Release Of Cardiac Troponin Research Articles

Troponin and non-traumatic subarachnoid haemorrhage

Introduction: Subarachnoid haemorrhage (SAH) is a devastating event, with a mortality of up to 50%. Acute cardiac dysfunction is common after such an event, and it is known to have a negative impact on the outcome of these patients. Cardiac troponin release occurs frequently after SAH and represents an early biomarker for neurogenic cardiac dysfunction.
 Objective: The present study aimed to evaluate the impact of a raised troponin value on the outcome of SAH patients.
 Methods: This is a prospective observational study held between 2014-2017 at the University Emergency Hospital, Bucharest. Data on clinical admission status, high-sensitivity troponin I, ECG and echocardiographic evaluation results, ICU length of stay and in-hospital mortality rate. Statistical analysis was performed using non-parametrical Mann-Whitney and chi-square tests. The results were considered significant at p<0.05.
 Results: A total of 335 consecutive patients with non-traumatic SAH were admitted during the study period. 92 of them were excluded and 243 were analyzed, 203 with aneurysmal SAH and 40 with non-aneurysmal, non-traumatic SAH. High-sensitivity troponin I reached its peak level 48 to 72 hours after SAH and was higher in patients with aneurysmal SAH. For all SAH patients, its median and peak values on days 1 and 2 were correlated with the ICU length of stay and inversely correlated with in-hospital length of stay. For the first 3 days, the median and maximum troponin values are higher in patients who died compared with those who survived and were discharged home (p-value < 0.001). Predictors of an elevated troponin on day 1 are loss of consciousness at ictus, a high Hunt and Hess and Fisher Scale grade, intraventricular haemorrhage and cerebral midline shift.
 Conclusions: The release of cardiac troponin is a valuable marker of neurogenic cardiac dysfunction in the first 3 days after SAH. The study replicates other data in the literature and highlights the association between SAH severity, early troponin elevation and in-hospital death.

Exercise-induced cardiac troponin release in middle-aged and older athletes with different degrees of coronary atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Radboud University Medical CenterAcademic Alliance Fund Maastricht - Nijmegen Background Current sports medical examinations do not appropriately detect occult coronary atherosclerosis in athletes, whereas coronary atherosclerosis is more prevalent in middle-aged and older athletes compared to physically active controls. Therefore, new diagnostic approaches need to be developed to identify individuals at risk. Cardiac troponin (cTn) is the standard biomarker to assess myocardial injury. Exercise is known to increase cTn concentrations and a delayed recovery of cTn concentrations after exercise cessation is suggested to be indicative of occult obstructive coronary artery disease. We hypothesized that the magnitude of exercise-induced cTn elevations may be associated with the degree of coronary atherosclerosis. Purpose To compare serial measures of exercise-induced cTnT elevations across middle-aged and older athletes with different degrees of coronary atherosclerosis. Methods A subgroup of 59 men from the Measuring Athlete’s Risk of Coronary events-2 study (MARC-2, n=291) were invited for this add-on study. All participants had undergone a cardiac computed tomography (CT) scan and coronary CT angiography to determine the prevalence and magnitude of coronary atherosclerosis. Athletes were stratified based on the degree of coronary atherosclerosis: I) n=20 with a coronary artery calcium score (CACS) of 0, II) n=20 with CACS ≥300 or ≥75th MESA-percentile, and III) n=19 with a >50% stenosis in any coronary artery, but without ischemia on a stress imaging tests. Participants performed an individualized exercise test (>1 hour, cycling) until volitional exhaustion. High-sensitivity cTnT concentrations were measured at baseline, after 30 minutes of exercise and at 0, 30, 60, 120, and 180 minutes post-exercise. Results Participants (age 60.8 [57.9-72.6] years, BMI 24.5 [23.9-27.3]) exercised for 76±14 minutes, up to 97.6 [94.4-101.8] % of their expected maximum heart rate. Exercise duration and workload did not differ across groups. Baseline hs-cTnT was detectable in everyone. Exercise induced a 1.98±1.63 fold increase in hs-cTnT concentrations. Peak hs-cTnT concentrations occurred at 180 minutes post-exercise (13.9 [9.4-17.0] ng/L versus 12.1 [10.0-21.5] ng/L versus 13.8 [9.1-19.9] ng/L, for group I, II and III, respectively) and the incidence of hs-cTnT concentrations above the URL (n=9 (45%) vs n=7 (35.0%) vs n=9 (47.4%)) was comparable across groups (p=0.92 and p=0.71, respectively). Patterns of time-dependent changes in hs-cTnT concentrations did not differ across groups (p=.49). Conclusion Exercise-induced elevations in hs-cTnT concentrations did not differ among middle-aged and older athletes with different degrees of coronary atherosclerosis. Our findings suggest that hs-cTnT sampled before, during or within 180 minutes following an exhaustive endurance cycling exercise test is not suitable to detect occult coronary atherosclerosis in athletes.

