The effect of high-dose selenium on mortality and postoperative organ dysfunction in post-cardiotomy cardiogenic shock patients supported with mechanical circulatory support - A post-hoc analysis of the SUSTAIN CSX trial.

PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial. METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients. PRIMARY OUTCOME: duration of tMCS therapy. SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality. RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62). CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.

Outcome of right ventricular microaxial pump support in patients undergoing cardiac surgery.

Right ventricular failure (RVF) after cardiac surgery is associated with an in-hospital mortality rate of up to 75%. Microaxial flow pumps are one of the mechanical circulatory supports (MCS) options available for the treatment of RVF, however the specifics of timing and indication for MCS, as well as predictors for survival, remain unclear due to a dearth of published data. We evaluated the clinical outcome of patients treated with Impella-RP for predictors of mortality and the hemodynamic effects of the pump. This is a single-center retrospective observational study involving adult patients who underwent cardiac surgery with cardiopulmonary bypass between January 2019 and December 2020 in cardiac surgery and required therapeutic management of RVF with an Impella-RP. Overall, 18 patients were included and analyzed for factors that could be associated with mortality, or that could be predictors of patient outcomes for this population. Treatment of RVF with Impella-RP improved the patient hemodynamics significantly and had a survival rate of 61% within 30 days. Patients with isolated CABG or better liver function before implantation had a better survival rate, which may indicate that underlying disease and timing of implantation are significant for successful treatment of RVF.

Follow-Up and Outcome after Coronary Bypass Surgery Preceded by Coronary Stent Implantation.

BACKGROUND: Guidelines on myocardial revascularization define recommendations for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Only little information exists on long-term follow-up and quality of life (QoL) after CABG preceded by PCI. The aim of our study was to evaluate the impact of prior PCI on outcome and QoL in patients with stable coronary artery disease who underwent CABG. METHODS: In our retrospective study, CABG patients were divided in: CABG preceded by PCI: PCI-first (PCF), and CABG-only (CO) groups. The PCF group was further divided in guideline-conform (GCO) and guideline nonconform (GNC) subgroups, according to the SYNTAX score (2014 European Society of Cardiology [ESC]/European Association for Cardio-Thoracic Surgery [EACTS] guidelines). Thirty days mortality, major adverse cardiac events, and QoL using the European Quality-of-Life-5 Dimensions were evaluated. RESULTS: A total of 997 patients were analyzed, of which 784 underwent CABG without (CO), and 213 individuals with prior PCI (PCF). The latter group consisted of 67 patients being treated in accordance (GCO), and 24 in discordance (GNC) to the 2014 ESC/EACTS guidelines. Reinfarction (PCF: 3.8% vs. CO: 1.0%; p = 0.024), re-angiography (PCF: 17.6% vs. CO: 9.0%; p = 0.004), and re-PCI (PCF: 10.4% vs. CO: 3.0%; p < 0.001) were observed more frequently in PCF patients. Also, patients reported better health status in the CO compared to PCF group (CO: 72.48 ± 19.31 vs. PCF: 68.20 ± 17.86; p = 0.01). Patients from the guideline nonconform subgroup reported poorer health status compared to the guideline-conform group (GNC: 64.23 ± 14.56 vs. GCO: 73.42 ± 17.66; p = 0.041) and were more likely to require re-PCI (GNC: 18.8% vs. GCO: 2.4%; p = 0.03). Also, GNC patients were more likely to have left main stenosis (GCO: 19.7% vs. GNC: 37.5%; p < 0.001) and showed higher preinterventional SYNTAX score (GCO: 18.63 ± 9.81 vs. GNC: 26.67 ± 5.07; p < 0.001). CONCLUSION: PCI preceding CABG is associated with poorer outcomes such as reinfarction, re-angiography, and re-PCI, but also worse health status and higher rehospitalization. Nevertheless, results were better when PCI was guideline-conformant. This data should impact the Heart Team decision.

Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting, and pharmacological α1AMPK activation: molecular proof of a protective key role of endothelial α1AMPK against environmental noise exposure.

AIMS: Environmental stressors such as traffic noise represent a global threat, accounting for 1.6 million healthy life years lost annually in Western Europe. Therefore, the noise-associated health side effects must be effectively prevented or mitigated. Non-pharmacological interventions such as physical activity or a balanced healthy diet are effective due to the activation of the adenosine monophosphate-activated protein kinase (α1AMPK). Here, we investigated for the first time in a murine model of aircraft noise-induced vascular dysfunction the potential protective role of α1AMPK activated via exercise, intermittent fasting, and pharmacological treatment. METHODS AND RESULTS: Wild-type (B6.Cg-Tg(Cdh5-cre)7Mlia/J) mice were exposed to aircraft noise [maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)] for the last 4 days. The α1AMPK was stimulated by different protocols, including 5-aminoimidazole-4-carboxamide riboside application, voluntary exercise, and intermittent fasting. Four days of aircraft noise exposure produced significant endothelial dysfunction in wild-type mice aorta, mesenteric arteries, and retinal arterioles. This was associated with increased vascular oxidative stress and asymmetric dimethylarginine formation. The α1AMPK activation with all three approaches prevented endothelial dysfunction and vascular oxidative stress development, which was supported by RNA sequencing data. Endothelium-specific α1AMPK knockout markedly aggravated noise-induced vascular damage and caused a loss of mitigation effects by exercise or intermittent fasting. CONCLUSION: Our results demonstrate that endothelial-specific α1AMPK activation by pharmacological stimulation, exercise, and intermittent fasting effectively mitigates noise-induced cardiovascular damage. Future population-based studies need to clinically prove the concept of exercise/fasting-mediated mitigation of transportation noise-associated disease.

Traffic noise, e.g. from aircraft, significantly contributes to an increased risk of cardiovascular or metabolic diseases in the general population by brain-dependent stress reactions leading to higher levels of circulating stress hormones and vasoconstrictors, all of which cause hypertension, oxidative stress, and inflammation. With the present experimental studies, we provide for the first time molecular mechanisms responsible for successful noise mitigation: Physical exercise, intermittent fasting, and pharmacological activation of the adenosine monophosphate-activated protein kinase (AMPK), a metabolic master regulator protein, prevent cardiovascular damage caused by noise exposure, such as hypertension, endothelial dysfunction, and reactive oxygen species formation (e.g. free radicals) and inflammation.These beneficial mitigation manoeuvers are secondary to an activation of the endothelial AMPK, thereby mimicking the antidiabetic drug metformin.

Mannitol Is Associated with Less Postoperative Delirium after Aortic Valve Surgery in Patients Treated with Bretschneider Cardioplegia.

BACKGROUND: Heart surgery with extracorporeal circulation (ECC) often leads to postoperative delirium (POD). This is associated with increased morbidity resulting in longer hospital stay and associated costs. The purpose of our study was to analyze the effect of intraoperative mannitol application on POD in patients undergoing elective aortic valve replacement (AVR). MATERIALS AND METHOD: s In our retrospective single-center study, 259 patients underwent elective AVR, using Bretschneider cardioplegic solution for cardiac arrest, between 2014 and 2017. Patients were divided in mannitol (n = 188) and nonmannitol (n = 71) groups. POD was assessed using the confusion assessment method for the intensive care unit (ICU). Statistical significance was assumed at p < 0.05. RESULTS: Baseline patient characteristics did not differ between the groups. Incidence of POD was significantly higher in the nonmannitol group (33.8 vs. 13.8%; p = 0.001). These patients required longer ventilation time (24.1 vs. 17.1 hours; p = 0.021), higher reintubation rate (11.3 vs. 2.7%; p = 0.009), ICU readmission (12.7 vs. 4.8%; p = 0.026), prolonged ICU (112 vs. 70 hours; p = 0.040), and hospital stay (17.8 vs. 12.6 days; p < 0.001), leading to higher expenses (19,349 € vs. 16,606 €, p < 0.001). A 30-day mortality was not affected, but nonmannitol group showed higher Simplified Acute Physiology Score II score (32.2 vs. 28.7; p < 0.001). Mannitol substitution was independently associated with lower incidence of POD (odds ratio: 0.40; 95% confidence interval: 0.18-0.89; p = 0.02). CONCLUSION: Treatment with mannitol during ECC was associated with decreased incidence of POD. This was accompanied by shorter ventilation time, ICU and hospital stay, and lower treatment expenses.

