Trissha Ybanez, Joshua Ingles, Eugene Du Toit, Jason Peart
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引用次数: 0
Abstract
Purpose: Myocardial reperfusion following ischaemia paradoxically exacerbates mitochondrial and thus cardiac dysfunction. Although various treatment strategies have been utilised to prevent irreversible myocardial injury, translation to positive clinical trial outcomes has been unsuccessful. This systematic review aimed to evaluate pharmacological interventions in animal models of ischaemia-reperfusion (I/R), with emphasis on cardiac and cell death outcomes and direct assessment of mitochondrial bioenergetics.
Methods: Search terms were entered into PubMed, Scopus, Embase and Web of Science. Screening, data extraction and quality assessment of papers were conducted according to the inclusion and exclusion criteria selected for this study. Eighteen papers from a total of 1571 studies were included. These studies investigated 15 drugs of interest in animals subjected to either in vivo or ex vivo I/R. Mitochondrial function parameters were assessed by measuring either mitochondrial respiration and/or enzyme activity, with 4 of these also assessing electron transport chain protein expression.
Results: Pharmaceuticals preserved mitochondrial respiratory capacity by directly targeting the electron transport chain complexes or indirectly via proteins involved in canonical cardioprotective pathways. This led to improved post-ischaemic cardiac function and reductions in markers of cellular injury and myocardial infarction.
Conclusion: Multi-targeted manipulation of components of mitochondrial signalling and function evidently reduces I/R injury. Quality assessment of most papers revealed an unclear risk of bias due to inadequate reporting of study parameters. Clear and consistent reporting of study outcomes, specifically mitochondrial bioenergetics across all experimental stages, is essential to enhance the translational potential of mitoprotective compounds in the clinical treatment of I/R.
目的：心肌缺血后再灌注矛盾地加剧了线粒体，从而加剧了心功能障碍。尽管各种治疗策略已被用于预防不可逆心肌损伤，但转化为积极的临床试验结果尚未成功。本系统综述旨在评估缺血再灌注（I/R）动物模型的药物干预，重点关注心脏和细胞死亡结果以及线粒体生物能量学的直接评估。方法：在PubMed、Scopus、Embase和Web of Science中输入检索词。根据本研究选择的纳入标准和排除标准对论文进行筛选、数据提取和质量评价。共纳入了1571项研究中的18篇论文。这些研究调查了15种感兴趣的药物在动物体内或体外I/R。通过测量线粒体呼吸和/或酶活性来评估线粒体功能参数，其中4项还评估电子传递链蛋白的表达。结果：药物通过直接靶向电子传递链复合物或间接通过参与典型心脏保护途径的蛋白质来维持线粒体呼吸能力。这导致缺血后心功能改善，细胞损伤和心肌梗死标志物减少。结论：多靶点调控线粒体信号和功能组分可明显减轻I/R损伤。大多数论文的质量评估显示，由于研究参数报告不足，存在不明确的偏倚风险。清晰和一致的研究结果报告，特别是在所有实验阶段的线粒体生物能量学，对于提高线粒体保护化合物在I/R临床治疗中的转化潜力至关重要。
期刊介绍：
Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field.
Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients.
Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.
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