 资助金额:
$ 50.67万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 50.67万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 50.67万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 50.67万 - 项目类别:
Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 50.67万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 50.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 50.67万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 50.67万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 50.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 50.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 50.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)