Abstract 3271: Up-regulation of Vascular Extracellular Superoxide Dismutase With Oxidative Stress in Acute Phase- Congestive Heart Failure

Background: In an acute exacerbation phase of congestive heart failure (CHF), reactive oxygen species (ROS) plays a pivotal role. However, an imbalance of ROS and defensive mechanisms against ROS is not fully understood. This study was undertaken to elucidate whether urinary 8-isoprostane (u-8-isoP), an oxygen stress marker, and vascular extracellular superoxide dismutase (EC-SOD), a major vascular anti-oxidative enzyme, would change in the course of CHF. Methods: Twenty patients (9 male, 69.6 (SD 12.1) y.o.) with CHF were studied u-8-isoP, plasma EC-SOD, BNP, ANP, angiotensin II and other parameters at acute and recovered stages, which was defined when NYHA classification was improved at least one class. Endothelium-bound level of EC-SOD was calculated as the difference between basal and post-heparin (15minutes after 100IU/kg injection intravenously) values. Age-sex-matched subjects were also employed as control (n=20, 9 male, 63.7(11.9) y.o.) and evaluated the same parameters at 14 days interval. Results: Patients with acute-CHF were recovered from NYHA class 3.9 (0.3) to 2.1(0.2) by 16.3(7.3) days interval. Basal and endothelium-bound levels of EC-SOD significantly elevated at acute stage (114.3 (54.8) and 187.0 (95.8) ng/ml) compared to those at recovered stage (92.9 (44.7) and 119.0 (45.4) ng/ml, p=0.019, p=0.007, respectively). Similarly, u-8-isoP also increased at acute phase (134.8 (83.5) pg/mg cr.) and significantly decreased to 88.4(60.6)pg/mg cr. (p=0.0007). The values of EC-SOD were well correlated with the plasma level of BNP or ANP, NYHA classification and heart rate, but not with u-8-isoP. Endothelium-bound EC-SOD at acute phase was also correlated with plasma angiotensin II (r=0.551, p=0.012). By contrast, the levels of u-8-isoP and EC-SOD were not changed in control group after similar intervals (14 days). Conclusion: This study suggests in the first time that the significant increase of vascular EC-SOD and u-8-isoP are recognized in acute-CHF and provides a clue of therapeutic potency of defensive mechanisms against ROS in severe CHF.