A comparison of conventional and advanced 3D imaging techniques for percutaneous left atrial appendage closure.

Background: Understanding complex cardiac anatomy is essential for percutaneous left atrial appendage (LAA) closure. Conventional multi-slice computed tomography (MSCT) and transesophageal echocardiography (TEE) are now supported by advanced 3D printing and virtual reality (VR) techniques for three-dimensional visualization of volumetric data sets. This study aimed to investigate their added value for LAA closure procedures. Methods: Ten patients scheduled for interventional LAA closure were evaluated with MSCT and TEE. Patient-specific 3D printings and VR models were fabricated based on MSCT data. Ten cardiologists then comparatively assessed LAA anatomy and its procedure relevant surrounding structures with all four imaging modalities and rated their procedural utility on a 5-point Likert scale questionnaire (from 1 = strongly agree to 5 = strongly disagree). Results: Device sizing was rated highest in MSCT (MSCT: 1.9 ± 0.8; TEE: 2.6 ± 0.9; 3D printing: 2.5 ± 1.0; VR: 2.5 ± 1.1; p < 0.01); TEE, VR, and 3D printing were superior in the visualization of the Fossa ovalis compared to MSCT (MSCT: 3.3 ± 1.4; TEE: 2.2 ± 1.3; 3D printing: 2.2 ± 1.4; VR: 1.9 ± 1.3; all p < 0.01). The major strength of VR and 3D printing techniques was a superior depth perception (VR: 1.6 ± 0.5; 3D printing: 1.8 ± 0.4; TEE: 2.9 ± 0.7; MSCT: 2.6 ± 0.8; p < 0.01). The visualization of extracardiac structures was rated less accurate in TEE than MSCT (TEE: 2.6 ± 0.9; MSCT: 1.9 ± 0.8, p < 0.01). However, 3D printing and VR insufficiently visualized extracardiac structures in the present study. Conclusion: A true 3D visualization in VR or 3D printing provides an additional value in the evaluation of the LAA for the planning of percutaneous closure. In particular, the superior perception of depth was seen as a strength of a 3D visualization. This may contribute to a better overall understanding of the anatomy. Clinical studies are needed to evaluate whether a more comprehensive understanding through advanced multimodal imaging of patient-specific anatomy using VR may translate into improved procedural outcomes.

Rational and design of the REMOTE trial: An exploratory, pilot study to analyze REtinal MicrOcirculaTion in wEightlessness.

BACKGROUND: "Spaceflight associated neuro-ocular syndrome" (SANS) represents a challenging health condition in modern space medicine. Forty-eight percent of astronauts are diagnosed with SANS after long-term space missions. The pathophysiological mechanism seems to be multifactorial, and yet remains unknown. In this proof-of-concept study we plan to investigate retinal microcirculatory changes in weightlessness and aim to identify their role in the development of SANS. METHODS AND DESIGN: Healthy individuals will take part in a parabolic flight campaign, which recreates fractioned total weightlessness periods. The airplane is specifically equipped, and designed for the execution of parabolic flight maneuvers and scientific research in microgravity. Retinal microcirculation will be assessed with a modified fundus camera, which allows dynamic vessel analysis. We will additionally measure intra-ocular pressure and hemodynamic changes during each phase of the flight. Blood samples will be analyzed at baseline, one hour and 24 hours after exposure to weightlessness. CONCLUSIONS: This pilot study aims to investigate the feasibility of retinal microcirculation assessment during varying gravity. Results of this study may generate insights whether venous stasis in the eye, surrogated by the dilatation of retinal vessels and increase in intraocular pressure as signs of venous insufficiency, may potentially contribute to the development of SANS.

Cytokine absorption in critically ill old COVID-19 patients with renal failure: A retrospective analysis of 503 intensive care unit patients.

