Abstract P322: Chamber-Specific Differences in Oxidative Stress in Newborn Versus Adult Rabbit Hearts Following Ischemia-Reperfusion

Abstract

Each year, tens of thousands of children undergo cardiopulmonary bypass (CPB) to correct congenital heart defects. While necessary for surgery, CPB involves stopping the heart and exposing it to ischemic conditions. While much is known about adult injury, little is known about the effects of global ischemia on newborn ventricles. The purpose of this study was to determine age- and chamber-specific differences in oxidative stress following global ischemia-reperfusion injury. We studied newborn (2–4 days) and adult (>8 weeks) rabbit hearts subjected to Langendorff ischemia-reperfusion (30 minutes ischemia, 60 minutes reperfusion). Catalase and superoxide dismutase (SOD) activities were measured, as well as real-time hydrogen peroxide (H 2 O 2 ) and superoxide (O 2 − ) generation using confocal microscopy in isolated left and right ventricular (LV and RV) myocytes exposed to hypoxia. Our data demonstrate chamber and age-specific changes in oxidative stress. During ischemia, H 2 O 2 increased significantly in the RV while remaining constant in the LV of newborn rat rabbit myocytes. In contrast, there was a smaller, nonsignificant increase in H 2 O 2 in both both RV and LV myocytes of adults. The increase seen in the RV of newborns was several fold higher than that of adults (4.3-fold vs. 2.2 fold; p<0.05). In whole heart tissue, catalase activity was significantly increased following ischemia in both adult ventricles, while no increase was seen in newborn hearts compared to sham hearts. Additionally, levels in newborns were several fold lower (p<0.05), indicating less scavenging potential. SOD activity was increased from sham vs. ischemia in the LV of both adult and newborn hearts, but only in the RV of the newborn heart (0.80±0.09 to 3.0±0.43 U/mg; p<0.001). Intra-cardiac injection of an H 2 O 2 scavenger, Ebselen, loaded in nanoparticles, improved recovery of developed pressure (49.53±16.25 to 80.0±11.31) in the RV of the newborn (p<0.05), suggesting the local delivery of an exogenous antioxidant is cardioprotective in newborn RVs. Our data demonstrate there are ventricle-specific differences in oxidative stress between newborn and adult rabbit hearts. Local therapy is able to address some of these differences and may limit damage during bypass surgery.