Abstract

Prior studies have demonstrated an increase in the levels of reactive oxygen species (ROS) in patients with heart failure (HF) compared to the general population. Increased oxidative stress is implicated in most types of heart failure, including that resulting from ischemic and non-ischemic cardiomyopathy. The adverse effects of oxidative stress in HF patients are vascular endothelial dysfunction, cardiac hypertrophy, interstitial fibrosis, myocyte contractile dysfunction, and adverse left ventricular remodeling. Little is known about the role of continuous flow LVADs on oxidative stress among HF patients. We measured free radical levels at the time of LVAD implant and at the time of heart transplantation to determine if ventricular assist devices reduce ROS levels At the time of LVAD implantation and at the time of heart transplantation a sample of peripheral blood and cardiac tissue were obtained. Methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) and an electron paramagnetic resonance (EPR) spectroscopy buffer were added to the samples, incubated for 1 hour and then frozen in liquid nitrogen. Using EPR, the CMH radical signal was recorded and EPR spectrum amplitude was measured. We collected blood and tissue from 33 patients at the time of LVAD surgery and from 7 patients at the time of transplant. Data was analyzed by unpaired t test. The free radical level in peripheral blood at the time of LVAD implantation was 3.23×106 ± 1.44×106 EPR AU/mL compared to 3.13×106 ± 1.38×106 EPR AU/mL at the time of heart transplant (p = 0.87) suggesting no difference between these groups. The free radical level in cardiac tissue was 5.25×105 ± 1.3×105 EPR AU/mg at the time of LVAD implantation and 5.49×105 ± 3.31×105 EPR AU/mg at time of transplant (p=0.79) also suggesting no difference between these groups. This study shows that LVAD implanted HF patients have elevated oxidative stress. Also, there was no difference in measured levels of free radicals in peripheral blood or cardiac tissue at the time of LVAD implantation compared to the level at the time of transplantation. Elevated oxidative stress may be directly or indirectly related to several consequences like inflammation, bacterial infections, GI bleeding, thromboembolism that are common complications found during LVAD support.

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