Exploring the predictors and prognostic significance of exercise-induced cardiac troponin release in master athletes following a 28 km mountain race. The Vamvakou research project

ABSTRACT Background/objective Aetiology and significance of exercise-induced troponin release remains a contentious issue. We investigated the effect of a 28 km mountain run on cardiac troponin I (cTnI), in relation to training, performance, nutritional, biochemical and echocardiography variables, in a group of 25 recreational male master athletes. Material and methods A comprehensive list of variables related with nutrition, training, performance and echocardiography, was collected pre- and post-race. Twenty-four months later, outcomes regarding cardiovascular events were obtained. Results Serum cTnI values were increased after the race, with mean values rising from 7.2 ± 2.2 (before) to 80.0 ± 33.2 ng/L (post race), (p < 0.001) and 23/25(92%) exceeding Upper Reference limit (50 ng/L). Echocardiography did not reveal significant alterations, or correlations with cTnI values. The percentage difference in hs-cTnI concentrations pre- and post-race correlated positively with age, race-induced changes of selected muscle damage indices, resistance training volume and negatively with endurance capacity and training volume (r: −0.727 to 0.725, p < 0.05). All athletes reported no cardiovascular event during the 24-month period post-race. Conclusion cTnI elevation induced by a 28 km mountain running race was not correlated with echocardiographic, nutritional parameters and was less pronounced in athletes with larger endurance training history, in contrast with resistance training and age.

The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients

BackgroundAlthough cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise. ObjectiveExamine cTnT and cTnI levels in relation to COVID-19 disease and MI. MethodsClinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care. ResultsLevels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1–0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7–14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/TnT ratio 14, IQR: 12–23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/cTnT ratio of 5,5 (IQR: 1,9–8,3). ConclusionsIn patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients.

Meta-Analysis Evaluating High-Sensitivity Cardiac Troponin T Kinetics after Coronary Artery Bypass Grafting in Relation to the Current Definitions of Myocardial Infarction

Various definitions of myocardial infarction type 5 after coronary artery bypass grafting (CABG) have been proposed (myocardial infarction [MI-5], also known as peri-procedural MI), using different biomarkers and different and arbitrary cut-off values. This meta-analysis aims to determine the expected release of high-sensitivity cardiac troponin T (hs-cTnT) after CABG in general and after uncomplicated surgery and off-pump CABG in particular. A systematic search was applied to 3 databases. Studies on CABG as a single intervention and reporting on postoperative hs-cTnT concentrations on at least 2 different time points were included. All data on hs-cTnT concentrations were extracted, and mean concentrations at various points in time were stratified. Eventually, 15 studies were included, encompassing 2,646 patients. Preoperative hs-cTnT was 17 ng/L (95% confidence interval [CI] 13 to 20 ng/L). Hs-cTnT peaked at 6 to 8 hours postoperatively (628 ng/L, 95% CI 400 to 856 ng/L; 45x upper reference limit [URL]) and was still increased after 48 hours. In addition, peak hs-cTnT concentration was 614 ng/L (95% CI 282 to 947 ng/L) in patients with a definite uncomplicated postoperative course (i.e., without MI). For patients after off-pump CABG compared to on-pump CABG, the mean peak hs-cTnT concentration was 186 ng/L (95% CI 172 to 200 ng/L, 13×URL) versus 629 ng/L (95% CI 529 to 726 ng/L, 45×URL), respectively. In conclusion, postoperative hs-cTnT concentrations surpass most of the currently defined cut-off values for MI-5, even in perceived uncomplicated surgery, suggesting thorough reassessment. Hs-cTnT release differences following on-pump CABG versus off-pump CABG were observed, implying the need for different cut-off values for different surgical strategies.

