利用对称投影吸引子重构从动脉血压数据中检测心脏收缩力变化

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Journal of pharmacological and toxicological methods Pub Date : 2024-07-26 DOI:10.1016/j.vascn.2024.107546
Esther Bonet-Luz , Manasi Nandi , Mark I. Christie , Jennifer Doyle , Jennifer B. Pierson , Michael K. Pugsley , Hugo M. Vargas , Philip J. Aston
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引用次数: 0

摘要

在药物开发过程中,药物可能会意外诱发心脏收缩力的变化,这是一个令人担忧的主要问题。虽然直接测量左心室压力(LVP)是测量体内心脏收缩力的黄金标准,但它需要大量资源,并对研究动物的福利造成负担。相比之下,动脉血压(BP)测量面临的挑战较少。对称投影吸引器重建(SPAR)是一种信号处理技术,可将生理时间序列信号转换为相应的视觉图像("吸引器"),放大生理波形的形态变化。据推测,对血压信号进行 SPAR 分析可通过特别放大收缩期上冲的最大斜率来替代测量心脏收缩力。对使用正性和负性肌力药物治疗的小猎犬的血压(腹主动脉)信号进行了回顾性分析,以确定与同时获得的 LVP 记录中 LVP 信号最大上坡相关的信号特征。血压信号的 SPAR 转换量化了药物引起的收缩期上冲最大斜率的变化。我们确定了一些关键的 SPAR 指标,它们与 LVP 最大上行斜率的相关性大于 0.8,优于单纯的血压收缩上行斜率。在所有 4 种不同药物、剂量和时间点的评估研究中都观察到了这种情况。因此,我们得出结论:在非临床药物研发过程中,从血压信号中得出的 SPAR 测量值可作为体内筛选的第一道关口,用于标记药物引起的心脏收缩力变化的任何风险,从而有可能减少或取代进行直接左心室测量的需要。
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Detection of contractility changes in the heart from arterial blood pressure data using symmetric Projection Attractor Reconstruction

The potential for unintended drug induced changes in cardiac contractility is a major concern in medicines development. Whilst direct left ventricular pressure (LVP) measurement is the gold standard for measuring cardiac contractility in vivo, it is resource intensive and poses a welfare burden on research animals. In contrast, arterial blood pressure (BP) measurement has fewer challenges. Symmetric Projection Attractor Reconstruction (SPAR) is a signal processing technique which transforms physiological time-series signals into a corresponding visual image (‘attractor’), amplifying morphology changes within physiological waveforms. It was hypothesized that SPAR analysis of BP signals would provide a surrogate measure of cardiac contractility by specifically amplifying the maximum slope of the systolic upstroke. BP (abdominal aorta) signals obtained from beagle dogs, treated with positive and negative inotropes, were retrospectively analysed to identify signal features that correlated with the maximum upslope of the LVP signal from simultaneously acquired LVP recordings. SPAR transformation of BP signals quantified drug induced changes in the maximum slope of the systolic upstroke. We identified key SPAR metrics that provided >0.8 correlation with the LVP maximum upslope, outperforming the BP systolic upstroke alone. This was observed for all 4 different drugs, doses and time points evaluated across studies. Thus, we conclude that the SPAR measures derived from the BP signal could be used as a first pass in vivo screen to flag any risk of drug induced changes in cardiac contractility during the conduct of non-clinical medicines development, potentially reducing or replacing the need to perform direct left ventricular measurements.

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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
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