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56 GENE EXPRESSION PROFILES FOLLOWING CARDIAC SURGERY IN DIABETIC PATIENTS AND THEIR CLINICAL CORRELATION.
  1. B. Ramlawi,
  2. T. A. Khan,
  3. M. Ruel,
  4. P. Voisine,
  5. C. Bianchi,
  6. M. Boodhwani,
  7. F. W. Sellke
  1. Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Abstract

Background Diabetes mellitus (DM) is an independent risk factor for complications following cardiac surgery. We examined peripheral gene expression and clinical responses to cardiopulmonary bypass (CPB) in patients with and without DM.

Methods Skeletal muscle was harvested from non-DM (n = 5) and insulin-treated DM (n = 5) patients before and after CPB. Oligonucleotide microarrays of 12,625 genes were performed on matched samples. Postoperative weight gain, systemic vascular resistance (SVR), temperature, and vasopressor requirements were determined. Nonparametric correlation analyses were used to examine clinical and gene expression relationships.

Results Mean CPB duration was 77.5 ± 4.0 minutes. Compared to pre-CPB, peripheral tissue post-CPB revealed 626 up-regulated and 348 down-regulated genes in non-DM vs 420 up-regulated and 473 down-regulated genes in DM patients (p < .001). Mean percent weight gain was 4.5 ± 1.4%. Expression of TR3, a nuclear receptor that mediates vascular endothelial cell function, was shown to negatively correlate with percent weight gain. When compared to non-DM, patients with DM had greater weight gain (1.8% ± 0.56 vs 7.3 ± 2.0%, non-DM vs DM, p = .03), which correlated with lower levels of TR3 expression (post/pre-CPB ratio 7.6 ± 3.3 vs 1.7 ± 0.3, non-DM vs DM; Spearman's rank correlation r = -.68, p = .03). SVR, temperature, and vasopressor requirements were not significantly different in non-DM and DM.

Conclusions The gene expression profile following CPB is quantitatively and qualitatively different in diabetic patients. Clinical correlation suggests that differential TR3 expression is associated with postoperative weight gain, likely due to vascular endothelial dysfunction and tissue edema. These results have possible implications for the design of tailored operative strategies for diabetic patients undergoing CPB.

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