Epinephrine vs placebo in neonatal resuscitation: ROSC and brain MRS/MRI in term piglets.

BACKGROUND: We aimed to investigate the effect of epinephrine vs placebo on return of spontaneous circulation (ROSC) and brain magnetic resonance spectroscopy and imaging (MRS/MRI) in newborn piglets with hypoxic cardiac arrest (CA). METHODS: Twenty-five piglets underwent hypoxia induced by endotracheal tube clamping until CA. The animals were randomized to CPR + intravenous epinephrine or CPR + placebo (normal saline). The primary outcome was ROSC, and secondary outcomes included time-to-ROSC, brain MRS/MRI, and composite endpoint of death or severe brain MRS/MRI abnormality. RESULTS: ROSC was more frequent in animals treated with epinephrine than placebo; 10/13 vs 4/12, RR = 2.31 (95% CI: 1.09-5.77). We found no difference in time-to-ROSC (120 (113-211) vs 153 (116-503) seconds, p = 0.7) or 6-h survival (7/13 vs 3/12, p = 0.2). Among survivors, there was no difference between groups in brain MRS/MRI. We found no difference in the composite endpoint of death or severe brain MRS/MRI abnormality; RR = 0.7 (95% CI: 0.37-1.19). CONCLUSIONS: Resuscitation with epinephrine compared to placebo improved ROSC frequency after hypoxic CA in newborn piglets. We found no difference in time-to-ROSC or the composite endpoint of death or severe brain MRS/MRI abnormality. IMPACT: In a newborn piglet model of hypoxic cardiac arrest, resuscitation with epinephrine compared to placebo improved the rate of return of spontaneous circulation and more than doubled the 6-h survival. Brain MRS/MRI biomarkers were used to evaluate the effect of epinephrine vs placebo. We found no difference between groups in the composite endpoint of death or severe brain MRS/MRI abnormality. This study adds to the limited evidence regarding the effect and safety of epinephrine; the lack of high-quality evidence from randomized clinical trials was highlighted in the latest ILCOR 2020 guidelines, and newborn animal studies were specifically requested.

NT-proBNP cut-off value for ruling out heart failure in atrial fibrillation patients - A prospective clinical study.

STUDY OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements can be used to rule out heart failure in patients with sinus rhythm. Atrial fibrillation often coexists with heart failure but affects NT-proBNP levels. This study aims to identify the optimal NT-proBNP cut-off value for ruling out heart failure among atrial fibrillation patients. METHODS: This prospective study included 409 atrial fibrillation patients admitted to the emergency department. The inclusion criterion was documented atrial fibrillation on a 12­lead electrocardiogram. All patients completed a NT-proBNP blood sample, a chest X-ray and an echocardiogram. Heart failure was defined as a left ventricular ejection fraction of <40%. RESULTS: In total, 409 patients were included (mean age: 75.2 ± 11.6). The median NT-proBNP level was 2577 ng/L (quartiles: 1185-5438) and 21% had heart failure. We found a lower median NT proBNP level of 3187 ± 3973 ng/L in patients without heart failure compared to 9254 ± 8008 ng/L in patients with heart failure (absolute difference: 4131, 95% (CI): 3299-4986, p < 0.001). The area under the receiver operating characteristic curve for diagnosing heart failure was 0.82 (95% confidence interval: 0.77-0.87). The optimal cut-off value for ruling out heart failure was 739 ng/L with a sensitivity of 99%, a specificity of 18%, and a negative predictive value of 98%. CONCLUSIONS: NT-proBNP can be used to rule out heart failure in atrial fibrillation patients with a high negative predictive value, but low specificity. TRIAL REGISTRATION NUMBER: NCT04125966. https://clinicaltrials.gov/ct2/show/NCT04125966.

Anterior-Lateral Versus Anterior-Posterior Electrode Position for Cardioverting Atrial Fibrillation.