Environmental risk factors and cardiovascular diseases: a comprehensive expert review.

Non-communicable diseases (NCDs) are fatal for more than 38 million people each year and are thus the main contributors to the global burden of disease accounting for 70% of mortality. The majority of these deaths are caused by cardiovascular disease (CVD). The risk of NCDs is strongly associated with exposure to environmental stressors such as pollutants in the air, noise exposure, artificial light at night, and climate change, including heat extremes, desert storms, and wildfires. In addition to the traditional risk factors for CVD such as diabetes, arterial hypertension, smoking, hypercholesterolaemia, and genetic predisposition, there is a growing body of evidence showing that physicochemical factors in the environment contribute significantly to the high NCD numbers. Furthermore, urbanization is associated with accumulation and intensification of these stressors. This comprehensive expert review will summarize the epidemiology and pathophysiology of environmental stressors with a focus on cardiovascular NCDs. We will also discuss solutions and mitigation measures to lower the impact of environmental risk factors with focus on CVD.

Role of acquired von Willebrand syndrome in the development of bleeding complications in patients treated with Impella RP devices.

Axial flow pumps are standard treatment in cases of cardiogenic shock and high-risk interventions in cardiology and cardiac surgery, although the optimal anticoagulation strategy remains unclear. We evaluated whether laboratory findings could predict bleeding complications and acquired von Willebrand syndrome (avWS) among patients who were treated using axial flow pumps. We retrospectively evaluated 60 consecutive patients who received Impella devices (Impella RP: n = 20, Impella CP/5.0: n = 40; Abiomed Inc., Danvers, USA) between January 2019 and December 2020. Thirty-two patients (53.3%) experienced major or fatal bleeding complications (Bleeding Academic Research Consortium score of > 3) despite intravenous heparin being used to maintain normal activated partial thromboplastin times (40-50 s). Extensive testing was performed for 28 patients with bleeding complications (87.5%). Relative to patients with left ventricular support, patients with right ventricular support were less likely to develop avWS (87.5% vs. 58.8%, p = 0.035). Bleeding was significantly associated with avWS (odds ratio [OR]: 20.8, 95% confidence interval [CI]: 3.3-128.5; p = 0.001) and treatment duration (OR: 1.3, 95% CI 1.09-1.55; p = 0.003). Patients with avWS had longer Impella treatment than patients without avWS (2 days [1-4.7 days] vs. 7.3 days [3.2-13.0 days]). Bleeding complications during Impella support were associated with avWS in our cohort, while aPTT monitoring was not sufficient to prevent bleeding complications. A more targeted anticoagulation monitoring might be needed for patients who receive Impella devices.

Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation.

BACKGROUND: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. METHODS: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. RESULTS: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. CONCLUSION: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG.