BACKGROUND: COVID-19 is associated with cytokine release in critical disease states. Thus, cytokine absorption has been proposed as a therapeutic option. This study investigated the influence of cytokine absorption on mortality in old critical patients with COVID-19 and renal failure admitted to intensive care units (ICU). METHODS: This retrospective analysis of a prospective international observation study (the COVIP study) analysed ICU patients≥70 years with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, clinical frailty scale (CFS), ICU therapy details including renal replacement therapy (RRT) with/without cytokine absorption were collected. The cytokine absorption group was compared to patients receiving RRT without cytokine absorptionRESULTS:Among 3927 patients, 503 received RRT; among them 47 patients were treated with cytokine absorption. Mortality rates were high in both groups with increased rates in the cytokine group for ICU mortality and 30-day mortality, but not for 3-month mortality. Logistic regression analysis indicated that SOFA-score, but not cytokine absorption was associated with mortality. CONCLUSIONS: Critical COVID-19 patients with renal failure treated with cytokine absorption showed higher short term mortality rates when compared to patients with renal replacement therapy alone. Mortality is associated with disease severity, but not cytokine absorption in a multivariate analysis.

Virtual and augmented reality in critical care medicine: the patient's, clinician's, and researcher's perspective.

Virtual reality (VR) and augmented reality (AR) are aspiring, new technologies with increasing use in critical care medicine. While VR fully immerses the user into a virtual three-dimensional space, AR adds overlaid virtual elements into a real-world environment. VR and AR offer great potential to improve critical care medicine for patients, relatives and health care providers. VR may help to ameliorate anxiety, stress, fear, and pain for the patient. It may assist patients in mobilisation and rehabilitation and can improve communication between all those involved in the patient's care. AR can be an effective tool to support continuous education of intensive care medicine providers, and may complement traditional learning methods to acquire key practical competences such as central venous line placement, cardiopulmonary resuscitation, extracorporeal membrane oxygenation device management or endotracheal intubation. Currently, technical, human, and ethical challenges remain. The adaptation and integration of VR/AR modalities into useful clinical applications that can be used routinely on the ICU is challenging. Users may experience unwanted side effects (so-called "cybersickness") during VR/AR sessions, which may limit its applicability. Furthermore, critically ill patients are one of the most vulnerable patient groups and warrant special ethical considerations if new technologies are to be introduced into their daily care. To date, most studies involving AR/VR in critical care medicine provide only a low level of evidence due to their research design. Here we summarise background information, current developments, and key considerations that should be taken into account for future scientific investigations in this field.

The role of anemia on admission in acute coronary syndrome - An umbrella review of systematic reviews and meta-analyses.

INTRODUCTION: The role of erythrocytes in the acute coronary syndrome (ACS) is complex. The aim of this review in terms of PICO (P: patients; I: intervention; C: comparison; O: outcome) was to summarize systematic reviews in patients (P) with acute coronary syndrome, evaluating the effects of (I) 1) iron deficiency, 2) administration of an erythropoiesis-stimulating agent (ESA), 3) anemia on admission, 4) red blood cell transfusion, 5) a restrictive transfusion strategy in comparison (C) to 1) no iron deficiency, 2) no ESA 3) no anemia on admission, 4) no red blood cell transfusion, 5) a liberal transfusion strategy on mortality (O). METHODS: We used AMSTAR2 to assess the methodological quality of systematic reviews and grade the available research. The primary endpoint was all-cause mortality. RESULTS: Using the data from 2,787,005 patients, the following conditions were associated with worse outcome in patients with ACS: anemia on admission (RR 2.08 95%CI 1.70-2.55) and transfusion (1.93 95%CI 1.12-3.34) of red blood cells. A liberal transfusion (RR 0.86 95%CI 0.70-1-05), administration of ESA (RR 0.55 95%CI 0.22-1.33) and iron deficiency (OR 1.24 95%CI 0.12-13.13) were not associated with altered all-cause mortality. CONCLUSION: Patients suffering from ACS and anemia on admission are at particular risk for adverse outcome. There is evidence of associations between adverse outcomes and receiving red blood cell transfusions.

Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens.

Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic treatment in patients with acute coronary syndromes (ACS) or high-risk percutaneous coronary interventions (PCI). It is administered intravenously as a bolus followed by continuous infusion. However, the dosage recommendations in the United States (US) and European Union (EU) differ considerably. Furthermore, in routine clinical practice, deviations from the recommendations may occur. The objective of the present study was to investigate the impact of different alterations on tirofiban plasma concentrations in US and EU administration regimens and to give suggestions for delay management in clinical practice. We therefore mathematically simulated the effects of different bolus-infusion delays and infusion interruptions in different scenarios according to the renal function. Here, we provide a systematic assessment of concentration patterns of tirofiban in the US versus EU dosage regimens. We show that differences between the two regimens have important effects on plasma drug levels. Furthermore, we demonstrate that deviations from the proper administration mode affect the concentration of tirofiban. Additionally, we calculated the optimal dosage of a second bolus to rapidly restore the initial concentration without causing overdosage. In conclusion, differences in tirofiban dosing regimens between the U.S and EU and potential infusion interruptions have important effects on drug levels that may impact on degrees of platelet inhibition and thus antithrombotic effects. Thus, the findings of our modelling studies may help to explain differences in clinical outcomes observed in previous clinical trials on tirofiban.

No impact of weather conditions on the outcome of intensive care unit patients.

Global warming leads to increased exposure of humankind to meteorological variation, including short-term weather changes. Weather conditions involve changes in temperature, heat and cold, in air pressure and in air humidity. Every single condition influences the incidence and mortality of different diseases such as myocardial infarction and stroke. This study investigated the impact of weather conditions on short- and long-term mortality of 4321 critically ill patients (66 ± 14 years, 2638 men) admitted to an intensive care unit (ICU) over a period of 5 years. Meteorological information (air temperature, air pressure and humidity) for the same period was retrieved. The influence of absolute weather parameters, different seasons, sudden weather changes including "warm" and "cold" spells on ICU and long-term mortality was analyzed. After correction for Simplified Acute Physiology Score (SAPS-2), no impact of meteorological conditions on mortality was found. Different seasons, sudden weather changes, "warm spells" or "cold spells" did not affect the outcome of critically ill patients.

Impella versus extracorporal life support in cardiogenic shock: a propensity score adjusted analysis.

AIMS: The mortality in cardiogenic shock (CS) is high. The role of specific mechanical circulatory support (MCS) systems is unclear. We aimed to compare patients receiving Impella versus ECLS (extracorporal life support) with regard to baseline characteristics, feasibility, and outcomes in CS. METHODS AND RESULTS: This is a retrospective cohort study including CS patients over 18 years with a complete follow-up of the primary endpoint and available baseline lactate level, receiving haemodynamic support either by Impella 2.5 or ECLS from two European registries. The decision for device implementation was made at the discretion of the treating physician. The primary endpoint of this study was all-cause mortality at 30 days. A propensity score for the use of Impella was calculated, and multivariable logistic regression was used to obtain adjusted odds ratios (aOR). In total, 149 patients were included, receiving either Impella (n = 73) or ECLS (n = 76) for CS. The feasibility of device implantation was high (87%) and similar (aOR: 3.14; 95% CI: 0.18-56.50; P = 0.41) with both systems. The rates of vascular injuries (aOR: 0.95; 95% CI: 0.10-3.50; P = 0.56) and bleedings requiring transfusions (aOR: 0.44; 95% CI: 0.09-2.10; P = 0.29) were similar in ECLS patients and Impella patients. The use of Impella or ECLS was not associated with increased odds of mortality (aOR: 4.19; 95% CI: 0.53-33.25; P = 0.17), after correction for propensity score and baseline lactate level. Baseline lactate level was independently associated with increased odds of 30 day mortality (per mmol/L increase; OR: 1.29; 95% CI: 1.14-1.45; P < 0.001). CONCLUSIONS: In CS patients, the adjusted mortality rates of both ECLS and Impella were high and similar. The baseline lactate level was a potent predictor of mortality and could play a role in patient selection for therapy in future studies. In patients with profound CS, the type of device is likely to be less important compared with other parameters including non-cardiac and neurological factors.

