Introduction: Our purpose was to study whether the time to target temperature correlates with neurologic outcome in patients after cardiac arrest with restoration of spontaneous circulation treated with therapeutic mild hypothermia in an academic emergency department. Methods: Temperature data between April 1995 and June 2008 were collected from 588 patients and analyzed in a retrospective cohort study by observers blinded to outcome. The time needed to achieve an esophageal temperature of less than 34°C was recorded. Survival and neurological outcomes were determined within six months after cardiac arrest. Results: The median time from restoration of spontaneous circulation to reaching a temperature of less than 34°C was 209 minutes (interquartile range [IQR]: 130-302) in patients with favorable neurological outcomes compared to 158 min (IQR: 101-230) (P < 0.01) in patients with unfavorable neurological outcomes. The adjusted odds ratio for a favorable neurological outcome with a longer time to target temperature was 1.86 (95% CI 1.03 to 3.38, P = 0.04). Conclusions: In comatose cardiac arrest patients treated with therapeutic hypothermia after return of spontaneous circulation, a faster decline in body temperature to the 34°C target appears to predict an unfavorable neurologic outcome.

Aims: Extracellular chromatin and deoxyribonuclease (DNase) have been identified as important players of thrombosis, inflammation, and homeostasis in a murine model. We previously demonstrated that activated neutrophils release neutrophil extracellular traps (NETs) at the culprit site in ST-elevation myocardial infarction (STEMI), which significantly contribute to extracellular chromatin burden, and are associated with larger infarcts. To understand the correlation between neutrophil activation, extracellular chromatin, and infarct size (IS), we investigated these parameters in a porcine myocardial infarction model, and at different time points and sites in a prospective STEMI trial with cardiac magnetic resonance (CMR) endpoints. Methods and results: In a prospective STEMI trial (NCT01777750), 101 STEMI patients were included and blood samples were obtained from first medical contact until 6 months after primary percutaneous coronary intervention (pPCI) including direct sampling from the culprit site. CMR was performed 4 ± 2 days and 6 months after pPCI. Neutrophil counts, markers of extracellular chromatin, and inflammation were measured. Double-stranded deoxyribonucleic acid (dsDNA), citrullinated histone 3, nucleosomes, myeloperoxidase, neutrophil elastase, and interleukin (IL)-6 were significantly increased, while DNase activity was significantly decreased at the culprit site in STEMI patients. High neutrophil counts and dsDNA levels at the culprit site correlated with high microvascular obstruction (MVO) and low ejection fraction (EF). High DNase activity at the culprit site correlated with low MVO and high EF. In correspondence, dsDNA correlated with IS in the porcine myocardial infarction model. In porcine infarcts, neutrophils and extracellular chromatin were detected in congested small arteries corresponding with MVO. Markers of neutrophil activation, extracellular chromatin, DNase activity and CMR measurements correlated with markers of systemic inflammation C-reactive protein and IL-6 in patients. Conclusions: NETs and extracellular chromatin are important determinants of MVO in STEMI. Rapid degradation of extracellular chromatin by DNases appears to be crucial for microvascular patency and outcome.

BACKGROUND Early outcome prediction in out-of-hospital cardiac arrest is still a challenge. End-tidal carbon dioxide (ETCO₂) has been shown to be a reliable parameter to reflect the quality of cardiopulmonary resuscitation and the chance of return of spontaneous circulation (ROSC). OBJECTIVES This study assessed the validity of early capnography as a predictive factor for ROSC and survival in out-of-hospital cardiac arrest victims with an underlying nonshockable rhythm. DESIGN Retrospective observational study. SETTING/PATIENTS During a 2-year observational period, data from 2223 out-of-hospital cardiac arrest victims within the city of Vienna were analysed. The focus was on the following patients: age more than 18 years, an underlying nonshockable rhythm, and advanced airway management within the first 15 min of advanced life support with subsequent capnography. INTERVENTION No specific intervention was set in this observational study. MAIN OUTCOME MEASURES The first measured ETCO₂, assessed immediately after placement of an advanced airway, was used for further analysis. The primary outcome was defined as sustained ROSC, and the secondary outcome was 30-day survival. RESULTS A total of 526 patients met the inclusion criteria. These were stratified into three groups according to initial ETCO₂ values (45 mmHg). Baseline data and resuscitation factors were similar among all groups. The odds of sustained ROSC and survival were significantly higher for patients presenting with higher values of initial ETCO₂ (>45 mmHg): 3.59 [95% CI, 2.19 to 5.85] P = 0.001 and 5.02 [95% CI, 2.25 to 11.23] P = 0.001, respectively. On the contrary ETCO₂ levels less than 20 mmHg were associated with significantly poorer outcomes. CONCLUSION Patients with a nonshockable out-of-hospital cardiac arrest who presented with higher values of initial ETCO₂ had an increased chance of sustained ROSC and survival. This finding could help decision making as regards continuation of resuscitation efforts.

