P232 Myocardial apoptosis initiation in CABG patients can be prevented by using the radical-scavenger N-acetylcysteine.
1P.Tossios, 1A.Hübner, 2W.Bloch, 3F.Dodos, 1R.Raji, 1U.M.Fischer, 1O.Klass, 1M.Südkamp, 4S.-M.Kasper, 5M.Hellmich, 1U.Mehlhorn
1Department of Cardiothoracic Surgery, University of Cologne, Cologne; 2Department of Anatomy, University of Cologne, Cologne; 3Department of Cardiology, University of Cologne, Cologne; 4Department of Anesthesiology, University of Cologne, Cologne; 5Department for Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne.

Objective: Reactive oxygen-derived species (ROS) have been suggested to be involved in apoptosis induction. We have shown that 1) cardioplegic arrest initiates myocardial apoptosis and 2) the ROS-scavenger N-acetylcysteine (NAC) attenuates direct ROS-mediated myocardial tissue injury. The purpose of our study was to investigate, if NAC prevents myocardial apoptosis initiation in cardiac surgery patients.

Methods: Forty coronary artery surgery patients subjected to cardiopulmonary bypass (CPB) and cardioplegic arrest were randomized in a double-blind fashion to receive either NAC (100 mg/kg into CPB prime followed by infusion at 20 mg/kg/h; n=20) or Placebo (n=20). We collected transmural LV biopsies prior to CPB and at CPB-end. Using polyclonal antibodies LV specimen were immuno-cytochemically stained against active caspase-3, an apoptosis signal-pathway key enzyme. Staining was quantitatively determined using densitometry. LV function was assessed by transesophageal echocardiography.

Results: Biometric and intraoperative patient data were similar between both groups. In the Placebo group, LV cardiac myocyte staining was significantly increased by 7.1±8.1 gray units at CPB-end (p=.002), demonstrating caspase-3 activation. In contrast, NAC prevented caspase-3 activation (-3.1±4.5 gray units at CPB-end; p<.0001 vs Placebo). Hemodynamics including LV function and cardiac index as well as clinical outcome were similar between NAC and Placebo.

Conclusions: Our data show that cardioplegic arrest initiates apoptosis signal-pathway in human LV myocardium that can be prevented by ROS-scavenging using NAC.