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丙酮酸乙酯可提高非体外循环冠状动脉搭桥大鼠模型的ATP水平,减轻氧化应激并维持心脏功能。

Ethyl pyruvate enhances ATP levels, reduces oxidative stress and preserves cardiac function in a rat model of off-pump coronary bypass.

作者信息

Taylor Matthew D, Grand Todd J, Cohen Jeffrey E, Hsu Vivien, Liao George P, Zentko Suzanne, Berry Mark F, Gardner Timothy J, Woo Y Joseph

机构信息

University of Pennsylvania School of Medicine, Division of Cardiothoracic Surgery, Department of Surgery, Silverstein 4, 3400 Spruce Street, Philadelphia, PA 19104, USA.

出版信息

Heart Lung Circ. 2005 Mar;14(1):25-31. doi: 10.1016/j.hlc.2004.12.021.

Abstract

BACKGROUND

Off-pump coronary artery bypass grafting is associated with transient periods of myocardial ischemia during revascularization resulting in myocardial contractile dysfunction and oxidative injury. The purpose of this study was to investigate the efficacy of ethyl pyruvate as a myocardial protective agent in a rat model of off-pump coronary artery bypass grafting associated with transient myocardial dysfunction without infarction.

METHODS

Wistar rats were subjected to transient ischemia via 10 min occlusion of the LAD coronary artery followed by 10 min of reperfusion. Animals received an IV bolus of Ringer's solution as a control (n=10) or Ringer's ethyl pyruvate (n=10) immediately before the initiation of ischemia and reperfusion. Myocardial ATP and lipid peroxidation levels were quantified for an estimation of energetics and oxidative stress, respectively. In vivo cardiac function was assessed throughout the ischemia and reperfusion periods.

RESULTS

Ethyl pyruvate significantly increased myocardial ATP levels compared to controls (2650+/-759 nmol/g versus 892+/-276 nmol/g, p=0.04). Myocardial oxidative stress was significantly reduced in animals treated with ethyl pyruvate compared to controls (70.4+/-2.6 nmol/g versus 81.8+/-2.4 nmol/g, p=0.04). dP/dt max and cardiac output were significantly greater in the ethyl pyruvate group compared to controls during ischemia and reperfusion.

CONCLUSIONS

Ethyl pyruvate enhances myocardial ATP levels, reduces oxidative stress, and preserves myocardial function in a model of transient ischemia/reperfusion injury not subject to myocardial infarction.

摘要

背景

非体外循环冠状动脉搭桥术在血管重建过程中会出现短暂的心肌缺血,导致心肌收缩功能障碍和氧化损伤。本研究的目的是在非体外循环冠状动脉搭桥术相关的短暂心肌功能障碍但无梗死的大鼠模型中,研究丙酮酸乙酯作为心肌保护剂的疗效。

方法

Wistar大鼠通过结扎左冠状动脉10分钟然后再灌注10分钟来诱导短暂缺血。在缺血和再灌注开始前,动物接受静脉推注林格氏液作为对照(n = 10)或丙酮酸乙酯林格氏液(n = 10)。分别对心肌ATP和脂质过氧化水平进行定量,以评估能量代谢和氧化应激。在整个缺血和再灌注期间评估体内心脏功能。

结果

与对照组相比,丙酮酸乙酯显著提高了心肌ATP水平(2650±759 nmol/g对892±276 nmol/g,p = 0.04)。与对照组相比,用丙酮酸乙酯治疗的动物心肌氧化应激显著降低(70.4±2.6 nmol/g对81.8±2.4 nmol/g,p = 0.04)。在缺血和再灌注期间,丙酮酸乙酯组的dP/dt max和心输出量显著高于对照组。

结论

在非心肌梗死的短暂缺血/再灌注损伤模型中,丙酮酸乙酯可提高心肌ATP水平,降低氧化应激,并保护心肌功能。

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