BACKGROUND: Smaller randomized studies have reported conflicting results regarding the optimal electrode position for cardioverting atrial fibrillation. However, anterior-posterior electrode positioning is widely used as a standard and believed to be superior to anterior-lateral electrode positioning. Therefore, we aimed to compare anterior-lateral and anterior-posterior electrode positioning for cardioverting atrial fibrillation in a multicenter randomized trial. METHODS: In this multicenter, investigator-initiated, open-label trial, we randomly assigned patients with atrial fibrillation scheduled for elective cardioversion to either anterior-lateral or anterior-posterior electrode positioning. The primary outcome was the proportion of patients in sinus rhythm after the first shock. The secondary outcome was the proportion of patients in sinus rhythm after up to 4 shocks escalating to maximum energy. Safety outcomes were any cases of arrhythmia during or after cardioversion, skin redness, and patient-reported periprocedural pain. RESULTS: We randomized 468 patients. The primary outcome occurred in 126 patients (54%) assigned to the anterior-lateral electrode position and in 77 patients (33%) assigned to the anterior-posterior electrode position (risk difference, 22 percentage points [95% CI, 13-30]; P<0.001). The number of patients in sinus rhythm after the final cardioversion shock was 216 (93%) assigned to anterior-lateral electrode positioning and 200 (85%) assigned to anterior-posterior electrode positioning (risk difference, 7 percentage points [95% CI, 2-12]). There were no significant differences between groups in any safety outcomes. CONCLUSIONS: Anterior-lateral electrode positioning was more effective than anterior-posterior electrode positioning for biphasic cardioversion of atrial fibrillation. There were no significant differences in any safety outcome. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03817372.

Rapid Rule-Out of Myocardial Infarction After 30 Minutes as an Alternative to 1 Hour: The RACING-MI Cohort Study.

STUDY OBJECTIVE: The aim of this study was to investigate whether myocardial infarction can be safely ruled in or out after 30 minutes as an alternative to 1 hour. METHODS: This was a prospective, single-center clinical study enrolling patients admitted to the emergency department. Patients with chest pain suggestive of myocardial infarction were eligible for inclusion. There was no walk-in to the emergency department, and patients with highly elevated out-of-hospital troponin were transferred directly to an invasive heart center. High-sensitivity troponin I was measured at admission (0 hour), 30 minutes, 1 hour, and 3 hours. Diagnostic performance was assessed using the sensitivity and negative predictive value (primary endpoints) as measures of ability to rule out myocardial infarction. Specificity and positive predictive value of myocardial infarction were used as measures for the ability to rule in myocardial infarction (secondary endpoints). RESULTS: In total, 1,003 patients qualified for analysis. Median age was 64 (interquartile range 52 to 74) years, and 42% were women. Myocardial infarction was confirmed in 9% of patients. In the validation cohort (n=503), the 0-h/30-min algorithm assigned 242 (48%) patients to rule out, 54 (11%) to rule in, and 207 (41%) to the observational zone. This resulted in a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (95% confidence interval 98.5% to 100%), specificity of 96.7% (94.7% to 98.2%), and positive predictive value of 72.2% (58.4% to 83.5%). In comparison, the 0-h/1-h algorithm performed with a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (98.5% to 100%), specificity of 97.2% (95.2% to 98.5%), and positive predictive value of 75.5% (61.7% to 86.2%). CONCLUSION: The accelerated 0-h/30-min algorithm allowed for safe rule-out of myocardial infarction 30 minutes after admission. The rule-in ability of the 0-h/30-min algorithm was comparable to that of the 0-h/1h algorithm.

The effects of obstetric emergency team training on patient outcome: A systematic review and meta-analysis.

INTRODUCTION: Little is known about the optimal simulation-based team training in obstetric emergencies. We aimed to review how simulation-based team training affects patient outcomes in obstetric emergencies. MATERIAL AND METHODS: Search Strategy: MEDLINE, Embase, Cochrane Library, and Cochrane Central Register of Controlled Trials were searched up to and including May 15, 2021. SELECTION CRITERIA: randomized controlled trials (RCTs) and cohort studies on obstetric teams in high-resource settings comparing the effect of simulation-based obstetric emergency team training with no training on the risk of Apgar scores less than 7 at 5 min, neonatal hypoxic ischemic encephalopathy, severe postpartum hemorrhage, blood transfusion of four or more units, and delay of emergency cesarean section by more than 30 min. DATA COLLECTION AND ANALYSIS: The included studies were assessed using PRISMA, EPCO, and GRADE. RESULTS: We found 21 studies, four RCTs and 17 cohort studies, evaluating patient outcomes after obstetric team training compared with no training. Annual obstetric emergency team training may reduce brachial plexus injury (six cohort studies: odds ratio [OR] 0.47, 95% CI 0.33-0.68; one RCT: OR 1.30, 95 CI% 0.39-4.33, low certainty evidence) and suggest a positive effect; but it was not significant on Apgar score below 7 at 5 min (three cohort studies: OR 0.77, 95% CI 0.51-1.19; two RCT: OR 0.87, 95% CI 0.72-1.05, moderate certainty evidence). The effect was unclear for hypoxic ischemic encephalopathy, umbilical prolapse, decision to birth interval in emergency cesarean section, and for severe postpartum hemorrhage. Studies with in situ multi-professional simulation-based training demonstrated the best effect. CONCLUSIONS: Emerging evidence suggests an effect of obstetric team training on obstetric outcomes, but conflicting results call for controlled trials targeted to identify the optimal methodology for effective team training.

