Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min). Increased CPB duration yielded in higher levels of circulating mitochondrial (mt)DNA, soluble thrombomodulin (sCD141) and ICAM-1, reflecting endothelial damage. Positive correlation between cfDNA and sCD141 was demonstrated at all time points. Plasma and cfDNA from patients with CPB > 100 min induced NETs release by neutrophils from healthy donors which was not suppressed by inhibitors of intracellular toll-like receptor (TLR)9. DNA binding to neutrophils’ surface (s)TLR9 has been evidenced. Altogether, we demonstrate that elevated plasma cfDNA might be useful to assess CPB-mediated detrimental effects, including endothelial damage, in cardiac surgical patients with prolonged CPB duration. cfDNA-triggered NETosis is independent of classical TLR9 signaling.

Considering patients with similar risk profiles, female gender per se is not associated with worse long-term survival and freedom from stroke after surgical aortic repair. Moreover, female patients might even benefit from a smoother early postoperative course and lower incidence of early postoperative complications.

Use of cardiopulmonary bypass in cardiac surgery triggers systemic inflammation by neutrophil activation leading to neutrophil extracellular traps (NETs) release. Hence, nuclear DNA released by necrotic and apoptotic cells might contribute to an increase in circulating cell-free DNA (cfDNA). cfDNA/NETs might induce endothelial damage and organ dysfunction. This study focuses on the accuracy of cfDNA to predict acute kidney injury (AKI) after on-pump surgery. 58 cardiac patients undergoing on-pump surgery were prospectively enrolled. Blood samples were taken preoperatively, immediately after surgery, at day 1, 2, 3 and 5 from patients with (n = 21) or without (n = 37) postoperative AKI development. Levels of cfDNA, neutrophil gelatinase-associated lipocalin (NGAL) and creatinine in patients’ plasma were quantified. ROC curves were used to assess the predictive value of the biomarkers for AKI. Further baseline characteristics and perioperative variables were analyzed.cfDNA and NGAL levels highly increased in AKI patients and significant intergroup differences (vs. non-AKI) were found until day 3 and day 5 after surgery, respectively. cfDNA levels were significantly elevated in patients who developed late AKI (>24 hours), but not in those with AKI development during the first 24 hours (early AKI). NGAL and creatinine, which were highest in patients with early AKI, accurately predicted during the first 24 postoperative hours (early AKI). At day 3, at a threshold of 260.53 ng/ml cfDNA was the best predictor for AKI (AUC = 0.804) compared to NGAL (AUC = 0.699) and creatinine (AUC = 0.688). NGAL, but not cfDNA, was strongly associated with AKI stages and mortality. Monitoring of cfDNA levels from the first postoperative day might represent a valuable tool to predict late AKI after on-pump surgery.

Background/Purpose: Recent evidence suggests that statin-mediated cardioprotection after chronic statin therapy decreases over time and can be reactivated by preprocedural high-dose statin reloading therapy. We tested in a porcine cardiopulmonary bypass (CPB) model whether statin-related cardioprotection is further enhanced by a preoperative rosuvastatin reloading therapy. Methods: Control (n = 6), rosuvastatin-pretreated (n = 6; 20 mg/day for 7 days p.o.) and rosuvastatin-reloaded (n = 6; p.o. treatment plus 0.10 mg/kg/h i.v. during surgery) pigs (Deutsche Landrasse) were subjected to CPB for 2 h with 1 h of cardioplegic cardiac arrest. Systemic hemodynamics, cardiac index (CI), coronary blood flow (CBF) and left ventricular (LV) function [pressure-volume area (PVA), preload recruitable stroke work (PRSW)] were determined before and 4 h after CPB. Myocardial expression (PCR) and protein content (Western blot) of endothelial NO synthase (eNOS) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) were measured, and right coronary relaxation was assessed postmortem. All data are given as mean ± SD. Results: Preoperative plasma LDL, HDL and cholesterol did not differ between treatment groups. Compared to control, oral treatment improved post-CPB CI, CBF, first derivative of maximal LV-pressure (LVdp/dt) and PVA (p < 0.05). Significant enhancement was achieved with perioperative reloading therapy (CI: 5.2 ± 1.0 vs. 3.9 ± 1.5 l/min/m²; CBF: 76 ± 32 vs. 43 ± 8 ml/min; LVdp/dt: 1,980 ± 333 vs. 1,249 ± 461 mm Hg/s; PVA: 6,954 ± 941 vs. 3,252 ± 1,822 mm Hg·ml; p < 0.05) with improved in vitro NO-dependent coronary relaxation (102 ± 10 vs. 79 ± 14%; p = 0.003). Irrespective of recapture therapy statin pretreatment augmented myocardial eNOS and PTEN (p < 0.05), but failed to increase cardiac eNOS or PTEN expression after CPB. Conclusions: Periprocedural statin reloading therapy enhances myocardial and coronary function after cardiac surgery with CPB and may therefore provide a valuable therapeutic approach for the reduction of myocardial ischemia-reperfusion injury.

