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J Thorac Cardiovasc Surg 2009;138:185-191
© 2009 The American Association for Thoracic Surgery

Perioperative Management

Increased vascular permeability after cardiopulmonary bypass in patients with diabetes is associated with increased expression of vascular endothelial growth factor and hepatocyte growth factor

Sirisha Emani, PhD, Basel Ramlawi, MD, Neel R. Sodha, MD, Jian Li, MD, PhD, Cesario Bianchi, MD, PhD, Frank W. Sellke, MD*

Cardiovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass

Received for publication March 3, 2008; revisions received December 8, 2008; accepted for publication December 25, 2008.

* Address for reprints: Frank W. Sellke, MD, 110 Francis St, Suite 2A, Boston, MA 02215. (Email: fsellke{at}bidmc.harvard.edu).

Background: Several inflammatory mediators such as vascular endothelial growth factor and hepatocyte growth factor are known to play a critical role in the regulation of vascular permeability and angiogenesis. We studied the serum levels of growth factors and gene expression profiles of genes involved in growth factor signaling in the peripheral blood of patients with and patients without diabetes following cardiopulmonary bypass and cardioplegic arrest.

Methods: Serum and total RNA were obtained from the blood samples collected from patients with diabetes and matched patients without diabetes (n = 7 patients each) who had coronary artery bypass graft before and 6 hours and 4 days after cardiopulmonary bypass/cardioplegic arrest. The cytokine panel, consisting of growth factors such as vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor, and epidermal growth factor, was quantified in patients with diabetes and patients without diabetes before and 6 hours and 4 days post–cardiopulmonary bypass/cardioplegic arrest using multiplex cytokine quantification system. cDNA microarray analysis was performed and fold-change was calculated.

Results: Length of hospitalization (10 vs 6 days; P = .04) and weight gain (5 vs 2.5 kg; P = .001) were significantly greater for patients with diabetes compared with patients without diabetes. The serum levels of vascular endothelial growth factor and hepatocyte growth factor were significantly elevated in patients with diabetes when compared with patients without diabetes before versus 6 hours post–cardiopulmonary bypass/cardioplegic arrest. In addition, significantly elevated mRNA expression of hypoxia-inducible factor-1{alpha}, cyclic adenosine monophosphate response element binding protein, and E1A binding protein p300 (more than twofold) was observed 4 days post–cardiopulmonary bypass/cardioplegic arrest exclusively in patients with diabetes.

Conclusions: The differential profile of gene and protein expression of growth factors and their related genes in patients with diabetes and patients without diabetes could be associated with increased edema and weight gain in patients with diabetes after cardiopulmonary bypass/cardioplegic arrest.

Abbreviations and Acronyms CABG = coronary artery bypass grafting; CPB = cardiopulmonary bypass; CREB = cyclic adenosine monophosphate response element binding protein; CRP = C-reactive protein; DM = diabetes mellitus; EP300 = E1A binding protein p300; HGF = hepatocyte growth factor; HIF-1{alpha} = hypoxia-inducible factor-1{alpha}; PCR = polymerase chain reaction; RMA = Robust Multichip average; VEGF = vascular endothelial growth factor






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