Elective Surgery but not Transjugular Intrahepatic Portosystemic Shunt Precipitates Acute-On-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome associated with organ failure and high short-term mortality. Presence of ACLF at interventions, such as surgery or transjugular intrahepatic portosystemic shunt (TIPS), has been shown to determine outcome, but those interventions have also been attributed to precipitate ACLF in different studies. However, dedicated investigation for the risk of ACLF development in these interventions, especially in elective settings, has not been conducted. Patients with cirrhosis undergoing elective surgery were propensity score matched and compared to patients receiving TIPS. The primary endpoint was ACLF development within 28 days after the respective procedure. The secondary endpoint was 3-month and 1-year mortality. In total, 190 patients were included. Within 28 days, ACLF developed in 24% of the surgery and 3% of the TIPS cohorts, with the highest ACLF incidence between 3 and 8 days. By day 28 after the procedure, ACLF improved in the TIPS cohort. In both cohorts, patients developing ACLF within 28 days after surgery or TIPS placement showed significantly worse survival than patients without ACLF development at follow-up. After 12 months, mortality was significantly higher in the surgery cohort compared to the TIPS cohort (40% vs. 23%, respectively; P = 0.031). Regression analysis showed a European Foundation Chronic Liver Failure Consortium acute decompensation (CLIF-C AD) score ≥50 and surgical procedure as independent predictors of ACLF development. CLIF-C AD score ≥50, C-reactive protein, and ACLF development within 28 days independently predicted 1-year mortality. Conclusion: Elective surgical interventions in patients with cirrhosis precipitate ACLF development and ultimately death, but TIPS plays a negligible role in the development of ACLF. Elective surgery in patients with CLIF-C AD ≥50 should be avoided, while the window of opportunity would be CLIF-C AD <50.

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction.

The CX3CL1/CX3CR1 axis mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and plays a pivotal role in the inflammation-driven pathology of cardiovascular disease. The cardiac immune response differs depending on the underlying causes. This suggests that for the development of successful immunomodulatory therapy in heart failure due to chronic pressure overload induced left ventricular (LV) hypertrophy, the underlying immune patterns must be examined. Here, the authors demonstrate that Fraktalkine-receptor CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in a mouse model of transverse aortic constriction (TAC). The comparison of C57BL/6 mice with CX3CR1 deficient mice displayed reduced LV hypertrophy and preserved cardiac function in response to pressure overload in mice lacking CX3CR1. Moreover, the normal immune response following TAC induced pressure overload which is dominated by Ly6Clow macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6Chigh macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6Chigh monocytes infiltrated the heart in response to a C-C chemokine ligand 2 burst. CX3CR1 expression impacts the immune response in the development of LV hypertrophy and its absence has clear cardioprotective effects. Hence, suppression of CX3CR1 may be an important immunomodulatory therapeutic target to ameliorate pressure-overload induced heart failure.

Objective method to evaluate the competency of residents in cardiac surgery.

OBJECTIVES: Cardiac surgery training has become more challenging as patients and their diagnoses become more complex. Our goal was to develop a multicategorical assessment model for evaluating residents in cardiac surgery. This model is intended to ensure goal-directed progress in their training as well as to recognize and support their surgical talents. METHODS: We developed a new questionnaire in a multistage, 3-round process based on the Delphi method 'estimate-talk-estimate', using 55 competencies, including 38 general and 17 domain-specific competencies. Each competency is evaluated with 1 or more questions, to which 1 (not competent) to 6 (very competent) points can be chosen as an answer. RESULTS: The resulting model achieved 2 main goals: first, presenting a well-defined competency list for cardiac surgical training and second, providing an objective and realistic evaluation of trainees' abilities. Residents were assessed by all trainers to achieve a high level of objectivity. CONCLUSIONS: This evaluation model is highly objective, because residents are evaluated by multiple trainers. It allows individual support and enables better transparency in residency training. Talents and skills are evaluated, recognized and adopted as a base for individual feedback and personalized training programmes.

CpG postconditioning after reperfused myocardial infarction is associated with modulated inflammation, less apoptosis, and better left ventricular function.

Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). The aim of this study was to investigate whether postconditioning with the cytosine-phosphate-guanine (CpG)-containing Toll-like receptor-9 (TLR9) ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Thirty minutes of left descending coronary artery (LAD) occlusion was conducted in 12-wk-old C57BL/6 mice. Mice were treated with CpG intraperitoneally 5 min before reperfusion. The control group received PBS; the sham group did not undergo ischemia. M-mode echocardiography (3, 7, and 28 days) and Millar left ventricular (LV) catheterization were performed (7 and 28 days) before the hearts were excised and harvested for immunohistochemical (6 h, 24 h, 3 days, 7 days, and 28 days), gene expression (6 h, 24 h, and 3 days; Taqman RT-qPCR), protein, and FACS analysis (24 h and 3 days). Mice treated with CpG showed significantly better LV function after 7 and 28 days of reperfusion. Protein and mRNA expressions of proinflammatory and anti-inflammatory cytokines were significantly induced after CpG treatment. Histology revealed fewer macrophages in CpG mice after 24 h, confirmed by FACS analysis with a decrease in both classically M1- and alternative M2a-monocytes. CpG treatment reduced apoptosis and cardiomyocyte loss and was associated with induction of adaptive mechanisms, e.g., of heme-oxigenase-1 and ß-/α-myosin heavy chain (MHC) ratio. Profibrotic markers collagen type Iα (Col-Ια) and Col-III induction was abrogated in CpG mice, accompanied by fewer myofibroblasts. This led to the formation of a smaller scar. Differential matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression contributed to attenuated remodeling in CpG, resulting in preserved cardiac function in a Toll-like receptor 1- and TLR9-dependent manner. Our study suggests a cardioprotective mechanism of CpG postconditioning, involving Toll-like receptor-driven modulation of inflammation. This is followed by attenuated remodeling and preserved LV function.NEW & NOTEWORTHY Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase-8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from α- to ß-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation.

A National Survey: Current Clinical Practice in Pediatric Anesthesia for Congenital Heart Surgery.

BACKGROUND: Providing anesthesia for pediatric patients undergoing congenital cardiac surgery is complex and requires profound knowledge and clinical experience. Prospective studies on best anesthetic management are missing, partially due to different standards. The aim of the present study was to survey the current standard practice in anesthetic management in pediatric cardiac surgical centers in Germany. METHODS: All 78 cardiac surgical centers in Germany were reviewed for a congenital cardiac surgery program. Centers with an active program for congenital cardiac surgery were interviewed to participate in the present online questionnaire to assess their current anesthetic practice. RESULTS: Twenty-seven German centers running an active program for congenital heart surgery were identified, covering more than 3,000 pediatric cardiac surgeries annually. Of these centers, 96.3% (26/27) participated in our survey. Standard induction agents were etomidate in 26.9% (7/26), propofol in 19.2% (5/26), a combination of benzodiazepines and ketamine in 19.2% (5/26), and barbiturates in 11.5% (3/26). General anesthesia was preferentially maintained using volatile agents, 61.5% (16/26), with sevoflurane being the most common volatile agent within this group, 81.2% (13/16). Intraoperative first-choice/first-line inotropic drug was epinephrine, 53.8% (14/26), followed by milrinone, 23.1% (6/26), and dobutamine 15.4% (4/26). Fast-track programs performing on-table extubation depending on the type of surgical procedure were established at 61.5% (16/26) of the centers. CONCLUSION: This study highlights the diversity of clinical standards in pediatric cardiac anesthesia for congenital cardiac surgery in Germany.

Surgical Revascularization of Chronically Occluded Coronary Arteries-What You See Is What You Get?

