Vascular Endothelial Growth Factor Improves Myocardial Functional Recovery Following Ischemia/Reperfusion Injury
Vascular Endothelial Growth Factor Improves Myocardial Functional Recovery Following Ischemia/Reperfusion Injury
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DOI：
10.1016/j.jss.2007.12.772
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发表时间：
2008-12-01
影响因子：
2.2
通讯作者：
Meldrum, Daniel R.
中科院分区：
文献类型：
--
作者：
Guzman, Michael J.;Crisostomo, Paul R.;Meldrum, Daniel R.
背景。血管内皮生长因子（VEGF）是内皮细胞和心肌细胞的中心生长和生存因子。最近的证据也表明，VEGF可能在干细胞介导的旁分泌心脏保护中发挥关键作用。然而，外源性VEGF对缺血后心肌的急性作用，以及单独分离的VEGF是否可能是一种临床有用的治疗方式，仍然未知。我们假设在缺血前立即输注外源性VEGF将改善心肌功能恢复。材料和方法。采用Langendorff模型对成年雄性大鼠心脏进行分离和灌注。所有心脏均进行15分钟的平衡，25分钟的全心热缺血和40分钟的再灌注。实验心脏缺血前立即接受3倍生理剂量（13 nM, n = 4）、5倍生理剂量（20 nM, n = 4）或10倍生理剂量（40 nM, n = 5）的VEGF输注。对照组（n = 5）输注灌注物。连续记录功能指标（左室发育压）、舒张末压、+/- dP/dt。缺血/再灌注后舒张末期压（mmHg）升高。然而，灌注10倍VEGF的心脏与对照组相比，在整个再灌注过程中舒张末期压明显降低（P < 0.05，方差分析和Bonferroni’s）（再灌注结束时49.82 +/- 10.35 mmHg与80.73 +/- 6.08 mmHg）。10x vegf处理的心脏也表现出显著（P < 0.05，方差分析和Bonferroni’s）更大的左心室发展压力恢复（69.97 +/- 9.69%对39.74 +/- 7.01%的平衡），+dP/dt和-dP/dt在再灌注结束时。然而，3倍或5倍VEGF均不能改善缺血后的恢复。血管内皮生长因子对缺血后冠状动脉血流无影响。这是首次证明外源性VEGF能显著改善缺血后心肌功能恢复。这些发现可能有助于阐明VEGF在急性干细胞介导的旁分泌效应中的作用，并表明分离的VEGF可能具有治疗价值。(C) 2008爱思唯尔公司版权所有。
Background. Vascular endothelial growth factor (VEGF) is a central growth and survival factor for both the endothelium and the myocardium. Recent evidence also suggests that VEGF may play a critical role in stem-cell-mediated paracrine cardioprotection. However, the acute effect of exogenous VEGF on myocardium after ischemia, indeed whether isolated VEGF alone may be a clinically useful therapeutic modality, remains unknown. We hypothesize that infusion of exogenous VEGF immediately prior to ischemia will improve myocardial functional recovery.Materials and methods. Adult male Sprague Dawley rat hearts were isolated and perfused via Langendorff model. All hearts were subject to 15-min equilibration, 25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received a VEGF infusion of 3x physiological (13 nM, n = 4), 5x physiological (20 nM, n = 4), or 10x physiological (40 nM, n = 5) immediately prior to ischemia. Controls (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular developed pressure), end diastolic pressure, +/- dP/dt were continuously recorded.Results. End diastolic pressure (mmHg) was elevated in response to ischemia/reperfusion. However, hearts infused with 10x VEGF demonstrated significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end diastolic pressure throughout reperfusion compared to control (49.82 +/- 10.35 mmHg versus 80.73 +/- 6.08 mmHg at end reperfusion). 10x VEGF-treated hearts also exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater recovery of left ventricular developed pressure (69.97 +/- 9.69% versus 39.74 +/- 7.01% of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither 3x nor 5 x VEGF improved recovery after ischemia. VEGF also did not influence coronary flow after ischemia.Conclusion. This is the first demonstration that exogenous VEGF administration acutely improves myocardial functional recovery after ischemia. These findings may help elucidate the role of VEGF in acute stem-cell-mediated paracrine effects and suggests that isolated VEGF may be of therapeutic value. (C) 2008 Elsevier Inc. All rights reserved.