Dataset Information

Oxidative stress, DNA damage and repair in heart failure patients after implantation of continuous flow left ventricular assist devices.

ABSTRACT:

Objective

To study the status of oxidative stress and DNA damage repair in circulating blood leukocytes of heart failure patients supported by continuous flow left ventricular assist devices (LVADs).

Materials and methods

Ten HF patients implanted with LVAD as bridge to transplant or destination therapy were enrolled in the study and 10 age and sex matched volunteers were recruited as the study control. Reactive oxygen species (ROS) in blood leukocytes and superoxide dismutase (SOD) in erythrocytes were measured by flow cytometry/immunofluorescence microscopy and spectrophotometry, respectively. ELISA was used to measure oxidized low density lipoproteins (oxLDL) in plasma. Markers of DNA damage (?-H2AX) and repairs (Mre11, DNA ligase IV, Ku70, and Ku80) were quantified in blood lymphocytes by immunocytochemistry.

Results

Levels of ROS and oxLDL were significantly higher in HF patients with LVAD than baseline as well as the control group; moreover, SOD levels were decreased with increasing post-operative periods. All the changes indicated enhanced oxidative stress among LVAD recipients. Significantly higher ?-H2AX foci in lymphocytes confirmed DNA double strand breaks in LVAD recipients. ?-H2AX foci numbers in lymphocytes were positively correlated with the ROS and oxLDL and negatively with SOD levels (p<0.0001). Expressions of DNA ligase IV, Ku70 and Ku80 proteins were highest after one week and Mre11 protein after 3 months of LVAD transplantation; indicated abnormal DNA repair.

Conclusions

The study, for the first time shows that, continuous flow LVAD implanted HF patients not only exhibit elevated oxidative stress and DNA damage in blood leukocytes but also have abnormalities in DNA repair pathways.

SUBMITTER: Mondal NK

PROVIDER: S-EPMC3675502 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Oxidative stress, DNA damage and repair in heart failure patients after implantation of continuous flow left ventricular assist devices.

Mondal Nandan Kumar NK Sorensen Erik E Hiivala Nicholas N Feller Erika E Griffith Bartley B Wu Zhongjun Jon ZJ

International journal of medical sciences 20130520 7

<h4>Objective</h4>To study the status of oxidative stress and DNA damage repair in circulating blood leukocytes of heart failure patients supported by continuous flow left ventricular assist devices (LVADs).<h4>Materials and methods</h4>Ten HF patients implanted with LVAD as bridge to transplant or destination therapy were enrolled in the study and 10 age and sex matched volunteers were recruited as the study control. Reactive oxygen species (ROS) in blood leukocytes and superoxide dismutase (SO ...[more]

PMID: 23781134

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Project description:BackgroundVasoplegia after routine cardiac surgery is associated with severe postoperative complications and increased mortality. It is also prevalent in patients undergoing implantation of pulsatile flow left ventricular assist devices (LVAD). However, less is known regarding vasoplegia after implantation of newer generations of continuous flow LVADs (cfLVAD). We aim to report the incidence, impact on outcome and predictors of vasoplegia in these patients.MethodsAdult patients scheduled for primary cfLVAD implantation were enrolled into a derivation cohort (n = 118, 2006-2013) and a temporal validation cohort (n = 73, 2014-2016). Vasoplegia was defined taking into consideration low mean arterial pressure and/or low systemic vascular resistance, preserved cardiac index and high vasopressor support. Vasoplegia was considered after bypass and the first 48 h of ICU stay lasting at least three consecutive hours. This concept of vasoplegia was compared to older definitions reported in the literature in terms of the incidence of postoperative vasoplegia and its association with adverse outcomes. Logistic regression was used to identify independent predictors. Their ability to discriminate patients with vasoplegia was quantified by the area under the receiver operating characteristic curve (AUC).ResultsThe incidence of vasoplegia was 33.1% using the unified definition of vasoplegia. Vasoplegia was associated with increased ICU length-of-stay (10.5 [6.9-20.8] vs 6.1 [4.6-10.4] p = 0.002), increased ICU-mortality (OR 5.8, 95% CI 1.9-18.2) and one-year-mortality (OR 3.9, 95% CI 1.5-10.2), and a higher incidence of renal failure (OR 4.3, 95% CI 1.8-10.4). Multivariable analysis identified previous cardiothoracic surgery, preoperative dopamine administration, preoperative bilirubin levels and preoperative creatinine clearance as independent preoperative predictors of vasoplegia. The resultant prediction model exhibited a good discriminative ability (AUC 0.80, 95% CI 0.71-0.89, p < 0.01). Temporal validation resulted in an AUC of 0.74 (95% CI 0.61-0.87, p < 0.01).ConclusionsIn the era of the new generation of cfLVADs, vasoplegia remains a prevalent (33%) and critical condition with worse short-term outcomes and survival. We identified previous cardiothoracic surgery, preoperative treatment with dopamine, preoperative bilirubin levels and preoperative creatinine clearance as independent predictors.

Project description:BackgroundBridge to transplantation (BTT) with left ventricular assist devices (LVADs) is a mainstay of therapy for heart failure in patients awaiting heart transplantation (HT). Criteria for HT listing do not differ between patients medically managed and those mechanically bridged to HT. The objectives of the present study were to evaluate the impact of BTT with LVAD on posttransplantation survival, to describe differences in causes of 1-year mortality in medically and mechanically bridged patients, and to evaluate differences in risk factors for 1-year mortality between those with and those without LVAD at the time of HT.MethodsUsing the United Network of Organ Sharing database, we identified 5486 adult, single-organ HT recipients transplanted between 2008 and 2015. Patients were propensity matched for likelihood of LVAD at the time of HT. Kaplan-Meier survival estimates were used to assess the impact of BTT on 1- and 5-year mortality. Logistic regression analysis was used to evaluate the odds ratio of 1-year mortality for patients BTT with LVAD compared with those with medical management across clinically significant variables at various thresholds.ResultsEarly mortality was higher in mechanically bridged patients: 9.5% versus 7.2% mortality at 1 year (P<0.001). BTT patients incurred an increased risk of 1-year mortality with an estimated glomerular filtration rate of 40 to 60 mL·min-1·1.73 m-2 (odds ratio, 1.69; P=0.003) and <40 mL·min-1·1.73 m-2 (odds ratio, 2.16; P=0.005). A similar trend was seen in patients with a body mass index of 25 to 30 kg/m2 (odds ratio, 1.88; P=0.024) and >30 kg/m2 (odds ratio, 2.11; P<0.001). When patients were stratified by BTT status and the presence of risk factors, including age >60 years, estimated glomerular filtration rate <40 mL·min-1·1.73 m-2, and body mass index >30 kg/m2, there were significant differences in 1-year mortality between medium- and high-risk medically and mechanically bridged patients, with 1-year mortality in high-risk BTT patients at 17.6% compared with 10.4% in high-risk medically managed patients.ConclusionsBridge to HT with LVAD, although necessary because of organ scarcity and capable of improving wait list survival, confers a significantly higher risk of early posttransplantation mortality. Patients bridged with mechanical support may require more careful consideration for transplant eligibility after LVAD placement.

Dataset Information

Oxidative stress, DNA damage and repair in heart failure patients after implantation of continuous flow left ventricular assist devices.

Objective

Materials and methods

Results

Conclusions

Publications

Oxidative stress, DNA damage and repair in heart failure patients after implantation of continuous flow left ventricular assist devices.

Similar Datasets

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