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Abstract

Introduction: Previous results suggest maternal gestational under nutrition selectively impairs right ventricular mitochondrial response to acute hypoxia. Hypothesis: After an acute ischemic event, ventricular cardiomyocyte viability in intrauterine growth restricted (IUGR) rat pups is lower than controls (CTR) while mitochondrial reactive oxygen species (ROS) production is increased. RV cardiomyocytes have less viability, and increased ROS, post ischemia compared to left ventricular (LV), and the IUGR RV group with the least. Methods: Pregnant Sprague Dawley rats were subjected to caloric restriction in the 3rd trimester- an established caloric restrictive diet to model IUGR (NR). NR and CTR neonatal hearts were harvested from age 2-3 day pups. RV and LV cardiomyocytes were cultured separately. On day 5 of culture, cells underwent 6 hours of oxygen glucose deprivation (OGD), and cell viability was assessed using an MTT Cell Proliferation Assay 18 hour later. Mitochondrial ROS production was measured by total superoxide production using confocal microscopy. Results: Baseline cell viability in CTR RV was 47% (p?0.01-19) of CTR LV.and NR RV was 30% NR LV (p?0.01-23). Total ROS in CTR RV was 118% of CTR LV (p?0.34) and NR RV was 140% NR LV (p?0.001). A significant increase in ROS production was seen in NR compared to CTR. Total ROS in NR LV was 174% CTR LV (p?0.01) and NR RV was 170% CTR RV (p?0.0001).No difference in cell viability was found following OGD (each group compared to its baseline), CTR LV=56%, CTR RV=61%, NR LV=53% and NR RV=56% (p?0.17). All cells for confocal microscopy died post OGD. Conclusions: Cell viability, using primary neonatal rat cardiomyocyte cultures, is significantly less in RV cardiomyocytes compared to LV. Cell viability was further reduced in cardiomyocytes isolated from NR pups, least in NR RV. OGD, simulating ischemia, decreased cell viability in both NR and CTR. ROS production is greater in mitochondria from cardiomyocytes isolated from NR pups. ROS production was greater NR RV compared to NR LV. Less viability and increased ROS production within the NR group may indicate a defect in bioenergetics as a result of intrauterine nutritional restriction.