Maximum-fixed energy shocks for cardioverting atrial fibrillation.

AIMS: Direct-current cardioversion is one of the most commonly performed procedures in cardiology. Low-escalating energy shocks are common practice but the optimal energy selection is unknown. We compared maximum-fixed and low-escalating energy shocks for cardioverting atrial fibrillation. METHODS AND RESULTS: In a single-centre, single-blinded, randomized trial, we allocated elective atrial fibrillation patients to cardioversion using maximum-fixed (360-360-360 J) or low-escalating (125-150-200 J) biphasic truncated exponential shocks. The primary endpoint was sinus rhythm 1 min after cardioversion. Safety endpoints were any arrhythmia, myocardial injury, skin burns, and patient-reported pain after cardioversion. We randomized 276 patients, and baseline characteristics were well-balanced between groups (mean ± standard deviation age: 68 ± 9 years, male: 72%, atrial fibrillation duration >1 year: 30%). Sinus rhythm 1 min after cardioversion was achieved in 114 of 129 patients (88%) in the maximum-fixed energy group, and in 97 of 147 patients (66%) in the low-escalating energy group (between-group difference; 22 percentage points, 95% confidence interval 13-32, P < 0.001). Sinus rhythm after first shock occurred in 97 of 129 patients (75%) in the maximum-fixed energy group compared to 50 of 147 patients (34%) in the low-escalating energy group (between-group difference; 41 percentage points, 95% confidence interval 30-51). There was no significant difference between groups in any safety endpoint. CONCLUSION: Maximum-fixed energy shocks were more effective compared with low-escalating energy shocks for cardioverting atrial fibrillation. We found no difference in any safety endpoint.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Basic life support training: Demonstration versus lecture - A randomised controlled trial.

INTRODUCTION: Basic life support (BLS) and the use of an automated external defibrillator (AED) improve survival from cardiac arrest. The gold standard for teaching BLS/AED is yet to be identified. The aim of this study was to compare the learning outcome of an instructor-led demonstration with a formal lecture for introducing BLS/AED skills. We hypothesized that a demonstration was superior to a lecture. METHODS: First year-medical students were randomised to either a demonstration or a lecture using PowerPoint® Presentation for skill introduction during European Resuscitation Council BLS/AED courses. Participants were skill-tested after training and required to perform all skills correctly to pass the test. Finally, all participants were asked to state their preferred teaching method. RESULTS: Overall, 247 participants were included in the analysis (demonstration group: 124, lecture group: 123). Pass rate was 63% in both groups, p = 1.00. Both groups performed median compression rates within guidelines recommendations, p = 0.09. Mean compression depth was 55 mm (10 mm) in the demonstration group compared with 52 mm (10 mm) in the lecture group, p = 0.05. Median tidal volume was 265 (192, 447) ml and 405 (262, 578) ml, p < 0.001, respectively. The lecture group was 3 s faster at initiating BLS, p < 0.001. In total, 226 (91%) participants preferred demonstration on a manikin for introducing BLS/AED. CONCLUSION: There was no statistically significant difference in pass rate when comparing a demonstration with a lecture for introducing BLS/AED. The lecture group was slightly faster at initiating BLS. Most participants preferred a demonstration as introduction.

Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways.

Congestive heart failure and poor clinical outcome after myocardial infarction are known complications in patients with type-2 diabetes mellitus (T2DM). Protein alterations may be involved in the mechanisms underlying these disarrays in the diabetic heart. Here we map proteins involved in intracellular metabolic pathways in the Zucker diabetic fatty rat heart as T2DM develops using MS based proteomics. The prediabetic state only induced minor pathway changes, whereas onset and late T2DM caused pronounced perturbations. Two actin-associated proteins, ARPC2 and TPM3, were up-regulated at the prediabetic state indicating increased actin dynamics. All differentially regulated proteins involved in fatty acid metabolism, both peroxisomal and mitochondrial, were up-regulated at late T2DM, whereas enzymes of branched chain amino acid degradation were all down-regulated. At both onset and late T2DM, two members of the serine protease inhibitor superfamily, SERPINA3K and SERPINA3L, were down-regulated. Furthermore, we found alterations in proteins involved in clearance of advanced glycation end-products and lipotoxicity, DCXR and CBR1, at both onset and late T2DM. These proteins deserve elucidation with regard to their role in T2DM pathogenesis and their respective role in the deterioration of the diabetic heart. Data are available via ProteomeXchange with identifiers PXD009538, PXD009554, and PXD009555.

