Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach.

OBJECTIVES: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival. DESIGN: Clinical case control study followed by translational laboratory study. SETTING: Research institution. PATIENTS/SUBJECTS: Adult cardiac arrest patients and male Sprague-Dawley rats. INTERVENTIONS: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle. MEASUREMENTS AND MAIN RESULTS: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect. CONCLUSIONS: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.

The Value of Extracellular Cold-Inducible RNA-Binding Protein (eCIRP) in Predicting the Severity and Prognosis of Patients After Cardiac Arrest: A Preliminary Observational Study.

BACKGROUND: Extracellular cold-inducible RNA-binding protein (eCIRP) acting as a novel damage-associated molecular pattern molecule promotes systemic inflammatory responses, including neuroinflammation in cerebral ischemia. We aimed to observe the changes of serum eCIRP and evaluate whether the increased serum eCIRP was associated with the severity and prognosis in patients with restoration of spontaneous circulation (ROSC). METHODS: A total of 73 patients after ROSC were divided into non-survivor (n = 48) and survivor (n = 25) groups based on 28-day survival. Healthy volunteers (n = 25) were enrolled as controls. Serum eCIRP, procalcitonin (PCT), the pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and high mobility group protein (HMGB1), the neurological damage biomarkers neuron-specific enolase (NSE), and soluble protein 100ß (S100ß) were measured on days 1, 3, and 7 after ROSC. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) were calculated concurrently. Cerebral performance category scores on day 28 after ROSC were recorded. RESULTS: Serum eCIRP, IL-6, TNF-α, PCT, and HMGB1, NSE and S100ß were significantly increased within the first week after ROSC. The increased levels of eCIRP were positively correlated with IL-6, TNF-α, lactate, NSE, S100ß, CPR time, SOFA score, APACHE II score, and HMGB1 after ROSC. Serum eCIRP on days 1, 3, and 7 after ROSC could predict 28-day mortality and neurological prognosis. Serum eCIRP on day 3 after ROSC had a biggest AUC [0.862 (95% CI: 0.741-0.941)] for 28-day mortality and a biggest AUC [0.807 (95% CI: 0.630-0.981)] for neurological prognosis. CONCLUSIONS: Systemic inflammatory response with increased serum eCIRP occurred in patients after ROSC. Increased eCIRP level was positively correlated with the aggravation of systemic inflammatory response and the severity after ROSC. Serum eCIRP serves as a potential predictor for 28-day mortality and poor neurological prognosis after ROSC.

A simple procedure in a complex patient: perioperative takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is a rare but life-threatening condition that is still not completely understood. Characterised by rapidly reversible ventricular dysfunction without any prior coronary artery disease, it can imitate a myocardial infarction and lead to death if not managed appropriately. This report examines a case of intraoperative cardiac arrest in a patient with no previous cardiac disease, and discusses the factors that may have precipitated this event, as well as the ways of distinguishing the cause of the arrest based on clinical course and investigations, eventually leading to a diagnosis of TTC.

Ultrafast Hypothermia Selectively Mitigates the Early Humoral Response After Cardiac Arrest.

Background Total liquid ventilation (TLV) has been shown to prevent neurological damage though ultrafast cooling in animal models of cardiac arrest. We investigated whether its neuroprotective effect could be explained by mitigation of early inflammatory events. Methods and Results Rabbits were submitted to 10 minutes of ventricular fibrillation. After resuscitation, they underwent normothermic follow-up (control) or ultrafast cooling by TLV and hypothermia maintenance for 3 hours (TLV). Immune response, survival, and neurological dysfunction were assessed for 3 days. TLV improved neurological recovery and reduced cerebral lesions and leukocyte infiltration as compared with control (eg, neurological dysfunction score=34±6 versus 66±6% at day 1, respectively). TLV also significantly reduced interleukin-6 blood levels during the hypothermic episode (298±303 versus 991±471 pg/mL in TLV versus control at 3 hours after resuscitation, respectively), but not after rewarming (752±563 versus 741±219 pg/mL in TLV versus control at 6 hours after resuscitation, respectively). In vitro assays confirmed the high temperature sensitivity of interleukin-6 secretion. Conversely, TLV did not modify circulating high-mobility group box 1 levels or immune cell recruitment into the peripheral circulation. The link between interleukin-6 early transcripts (<8 hours) and neurological outcome in a subpopulation of the previously described Epo-ACR-02 (High Dose of Erythropoietin Analogue After Cardiac Arrest) trial confirmed the importance of this cytokine at the early stages as compared with delayed stages (>8 hours). Conclusions The neuroprotective effect of hypothermic TLV was associated with a mitigation of humoral interleukin-6 response. A temperature-dependent attenuation of immune cell reactivity during the early phase of the post-cardiac arrest syndrome could explain the potent effect of rapid hypothermia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00999583.