BACKGROUND: Revascularization strategy in coronary artery bypass grafting (CABG) surgery usually depends on coronary dimension and stenosis severity. Little is known about the relation of preoperative evaluation of scarcely or invisibly chronic occluded coronary arteries (chronic total occlusion [CTO]) and revascularization rate or anastomosis quality. We aimed to evaluate the success rates of CTO revascularization in CABG surgery and determine the influence of coronary lumen visibility and collateralization in preoperative angiograms on revascularization rates, bypass blood flow, and target vessel diameter. METHOD: Preoperative coronary angiograms were evaluated for 938 consecutive patients who underwent isolated CABG surgery between 2014 and 2016 and screened for occluded coronary arteries. The occluded vessels were scored for visibility using the Rentrop grading of collateral filling. Intraoperatively, dimensions of the occluded arteries were measured using conventional vessel probes, and anastomosis quality was assessed by transit time flow measurement. RESULTS: A total of 404 (43.1%) patients were identified with at least one CTO. Revascularization rates differed from 96.2% in the left anterior descending artery, to 85.0% in left circumflex artery-dependent vessels, and 78.8% in right coronary artery territory. Coronary visibility and grade of collateralization in the preoperative angiogram had no influence on intraoperatively measured coronary diameter. Bypass blood flow in grafts revascularizing CTOs lacking collateralization were not significantly lower than those grafts leading to CTOs with higher Rentrop scores. CONCLUSION: Preoperative coronary assessment often differs from intraoperative findings. Our study confirms that even patients with scarcely collateralized CTOs and impaired visibility in the coronary angiogram have a high chance of complete revascularization during CABG surgery.

Low-tidal-volume prevent ventilation induced inflammation in a mouse model of sepsis.

BACKGROUND AND GOAL OF THE STUDY: Pulmonary inflammation, increased vascular permeability, and pulmonary edema, occur in response to primary pulmonary infections like pneumonia but are also evident in endotoxemia or sepsis. Mechanical ventilation augments pre-existing lung injury and inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that low-tidal-volume prevent ventilation induced lung injury in sepsis. MATERIALS AND METHODS: 10-12-week-old male C57BL/6N-mice received an intraperitoneal (i.p.) injection with equipotent dosages of LPS, 1668-thioate, 1612-thioate, or PBS. 120 min after injection, mice were randomized to low- (LV, 7 ± 1 ml/kg) or high-tidal-volume (HV, 25 ± 1 ml/kg) ventilation. Hemodynamic and ventilatory parameters were recorded and inflammatory markers were analyzed form BAL that was generated after 90 minute ventilation. RESULTS AND DISCUSSION: Arterial blood pressures declined during mechanical ventilation in all groups. pO2 decreased in LPS injected and CO2 increased in sham, LPS, and 1612-thioate administered mice at 45 min and in 1668-thioate injected mice after 90 minute LV ventilation compared to respective HV groups. BAL protein concentrations increased in HV ventilated and 1668- or 1612-thioat pre-treated mice. BAL TNF-α protein concentrations increased in both LPS- and 1668-thioate-injected and IL-1ß protein concentrations only in LPS-injected and HV ventilated mice. Most notably, no increased protein concentrations were observed in any of the LV ventilated groups. CONCLUSION: We conclude that low-tidal-volume ventilation may be a potential strategy for the prevention of ventilator induced lung injury in a murine model of systemic TLR agonist induced lung injury.

Timely extracorporeal membrane oxygenation assist reduces mortality after bypass surgery in patients with acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at high risk when undergoing emergency coronary artery bypass graft (CABG)-surgery. Their outcome remains poor despite increased use of extracorporeal membrane oxygenation (ECMO). We investigated the impact of timing for perioperative ECMO-support in these patients. METHODS: In this retrospective double-center study, we evaluated 201 patients with AMI undergoing CABG, dividing them into the following groups: No-ECMO (n = 101), preoperative ECMO (pre-ECMO, n = 6), intraoperative ECMO (ECC-ECMO, n = 67), and postoperative ECMO (post-ECMO, n = 27). We evaluated the impact of ECMO timing on postoperative mortality, organ function, and length of stay, comparing these to predicted outcome using different risk-scores. RESULTS: Post-ECMO patients showed lowest 30-day-survival (40.7%), while earlier ECMO-start was associated with better outcome (50.7% in extracorporeal circulation [ECC]-ECMO and 66.7% in pre-ECMO patients). On admission, only pre-ECMO and ECC-ECMO patients showed higher surgery- and intensive-care-unit (ICU)-related risk-scores. In pre- and ECC-ECMO patients, the first significant increase in lactate-levels (>4 mmol/L) was observed preoperatively, while this occurred 1 hour postoperatively in post-ECMO patients. Bilirubin was increased in all patients, decreasing after 3 and 12 days in pre- and ECC-ECMO patients, respectively, but only after 18 days in post-ECMO patients. Multiple ICU risk-scores did not discriminate survival-probability correctly. Only the ECMO-related survival after veno-arterial-ECMO-score correctly predicted the significantly lower survival in post-ECMO patients. CONCLUSION: Our study shows that timely ECMO-support is associated with earlier bilirubin-downtrend and higher survival in patients with AMI after CABG. Lactate-increase greater than 4 mmol/L seems to be a helpful threshold to trigger the timely onset of ECMO-therapy, providing better survival.

