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European Heart Journal 2000 21(20):1708-1713; doi:10.1053/euhj.2000.2177
Copyright © 2000 by the European Society of Cardiology.
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Vascular endothelial growth factor release following coronary artery bypass surgery: extracorporeal circulation versus ‘beating heart’ surgery

P.B.J Burtona,f1, V.J Owena, S Hafizia, P.J.R Bartona, G Carr-Whiteb, T Kohb, A De Souzaa, M.H Yacouba and J.R Peppera

a Cardiothoracic Surgery, Imperial College School of Medicine at the National Heart and Lung Institute, London, U.K.
b Cardiac Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, U.K.

revised February 28, 2000; accepted March 1, 2000

Abstract

Aims 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.

Background 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.

Methods and Results 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±16·3pg.µl–18 and 24h post-operatively, declining to 14·9±9·9pg.µl–1by 48h to pre-operative values (14·4±8·6pg.µl–1). Significantly higher vascular endothelial growth factor levels were also present in the OP-CABG group 3, 6 and 24h post-operatively (levels 136·6±29·3, 143±26·12pg.µl–1and 93·5±20·1pg.µl–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±6·1pg.µl–1). Either 15min or 3h of hypoxia stimulated vascular endothelial growth factor release from neonatal rat cardiac myocytes in vitro. Twenty-four and 48h post hypoxia, levels of vascular endothelial growth factor were significantly elevated by approximately 17·5- and 48·5-fold respectively.

Conclusions 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.

Key Words: Vascular endothelial growth factor, bypass surgery, beating heart

f1 Correspondence: Paul Burton, BSc, MB, BS, PhD, Cardiothoracic Surgery, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY.

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