Synergistic Effects of Moderate Therapeutic Hypothermia and Levosimendan on Cardiac Function and Survival After Asphyxia-Induced Cardiac Arrest in Rats.

Background This study investigated whether levosimendan, an inotropic calcium sensitizer, when combined with moderate therapeutic hypothermia, may exert synergistic benefits on post-cardiac arrest myocardial dysfunction and improve outcomes. Methods and Results After 9.5-minute asphyxia-induced cardiac arrest and resuscitation, 48 rats were randomized equally into 4 groups following return of spontaneous circulation (ROSC), including normothermia, hypothermia, normothermia-levosimendan, and hypothermia-levosimendan groups. For the normothermia group, the target temperature was 37°C while for the hypothermia group, the target temperature was 32°C, both of which were to be maintained for 4 hours after ROSC. Levosimendan was administered after ROSC with a loading dose of 10 µg/kg and then infused at 0.1 µg/kg per min for 4 hours. In the hypothermia-levosimendan group, left ventricular systolic function and cardiac output increased significantly, whereas the heart rate and systemic vascular resistance decreased significantly compared with the normothermia group. Also, the concentrations of interleukin 1ß at 4 hours post-ROSC and the production of NO between 1 hour and 4 hours post-ROSC were reduced significantly in the hypothermia-levosimendan group compared with the normothermia group. The 72-hour post-ROSC survival and neurological recovery were also significantly better in the hypothermia-levosimendan group compared with the normothermia group (survival, 100% versus 50%, χ2 test, P=0.006). Conclusions Compared with normothermia, only combined moderate therapeutic hypothermia and levosimendan treatment could consistently improve post-cardiac arrest myocardial dysfunction and decrease the release of pro-inflammatory molecules, thereby improving survival and neurological outcomes. These findings suggest synergistic benefits between moderate therapeutic hypothermia and levosimendan.

The Role of Inflammatory Cytokines in Cardiac Arrest.

INTRODUCTION: Post-cardiac arrest syndrome (PCAS) is characterized by systemic ischemia/reperfusion injury, anoxic brain injury, and post-arrest myocardial dysfunction superimposed on a precipitating pathology. The role of inflammatory cytokines in cardiac arrest remains unclear. AIMS: We aimed to describe, with an emphasis on clinical applications, what is known about the role of inflammatory cytokines in cardiac arrest. DATA SOURCES: A PubMed literature review was performed for relevant articles. Only articles in English that studied cytokines in patients with cardiac arrest were included. RESULTS: Cytokines play a crucial role in the pathogenesis of PCAS. Following cardiac arrest, the large release of circulating cytokines mediates the ischemia/reperfusion injury, brain dysfunction, and myocardial dysfunction seen. Interleukins, tumor necrosis factor, and matrix metalloproteinases all play a unique prognostic role in PCAS. High levels of inflammatory cytokines have been associated with mortality and/or poor neurologic outcomes. Interventions to modify the systemic inflammation seen in PCAS continue to be heavily studied. Currently, the only approved medical intervention for comatose patients following cardiac arrest is targeted temperature management. Medical agents, including minocycline and sodium sulfide, have demonstrated promise in animal models. CONCLUSIONS: The role of inflammatory cytokines for both short- and long-term outcomes is an important area for future investigation.

[Biomarkers after resuscitation : Relevance in daily clinical practice for prognosis estimation and definition of therapeutic goals]. / Biomarker nach Reanimation : Relevanz im klinischen Alltag für Prognoseeinschätzung und Therapiezieldefinition.