Introduction: Animal and human studies suggest beneficial outcome effects of mild hypothermia for stroke, for acute myocardial infarction, and for cardiogenic shock. The aim of this study was to investigate the feasibility and safety of non-invasive surface cooling for induction and maintenance of mild hypothermia (32 to 34°C) in healthy, conscious volunteers. Methods: The trial was set at a clinical research ward in a tertiary care center, and included 16 healthy male volunteers 18 to 70 years old. Surface cooling was established by a novel non-invasive cooling pad with an esophageal target temperature of 32 to 34°C and maintenance for six hours. Shivering-control was achieved with meperidine and buspirone and additional administration of magnesium in eight subjects. Results: The primary endpoint to reach a target temperature of 32 to 34°C was only reached in 6 of the 16 participating subjects. Temperatures below 35°C were reached after a median cooling time of 53 minutes (38 to 102 minutes). Cooling rate was 1.1°C/h (0.7 to 1.8°C). Additional administration of magnesium had no influence on cooling rate. At no time during the cooling procedure did the participants report uncomfortable conditions for which termination of cooling had to be considered. No severe skin damage was reported. Conclusions: Cooling to body temperature below 35°C by the use of non-invasive surface cooling is feasible and safe in conscious healthy volunteers. Further studies are needed to investigate an altered cooling protocol to achieve temperatures below 35°C. Trial Registration: ISRCTN: ISRCTN50530495

Background: In elder patients after out‐of‐hospital cardiac arrest, diminished neurologic function as well as reduced neuronal plasticity may cause a low response to targeted temperature management (TTM). Therefore, we investigated the association between TTM (32‐34°C) and neurologic outcome in cardiac arrest survivors with respect to age.Material and Methods: This retrospective cohort study included patients 18 years of age or older suffering a witnessed out‐of‐hospital cardiac arrest with presumed cardiac cause, which remained comatose after return of spontaneous circulation. Patients were a priori split by age into four groups (75 years (n = 280)). Subsequently, within these groups, patients receiving TTM were compared to those not treated with TTM.Results: Out of 1885 patients, 921 received TTM for 24 hours. TTM was significantly associated with good neurologic outcome in patients <65 years of age whereas showing no effect in elders (65‐74 years: OR: 1.49 (95% CI: 0.90‐2.47); > 75 years: OR 1.44 (95% CI 0.79‐2.34)).Conclusion: In our cohort, it seems that TTM might not be able to achieve the same benefit for neurologic outcome in all age groups. Although the results of this study should be interpreted with caution, TTM was associated with improved neurologic outcome only in younger individuals, patients with 65 years of age or older did not benefit from this treatment.

Background and Aims: Neutrophil extracellular traps (NETs) trigger atherothrombosis during acute myocardial infarction (AMI), but mechanisms of induction remain unclear. Levels of extracellular vesicles (EV) carrying oxidation-specific epitopes (OSE), which are targeted by specific natural immunoglobulin M (IgM), are increased at the culprit site in AMI. This study investigated EV as inducers of NETosis and assessed the inhibitory effect of natural anti-OSE–IgM in this process. Methods: Blood from the culprit and peripheral site of ST-segment elevation myocardial infarction (STEMI) patients (n = 28) was collected, and myocardial function assessed by cardiac magnetic resonance imaging (cMRI) 4 ± 2 days and 195 ± 15 days post-AMI. Extracellular vesicles were isolated from patient plasma and cell culture supernatants for neutrophil stimulation in vitro and in vivo, in the presence of a malondialdehyde (MDA)-specific IgM or an isotype control. NETosis and neutrophil functions were assessed via enzyme-linked immunosorbent assay and fluorescence microscopy. Pharmacological inhibitors were used to map signalling pathways. Neutrophil extracellular trap markers and anti-OSE–IgM were measured by ELISA. Results: CD45+ MDA+ EV and NET markers were elevated at the culprit site. Extracellular vesicles induced neutrophil activation and NET formation via TLR4 and PAD4, and mice injected with EV showed increased NETosis. Malondialdehyde-specific IgM levels were inversely associated with citH3 in STEMI patient blood. An MDA-specific IgM inhibited EV-induced NET release in vitro and in vivo. CD45+ MDA+ EV concentrations inversely correlated with left ventricular ejection fraction post-AMI. Conclusions: Culprit site–derived EV induce NETosis, while MDA-specific natural IgM inhibit this effect, potentially impacting outcome after AMI.