2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary.

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 pediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have prioritized and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question.

Effects of hyperoxia on myocardial injury following cardioversion-A randomized clinical trial.

Oxygen has long been assumed beneficial for all ill and injured patients. However, hyperoxia may be harmful and aggravate myocardial injury such as that caused by myocardial infarction. We aimed to investigate if hyperoxia increases myocardial injury following direct current cardioversion compared with room air. METHODS: Patients undergoing elective biphasic cardioversion for atrial fibrillation or atrial flutter were randomized to receive room air or oxygen (10-15 L/min) during the procedure. The primary endpoint was the difference in high-sensitive Troponin I (hs-cTnI) and -T (hs-cTnT) measured 2 hours before and 4 hours after cardioversion. Secondary endpoints were differences in Copeptin and NT-pro-BNP. RESULTS: A total of 65 patients were randomized to high-flow oxygen (male: 71%, mean age 66.9 years) and 59 patients to room air (male: 80%, mean age 65.5 years). There was no difference in hs-cTnI between patients treated with oxygen compared to patients treated with room air (P=.09) and no significant difference for hs-cTnT, ratio 1.08 (95% CI: 0.99-1.18) (P=.09). Median hs-cTnI difference before and after cardioversion was 0.1 (interquartile range (IQR): -0.5 to 0.5) ng/L for the high-flow oxygen group and -0.3 (IQR: -1.1 to 0.4) ng/L for the room air group. There was no difference in Copeptin between patients treated with oxygen compared to room air (ratio 1.06 (95% CI: 0.89-1.27) (P=.51) or NT-pro-BNP (difference-6.0 ng/L (95% CI: -78.5 to 66.6) P=.87). CONCLUSION: Direct current cardioversion of atrial fibrillation/flutter with and without high-flow oxygen supplement was not associated with myocardial injury evaluated by high sensitive myocardial biomarkers.

In a bed or on the floor? - The effect of realistic hospital resuscitation training: A randomised controlled trial.

INTRODUCTION: In-hospital cardiac arrest has a poor prognosis and often occurs in patients lying in a hospital bed. A bed mattress is a soft compressible surface that may decrease cardiopulmonary resuscitation (CPR) quality. Often hospital CPR training is performed with a manikin on the floor. AIM: To study CPR quality following realistic CPR training with a manikin in a bed compared with one on the floor. METHODS: We conducted a randomised controlled study. Healthcare professionals were randomised to CPR training with a manikin in a hospital bed or one on the floor. Data on CPR quality was collected from manikins. The primary outcome measure was chest compression depth. RESULTS: In total, 108 healthcare professionals (age: 40years, female: 94%) were included. The mean chest compression depth was 39mm (standard deviation (SD): 10), for the bed group compared with 38mm (SD: 9) for the floor group, p=0.49. A post hoc analysis showed that regardless of the training method, the participants who optimised their working position by jumping onto the bed or lowering the bed had a median chest compression depth of 39mm (25th-75th percentiles: 33-45) compared with 29mm (25th-75th percentiles: 23-41) for participants who did neither, p=0.04. CONCLUSION: There was no significant difference in chest compression depth between healthcare professionals who trained CPR on a manikin in a hospital bed compared with one on the floor. Chest compression depth was too shallow in both groups. Irrespective of the training method, participants who optimised their working position performed deeper chest compressions.

The Right Ventricle Is Dilated During Resuscitation From Cardiac Arrest Caused by Hypovolemia: A Porcine Ultrasound Study.

OBJECTIVES: Dilation of the right ventricle during cardiac arrest and resuscitation may be inherent to cardiac arrest rather than being associated with certain causes of arrest such as pulmonary embolism. This study aimed to compare right ventricle diameter during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, or primary arrhythmia (i.e., ventricular fibrillation). DESIGN: Thirty pigs were anesthetized and then randomized to cardiac arrest induced by three diffrent methods. Seven minutes of untreated arrest was followed by resuscitation. Cardiac ultrasonographic images were obtained during induction of cardiac arrest, untreated cardiac arrest, and resuscitation. The right ventricle diameter was measured. Primary endpoint was the right ventricular diameter at the third rhythm analysis. SETTING: University hospital animal laboratory. SUBJECTS: Female crossbred Landrace/Yorkshire/Duroc pigs (27-32 kg). INTERVENTIONS: Pigs were randomly assigned to cardiac arrest caused by either hypovolemia, hyperkalemia, or primary arrhythmia. MEASUREMENTS AND MAIN RESULTS: At the third rhythm analysis during resuscitation, the right ventricle diameter was 32 mm (95% CI, 29-35) in the hypovolemia group, 29 mm (95% CI, 26-32) in the hyperkalemia group, and 25 mm (95% CI, 22-28) in the primary arrhythmia group. This was larger than baseline for all groups (p = 0.03). When comparing groups at the third rhythm analysis, the right ventricle was larger for hypovolemia than for primary arrhythmia (p < 0.001). CONCLUSIONS: The right ventricle was dilated during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, and primary arrhythmia. These findings indicate that right ventricle dilation may be inherent to cardiac arrest, rather than being associated with certain causes of arrest. This contradicts a widespread clinical assumption that in hypovolemic cardiac arrest, the ventricles are collapsed rather than dilated.