BACKGROUND: The assessment of the neurological prognosis after cardiac arrest should be made using a multimodal approach involving clinical, physical and laboratory findings. Here, biomarkers are of high importance. The reliable prognostication has far-reaching consequences for the patient on the further course of therapy and rehabilitation. OBJECTIVES: Which biomarkers help in prognosis estimation and therapy target definition and are currently used in daily clinical practice? MATERIALS AND METHODS: Presentation of the multimodal approach for prognosis generation in patients after resuscitation with hypoxic-ischemic encephalopathy with special consideration and discussion of various biomarkers. RESULTS AND CONCLUSION: Neuron-specific enolase (NSE) is the best-established predictive biomarker in patients with hypoxic-ischemic encephalopathy after cardiac arrest. In combination with other methods (clinical examination, physical testing) and considering possible interfering factors (hemolysis, tumor diseases), NSE is used after 48-72 h with a cutoff value of 90 ng/ml. Most other biomarkers have so far only been studied in smaller groups or individual studies and thus cannot currently be routinely used outside of studies.

Combination of S100B and procalcitonin improves prognostic performance compared to either alone in patients with cardiac arrest: A prospective observational study.

This study aimed to determine whether the combination of procalcitonin (PCT) and S100B improves prognostic performance compared to either alone in cardiac arrest (CA) patients treated with targeted temperature management (TTM).We performed a prospective cohort study of CA patients treated with TTM. PCT and S100B levels were obtained at 0, 24, 48, and 72 hours after return of spontaneous circulation. The prognostic performance was analyzed using each marker and the combination of the 2 markers for predicting poor neurological outcome at 3 months and mortality at 14 days and 3 months.A total of 97 patients were enrolled, of which 67 (69.1%) had poor neurological outcome. S100B showed a better prognostic performance (area under the curve [AUC], 0.934; sensitivity, 77.6%; and specificity, 100%) than PCT (AUC, 0.861; sensitivity, 70.2%; and specificity, 83.3%) with the highest prognostic value at 24 hours. The combination of 24-hour PCT and S100B values (S100B ≥0.2 µg/L or PCT ≥6.6 ng/mL) improved sensitivity (85.07%) compared with S100B alone. In multivariate analysis, PCT was associated with mortality at 14 days (odds ratio [OR]: 1.064, 95% confidence interval [CI]: 1.014-1.118), whereas S100B was associated with neurological outcomes at 3 months (OR: 9.849, 95% CI: 2.089-46.431).The combination of PCT and S100B improved prognostic performance compared to the use of either biomarker alone in CA patient treated with TTM. Further studies that will identify the optimal cutoff values for these biomarkers must be conducted.

A Case of Persistence of Normal Tissue Oxygenation Monitored by Near-Infrared Spectroscopy (NIRS) Values Despite Prolonged Perioperative Cardiac Arrest.

BACKGROUND Patients undergoing cardiac surgery are at risk of adverse perioperative neurological complications. Cerebral oximetry monitoring is increasingly used in these patients to detect intraoperative cerebral hypoxia or ischemic events. Near-infrared spectroscopy (NIRS) uses the near-infrared region of the electromagnetic spectrum for oximetry imaging. A case is reported of the persistence of normal tissue oxygenation monitored by NIRS values despite a prolonged perioperative cardiac arrest. CASE REPORT A 65-year-old man was admitted to the Emergency Department with dysarthria, left facial ptosis, left hemiplegia, and arterial hypotension of 75/50 mmHg. Computed tomography (CT) angiography showed a Stanford type A aortic dissection extending to the right common carotid artery. Shortly after arrival in the operating room, his hemodynamic condition rapidly deteriorated resulting in cardiac arrest. Despite the rapid onset of extracorporeal circulation, adequate systemic blood flow could not be restored. Cerebral NIRS values remained within the normal range (70-80%) from the start of emergency resuscitation, during a prolonged period of extremely low global blood perfusion values, and until all resuscitation ceased. CONCLUSIONS Cerebral oximetry values reflect a balance between cerebral oxygen delivery and consumption. This case demonstrated the persistence of normal tissue oxygenation monitored by NIRS values despite a prolonged perioperative cardiac arrest.

