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聚乙二醇化牛羧基血红蛋白(SANGUINATE)可改善大鼠模型中的心肌梗死。

PEGylated carboxyhemoglobin bovine (SANGUINATE) ameliorates myocardial infarction in a rat model.

作者信息

Kawaguchi Akira T, Salybekov Amankeldi A, Yamano Mariko, Kitagishi Hiroaki, Sekine Kaori, Tamaki Tetsuro

机构信息

Cell Transplantation and Regenerative Medicine, Tokai University, Kanagawa, Japan.

Department of Rehabilitation, Osaka Prefecture University, Osaka, Japan.

出版信息

Artif Organs. 2018 Dec;42(12):1174-1184. doi: 10.1111/aor.13384.

DOI:10.1111/aor.13384
PMID:30375680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6590322/
Abstract

Artificial oxygen (O ) carriers were reported to be protective in ischemia/reperfusion (I/R) in various organs including the heart. In the current study, 20 rats underwent ligation (MI) of the left anterior descending artery, were treated with 10 mL/kg of PEGylated carboxyhemoglobin bovine (SANGUINATE, S+, n = 10) or saline (S-, n = 10) 10 minutes after MI and daily thereafter for 3 days, and were followed by weekly echocardiography for 4 weeks, when they had left ventricular pressure volume relationship (PVR) analyses followed by necropsy. Echocardiography showed an increase in end-systolic dimension rather than end-diastolic dimension, preserved fractional shortening (36 vs. 26%, P < .01), and milder mitral regurgitation in S+ compared with S- rats. PVR revealed a milder increase in end-systolic volume, larger stroke volume (101 vs. 74 μL, P < .005) and cardiac output (33.4 vs. 23.8 mL/min, P = .004) in S+ rats in actual determination and under a wide range of standardized loading conditions 4 weeks after MI. Excised heart showed significantly limited area of MI (8.9 vs. 13.3%, P = .028). The results suggest that SANGUINATE in short-term repeated doses may accelerate weight recovery, preserving the myocardium, mitral competence, and cardiac function after MI. The mechanism of action and optimal treatment for MI remain to be studied.

摘要

据报道,人工氧(O)载体对包括心脏在内的各种器官的缺血/再灌注(I/R)具有保护作用。在本研究中,20只大鼠接受左前降支动脉结扎(MI),在MI后10分钟用10 mL/kg聚乙二醇化牛羧基血红蛋白(SANGUINATE,S+,n = 10)或生理盐水(S-,n = 10)治疗,此后每天治疗3天,并在4周内每周进行超声心动图检查,之后进行左心室压力容积关系(PVR)分析,然后进行尸检。超声心动图显示,与S-大鼠相比,S+大鼠的收缩末期内径增加而非舒张末期内径增加,保留了分数缩短率(36%对26%,P <.01),二尖瓣反流较轻。PVR显示,在MI后4周的实际测定中以及在广泛的标准化负荷条件下,S+大鼠的收缩末期容积增加较轻,每搏输出量较大(101 μL对74 μL,P <.005),心输出量较高(33.4 mL/min对23.8 mL/min,P =.004)。切除的心脏显示MI面积明显受限(8.9%对13.3%,P =.028)。结果表明,短期重复剂量的SANGUINATE可能会加速体重恢复,在MI后保留心肌、二尖瓣功能和心脏功能。MI的作用机制和最佳治疗方法仍有待研究。

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本文引用的文献

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J Am Chem Soc. 2016 Apr 27;138(16):5417-25. doi: 10.1021/jacs.6b02211. Epub 2016 Apr 18.
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Left ventricular remodeling after acute myocardial infarction: the influence of viability and revascularization - an echocardiographic substudy of the VIAMI-trial.
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Biology (Basel). 2022 Jan 10;11(1):106. doi: 10.3390/biology11010106.
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Extracellular Vesicles Derived From Regeneration Associated Cells Preserve Heart Function After Ischemia-Induced Injury.源自再生相关细胞的细胞外囊泡在缺血诱导损伤后可维持心脏功能。
Front Cardiovasc Med. 2021 Oct 20;8:754254. doi: 10.3389/fcvm.2021.754254. eCollection 2021.
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