丙酮酸乙酯可在长时间心肌缺血后维持心脏功能并减轻氧化损伤。

Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia.

作者信息

Woo Y Joseph, Taylor Matthew D, Cohen Jeffrey E, Jayasankar Vasant, Bish Lawrence T, Burdick Jeffrey, Pirolli Timothy J, Berry Mark F, Hsu Vivian, Grand Todd

机构信息

Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

出版信息

J Thorac Cardiovasc Surg. 2004 May;127(5):1262-9. doi: 10.1016/j.jtcvs.2003.11.032.

DOI:10.1016/j.jtcvs.2003.11.032

PMID:15115981

Abstract

OBJECTIVE

Myocardial injury and dysfunction following ischemia are mediated in part by reactive oxygen species. Pyruvate, a key glycolytic intermediary, is an effective free radical scavenger but unfortunately is limited by aqueous instability. The ester derivative, ethyl pyruvate, is stable in solution and should function as an antioxidant and energy precursor. This study sought to evaluate ethyl pyruvate as a myocardial protective agent in a rat model of ischemia-reperfusion injury.

METHODS

Rats underwent 30-minute ischemia and 30-minute reperfusion of the left anterior descending coronary artery territory. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of either ethyl pyruvate (n = 26) or vehicle control (n = 26). Myocardial high-energy phosphate levels were determined by adenosine triphosphate assay, oxidative injury was measured by lipid peroxidation assay, infarct size was quantified by triphenyltetrazolium chloride staining, and cardiac function was assessed in vivo.

RESULTS

Ethyl pyruvate administration significantly increased myocardial adenosine triphosphate levels compared with control (87.6 +/- 29.2 nmol/g vs 10.0 +/- 2.4 nmol/g, P =.03). In ischemic myocardium, ethyl pyruvate reduced oxidative injury compared with control (63.8 +/- 3.3 nmol/g vs 89.5 +/- 3.0 nmol/g, P <.001). Ethyl pyruvate diminished infarct size as a percentage of area at risk (25.3% +/- 1.5% vs 33.6% +/- 2.1%, P =.005). Ethyl pyruvate improved myocardial function compared with control (maximum pressure: 86.6 +/- 2.9 mm Hg vs 73.5 +/- 2.5 mm Hg, P <.001; maximum rate of pressure rise: 3518 +/- 243 mm Hg/s vs 2703 +/- 175 mm Hg/s, P =.005; maximal rate of ventricular systolic volume ejection: 3097 +/- 479 microL/s vs 2120 +/- 287 microL/s, P =.04; ejection fraction: 41.9% +/- 3.8% vs 31.4% +/- 4.1%, P =.03; cardiac output: 26.7 +/- 0.9 mL/min vs 22.7 +/- 1.3 mL/min, P =.01; and end-systolic pressure-volume relationship slope: 1.09 +/- 0.22 vs 0.59 +/- 0.2, P =.02).

CONCLUSIONS

In this study of myocardial ischemia-reperfusion injury, ethyl pyruvate enhanced myocardial adenosine triphosphate levels, attenuated myocardial oxidative injury, decreased infarct size, and preserved cardiac function.

摘要

目的

缺血后心肌损伤和功能障碍部分是由活性氧介导的。丙酮酸作为糖酵解的关键中间产物，是一种有效的自由基清除剂，但遗憾的是其在水溶液中不稳定，限制了应用。丙酮酸乙酯这种酯衍生物在溶液中稳定，应可作为抗氧化剂和能量前体发挥作用。本研究旨在评估丙酮酸乙酯在大鼠缺血再灌注损伤模型中作为心肌保护剂的效果。

方法

大鼠接受左前降支冠状动脉区域30分钟的缺血和30分钟的再灌注。在缺血和再灌注前即刻，动物分别接受静脉推注丙酮酸乙酯（n = 26）或溶剂对照（n = 26）。通过三磷酸腺苷测定法测定心肌高能磷酸水平，通过脂质过氧化测定法测量氧化损伤，通过氯化三苯基四氮唑染色定量梗死面积，并在体内评估心脏功能。

结果

与对照组相比，给予丙酮酸乙酯显著提高了心肌三磷酸腺苷水平（87.6±29.2 nmol/g对10.0±2.4 nmol/g，P = 0.03）。在缺血心肌中，与对照组相比，丙酮酸乙酯减少了氧化损伤（63.8±3.3 nmol/g对89.5±3.0 nmol/g，P <0.001）。丙酮酸乙酯使梗死面积占危险区域面积的百分比降低（25.3%±1.5%对33.6%±2.1%，P = 0.005）。与对照组相比，丙酮酸乙酯改善了心肌功能（最大压力：86.6±2.9 mmHg对73.5±2.5 mmHg，P <0.001；最大压力上升速率：3518±243 mmHg/s对2703±175 mmHg/s，P = 0.005；心室收缩期容积最大射血速率：3097±479 μL/s对2120±287 μL/s，P = 0.04；射血分数：41.9%±3.8%对31.4%±4.1%，P = 0.03；心输出量：26.7±0.9 mL/min对22.7±1.3 mL/min，P = 0.01；收缩末期压力-容积关系斜率：1.09±0.22对0.59±0.2，P = 0.02）。