Oxidative Stress Induced DNA Damage and Repair in Heart Failure Patients Supported by Continuous Flow Ventricular Assist Devices

Abstract

Purpose The blood contacting surfaces of a left ventricular assist device (LVAD) is made of biologically inert compounds such as titanium, polytetrafluoroethylene, and acrylics. These inert materials as well as non-physiological high shear stress can affect different cellular processes in recipients. To evaluate the effects of LVAD among congestive heart failure (CHF) patients on oxidative stress and DNA damage repair, the present study have been conducted. Methods and Materials We recruited 5 CHF patients implanted with continuous flow LVADs as bridge to transplant and 5 non-smoking healthy control. Reactive oxygen species (ROS) generation in blood leukocytes and the levels of antioxidant enzyme superoxide dismutase (SOD) in erythrocytes were measured by flow cytometry/immunofluorescence microscopy and spectrophotometry respectively. ELISA was used to measure oxidized low density lipoproteins ( ox LDL) in plasma. γ-H2AX foci count as DNA double strand break marker and different key proteins involved in DNA repair via non-homologous-end-joining (NHEJ) and homologous recombination (HR) were done by immunocytochemistry in lymphocytes. Results Our study clearly indicated that the levels of ROS and ox LDL were significantly higher in CHF patients after LVAD implantation compared to baseline and controls. Moreover, SOD levels were decreased with increasing post-operative days. All the changes indicated oxidative stress among LVAD recipients. Increasing numbers of γ-H2AX foci in lymphocytes were positively correlated with the ROS (r=0.9429) and oxLDL (r=0.9753) and negatively with SOD (r=–0.9924) levels (p Conclusions Our result, for the first time showed that, LVAD not only induce oxidative stress and DNA damage in lymphocytes but also modulates the DNA repair pathways among CHF patients.