Comprehensive Analysis of Macrocirculation and Microcirculation in Microgravity During Parabolic Flights.

BACKGROUND: Profound knowledge about cardiovascular physiology in the setting of microgravity can help in the course of preparations for human space missions. So far, influences of microgravity on the cardiovascular system have been demonstrated, particularly pertaining to venous fluid shifts. Yet, little is known about the mechanisms of these adaptations on continuous macrocirculatory level and regarding the microcirculation. METHODS: Twelve healthy volunteers were subjected to alternating microgravity and hypergravity in the course of parabolic flight maneuvers. Under these conditions, as well as in normal gravity, the sublingual microcirculation was assessed by intravital sidestream dark field microscopy. Furthermore, hemodynamic parameters such as heart rate, blood pressure, and cardiac output were recorded by beat-to-beat analysis. In these settings, data acquisition was performed in seated and in supine postures. RESULTS: Systolic [median 116 mmHg (102; 129) interquartile range (IQR) vs. 125 mmHg (109; 136) IQR, p = 0.01] as well as diastolic [median 72 mmHg (61; 79) IQR vs. 80 mmHg (69; 89) IQR, p = 0.003] blood pressure was reduced, and cardiac output [median 6.9 l/min (6.5; 8.8) IQR vs. 6.8 l/min (6.2; 8.5) IQR, p = 0.0002] increased in weightlessness compared to normal gravitation phases in the seated but not in the supine posture. However, microcirculation represented by perfused proportion of vessels and by total vessel density was unaffected in acute weightlessness. CONCLUSION: Profound changes of the macrocirculation were found in seated postures, but not in supine postures. However, microcirculation remained stable in all postures.

Sex-Specific Outcomes of Patients Treated With Extracorporeal Cardiopulmonary Resuscitation.

INTRODUCTION: Patients after cardiac arrest (CA) treated with extracorporeal cardiopulmonary resuscitation (eCPR) evidence high mortality. Recently, women were reported to evidence even worse outcomes after CA. However, sex-specific data on CA patients treated with eCPR are lacking. We therefore aimed to evaluate potential sex differences in risk distribution, management, and outcomes in patients treated with eCPR. METHODS: Sixty-four patients - 16 females (25%) and 48 males (75%) - were included in this retrospective analysis. Two propensity scores were calculated on sex using multivariable logistic regression. Propensity score 1 included baseline characteristics only, and propensity score 2 included the previous variables plus pH as well as lactate concentration. Univariable and multivariable logistic regression models were used to assess associations with the endpoints. RESULTS: The distribution of risk factors and baseline characteristics showed no sex-specific differences. Sex was neither associated with mortality nor with bad neurological outcomes, and remained so after adjustment for both propensity scores. Baseline lactate (adjust odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.02-1.38; P=.03), lactate after 6 hours (aOR, 1.23; 95% CI, 1.04-1.45; P=.01), and lactate clearance at 6 hours (aOR, 0.979; 95% CI, 0.959-0.999; P=.04) were independently associated with 30-day mortality. Higher lactate clearance after 6 hours was associated with lower rates of bad Glasgow Outcomes Scale both in univariable (OR, 0.967; 95% CI, 0.941-0.991; P=.02) and multivariable logistic regression models (aOR, 0.967; 95% CI, 0.941-0.994; P=.02). CONCLUSION: There were no sex-specific outcome differences in patients treated with eCPR. Both lactate concentration and lactate clearance could help with the selection of patients for inclusion in eCPR trials.

Influence of Timing and Predicted Risk on Mortality in Impella-Treated Infarct-Related Cardiogenic Shock Patients.