New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB.

BackgroundActivation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection.MethodsMale Sprague Dawley rats (n = 160) were randomized into eight groups (n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion.ResultsMP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1β, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection.ConclusionHSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.

Response by Hasselbalch et al to Letter Regarding Article, “Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans”

Response by Hasselbalch et al to Letter Regarding Article, “Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans”

Pharmacological postconditioning with sappanone A ameliorates myocardial ischemia reperfusion injury and mitochondrial dysfunction via AMPK-mediated mitochondrial quality control

Pharmacological postconditioning (PPC), drug intervention before or during the early minutes of reperfusion, could stimulate cardioprotection as ischemic postconditioning. In this study, we examined whether PPC with sappanone A (SA), a homoisoflavanone with potent antioxidant and anti-inflammatory activity, has a protective effect on myocardial ischemia reperfusion injury (MIRI), and explored the underlying mechanism. A MIRI model was established using the Langendorff method. After 30 min of ischemia, isolated rat hearts were treated with SA at the onset of reperfusion to stimulate PPC. The changes in myocardial infarct size, mitochondrial function, mitochondrial biogenesis, mitophagy, and mitochondrial fission and fusion were detected. The results showed that SA postconditioning decreased the myocardial infarct size, inhibited the release of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and cardiac troponin (cTnI), as well as improved cardiac function, enhanced myocardial ATP content and mitochondrial complex activity, and prevented the loss of mitochondrial membrane potential and opening of mitochondrial permeability transition pore (mPTP). Mechanistically, we found that SA was an AMP-activated protein kinase (AMPK) activator, and SA postconditioning could facilitate mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) copy number and the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). In addition, it balanced mitochondrial dynamics by decreasing fission and increasing fusion, and enhanced mitophagy in an AMPK-dependent manner. Moreover, AMPK silencing abolished the cardioprotection of SA postconditioning. Collectively, our study demonstrated that SA postconditioning ameliorated MIRI and mitochondrial dysfunction by regulation of mitochondrial quality control via activating AMPK. This finding provides a new insight into pharmacological action and clinical use of SA.

Correction to: Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans.

Correction to: Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans.

RETRACTED: Two Dy(III) complexes: Crystal structures and treatment activity on cardiovascular disease

Two new lanthanide coordination polymers (CPs) of {[Dy(L) (H 2 O)]·3CH 3 CN} n ( 1 ) and {(Me 2 NH 2 ) 0.5 [Dy(L) (HCOO − ) 0.5 H 2 O]·DMF·4EtOH·H 2 O} n ( 2 ) have been prepared via utilizing the tris(4-carboxyphenyl)phosphane oxide (H 3 L) as the organic linker under solvothermal conditions. The treatment activity of the compounds on cardiovascular disease in children was evaluated. Several experiments were performed to develop new candidates for the cardiovascular disease treatment. For biological activity evaluation, the release of Creatine kinase isoenzyme (CK) and serum cardiac troponin (CT) was evaluated with enzyme linked immunosorbent assay (ELISA) detection kit. The cardiomyocytes apoptosis was determined by the apoptosis detection kit and Western blot. The accumulation of the ROS in the cardiomyocytes was also detected by flow cytometry. • Two lanthanide coordination polymers have been prepared. • The treatment activity of the compounds on cardiovascular disease in children was evaluated. • The treatment activity of the compounds on cardiovascular disease in children was evaluated.

