酮体3-羟基丁酸增加猪心源性休克模型的心输出量和心脏收缩力:一项随机、盲法、交叉试验

IF 7.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Oskar Kjærgaard Hørsdal, Alexander Møller Larsen, Kasper Lykke Wethelund, Frederik Flyvholm Dalsgaard, Jacob Marthinsen Seefeldt, Ole Kristian Lerche Helgestad, Niels Moeslund, Jacob Eifer Møller, Hanne Berg Ravn, Roni Ranghøj Nielsen, Henrik Wiggers, Kristoffer Berg-Hansen, Nigopan Gopalasingam
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引用次数: 0

摘要

心源性休克(CS)的特点是心输出量(CO)减少,终末器官灌注减少,死亡率高。药物治疗未能提高生存率。酮体3-羟基丁酸酯(3-OHB)对心力衰竭和CS患者的心功能有增强作用。我们的目的是阐明在CS期间3-OHB治疗对心血管和心脏代谢的影响。在随机、评估盲交叉设计中,我们研究了16头母猪(60公斤,5月龄)。左主干冠状动脉微球注射诱导CS。CS的预定义标准是一氧化碳或混合静脉饱和度(SvO2)降低30%。随机给予3-OHB静脉输注和相应对照溶液120 min。血流动力学测量是通过肺动脉导管和左心室(LV)压力-容量导管获得的。采用高分辨率呼吸仪评估心肌线粒体功能。在CS期间,与对照组相比,3-OHB输注使CO增加0.9 L/min (95%CI 0.4-1.3 L/min)。SvO2 (P = 0.026)和心率(P < 0.001)升高。卒中容量(P = 0.6)未发生改变。3-OHB输注组左室收缩末期弹性测定左室收缩功能较对照组改善(P = 0.004)。全身和肺血管阻力降低,利尿增加。3-OHB输注后左室线粒体功能高于对照组。我们得出结论,在大型缺血性CS动物模型中,3-OHB输注通过增加收缩力和降低血管阻力来增强心功能,同时也保持心肌线粒体呼吸功能。这些新发现支持了外源性酮补充剂在CS治疗中的治疗潜力。图形抽象
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock: a randomized, blinded, crossover trial

Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60 kg, 5 months of age). CS was induced by left main coronary artery microsphere injections. Predefined criteria for CS were a 30% reduction in CO or mixed venous saturation (SvO2). Intravenous 3-OHB infusion and a matching control solution were administered for 120 min in random order. Hemodynamic measurements were obtained by pulmonary artery catheterization and a left ventricular (LV) pressure–volume catheter. Myocardial mitochondrial function was assessed using high resolution respirometry. During CS, infusion with 3-OHB increased CO by 0.9 L/min (95%CI 0.4–1.3 L/min) compared with control infusion. SvO2 (P = 0.026) and heart rate (P < 0.001) increased. Stroke volume (P = 0.6) was not altered. LV contractile function as determined by LV end-systolic elastance improved during 3-OHB infusion compared with control infusion (P = 0.004). Systemic and pulmonary vascular resistance decreased, and diuresis increased. LV mitochondrial function was higher after 3-OHB infusion compared with control. We conclude that 3-OHB infusion enhances cardiac function by increasing contractility and reducing vascular resistance, while also preserving myocardial mitochondrial respiratory function in a large animal model of ischemic CS. These novel findings support the therapeutic potential of exogenous ketone supplementation in CS management.

Graphical abstract

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来源期刊
Basic Research in Cardiology
Basic Research in Cardiology 医学-心血管系统
CiteScore
16.30
自引率
5.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Basic Research in Cardiology is an international journal for cardiovascular research. It provides a forum for original and review articles related to experimental cardiology that meet its stringent scientific standards. Basic Research in Cardiology regularly receives articles from the fields of - Molecular and Cellular Biology - Biochemistry - Biophysics - Pharmacology - Physiology and Pathology - Clinical Cardiology
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