Background: In-hospital mortality in acute myocardial infarction-related cardiogenic shock (AMI-CS) remains high. The only adequately powered randomized trial showed no benefit of routine use of the intra-aortic balloon pump in AMI-CS. We compared individually predicted mortality using CardShock- and IABP-Shock II-scores in AMI-CS patients treated with an Impella microaxial pump, who met the IABP-Shock II-trials inclusion/exclusion criteria, to observed mortality on circulatory support in order to determine whether standardized use of an Impella microaxial flow-pump in AMI-CS is associated with lower than predicted mortality rates and whether timing of implantation or selecting patients based on predicted risk is meaningful. Methods and Results: We analyzed data from 166 consecutive Impella-treated AMI-CS patients meeting the inclusion/exclusion criteria of the IABP-Shock II-trial (age 64 ± 11 years). Thirty-nine percentage of 64 patients had been resuscitated before Impella implantation. Overall 30-day mortality was 42%. Mortality was higher in resuscitated patients (50 vs. 36%, p = 0.0452) and when Impella was implanted post-PCI (Impella-pre-PCI: 28%, Impella-post-PCI: 51%, p = 0.0039). While in both score systems there was no significant difference between predicted and observed overall 30-day mortality, predicted mortality was significantly higher than observed mortality on Impella support only for individuals with highest predicted risk based on CardShock score (predicted 77 vs. observed 51%, p = 0.025). Conclusions: Our retrospective analysis suggests that the use of the Impella microaxial pump may be effective in selected cases of high risk patients with AMI-CS. Condensed abstract: Mortality is high in acute myocardial infarction-related cardiogenic shock despite rapid revascularization. Haemodynamic support with an intraortic balloon pump does not reduce mortality. In this retrospective registry including 166 consecutive IABP-Shock II-eligible cardiogenic shock patients in four dedicated shock centers, observed mortality on circulatory support with an Impella was significantly lower than predicted in patients with highest mortality risk. Implantation prior to PCI in acute myocardial infarction-related cardiogenic shock seemed to be associated with lower mortality than implantation post PCI.

Extracorporeal life support system during cardiovascular procedures: Insights from the German Lifebridge registry.

The frequency of mechanical circulatory support (MCS) device application has increased in recent years. Besides implantation in the emergency setting, such as circulatory arrest, MCS is also increasingly used electively to ensure hemodynamic stability in high-risk patients, for example, during percutaneous coronary interventions (PCI), valve interventions or off-pump coronary bypass surgery. Lifebridge (Zoll Medical GmbH, Germany) is a compact percutaneous MCS device widely used in daily clinical routine. The present study aimed to investigate the indications, feasibility, and outcomes after use of Lifebridge in cardiac interventions, evaluating a large-scale multicenter database. A total of 60 tertiary cardiovascular centers were questioned regarding application and short-term outcomes after the use of the Lifebridge system (n = 160 patients). Out of these 60 centers, eight consented to participate in the study (n = 39 patients), where detailed data were collected using standardized questionnaires. Demographic and clinical characteristics of the patient population, procedural as well as follow-up data were recorded and analyzed. In 60 interrogated centers, Lifebridge was used in 74% of emergency cases and 26% in the setting of planned interventions. The subcohort interrogated in detail displayed the same distribution of application scenarios, while the main cardiovascular procedure was high-risk PCI (82%). All patients were successfully weaned from the device and 92% (n = 36) of the patients studied in detail survived after 30 days. As assessed 30 days after insertion of the device, bleeding requiring red blood cell (RBC) transfusion constituted the main complication, occurring in 49% of cases. In our analysis of clinical data, the use of Lifebridge in cardiac intervention was shown to be feasible. Further prospective studies are warranted to identify patients who benefit from hemodynamic MCS support despite the increased rate of RBC transfusion due to challenges in access sites during cardiovascular procedures.

Sublingual microcirculation detects impaired perfusion in dehydrated older patients.