Impact of Crystalloid or Albumin Priming of the Heart-Lung Machine on Inhospital Outcome after Coronary Artery Bypass Surgery.

BACKGROUND: Crystalloid priming is a cost-effective, free from immunological reactions, and independent from human plasma delivery. However, there is some debate on the negative impact of low plasma colloid pressure and higher incidence of systemic inflammatory response syndrome (SIRS). The aim of the study was to rule out any adverse effects of crystalloid priming on the postoperative outcome. METHODS: We investigated 520 consecutive patients, including emergencies, who had isolated on-pump coronary artery bypass grafting in 2009 by retrospective analysis in our clinic. Crystalloid priming (n = 294) was introduced as an alternative to albumin (n = 226). Reviewing patient charts and IT-based data generated a dataset of perioperative parameters. RESULTS: There were no differences with respect to demographical data and preexisting comorbidities between both groups. Despite equal perfusion times, more volume had to be substituted during extracorporeal circulation following crystalloid priming. However, this did not influence the inhospital outcomes. According to the definition of the "Sepsis-3 Guidelines," the incidence of SIRS was similar. There was no difference in the need for a vasopressor treatment, and only transient higher serum lactate levels were found in the crystalloid group. The incidence of neurologic and organ-related adverse events, as well as 30-day mortality was comparable. CONCLUSION: The use of crystalloid priming is safe in coronary artery bypass grafting surgery in adults. However, there might be a greater need for crystalloid fluids during surgery.

CB2-deficiency is associated with a stronger hypertrophy and remodeling of the right ventricle in a murine model of left pulmonary artery occlusion.

AIMS: Pulmonary hypertension (PH) leads to right ventricular (RV) adaptation and remodeling and has deleterious long-term effects on RV function. The endocannabinoid receptor CB2 has been associated with protective effects in adaptation and remodeling of the left ventricle after ischemia. Therefore, we investigated the role of CB2 receptor in RV adaptation after occlusion of the left pulmonary artery (LPA) in a murine model. MAIN METHODS: C57/Bl6 (WT)- and CB2 receptor-deficient (Cnr2-/-)-mice underwent paramedian sternotomy and LPA was occluded using a metal clip. Right heart hemodynamic study (Millar®) preceded organ harvesting for immunohistochemistry and mRNA analysis 7 and 21 days (d) post-occlusion. KEY FINDINGS: LPA occlusion led to higher RV systolic pressure in Cnr2-/--hearts, while hemodynamics were comparable with WT-hearts after 21d. Cnr2-/--hearts showed higher macrophage infiltration and lower interleukin-10 expression after 7 d, but otherwise a comparable inflammatory mediator expression profile. Cardiomyocyte-hypertrophy was stronger in Cnr2-/--mice, presenting with higher tenascin-C expression than WT-hearts. Planimetry revealed higher collagen area in Cnr2-/--hearts and small areas of cardiomyocyte-loss. Surrounding cardiomyocytes were cleaved caspase-3- and TUNEL positive in Cnr2-/--hearts. This was associated by maladaptation of myosin heavy-chain isoforms and lower reactive oxygen scavenger enzymes induction in Cnr2-/--hearts. We found comparable morphological changes in both lungs between the two genotypes. SIGNIFICANCE: LPA occlusion led to increased systolic pressure and adaptation of RV in CB2-deficient mice. CB2 receptor seems to modulate RV adaptation through expression of contractile elements, reactive oxygen scavenger enzymes, and inflammatory response in order to prevent cardiomyocyte apoptosis.

