Burton P B, Owen V J, Hafizi S, Barton P J, Carr-White G, Koh T, De Souza A, Yacoub M H, Pepper J R
Cardiothoracic Surgery, Imperial College School of Medicine at the National Heart and Lung Institute, London, U.K.
Eur Heart J. 2000 Oct;21(20):1708-13. doi: 10.1053/euhj.2000.2177.
The aim of this study was to examine the circulating levels of vascular endothelial growth factor, following coronary artery bypass graft surgery performed using both standard cardiopulmonary bypass or the 'octopus technique' on the beating heart.
Vascular endothelial growth factor has a number of effects that are beneficial in the setting of coronary artery bypass graft surgery including cardioprotection, potent angiogenic activity and amelioration of intimal hyperplasia. Hypoxia is a powerful stimulator of vascular endothelial growth factor expression yet the ability of ischaemia, occurring during coronary artery bypass graft surgery, to induce vascular endothelial growth factor production is unknown.
Serum vascular endothelial growth factor levels were determined in patients undergoing coronary artery bypass graft surgery with standard cardiopulmonary bypass (CPB-CABG group; n=20), with off-pump coronary artery bypass; (OP-CABG; n=12) and in patients undergoing non-cardiac major surgery (n=6). The effect of hypoxia on vascular endothelial growth factor release by neonatal rat cardiac myocytes in vitro was studied. In the CPB-CABG group vascular endothelial growth factor levels were significantly increased to 78.5+/-39.3 and 110.5+/-16.3 pg. microl(-1)8 and 24 h post-operatively, declining to 14.9+/-9.9 pg. microl(-1)by 48 h to pre-operative values (14.4+/-8.6 pg. microl(-1)). Significantly higher vascular endothelial growth factor levels were also present in the OP-CABG group 3, 6 and 24 h post-operatively (levels 136. 6+/-29.3, 143+/-26.12 pg. microl(-1)and 93.5+/-20.1 pg. microl(-1), respectively). However, non-cardiac major surgery did not result in elevated vascular endothelial growth factor levels post-operatively (46.36+/-9.76 vs pre-surgery levels of 26.84+/-6.1 pg. microl(-1)). Either 15 min or 3 h of hypoxia stimulated vascular endothelial growth factor release from neonatal rat cardiac myocytes in vitro. Twenty-four and 48 h post hypoxia, levels of vascular endothelial growth factor were significantly elevated by approximately 17.5- and 48.5-fold respectively.
These data demonstrate myocardial ischaemia secondary to CPB-CABG and OP-CABG to be a potent stimulator of vascular endothelial growth factor production, which may have implications for graft endothelialization and cardiovascular haemodynamics post-operatively.
本研究旨在检测在使用标准体外循环或心脏跳动下的“章鱼技术”进行冠状动脉旁路移植术后血管内皮生长因子的循环水平。
血管内皮生长因子具有多种在冠状动脉旁路移植手术中有益的作用,包括心脏保护、强大的血管生成活性和内膜增生的改善。缺氧是血管内皮生长因子表达的有力刺激因素,但冠状动脉旁路移植手术期间发生的缺血诱导血管内皮生长因子产生的能力尚不清楚。
测定接受标准体外循环冠状动脉旁路移植术的患者(体外循环冠状动脉旁路移植术组;n = 20)、非体外循环冠状动脉旁路移植术患者(非体外循环冠状动脉旁路移植术组;n = 12)以及接受非心脏大手术的患者(n = 6)的血清血管内皮生长因子水平。研究了缺氧对新生大鼠心肌细胞体外释放血管内皮生长因子的影响。在体外循环冠状动脉旁路移植术组中,术后8小时和24小时血管内皮生长因子水平显著升高至78.5±39.3和110.5±16.3 pg/μl,到48小时降至14.9±9.9 pg/μl,恢复到术前值(14.4±8.6 pg/μl)。非体外循环冠状动脉旁路移植术组术后3小时、6小时和24小时血管内皮生长因子水平也显著更高(水平分别为136.6±29.3、143±26.12 pg/μl和93.5±20.1 pg/μl)。然而,非心脏大手术术后并未导致血管内皮生长因子水平升高(46.36±9.76 vs术前水平26.84±6.1 pg/μl)。缺氧15分钟或3小时均可刺激新生大鼠心肌细胞体外释放血管内皮生长因子。缺氧后24小时和48小时,血管内皮生长因子水平分别显著升高约17.5倍和48.5倍。
这些数据表明,体外循环冠状动脉旁路移植术和非体外循环冠状动脉旁路移植术继发的心肌缺血是血管内皮生长因子产生的有力刺激因素,这可能对术后移植物内皮化和心血管血流动力学有影响。