BACKGROUND: Dehydration occurs frequently in older patients and constitutes a significant clinical problem. OBJECTIVE: This proof-of-concept study examines whether 1) sublingual measurement in dehydrated old patients is feasible, 2) frailty and incompliance in old, awake patients affects video-quality, 3) dehydration impacts microcirculationMETHODS:This prospective observational study included clinically dehydrated patients aged ≥65 years immediately after admission. Dehydration was assessed clinically. A sidestream dark field camera (SDF) was used for measurement. Video-quality was evaluated with MIQS (microcirculation image quality score). Both AVA 4.3C- and AVA POEM-software analyzed the videos. Seventeen patients ≥65 years not showing dehydration served as control. RESULTS: Thirteen patients (8 female) were included. The average age was 83±8 years. The mini-mental test was 17±15 points, the Clinical Frailty Scale 4±3, the Barthel-Index 59±39. None of these parameters correlated with MIQS (3.4±4.2 SD ("acceptable")). Dehydrated patients had a slightly impaired microcirculation, with a significantly lower percentage of perfused small vessels compared to control (83.1±7.7% versus 88.0±6.0%, P < 0.05). After rehydration, there was acute improvement in the microcirculation. CONCLUSIONS: Sublingual microcirculatory SDF-measurement is both, safe and valid for dehydrated old patients - regardless of frailty, age or cognitive performance. Dehydration leads to an impaired microcirculation.

Acidosis predicts mortality independently from hyperlactatemia in patients with sepsis.

RATIONALE AND OBJECTIVES: Acidosis and hyperlactatemia predict outcome in critically ill patients. We assessed BE and pH for risk prediction capabilities in a sub-group of septic patients in the MIMIC-III database. METHODS: Associations with mortality were assessed by logistic regression analysis in 5586 septic patients. Baseline parameters, lactate concentrations, pH, and BE were analyzed at baseline and after 6 hours. MEASUREMENTS AND MAIN RESULTS: We combined acidosis (defined as either BE ≤-6 and/or pH ≤7.3) and hyperlactatemia and split the cohort into three subgroups: low-risk (no acidosis and lactate <2.3 mmol/L; n = 2294), medium-risk (either acidosis or lactate >2.3 mmol/L; n = 2125) and high-risk (both acidosis and lactate >2.3 mmol/L; n = 1167). Mortality was 14%, 20% and 38% (p<0.001) in low-risk, medium-risk and high-risk patients, respectively. The predictiveness of this model (AUC 0.63 95%CI 0.61-0.65) was higher compared to acidosis (AUC 0.59 95%CI 0.57-0.61; p<0.001) and lactate >2.3 mmol/L (AUC 0.60 95%CI 0.58-0.62; p<0.001) alone. Hyperlactatemia alone was only moderately predictive for acidosis (AUC 0.60 95%CI 0.59-0.62). CONCLUSIONS: Acidosis and hyperlactatemia can occur independently to a certain degree. Combining acidosis and hyperlactatemia in a model yielded higher predictiveness for ICU-mortality. Septic patients with acidosis should be treated even more aggressively in the future.

Sublingual microcirculation in prehospital critical care medicine: A proof-of-concept study.

OBJECTIVE: Diagnostic and risk stratification are limited in emergencies. The measurement of microcirculation might identify patients with poor perfusion but compensated macrocirculation such as in beginning shock. This proof-of-concept study examines whether sublingual prehospital sidestream dark-field microscopy is feasible. METHODS: This prospective observational study included patients receiving medical aid by an emergency ambulance who had a spontaneous circulation and offered access to the sublingual mucosa. Sublingual measurement of microcirculation was performed using a sidestream dark field camera. Video quality was evaluated with microcirculation image quality score (microcirculation image quality score). AVA 4.3C software calculated microcirculatory parameters. RESULTS: Thirty patients (47% male) were included. The average age was 63 years (±20 years SD), the severity of the disease (quantified by National Advisory Committee on Aeronautics) was 3.4 (±0.7 SD). Macrocirculation presented within the normal range. The most frequent cause preventing the measurement was a time-critical disease (64%). In 17 patients (57%), the videos could be analyzed immediately. The average quality of the video was 2.2 ± 0.45 points ('acceptable'). There were minor restrictions of microcirculation. Microcirculation correlated with National Advisory Committee on Aeronautics, but not with the macrocirculation. No complications occurred. CONCLUSION: The prehospital sublingual measurement is safe and valid. Despite normal macrocirculation, microcirculation was impaired and correlated with National Advisory Committee on Aeronautics.

Poor glycemic control impairs the cardioprotective effects of red blood cells on myocardial ischemia/reperfusion injury.