Comparison of stroke volumes assessed by three-dimensional echocardiography and transpulmonary thermodilution in a pediatric animal model.

To compare stroke volumes (SV) in small hearts assessed by real-time three-dimensional echocardiography (3DE) with SV measured by transpulmonary thermodilution (TPTD) and continuous pulse contour analysis (PC) under various hemodynamic conditions. In thirteen anesthetized piglets (range 3.6-7.1 kg) SV were measured by 3DE, TPTD and PC at baseline and during phenylephrine and esmolol administration. 3DE and TPTD measurements were done successively while SV calculated by PC was documented at the time of 3DE. 3DE and TPTD showed a good correlation (r2 = 0.74) and a bias of -1.3 ml (limits of agreement -4.1 to 1.5 ml). While TPTD measured higher SV than 3DE, both methods tracked SV changes with a concordance rate of 91 %. PC and 3DE showed a lower correlation coefficient of r2 = 0.57 and a bias of -2.1 ml (limits of agreement -5.9 to 1.8 ml). Inter- and intra-observer variability of SV measured by 3DE was good with a mean bias <5 %. SV3DE showed a small variance and tracked acute small changes in SV in acceptable concordance with TPTD. PC measured SV with a higher variance and mean difference compared to 3DE. In an experimental setting 3DE has the possibility to offer non-invasive assessments of ventricular volumes volume changes. To determine whether 3DE could be used for SV assessment in a clinical routine our results need confirmation in a clinical setting.

Endothelial permeability following coronary artery bypass grafting: an observational study on the possible role of angiopoietin imbalance.

BACKGROUND: Unresolved inflammation resulting in capillary leakage with endothelial barrier dysfunction is a major contributor to postoperative morbidity and mortality after coronary artery bypass graft (CABG). Angiopoietins (ANGs) are vascular growth factors, also mediating inflammation and disruption of the endothelium, thus inducing capillary leakage. We hypothesized that changes in the relative serum levels of ANG1 and ANG2 influence endothelial barrier function and perioperative morbidity after CABG. METHODS: After approval and informed consent, serum samples (n = 28) were collected pre CABG surgery, 1, 6, and 24 h after aortic de-clamping. ANG1, ANG2, soluble ANG receptor TIE2 (sTIE2), and IL-6 serum concentrations were analyzed by ELISA. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with patient serum and FITC-dextran permeability was assessed. Furthermore, ANG2 secretion of HPMECs was analyzed after incubation with IL-6-containing patient serum. RESULTS: CABG induced an early and sustained increase of ANG2/ANG1 ratio (5-fold after 24 h compared to pre-surgery). These changes correlated with elevated serum lactate levels, fluid balance, as well as the duration of mechanical ventilation. Permeability of HPMECs significantly increased after incubation with post-surgery serum showing a marked shift of ANG2/ANG1 balance (18-fold) compared to serum with a less pronounced increase (6-fold). Furthermore, CABG resulted in increased IL-6 serum content. Pre-incubation with serum containing high levels of IL-6 amplified the ANG2 secretion by HPMECs; however, this was not influenced by blocking IL-6. CONCLUSIONS: CABG affects the balance between ANG1 and ANG2 towards a dominance of the barrier-disruptive ANG2. Our data suggest that this ANG2/ANG1 imbalance contributes to an increased postoperative endothelial permeability, likewise being reflected by the clinical course. The results strongly suggest a biological effect of altered angiopoietin balance during cardiac surgery on endothelial permeability.