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DOI: 10.1055/s-2004-816769
Anti-oxidative treatment for prevention of cardiopulmonary bypass-induced pneumocyte apoptosis
Objective: Pulmonary ischemia/reperfusion has been suggested to induce pneumocyte apoptosis mediated by reactive oxygen-derived species (ROS). The purpose of our study was to investigate, if (1) pulmonary ischemia/reperfusion during standard cardiopulmonary bypass (CPB) and aortic cross-clamping induces pneumocyte apoptosis, and (2) if ROS-scavenging using N-acetylcysteine (NAC) attenuates pneumocyte apoptosis.
Methods: Eleven pigs (41±8kg) were randomized to receive either NAC (100mg/kg prior to CPB; n=7) or placebo (n=4) and subjected to CPB and 60min cold crystalloid cardioplegic arrest. We collected lung biopsies prior to CPB, at 60min CPB, as well as at 30, 60, and 120 minutes post CPB. Using polyclonal antibodies, lung specimen were immuno-cytochemically stained against nitrotyrosine as indicator for peroxynitrite (ONOO-)-mediated tissue injury and active caspase-3, an apoptosis signal-pathway key enzyme. Nitrotyrosine staining was judged using a scale from 1–4 (low to intensive staining) and caspase-3-positive pneumocytes were counted per viewfield.
Results: In the placebo group, the number of caspase-3-positive pneumocytes significantly increased over time to reach a maximum at 120min post CPB (p=0.03 vs. baseline). In contrast, NAC completely prevented caspase-3 activation in pneumocytes over time (p=0.001 vs. Placebo). Similarly, pneumocyte nitrotyrosine staining significantly increased over time (p=0.003) in the placebo group, but decreased in the NAC group (p=0.004).
Conclusions: Our data show that standard CPB and cardioplegic arrest initiate ROS-mediated tissue injury and apoptosis in pneumocytes that can be prevented by NAC. Thus, ROS-scavenging using NAC may represent a novel approach to minimize lung injury associated with CPB.