Esther Bonet-Luz , Manasi Nandi , Mark I. Christie , Jennifer Doyle , Jennifer B. Pierson , Michael K. Pugsley , Hugo M. Vargas , Philip J. Aston
{"title":"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","authors":"Esther Bonet-Luz , Manasi Nandi , Mark I. Christie , Jennifer Doyle , Jennifer B. Pierson , Michael K. Pugsley , Hugo M. Vargas , Philip J. Aston","doi":"10.1016/j.vascn.2024.107546","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":16767,"journal":{"name":"Journal of pharmacological and toxicological methods","volume":"129 ","pages":"Article 107546"},"PeriodicalIF":1.3000,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S105687192400056X/pdfft?md5=8e0a0c5e71d9db51cee6e01697634e4b&pid=1-s2.0-S105687192400056X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Detection of contractility changes in the heart from arterial blood pressure data using symmetric Projection Attractor Reconstruction\",\"authors\":\"Esther Bonet-Luz , Manasi Nandi , Mark I. Christie , Jennifer Doyle , Jennifer B. Pierson , Michael K. Pugsley , Hugo M. Vargas , Philip J. Aston\",\"doi\":\"10.1016/j.vascn.2024.107546\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":16767,\"journal\":{\"name\":\"Journal of pharmacological and toxicological methods\",\"volume\":\"129 \",\"pages\":\"Article 107546\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2024-07-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S105687192400056X/pdfft?md5=8e0a0c5e71d9db51cee6e01697634e4b&pid=1-s2.0-S105687192400056X-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of pharmacological and toxicological methods\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S105687192400056X\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmacological and toxicological methods","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S105687192400056X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.