Detection of Pulmonary Embolism During Cardiac Arrest-Ultrasonographic Findings Should Be Interpreted With Caution.

OBJECTIVES: The aim of this study was to test the hypothesis that the right ventricle is more dilated during resuscitation from cardiac arrest caused by pulmonary embolism, compared with hypoxia and primary arrhythmia. DESIGN: Twenty-four pigs were anesthetized and cardiac arrest was induced using three different methods. Pigs were resuscitated after 7 minutes of untreated cardiac arrest. Ultrasonographic images were obtained and the right ventricular diameter was measured. SETTING: University hospital animal laboratory. SUBJECTS: Female crossbred Landrace/Yorkshire/Duroc pigs (27-32 kg). INTERVENTIONS: Pigs were randomly assigned to cardiac arrest induced by pulmonary embolism, hypoxia, or primary arrhythmia. MEASUREMENTS AND MAIN RESULTS: There was no difference at baseline. During induction of cardiac arrest, the right ventricle dilated in all groups (p < 0.01 for all). The primary endpoint was right ventricle diameter at the third rhythm analysis: 32 mm (95% CI, 29-36) for pulmonary embolism which was significantly larger than both hypoxia: 23 mm (95% CI, 20-27) and primary arrhythmia: 25 mm (95% CI, 22-28)-the absolute difference was 7-9 mm. Physicians with basic training in focused cardiac ultrasonography were able to detect a difference in right ventricle diameter of approximately 10 mm with a sensitivity of 79% (95% CI, 64-94) and a specificity of 68% (95% CI, 56-80). CONCLUSIONS: The right ventricle was more dilated during resuscitation when cardiac arrest was caused by pulmonary embolism compared with hypoxia and primary arrhythmia. However, the right ventricle was dilated, irrespective of the cause of arrest, and diagnostic accuracy by physicians with basic training in focused cardiac ultrasonography was modest. These findings challenge the paradigm that right ventricular dilatation on ultrasound during cardiopulmonary resuscitation is particularly associated with pulmonary embolism.

Elevated calprotectin in patients with atrial fibrillation with and without heart failure.

Calprotectin is an inflammatory marker, which has been found elevated in patients suffering from cardiac conditions, e.g. myocardial infarction, unstable angina and chronic heart failure. Inflammation has further been linked to atrial fibrillation (AF). However, the association between calprotectin and AF is unknown. We aimed to compare calprotectin levels in patients suffering from AF with healthy adults. In addition, AF patients with and without heart failure were compared. Calprotectin was measured in patients undergoing elective direct current cardioversion for AF. Calprotectin was determined before, 4 hours and 3 months after cardioversion. Healthy blood donors were used to verify the reference interval for calprotectin. In total, 104 prospectively enrolled patients were included. The median serum calprotectin level for AF patients was 1.6 µg/mL before cardioversion. Calprotectin levels increased significantly 4 h (1.9 µg/mL) and 3 months (2.2 µg/mL) after cardioversion. Blood donors' median serum calprotectin (1.3 µg/mL) was significantly lower than AF patients. AF patients with heart failure had significantly higher calprotectin at baseline compared with AF patients without a history of heart failure (2.0 µg/mL vs. 1.5 µg/mL). The difference was not significant at 4 h (2.0 µg/mL vs. 1.7 µg/mL) or 3 months (2.5 µg/mL vs. 2.2 µg/mL). In conclusion, the calprotectin levels in patients with AF were significantly higher than healthy blood donors and were further increased after cardioversion. AF patients with heart failure had significantly higher levels of calprotectin than AF patients without heart failure.

The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection.

Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10 min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5 h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5 min of reperfusion. The hearts were subsequently exposed to 25 min of global ischemia and 60 min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2 min offered the same protection as cycles of 5 min ischemia, whereas prolonged cycles lasting 10 min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5 h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC.