Inflammatory response to cardiopulmonary bypass with enoximone or steroids in patients undergoing myocardial revascularization: a preliminary report study

Int J Clin Pharmacol Ther. 2009 Feb;47(2):78-88. doi: 10.5414/cpp47078.

Abstract

Objective: Recent reports have showed an antiinflammatory effect of phosphodiesterase III inhibitors (PDEi) in patients undergoing cardiopulmonary bypass (CPB). We sought to evaluate the immunological and hemodynamic response to enoximone and methylprednisolone in patients undergoing CABG.

Design: Prospective, randomized, controlled study.

Setting: Cardiac surgery unit in a university hospital.

Patients: 40 patients undergoing CPB-CABG.

Interventions: Patients receive enoximone (20, Group A) or methylprednisolone (20, Group B).

Measurements and main results: Hemodynamic response was evaluated by Swan-Ganz catheter serial measurements and perioperative Lactate and Troponin I leakage, immunological response was analyzed by IL-2, IL-4, IL-6, TNF-alpah, IFN-gamma, IL-10 before anesthetic induction (T0), at aortic-declamping (T1), at the end of surgery (T2), ITU admission (T3), 24 hs (T4) postoperatively. Morbidity and mortality were comparable between the two groups. Group A demonstrated higher cardiac index at T2 (2.93 l/min m2 vs 2.06, p < 0.001), at T3 (3.01 vs 2.18, p < 0.001), lower indexed systemic vascular resistance at T2 (2,044 dyne s cm-5 m-2 vs 3,132, p < 0.001). Except for higher TNF-alpha in Group B at T2 (15.89 vs 22.68, p = 0.005) proinflammatory cytokines were comparable. IL-10 was higher in Group B at any postoperative time (IL-10: T1 80.74 vs 143.3, p < 0.001, T2 165.7 vs 377.4, p < 0.001, T3 203.4 vs 443.5, p < 0,001, T4 251.8 vs 437.1, p < 0.001), whereas IL-4 and IFN-gamma proved higher in Group A at all time-points (IL-4: T1 45.9 vs 31.2, p = 0.008, T2 67.2 vs 39.7, p < 0.001, T3 77.9 vs 39.2, p < 0.001, T4 102.9 vs 42.2, p < 0.001. IFN-gamma: T1 25.8 vs 15.8, p < 0.001, T2 52.2 vs 30.3, p < 0.001, T3 78.4 vs 40.8, p < 0.001, T4 159.9 vs 67.4, p < 0.001).

Conclusions: Despite comparable major clinical endpoints enoximone showed a different antiinflammatory pattern compared to methylprednisolone, however, the better hemodynamic response in enoximone compared to methylprednisolone suggests enoximone as a potential antiinflammatory tool to improve the outcome in cardiac surgery.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Cardiopulmonary Bypass / adverse effects*
  • Enoximone / pharmacology*
  • Female
  • Hemodynamics / drug effects
  • Hospitals, University
  • Humans
  • Interferon-gamma / drug effects
  • Interferon-gamma / metabolism
  • Interleukins / metabolism
  • Male
  • Methylprednisolone / pharmacology*
  • Middle Aged
  • Myocardial Revascularization*
  • Phosphodiesterase Inhibitors / pharmacology
  • Postoperative Complications / prevention & control
  • Prospective Studies
  • Time Factors
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Interleukins
  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Enoximone
  • Methylprednisolone