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Systemic plasma vascular endothelial growth factor levels as a marker for increased angiogenesis during the single ventricle surgical pathway

^a Division of Cardiothoracic Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
^b Division of Cardiothoracic Surgery, Children's Heart Center, Wilhelmina Kinder Ziekenhuis, University of Utrecht, Utrecht, The Netherlands
^c Division of Cardiology, Children's Heart Center, Wilhelmina Kinder Ziekenhuis, University of Utrecht, Utrecht, The Netherlands

^* Corresponding author. Afdeling Cardiothoracale Chirurgie, Academic Medical Center, Postbus 22660, 1100 DD Amsterdam, The Netherlands. Tel.: +31-20-566-6005; fax: +31-20-696-2289
a.dodgekhatami{at}amc.uva.nl

Cyanosis and the cavopulmonary anastomosis (CPA) are associated with pulmonary arterio-venous malformations (PAVMs) in single ventricle physiology. Vascular endothelial growth factor (VEGF) may be a marker of abnormal angiogenesis in this setting. Plasma VEGF levels were measured in 14 patients undergoing the surgical pathway leading to total cavopulmonary connection (TCPC). Venous blood samples were taken before and then months after CPA , and immediately before TCPC and 1 month thereafter . Corresponding arterial saturations were correlated with VEGF levels at each time frame. In six patients, pre-CPA plasma VEGF levels rose from a mean of 24.4–112.4 pg/ml just prior to completion of TCPC. In nine patients, VEGF levels diminished from 115.7 to 48.9 pg/ml after TCPC. VEGF levels were disproportionately elevated to arterial saturations most notably after CPA , suggesting an additional angiogenic stimulus besides cyanosis. Plasma VEGF levels fluctuate during the single ventricle surgical pathway, with maximal levels after CPA, and regression after completion of TCPC. High VEGF levels are disproportionate to hypoxia after CPA, potentially incriminating the absence of hepatic flow to the lungs as an abnormal angiogenic stimulus. Measuring VEGF in venous blood may serve as a biochemical marker of angiogenesis after CPA.

Key Words: Vascular endothelial growth factor; Single ventricle; Angiogenesis