Vasoplegic syndrome in cardiac surgery: role of synergism between polymorphism of tumor necrosis factor beta and plasminogen activator inhibitor type 1

Abstract

Introduction Cardiopulmonary bypass can lead to postoperative hemodynamic disorders. Several genetic polymorphisms have been studied in this setting. We investigated the possible existence of a synergism between polymorphisms of plasminogen activator inhibitor type 1 (PAI-1) and tumoral necrosis factor beta (TNF-B) on hemodynamic response after cardiac surgery. Methods We prospectively studied the association between hemodynamic response and polymorphisms of TNF-B and PAI-1 in 563 patients undergoing elective cardiac surgery during the years 2008 to 2011. We tested the Hardy-Weinberg equilibrium in the sample. V18 SPSS was used. Results We studied 563 patients. We found significant differences in TNF-B polymorphisms regarding norepinephrine requirements at 4 hours (F: 15.9; P <0.001), post hoc Scheffe (GG vs. AA, 0.32 (0.11 to 0.65) vs. 0.06 (0.04 to 0.09) mug/kg/minute, P <0.001; GG vs. AG, 0.32 (0.11 to 0.65) vs. 0.06 (0.03 to 0.08), P <0.001)) and at 24 hours (F: 8; P = 0.005), post hoc Scheffe (GG vs. AA, 0.27 (0.01 to 0.52) vs. 0.10 (0.06 to 0.14), P = 0.019; GG vs. AG, 0.27 (0.01 to 0.52) vs. 0.07 (0.04 to 0.09), P = 0.003)). Unfavorable TNF-B (G homozygous vs. allele A) and PAI-1 unfavorable (4G homozygous vs. allele 5G) were grouped, after adjusting for perioperative significant variables. The homozygous GG and 4G alleles were significant for NA 4 hours (F: 5.5; P = 0.02 and F: 4.1; P = 0.04, respectively) and GG-4G allele interaction (F: 6; P = 0.01) (Figure 1), while for NA at 24 hours statistics showed GG (F: 3.2; P = 0.07), 4G allele (F: 2; P = 0.15) and interaction (F: 3.6, P = 0.05). Conclusion GG homozygous polymorphism TNF-B is associated with an increased dependence on norepinephrine after cardiopulmonary bypass, showing a synergistic action with the 4G allele of PAI-1.