在早期再灌注期间给予1,6 - 二磷酸果糖可显著改善缺血后心脏收缩功能的恢复。

Administration of fructose 1,6-diphosphate during early reperfusion significantly improves recovery of contractile function in the postischemic heart.

作者信息

Takeuchi K, Cao-Danh H, Friehs I, Glynn P, D'Agostino D, Simplaceanu E, McGowan F X, del Nido P J

机构信息

Department of Cardiac Surgery, Children's Hospital and Harvard Medical School, Boston, Mass 02115, USA.

出版信息

J Thorac Cardiovasc Surg. 1998 Aug;116(2):335-43. doi: 10.1016/s0022-5223(98)70135-7.

DOI:10.1016/s0022-5223(98)70135-7

PMID:9699588

Abstract

OBJECTIVES

Fructose-1,6-diphosphate is a glycolytic intermediate that has been shown experimentally to cross the cell membrane and lead to increased glycolytic flux. Because glycolysis is an important energy source for myocardium during early reperfusion, we sought to determine the effects of fructose-1,6-diphosphate on recovery of postischemic contractile function.

METHODS

Langendorff-perfused rabbit hearts were infused with fructose-1,6-diphosphate (5 and 10 mmol/L, n = 5 per group) in a nonischemic model. In a second group of hearts subjected to 35 minutes of ischemia at 37 degrees C followed by reperfusion (n = 6 per group), a 5 mmol/L concentration of fructose-1,6-diphosphate was infused during the first 30 minutes of reperfusion. We measured contractile function, glucose uptake, lactate production, and adenosine triphosphate and phosphocreatine levels by phosphorus 31-nuclear magnetic resonance spectroscopy.

RESULTS

In the nonischemic hearts, fructose-1,6-diphosphate resulted in a dose-dependent increase in glucose uptake, adenosine triphosphate, phosphocreatine, and inorganic phosphate levels. During the infusion of fructose-1,6-diphosphate, developed pressure and extracellular calcium levels decreased. Developed pressure was restored to near control values by normalizing extracellular calcium. In the ischemia/reperfusion model, after 60 minutes of reperfusion the hearts that received fructose-1,6-diphosphate during the first 30 minutes of reperfusion had higher developed pressures (83 +/- 2 vs 70 +/- 4 mm Hg, p < 0.05), lower diastolic pressures (7 +/- 1 vs 12 +/- 2 mm Hg, p < 0.05), and higher phosphocreatine levels than control untreated hearts. Glucose uptake was also greater after ischemia in the hearts treated with fructose-1,6-diphosphate.

CONCLUSIONS

We conclude that fructose-1,6-diphosphate, when given during early reperfusion, significantly improves recovery of both diastolic and systolic function in association with increased glucose uptake and higher phosphocreatine levels during reperfusion.

摘要

目的

果糖-1,6-二磷酸是一种糖酵解中间产物，实验表明其可穿过细胞膜并导致糖酵解通量增加。由于糖酵解是心肌早期再灌注期间的重要能量来源，我们试图确定果糖-1,6-二磷酸对缺血后收缩功能恢复的影响。

方法

在非缺血模型中，用果糖-1,6-二磷酸（5和10 mmol/L，每组n = 5）灌注Langendorff离体兔心。在另一组于37℃经历35分钟缺血后再灌注的心脏中（每组n = 6），在再灌注的前30分钟内输注5 mmol/L浓度的果糖-1,6-二磷酸。我们通过31磷核磁共振波谱法测量收缩功能、葡萄糖摄取、乳酸生成以及三磷酸腺苷和磷酸肌酸水平。

结果

在非缺血心脏中，果糖-1,6-二磷酸导致葡萄糖摄取、三磷酸腺苷、磷酸肌酸和无机磷酸水平呈剂量依赖性增加。在输注果糖-1,6-二磷酸期间，左心室发展压和细胞外钙水平降低。通过使细胞外钙正常化，左心室发展压恢复至接近对照值。在缺血/再灌注模型中，再灌注60分钟后，在再灌注前30分钟接受果糖-1,6-二磷酸的心脏具有更高的左心室发展压（83±2对70±4 mmHg，p<0.05）、更低的舒张压（7±1对12±2 mmHg，p<0.05），并且磷酸肌酸水平高于未治疗的对照心脏。在缺血后，用果糖-1,6-二磷酸治疗的心脏的葡萄糖摄取也更高。