Resistin-Can it be a new early marker for prognosis in patients who survive after a cardiac arrest? A pilot study.

AIM: The aim of our study was to evaluate the potential role of resistin in estimating the 30 days prognosis in patients with hypoxic-ischemic organ injury who survived after a cardiac arrest (CA). MATERIALS AND METHODS: The study included 40 patients resuscitated after a non-traumatic out-of-hospital CA admitted in Emergency Department (ED). All patients were followed for 30 days after CA or until death. Clinical data on admission were recorded. Blood samples were collected on admission in ED (0-time interval), and at 6, 12, 24, 48- and 72-hours following resuscitation. Serum concentrations of resistin, S100B and neuron specific enolase (NSE) were measured. Several predictive scores for the mortality at 30 days were created with logistic regressions. RESULTS: At each time interval, median serum levels of resistin and S100 B were significantly higher in non-survivors compared to survivors. For NSE, plasma levels were significantly lower in survivors as compared to non-survivors at 48 and 72 hours, respectively. Accurate predictive scores for 30-days mortality were the ones which included the values of resistin and S100B measured at 12 hours after admittance [AUC 0.938 (0.813-0.989), sensitivity 85.71% (67.3%- 96%), specificity 91.67% (61.5%'99.8%), p<0.001], which included the values of all three markers measured at 12 hours after admittance [AUC 0.955 (0.839-0.995), sensitivity 82.14% (63.1%'93.9%), specificity 100.00% (73.5%'100.0%), p<0.001] and the that included the values of resistin and S-100B at 6 hours together with serum lactate on admission [AUC = 0.994 (0.901-1.0), sensitivity 96.4% (81.7%'99.9%), specificity 100.00% (73.5%'100.0%), p<0.001]. CONCLUSION: In our study, serum levels of resistin or a combination of resistin with S-100B or resistin with S-100B and lactate, were highly predictive for 30 days mortality in resuscitated patients after CA. Further studies on large number of patients are needed to confirm our data.

Mild Therapeutic Hypothermia Increases Glutathione Levels in Postcardiac Arrest Patients.

Ischemia-reperfusion (I/R)-induced oxidative stress is one of the main mechanisms of tissue injury after cardiac arrest (CA). A decrease in antioxidant defenses may contribute to I/R injury. The present study aims to investigate the influence of mild therapeutic hypothermia (MTH) on levels of nonenzymatic antioxidants after CA. We investigated antioxidant levels at 6, 12, 36, and 72 hours after CA in central venous blood samples of patients admitted to intensive care. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 hours of MTH (33°C). Erythrocyte glutathione (GSH) levels were elevated by MTH, increasing at 6, 12, 36, and 72 hours after CA in hypothermic patients (mean GSH levels in normothermic patients: 6 hours = 73.89, 12 hours = 56.45, 36 hours = 56.46, 72 hours = 61.80 vs. hypothermic patients: 6 hours = 176.89, 12 hours = 198.78, 36 hours = 186.96, and 72 hours = 173.68 µmol/g of protein). Vitamin C levels decreased significantly at 6 and 12 hours after CA in hypothermic patients (median vitamin C levels in normothermic patients: 6 hours = 7.53, 12 hours = 9.40, 36 hours = 8.56, and 72 hours = 8.51 vs. hypothermic patients: 6 hours = 5.46, 12 hours = 5.44, 36 hours = 6.10, and 72 hours = 5.89 mmol/L), coinciding with the period of therapeutic hypothermia. Vitamin E and nitric oxide levels were not altered by hypothermic treatment. These findings suggest that MTH alters nonenzymatic antioxidants differently, decreasing circulating vitamin C levels during treatment; however, MTH elevates GSH levels, possibly protecting tissues from I/R injury after CA.

Plasma Adenylate Levels are Elevated in Cardiopulmonary Arrest Patients and May Predict Mortality.

