ENDOTHELIAL-DEPENDENT VASCULAR REACTIVITY AFTER CARDIOPULMONARY BYPASS IS ASSOCIATED WITH UNIQUE METABOLOMIC SIGNATURES.

IF 2.7 3区医学 Q2 CRITICAL CARE MEDICINE

SHOCK Pub Date : 2024-11-01 Epub Date: 2024-08-12 DOI:10.1097/SHK.0000000000002446

Ryan J Stark, Alexandra C Schrimpe-Rutledge, Simona G Codreanu, Stacy D Sherrod, John A McLean, Luke T Krispinsky, Fred S Lamb

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引用次数: 0

Abstract

Abstract: Cardiopulmonary bypass (CPB), an extracorporeal method necessary for the surgical correction of complex congenital heart defects, incites significant inflammation that affects vascular function. These changes are associated with alterations in cellular metabolism that promote energy production to deal with this stress. Utilizing laser Doppler perfusion monitoring coupled with iontophoresis in patients undergoing corrective heart surgery, we hypothesized that temporal, untargeted metabolomics could be performed to assess the link between metabolism and vascular function. Globally, we found 2,404 unique features in the plasma of patients undergoing CPB. Metabolites related to arginine biosynthesis were the most altered by CPB. Correlation of metabolic profiles with endothelial-dependent (acetylcholine [ACh]) or endothelial-independent (sodium nitroprusside [SNP]) vascular reactivity identified purine metabolism being most consistently associated with either vascular response. Concerning ACh-mediated responses, acetylcarnitine levels were most strongly associated, while glutamine levels were associated with both ACh and SNP responsiveness. These data provide insight into the metabolic landscape of children undergoing CPB for corrective heart surgery and provide detail into how these metabolites relate to physiological aberrations in vascular function.

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心肺旁路术后内皮依赖性血管反应与独特的代谢组学特征有关。

摘要：心肺旁路（CPB）是手术矫正复杂先天性心脏缺陷所必需的一种体外方法，会引发严重的炎症，影响血管功能。这些变化与细胞新陈代谢的改变有关，细胞新陈代谢会促进能量的产生以应对这种压力。通过对接受心脏矫正手术的患者进行激光多普勒灌注监测和离子透入疗法（LDPMI），我们假设可以进行时间性、非靶向代谢组学研究，以评估代谢与血管功能之间的联系。从全球范围来看，我们在接受 CPB 的患者血浆中发现了 2404 个独特的特征。与精氨酸生物合成相关的代谢物受 CPB 影响最大。代谢特征与内皮依赖性（乙酰胆碱，ACh）或内皮非依赖性（硝普钠，SNP）血管反应性的相关性发现，嘌呤代谢与这两种血管反应的关系最为一致。在乙酰胆碱介导的反应中，乙酰肉碱水平的相关性最强，而谷氨酰胺水平与乙酰胆碱和 SNP 反应性都有关联。这些数据让我们了解了接受 CPB 进行心脏矫正手术的儿童的代谢情况，并详细说明了这些代谢物与血管功能生理异常的关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

SHOCK 医学-外科

CiteScore

6.20

自引率

3.20%

发文量

199

审稿时长

1 months

期刊介绍： SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.