The aim of this study was to provide early and mid-term results of the newly established extracorporeal membrane oxygenation (ECMO) retrieval service in a tertiary cardiothoracic center using the miniaturized portable Cardiohelp System (Maquet, Rastatt, Germany). A particular attention was paid to organizational and logistic specifics as well as challenges and pitfalls associated with initial phase of the program. From January 2015 until January 2017 a heterogenic group of 28 consecutive patients underwent ECMO implantation in distant hospitals for acute cardiac, pulmonary or combined failure as a bridge-to-decision and were subsequently transported to our institution. Each cannulation was performed bedside on intensive care units (ICU) using the Seldinger's technique. Early outcomes and mid-term overall survival with up to two-year follow-up along with the impact of ongoing cardiopulmonary resuscitation (CPR) on outcome were presented. Also, changes in hemodynamics and tissue perfusion factors 24 h after ECMO implantation were evaluated. ECMO implantations were performed in 15 distant departments with the median distance of 23(10;40) (maximum 60) km. A total of 15 patients (54%) were cannulated under CPR with the median duration of 30(20;110) (maximum 180) min. After 24 h of support there were significant improvements in SvO (P = 0.021), mean arterial pressure (P = 0.027), FiO (P = 0.001), lactate (P = 0.001), and pH (P < 0.001). The mean ECMO support duration was 96 ± 100 (maximum 384) hours, whereas 11 patients (40%) were weaned off support and discharged from hospital. Overall cumulative survival in patients without the need for CPR was 61.5% at one week and 38.5% at 1 month, 6 month, and 1 year, whereas patients requiring CPR survived in 40% at one week, and 33.3% at 1 month, 6 month, and 1 year (Log-Rank (Mantel-Cox) P = 0.374, Breslow (Generalized Wilcoxon) P = 0.162). Our initial experience shows that launching new ECMO retrieval programs in centers with sufficient ICU capacities and local ECMO experience can be feasible and associated with acceptable "real world" results despite the initial learning curve. Rapid logistical organization and team flexibility are the key points to ensure comparable survival of patients requiring prolonged CPR.

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Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction.

Background There has been conflicting evidence concerning the effect of levosimendan on clinical outcomes in patients undergoing cardiac surgery. Therefore, we performed a systematic review and conducted this meta-analysis to provide evidence for/against the administration of levosimendan in cardiac surgery patients. Methods We performed a meta-analysis from literature search in PubMed, EMBASE, and Cochrane Library. Only randomized controlled trials comparing the administration of levosimendan in cardiac surgery patients with a control group (other inotrope, standard therapy/placebo, or an intra-aortic balloon pump) were included. In addition, at least one clinical outcome had to be mentioned: mortality, myocardial infarction, low cardiac output syndrome (LCOS), acute kidney injury, renal replacement therapy, atrial fibrillation, prolonged inotropic support, length of intensive care unit, and hospital stay. The pooled treatment effects (odds ratio [OR], 95% confidence intervals [CI]) were assessed using a fixed or random effects model. Results The literature search retrieved 27 randomized, controlled trials involving a total of 3,198 patients. Levosimendan led to a significant reduction in mortality (OR: 0.67; 95% CI: 0.49–0.91; p = 0.0087). Furthermore, the incidence of LCOS (OR: 0.56, 95% CI: 0.42–0.75; p < 0.0001), acute kidney injury (OR: 0.63; 95% CI: 0.46–0.86; p = 0.0039), and renal replacement therapy (OR: 0.70; 95% CI: 0.50–0.98; p = 0.0332) was significantly decreased in the levosimendan group. Conclusion Our meta-analysis suggests beneficial effects for the prophylactic use of levosimendan in patients with severely impaired left ventricular function undergoing cardiac surgery. The administration of levosimendan was associated with a reduced mortality, less LCOS, and restored adequate organ perfusion reflected in less acute kidney injury.