Thorac Cardiovasc Surg 2007; 55 - MP_51
DOI: 10.1055/s-2007-967391

A low dose combination of clopidogrel and aspirin reduces bleeding and inflammatory mediator release after coronary artery bypass grafting in a porcine model

B Bierbach 1, D Schneider 2, M Junger 3, CF Vahl 2, O Kempski 3, G Horstick 4, M Dahm 2
  • 1Universitätsklinik, Klinik und Poliklinik für Herz-, Thorax- und Gefäßchirurgie, Homburg, Germany
  • 2Universitätsklinik Mainz, Klinik und Poliklinik für Herz-, Thorax- und Gefäßchirurgie, Mainz, Germany
  • 3Universität Mainz, Institut für Neurochirurgische Pathophysiologie, Mainz, Germany
  • 4Universitätsklinik Mainz, II. Medizinische Klinik, Mainz, Germany

Objectives: High-dose dual antiplatelet therapy (HD: clopidogrel 5mg/kg + aspirin 7mg/kg) is beneficial prior to stent implantation in acute coronary syndromes. However mediastinal bleeding complications after acute surgery are increased after such medication. We demonstrated that a low-dose combination (LD: clopidogrel 0.1mg/kg + aspirin 1mg/kg) was efficent in reducing platelet activity and subsequently eliminating thrombus formation in a model of acute coronary thrombosis. Therefore we studied the effect of this two medications on postoperative drainage volume and inflammatory mediator release.

Methods: A left internal mammary artery to the left decending coronary artery bypass utilizing extracorporal circulation (120min) and cardioplegic arrest (90min) was constructed in 24 pigs and eight pigs were sham operated. Three dose regimens were applied: HD, LD and no antiplatelet therapy (ECC). Medication was administered 4h prior to surgery via a jejunal catheter. Chest drainage was quantified every hour after surgery. Interleukin 6, 8 and TNF-α concentrations were determined.

Results: Drainage volume 4h after surgery was significantly increased in HD, whereas LD and ECC did not result in increased drainage volumes (HD: 977±226, LD: 284±160, ECC: 262±92 Sham: 159±77 [ml] p<0.05). Inflammatory mediators were significantly elevated in HD and ECC (HD: Il-6: 216.3±136.4, Il-8: 374.2±468.8, TNF-α: 466.9±186; ECC: Il-6: 234.7±146.4, Il-8: 639.7±704.9, TNF-α: 213.2±138.9[pg/ml] p<0.05). However in sham and LD no significant mediator release was observed (Sham: Il-6: 109.5±78.8, Il-8: 90.2±133.5, TNF-α: 91.1±37.5; LD: Il-6: 167.9±68.2, Il8: 46.6±12.9, TNF-α: 170.8±88.5 [pg/ml]).

Conclusions: A low-dose combination of clopidogrel and aspirin reduces bleeding and inflammatory mediator release after coronary artery bypass grafting in a porcine model. The conventionally used high-dose regime causes significant blood loss and further more generates a significantly elevated inflammatory mediator level.