Red blood cells (RBCs) play an important role in the cardiac ischemia/reperfusion (I/R) injury. Cardiovascular risk factors impair the RBC function in an endothelial nitric oxide synthase (eNOS) dependent manner. However, it is unclear whether the protective role of RBCs can be rescued by modifying cardiovascular risk factors or by pharmacologic intervention. RBCs obtained from elderly patients with or without diabetes as well as from young volunteers were treated with vehicle, eNOS inhibitor l-NAME and/or arginase inhibitor nor-NOHA before loading to the coronary system of isolated murine hearts in a Langendorff system before 40 min of global ischemia. RBCs from young and healthy volunteers as well as from aged persons and elderly diabetes patients with satisfying blood glucose control improved left ventricular function upon 60 min of reperfusion with Krebs-Henseleit buffer and reduced the infarct size compared to buffer treated controls. This cardioprotective effect was abolished in RBCs from aged diabetes patients with poor blood glucose control. Treatment of RBCs from elderly diabetes patients with nor-NOHA partly rescued the cardioprotective function. Thus, effective glucose control in aged diabetes patients rescues RBC-dependent cardioprotection in an ex-vivo model of myocardial I/R injury.

A Model of Blood Component-Heart Interaction in Cardiac Ischemia-Reperfusion Injury using a Langendorff-Based Ex Vivo Assay.

INTRODUCTION: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide. Cellular interactions of red blood cells (RBCs) and platelets with endothelial cells and cardiomyocytes play a crucial role in cardiac ischemia/reperfusion (I/R) injury. However, addressing the specific impact of such cell-to-cell interactions in commonly employed in vivo models of cardiac I/R injury is challenging due to overlap of neuronal, hormonal, and immunological pathways. This study aimed to refine a Langendorff-based ex vivo transfer model to evaluate the impact of specific blood components on cardiac I/R injury. MATERIAL AND METHODS: Murine whole blood, defined murine blood components (RBCs, platelet-rich plasma [PRP], and platelet-poor plasma [PPP], respectively) as well as human RBCs were loaded to the coronary system of isolated murine hearts in a Langendorff system before initiating global ischemia for 40 minutes. Following 60 minutes of reperfusion with Krebs Henseleit Buffer, left ventricular function and coronary flow were assessed. Infarct size was determined by specific histological staining following 120 minutes of reperfusion. RESULTS: Loading of murine whole blood to the coronary system of isolated murine hearts at the beginning of 40 minutes of global ischemia improved left ventricular function after 60 minutes of reperfusion and reduced the infarct size in comparison to buffer-treated controls. Similarly, isolated murine RBCs, PRP, and PPP mediated a protective effect in the cardiac I/R model. Furthermore, human RBCs showed a comparable protective capacity as murine RBCs. CONCLUSION: This Langendorff-based transfer model of cardiac I/R injury is a feasible, time-, and cost-effective model to evaluate the impact of blood components on myocardial infarction. The presented method facilitates loading of blood components of genetically modified mice to murine hearts of a different mouse strain, thus complementing time- and cost-intensive chimeric models and contributing to the development of novel targeted therapies.

Real-world clinical experience with the percutaneous extracorporeal life support system: Results from the German Lifebridge® Registry.

BACKGROUND: The concept of percutaneous extracorporeal life support (ECLS) is based on immediate cardiovascular stabilization allowing for sufficient end-organ perfusion, thus improving the outcome in patients with circulatory arrest. Lifebridge® (Zoll Medical GmbH, Germany) is a portable ECLS device designed for rapid application due to its automated set-up. METHODS: A total of 60 tertiary cardiovascular centers were interrogated with regard to application and short-term results after use of Lifebridge ECLS system. Detailed data were collected by standardized case report forms in all centers consented to participate in the study. Demographic and clinical baseline characteristics of the patient population, procedural and follow-up data were recorded and analyzed. RESULTS: In total, 444 patients were analyzed regarding mortality. The detailed study cohort consisted of 112 patients. A total of 80% of the study subjects represented patients post cardiopulmonary resuscitation, 43% were in cardiogenic shock and 50% suffered from acute myocardial infarction. The survival rates were 36% immediately after device implementation and 16% after 30 days. Multivariable analysis revealed that only serum lactate concentration at admission could be proven as independent predictor of patients' outcome. Patients with lactate concentrations above 10 mmol/L exhibited > 95% mortality (p < 0.05 versus below 10 mmol/L). CONCLUSION: The present study provides real-world clinical data of patients treated with a transportable automated ECLS system. In conclusion, Lifebridge is a safely applicable cardiorespiratory stabilization tool associated with acceptable complication rates. Nevertheless, mortality rates were high in these critically ill patients, especially in those showing high lactate concentrations at admission.

Admission Body Temperature in Critically Ill Patients as an Independent Risk Predictor for Overall Outcome.

INTRODUCTION: Body temperature (BT) abnormalities are frequently observed in critically ill patients. We aimed to assess admission BT in a heterogeneous critically ill patient population admitted to an intensive care unit (ICU) as a prognostic parameter for intra-ICU and long-term mortality. METHODS: A total of 6,514 medical patients (64 ± 15 years) admitted to a German ICU between 2004 and 2009 were included. A follow-up of patients was performed retrospectively. The association of admission BT with both intra-ICU and long-term mortality was investigated by logistic regression. RESULTS: Patients with hypothermia (<36°C BT) were clinically worse and had more pronounced signs of multi-organ failure. Admission BT was associated with adverse overall outcome, with a 2-fold increase for hyperthermia (mortality 12%; odds ratio [OR] 1.80, 95% confidence interval [CI] 1.43-2.26; p < 0.001), and a 4-fold increase for the risk of hypothermia (mortality 24%; OR 4.05, 95% CI 3.38-4.85; p < 0.001) with respect to intra-ICU and long-term mortality. Moreover, hypothermia was even more harmful than hyperthermia, and both were strongly associated with intra-ICU mortality, especially in patients admitted with acute coronary syndrome (hypothermia: hazard ratio 6.12, 95% CI 4.12-9.11; p < 0.001; hyperthermia: OR 2.70, 95% CI 1.52-4.79; p< 0.001). CONCLUSION: Admission BT is an independent risk predictor for both overall intra-ICU and long-term mortality in critically ill patients admitted to an ICU. Therefore, BT at admission might not only serve as a parameter for individual risk stratification but can also influence individual therapeutic decision-making.

Syndecan-1 Predicts Outcome in Patients with ST-Segment Elevation Infarction Independent from Infarct-related Myocardial Injury.

Syndecan-1 (sdc1) is a surface protein part of the endothelial glycocalyx (eGC). Soluble sdc1 is derived from shedding and indicates damaged eGC. We assessed the predictive value of plasma sdc1 concentrations for future cardiovascular events in acute reperfused ST-segment elevation myocardial infarction (STEMI) patients. A total of 206 patients admitted for STEMI were included in this study (29% female; age 65 ± 12 years) and followed-up for six months. Plasma samples were obtained post-intervention and analyzed for sdc1 by Enzyme-linked Immunosorbent Assay (ELISA). Primary outcome was six-month-mortality. Sdc1 did not correlate with biomarkers such as creatine kinase (CK) (r = 0.11; p = 0.01) or troponin (r = -0.12; p = 0.09), nor with infarct size (r = -0.04; p = 0.67) and myocardial salvage index (r = 0.11; p = 0.17). Sdc-1 was associated with mortality (changes per 100 ng/mL sdc-1 concentration; HR 1.08 95% 1.03-1.12; p = 0.001). An optimal cut-off was calculated at >120 ng/mL. After correction for known risk factors sdc1 >120 ng/mL was independently associated with mortality after 6 months. In our study, sdc1 is independently associated with six-month-mortality after STEMI. Combining clinical evaluation and different biomarkers assessing both infarct-related myocardial injury and systemic stress response might improve the accuracy of predicting clinical prognosis in STEMI patients.