Daytime and outcomes after cardiac surgery: Systematic review and metaanalysis, insights from a large UK database review and post-hoc trial analysis.

BackgroundSeveral studies have suggested a variation of myocardial tolerance to ischaemia depending on the daytime of surgery. To test this hypothesis, we conducted a three-level analysis: metaanalysis, national patient-level dataset analysis and a post-hoc trial analysis.MethodsWe first performed a systematic review and metaanalysis of available studies comparing clinical outcomes following cardiac surgery performed in the morning (am) versus afternoon (pm). Then, we interrogated the UK national adult cardiac surgery audit database (NACSA) and analysed the am or pm outcomes of patients undergoing non-emergency aortic valve replacement (AVR) or coronary artery bypass grafting (CABG). In a post-hoc analysis, we further investigated the effect of time of surgery on serum troponin release and ventricular myocardial biopsy adenine nucleotide metabolism.ResultsA total of 18377 patients undergoing uncomplicated isolated CABG or isolated AVR on the same day am or pm were included in the metaanalysis. Meta-analytic estimates showed no difference in the risk of MI between patients operated in pm vs am (OR 1.02, 95% CI:0.79–1.32) and in the risk of mortality (OR 1.1, 95% CI:0.85-1.42). Outcomes of 91248 patients from the NACSA dataset were analysed according to the daytime of the procedure. Patient-level analysis showed no significant effect of daytime for both isolated AVR (p=0.094) and isolated CABG (p=0.425). Finally, we performed a post-hoc trial database analysis in 124 patients undergoing isolated AVR or CABG of serial cardiac troponin and nucleotides metabolism on ventricular myocardial biopsies. We found no significant diurnal changes in the perioperative cardiac troponin release or nucleotide metabolism in the AVR (p=0.30) or the CABG cohort (p=0.97).ConclusionThe present three-level analysis found no evidence that daytime influences clinical outcomes and myocardial injury in patients undergoing cardiac surgery.

Cardiac Troponin-T Release After Sport and Differences by Age, Sex, Training Type, Volume, and Intensity: A Critical Review.

Postexercise release of cardiac troponin (cTn) is a well-known phenomenon, although the influence of various confounders remains unclear. The aim of this critical review was to analyze the postexercise release of cTn according to age, sex, different types of sport, exercise intensity and duration, and training level. A literature search was performed within the National Library of Medicine using the following keywords: cTn, peak, release, and exercise. The search was further refined by adding the keywords athletes, children/adolescents, and sport. For final analysis, 52 studies were included: 43 adult studies, 4 pediatric studies, and 5 with a mixed population of adults and children. Several studies have investigated the kinetics of cTn response after exercise with different biomarkers. The current evidence suggests that sport intensity and duration have significant effects on postexercise cTn elevation, whereas the influence of the type of sport, age, and sex have been not completely defined yet. Most data were obtained during endurance races, whereas evidence is limited (or almost absent), particularly for mixed sports. Data on young adults and professional athletes are limited. Finally, studies on women are extremely limited, and those for non-White are absent. Postexercise release of cTn can be observed both in young and master athletes and usually represents a physiological phenomenon; however, more rarely, it may unmask a subclinical cardiac disease. The influence of different confounders (age, sex, sport type/intensity/duration, and training level) should be better clarified to establish individualized ranges of normality for postexercise cTn elevation.

Daytime and Outcomes After Cardiac Surgery: Systematic Review and Meta-Analysis, Insights From a Large UK Database Review and Post-Hoc Trial Analysis

Background: Several studies have suggested a variation of myocardial tolerance to ischaemia depending on the daytime of surgery. To test this hypothesis, we conducted a three-level analysis: meta-analysis, national patient-level dataset analysis and a post-hoc trial analysis. Methods: We first performed a systematic review and meta-analysis of available studies comparing clinical outcomes following cardiac surgery performed in the morning (am) versus afternoon (pm). Then, we interrogated the UK national adult cardiac surgery audit database (NACSA) and analysed the am or pm outcomes of patients undergoing non-emergency aortic valve replacement (AVR) or coronary artery bypass grafting (CABG). In a post-hoc analysis, we further investigated the effect of time of surgery on serum troponin release and ventricular myocardial biopsy adenine nucleotide metabolism. Results: A total of 18377 patients undergoing uncomplicated isolated CABG or isolated AVR on the same day am or pm were included in the meta-analysis. Meta-analytic estimates showed no difference in the risk of MI between patients operated in pm vs am (OR 1.02, 95% CI:0.79–1.32) and in the risk of mortality (OR 1.1, 95% CI:0.85-1.42). Outcomes of 91248 patients from the NACSA dataset were analysed according to the daytime of the procedure. Patient-level analysis showed no significant effect of daytime for both isolated AVR (p=0.094) and isolated CABG (p=0.425). Finally, we performed a post-hoc trial database analysis in 124 patients undergoing isolated AVR or CABG of serial cardiac troponin and nucleotides metabolism on ventricular myocardial biopsies. We found no significant diurnal changes in the perioperative cardiac troponin release or nucleotide metabolism in the AVR (p=0.30) or the CABG cohort (p=0.97). Conclusion: The present three-level analysis found no evidence that daytime influences clinical outcomes and myocardial injury in patients undergoing cardiac surgery. Funding: This study was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust, and the University of Bristol. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Declaration of Interest: None to declare.

Exercise-Induced Release of Cardiac Troponins in Adolescent vs. Adult Swimmers.

To examine the exercise-induced release of cardiac troponin T (cTnT) in adolescent and adult swimmers. Thirty-two trained male (18 adolescents, 14 adults) swam at maximal pace in a 45 min distance trial, and blood samples were drawn before, immediately and 3 h after exercise for subsequent cTnT analysis and comparison. Having comparable training experience and baseline values of cTnT (p = 0.78 and p = 0.13), adults exercised at lower absolute and relative intensity (p < 0.001 and p < 0.001, respectively), but presented higher immediate cTnT after exercise than adolescents (p < 0.001). Despite that, peak concentrations were observed at 3 h post exercise and peak elevations were comparable between groups (p = 0.074). Fourteen (44%) apparently healthy subjects exceeded the cutoff value for myocardial infarction (MI). Adolescents presented a delayed elevation of cTnT compared with adults, but achieved similar peak values.

The optimization conditions of establishing an H9c2 cardiomyocyte hypoxia/reoxygenation injury model based on an AnaeroPack System.

Ischemia-reperfusion (I/R) injury is a major cause of cardiomyocyte apoptosis after vascular recanalization, which was mimicked by a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes in vitro. In this study, we explored an optimal H/R duration procedure using the AnaeroPack System. To study the H/R procedure, cardiomyocytes were exposed to the AnaeroPack System with sugar and serum-free medium, followed by reoxygenation under normal conditions. Cell injury was detected through lactate dehydrogenase (LDH) and cardiac troponin (c-Tn) release, morphological changes, cell apoptosis, and expression of apoptosis-related proteins. The results showed that the damage to H9c2 cells increased with prolonged hypoxia time, as demonstrated by increased apoptosis rate, LDH and c-Tn release, HIF-1α expression, as well as decreased expression of Bcl-2. Furthermore, hypoxia for 10 h and reoxygenation for 6 h exhibited the highest apoptosis rate and damage and cytokine release; in addition, cells were deformed, small, and visibly round. After 12 h of hypoxia, the majority of the cells were dead. Taken together, this study showed that subjecting H9c2 cells to the AnaeroPack System for 10 h and reoxygenation for 6 h can achieve a practicable and repeatable H/R injury model.

Liraglutide restores late cardioprotective effects of remote preconditioning in diabetic rats via activation of hydrogen sulfide and nuclear factor erythroid 2-related factor 2 signaling pathway.

ABSTRACTPurposeThe present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1α) and hydrogen sulfide (H2S).MethodsStreptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H2S and HIF-1α levels.ResultsIn diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H2S and HIF-1α levels in remote preconditioning-subjected diabetic rats.ConclusionsLiraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H2S and HIF-1α.

Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans.

Cardiac troponins (cTns) are the cornerstone of diagnosing acute myocardial infarction. There is limited knowledge on the duration of ischemia necessary to induce a measurable release of cTns or the very-early-release kinetics of cTns after an ischemic event. Copeptin may have a supplementary role in ruling out myocardial infarction early. We investigated the release of cTns and copeptin in the first hours after experimental balloon-induced ischemia in humans. Thirty-four patients (median age, 60 years [interquartile range, 51-64]; 15 men, 43%) with angiographically normal coronary arteries were randomly assigned into 4 groups with different durations of induced myocardial ischemia (0, 30, 60, 90 s). Ischemia was induced by inflating a balloon in the left anterior descending artery between the first and second diagonal branch. Blood was collected before balloon inflation (baseline) every 15 minutes for the first 3 hours, and every 30 minutes for the next 3 hours. The cTns were analyzed by 3 high-sensitivity (hs) cTn assays: hs-cTnT (Roche), hs-cTnI (Siemens), and hs-cTnI (Abbott). Copeptin was analyzed by a sandwich immunoluminometric assay. None of the patients had any complications. Increased cTn concentrations were detected by all 3 assays, and the magnitude of the increase was associated with the duration of ischemia. Increased hs-cTnI (Siemens) concentrations were first detectable 15 minutes after 90-s ischemia (median 43.7% increase) and increased more steeply and had a higher peak than the other assays. Copeptin levels did not significantly change. Using the cTnT, hs-cTnI (Siemens), and hs-cTnI (Abbott) concentrations at 0 and 180 minutes, 1 (11%), 0, and 0 patients from the 60-s ischemia group and 5 (63%), 2 (25%), and 1 (11%) from the 90-s ischemia group, respectively, fulfilled criteria for a biochemical myocardial infarction. This study is the first to report the early-release kinetics of cTn concentrations after different durations of experimental coronary balloon occlusion in humans. All assays detected a cTn increase after only 30 s of ischemia. hs-cTnI (Siemens) rose faster and reached a higher peak. Copeptin levels did not change significantly. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03203057.

Ventilation With Argon Improves Survival With Good Neurological Recovery After Prolonged Untreated Cardiac Arrest in Pigs.

BackgroundVentilation with the noble gas argon (Ar) has shown neuroprotective and cardioprotective properties in different in vitro and in vivo models. Hence, the neuroprotective effects of Ar were investigated in a severe, preclinically relevant porcine model of cardiac arrest.Methods and ResultsCardiac arrest was ischemically induced in 36 pigs and left untreated for 12 minutes before starting cardiopulmonary resuscitation. Animals were randomized to 4‐hour post‐resuscitation ventilation with: 70% nitrogen–30% oxygen (control); 50% Ar–20% nitrogen–30% oxygen (Ar 50%); and 70% Ar–30% oxygen (Ar 70%). Hemodynamic parameters and myocardial function were monitored and serial blood samples taken. Pigs were observed up to 96 hours for survival and neurological recovery. Heart and brain were harvested for histopathology. Ten animals in each group were successfully resuscitated. Ninety‐six‐hour survival was 60%, 70%, and 90%, for the control, Ar 50%, and Ar 70% groups, respectively. In the Ar 50% and Ar 70% groups, 60% and 80%, respectively, achieved good neurological recovery, in contrast to only 30% in the control group (P<0.0001). Histology showed less neuronal degeneration in the cortex (P<0.05) but not in the hippocampus, and less reactive microglia activation in the hippocampus (P=0.007), after Ar compared with control treatment. A lower increase in circulating biomarkers of brain injury, together with less kynurenine pathway activation (P<0.05), were present in Ar‐treated animals compared with controls. Ar 70% pigs also had complete left ventricular function recovery and smaller infarct and cardiac troponin release (P<0.01).ConclusionsPost‐resuscitation ventilation with Ar significantly improves neurologic recovery and ameliorates brain injury after cardiac arrest with long no‐flow duration. Benefits are greater after Ar 70% than Ar 50%.

Abstract 17219: Non-Invasive, Blood-Free Point of Care Test to Rapidly Exclude Myocardial Injury: The AI ECG

Background: Myocardial injury results in release of cardiac troponin (cTn) into the bloodstream, readily detected by high-sensitivity cTn (hs-cTn) assays. A noninvasive, rapid, home-based test to exclude acute myocardial injury at the time of the test and for the next 7 hours would help manage patients with suspected myocardial infarction. Since myocyte injury is associated with ECG changes, we hypothesized an artificial intelligence ECG (AI-ECG) could identify absence of injury. Objective: To train and test an AI-ECG convolutional neural network (CNN) to identify patients using a single ECG who are suspected of myocardial infarction who are low risk, with hs-cTn levels below the 99 th percentile at test time and for the subsequent 7 hours. Methods: A CNN tuned to identify the absence of a hs-cTnT (5 th Gen cTnT Roche Diagnostics) &gt;15ng/L for men and &gt;10ng/L for women was developed. All ECGs were recorded within one hour of the hs-cTnT assay. We used 73,012 ECGs and hs-cTnT pairs from 47,542 unique patients to train the network, 9031 ECGs from 5,811 patients for internal validation to optimize hyperparameters, and 11,904 ECGs with 21,191 hs-cTnT measurements up to 7 hours after the ECG, from 11,904 different patients as a holdout test set. Results: The mean age was 63.9±17.5 years, and 30,348 of the 59,446 patients (51%) were male. 5,852 patients (49.1%) had no elevation of hs-cTnT and 6,052 (50.9%) had an hs-cTnT above the 99 th percentile at baseline or within 7 hours of the test. Of the 11,904 patients in the test set, using a sensitive threshold, the 12 lead AI ECG identified 1037 patients (8.7%) likely to have a low risk for subsequent hs-cTnT increases &gt; 99 th % (AUC 0.86), and the single lead ECG identified 685 patients. Of the 1037 low risk pts, 59 had an hs-cTnT &gt; 99 th percentile within 7 hours. The mean maximum hs-cTnT among the 59 low-risk patients was 53 ng/L ± 92 vs 184 ng/L ± 1474 in the others. None of these low risk patients died within 14 days of the test. Conclusion: Use of the AI ECG to identify patients without cardiac injury at the time of the test and for 7 subsequent hours is feasible. This may permit rapid, point of care, home-based, bloodless, painless testing to exclude cardiac injury, facilitating care and management of patients with suspected ischemia.

Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome.

Shikonin (SHI) is an anti-inflammatory agent extracted from natural herbs. It is still unknown whether SHI ameliorates lipopolysaccharide (LPS)-induced cardiac dysfunction. This study aims to explore the protective effects of SHI on LPS-induced myocardial injury and its mechanism. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of SHI. In the present study, we found that SHI treatment improved the survival rate and cardiac function and remarkably ameliorated the release of inflammatory cytokines and macrophage infiltration in heart tissue of LPS-treated mice. SHI also reduced lactate dehydrogenase (LDH) and cardiac troponin (cTn) release, cell inflammation, and apoptosis in LPS plus adenosine triphosphate (ATP)-treated H9c2 cells. In addition, SHI significantly upregulated silent information regulator 1 (SIRT1) expression and suppressed the upregulation of NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Meanwhile, we got the same results in LPS plus ATP-treated H9c2 cells in vitro. Further, SIRT1 inhibitor or siRNA partially blocked SHI-mediated upregulation of SIRT1 expression and downregulation of NLRP3, cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Therefore, we conclude that SHI ameliorates LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes and might be a promising therapeutic strategy for the treatment of LPS-induced cardiac dysfunction.