Cerebral and cardiac dysfunction cause morbidity and mortality in postcardiac arrest syndrome (PCAS) patients. Predicting clinical outcome is necessary to provide the optimal level of life support for these patients. In this pilot study, we examined whether plasma ATP and adenylate levels have value in predicting clinical outcome in PCAS patients. In total, 15 patients who experienced cardiac arrest outside the hospital setting and who could be reanimated were enrolled in this study. Healthy volunteers (n = 8) served as controls. Of the 15 PCAS patients, 8 died within 4 days after resuscitation. Of the 7 survivors, 2 lapsed into vegetative states, 1 survived with moderate disabilities, and 4 showed good recoveries. Arterial blood samples were drawn immediately after successful resuscitation and return of spontaneous circulation (ROSC). The concentrations of ATP and other adenylates in plasma were assessed with high-performance liquid chromatography. PCAS patients had significantly higher ATP levels than healthy controls. Plasma ATP levels correlated with lactate levels, Acute Physiology and Chronic Health Evaluation II scores, and the time it took to ROSC (time-to-ROSC). Plasma adenylate levels in patients who died after resuscitation were significantly higher than in survivors. Based on our results and receiver-operating characteristic curve analysis, we conclude that plasma adenylate levels may help predict outcome in PCAS patients.

Effects of Mild Hypothermia on Cardiac and Neurological Function in Piglets Under Pathological and Physiological Stress Conditions.

To investigate the different effects of mild hypothermia on pathological and physiological stress conditions in piglets, 30 pigs were randomized into four groups: cardiac arrest and mild hypothermia (CA-MH group), cardiac arrest and normothermia (CA-NH group), non-CA-MH (NCA-MH group), and a sham operation. The same hypothermia intervention was implemented in both CA-MH and NCA-MH groups. The CA-NH group did not undergo therapeutic hypothermia after resuscitation. The hemodynamic parameters were recorded. Cerebral metabolism variables and neurotransmitters in the extracellular fluid were collected through microdialysis tubes. The serum of venous blood was used to detect levels of inflammatory factors. The cerebral function was evaluated. At 24 and 72 hours after resuscitation, the cerebral performance category and neurological deficit score in the CA-NH group had higher values. Heart rate and cardiac output (CO) in the CA-MH group during cooling were lower than that of the CA-NH group, but CO was higher after rewarming. Glucose was higher during cooling, and extracellular lactate and lactate/pyruvate ratio in the CA-MH group were lower than that of the CA-NH group. Noradrenaline and 5-hydroxytryptamine in the CA-MH and NCA-MH groups were lower than that of the CA-NH group and sham group during cooling, respectively. Inflammatory factor levels, including interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, and tumor necrosis factor-α, in the CA-MH group were lower than that of the CA-NH group at cooling for 12 hours. These values in the NCA-MH group were higher than that of the sham group. Under a light and an electron microscope, the worse pathological results of heart and brain were observed in the two cardiac arrest groups. Mild hypothermia can provide limited organ protection in the specific pathological condition caused by ischemia-reperfusion, but it may produce a negative effect in a normal physiological state.

Multi-organ protection of ulinastatin in traumatic cardiac arrest model.

Background: Post-cardiac arrest syndrome, which has no specific curative treatment, contributes to the high mortality rate of victims who suffer traumatic cardiac arrest (TCA) and initially can be resuscitated. In the present study, we investigated the potential of ulinastatin to mitigate multiple organ injury after resuscitation in a swine TCA model. Methods: Twenty-one male pigs were subjected to hemodynamic shock (40% estimated blood loss in 20 min) followed by cardiac arrest (electrically induced ventricular fibrillation) and respiratory suspension for 5 min, and finally manual resuscitation. At 5 min after resuscitation, pigs were randomized to receive 80,000 U/kg ulinastatin (n = 7) or the same volume of saline (n = 9) in the TCA group. Pigs in the sham group (n = 5) were not exposed to bleeding or cardiac arrest. At baseline and at 1, 3, and 6 h after the return of spontaneous circulation, blood samples were collected and assayed for tumor necrosis factor-alpha, interleukin 6, and other indicators of organ injury. At 24 h after resuscitation, pigs were sacrificed and apoptosis levels were assessed in samples of heart, brain, kidney, and intestine. Results: One pig died in the ulinastatin group and one pig died in the TCA group; the remaining animals were included in the final analysis. TCA and resuscitation caused significant increases in multiple organ function biomarkers in serum, increases in tumor necrosis factor-alpha, and interleukin 6 in serum and increases in the extent of apoptosis in key organs. All these increases were lower in the ulinastatin group. Conclusion: Ulinastatin may attenuate multiple organ injury after TCA, which should be explored in clinical studies.

Arterial blood gas changes during cardiac arrest and cardiopulmonary resuscitation combined with passive oxygenation/ventilation: a METI HPS study.

OBJECTIVE: High-fidelity simulators can simulate physiological responses to medical interventions. The dynamics of the partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygen pulse saturation (SpO2) during simulated cardiopulmonary resuscitation (CPR) were observed and compared with the results from the literature. METHODS: Three periods of cardiac arrest were simulated using the METI Human Patient Simulator™ (Medical Education Technologies, Inc., Sarasota, FL, USA): cardiac arrest, chest compression-only CPR, and chest compression-only CPR with continuous flow insufflation of oxygen (CFIO). RESULTS: In the first period, the observed values remained constant. In the second period, PaCO2 started to rise and peaked at 63.5 mmHg. In the CFIO period, PaCO2 slightly fell. PaO2 and SpO2 declined only in the second period, reaching their lowest values of 44 mmHg and 70%, respectively. In the CFIO period, PaO2 began to rise and peaked at 614 mmHg. SpO2 exceeded 94% after 2 minutes of CFIO. CONCLUSIONS: The METI Human Patient Simulator™ accurately simulated the dynamics of changes in PaCO2. Use of this METI oxygenation model has some limitations because the simulated levels of PaO2 and SpO2 during cardiac arrest correlate poorly with the results from published studies.

Case Report of Cardiac Arrest After Succinylcholine in a Child With Muscle-Eye-Brain Disease.

Muscle-eye-brain disease is a rare autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and brain malformation. We report an intraoperative hyperkalemic cardiac arrest following the administration of succinylcholine in a child with muscle-eye-brain disease. The disease was diagnosed only after this event. Our experience suggests that preoperative determinations of serum concentrations of lactate and creatine kinase may be useful if clinical signs consistent with myopathy are present.

Investigation of the pathophysiology of cardiopulmonary bypass using rodent extracorporeal life support model.

BACKGROUND: Extracorporeal life support (ECLS) systems are life-saving devices used for treating patients with severe cardiopulmonary failure. In this study, we implemented a rat model of ECLS without the administration of inotropes or vasopressors. METHODS: The rats underwent 5 min of untreated asphyxial cardiac arrest and were resuscitated by ECLS for 30 min. The right external jugular vein and right femoral artery were separately cannulated to the ECLS outflow and inflow, respectively. Thereafter, ECLS was terminated, wounds were closed, and mechanical ventilation was provided for another 90 min. Subsequently, blood gas and hemodynamic analyses were performed. The plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) were measured 120 min after reperfusion. RESULTS: The metabolic rate of lactate in the group of asphyxial cardiac arrest rescued by ECLS was slow; therefore, the pH at 120 min after reperfusion was significantly lower in this group than that in the group of normal rats treated with ECLS. The hemodynamic data showed no between-group differences. The plasma levels of CRP, IL-6, IL-10, and TNF-α increased after ECLS treatment. CONCLUSIONS: We successfully established a rodent ECLS model, which might be a useful approach for studying the pathophysiology induced by ECLS under clinical conditions.

Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management: A Multicenter Study on 1,053 Patients.

OBJECTIVE: Outcome prediction after cardiac arrest is important to decide on continuation or withdrawal of intensive care. Neuron-specific enolase is an easily available, observer-independent prognostic biomarker. Recent studies have yielded conflicting results on its prognostic value after targeted temperature management. DESIGN, SETTING, AND PATIENTS: We analyzed neuron-specific enolase serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out-of-hospital cardiac arrest and outcome of patients from five hospitals in Germany, Austria, and Italy. Patients were treated at 33°C for 24 hours. Cerebral Performance Category was evaluated upon ICU discharge. We performed case reviews of good outcome patients with neuron-specific enolase greater than 90 µg/L and poor outcome patients with neuron-specific enolase less than or equal to 17 µg/L (upper limit of normal). MEASUREMENTS AND MAIN RESULTS: A neuron-specific enolase serum concentration greater than 90 µg/L predicted Cerebral Performance Category 4-5 with a positive predictive value of 99%, false positive rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific enolase greater than 90 µg/L and Cerebral Performance Category 1-2 had confounders for neuron-specific enolase elevation. An neuron-specific enolase serum concentration less than or equal to 17 µg/L excluded Cerebral Performance Category 4-5 with a negative predictive value of 92%. The majority of 14 patients with neuron-specific enolase less than or equal to 17 µg/L who died had a cause of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity for prediction of poor outcome were independent of age, sex, and initial rhythm but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. CONCLUSION: High neuron-specific enolase serum concentrations reliably predicted poor outcome at ICU discharge. Prediction accuracy differed and was better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest patients. Our "in-the-field" data indicate 90 µg/L as a threshold associated with almost no false positives at acceptable sensitivity. Confounders of neuron-specific enolase elevation should be actively considered: neuron-specific enolase-producing tumors, acute brain diseases, and hemolysis. We strongly recommend routine hemolysis quantification. Neuron-specific enolase serum concentrations less than or equal to 17 µg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening.

Serum Acylcarnitines and Risk of Cardiovascular Death and Acute Myocardial Infarction in Patients With Stable Angina Pectoris.

BACKGROUND: Excess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris. METHODS AND RESULTS: This study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl-, octanoyl-, palmitoyl-, propionyl-, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry. Hazard ratios (HRs) and 95% CIs for quartile 4 versus quartile 1 are reported. The multivariable model included age, sex, body mass index, fasting status, current smoking, diabetes mellitus, apolipoprotein A1, apolipoprotein B, creatinine, left ventricular ejection fraction, extent of coronary artery disease, study center, and intervention with folic acid or vitamin B6. During median 10.2 years of follow-up, 10.0% of the patients died of cardiovascular disease and 12.8% suffered a fatal or nonfatal acute myocardial infarction. Higher levels of the even-chained acetyl-, octanoyl-, and palmitoyl-carnitines were significantly associated with elevated risk of cardiovascular death, also after multivariable adjustments (HR [95% CI]: 1.52 [1.12, 2.06]; P=0.007; 1.73 [1.23, 2.44]; P=0.002; and 1.61 [1.18, 2.21]; P=0.003, respectively), whereas their associations with acute myocardial infarction were less consistent. CONCLUSIONS: Among patients with suspected stable angina pectoris, elevated serum even-chained acylcarnitines were associated with increased risk of cardiovascular death and, to a lesser degree with acute myocardial infarction, independent of traditional risk factors. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354081.

Transition of intestinal fatty acid-binding protein on hypothermic circulatory arrest with cardiopulmonary bypass.

INTRODUCTION: Intestinal fatty acid-binding protein (I-FABP) is increasingly employed as a highly specific marker of intestinal necrosis. However, the value of this marker associated with cardiovascular surgery with hypothermic circulatory arrest is unclear. The aim of this study was to measure serum I-FABP levels and provide the transition of I-FABP levels with hypothermic circulatory arrest to help in the management of intestinal perfusion. METHODS: From August 2011 to September 2013, 33 consecutive patients who had aortic arch surgery with hypothermic circulatory arrest or heart valve surgery performed were enrolled in the study. Twenty patients had aortic surgery with hypothermic (23-29°C) circulatory arrest and 13 patients had heart valve surgery with cardiopulmonary bypass (33°C). RESULTS: I-FABP levels increased, both in patients undergoing aortic surgery with hypothermic circulatory arrest and heart valve surgery with cardiopulmonary bypass, reaching peak levels shortly after the administration of protamine. I-FABP levels in patients with aortic surgery were significantly higher with circulatory arrest. They reached peak levels immediately after recirculation and there was a significant drop at the end of surgery (p<0.001). I-FABP levels in heart valve surgery were gradually increased, with the highest at the administration of protamine; they gradually decreased. Peak I-FABP levels were significantly higher in patients undergoing aortic surgery with hypothermic circulatory arrest than in patients with heart valve surgery. However, no postoperative reperfusion injury occurred in the intestinal tract due to the use of hypothermic organ protection. CONCLUSION: Plasma I-FABP monitoring could be a valuable method for finding an intestinal ischemia in patients with cardiovascular surgery.