Circadian dependence of the acute immune response to myocardial infarction

Abstract Aim Circadian rhythms control many physiological processes, including numerous aspects of the immune system. Whether these immunological oscillations play a role in the pathophysiology after ischemic injury, such as myocardial infarction (MI), remains unclear. In this study, we aimed to characterize circadian rhythms during the acute inflammatory responses after MI. Methods and results Balb/c mice were operated at Zeitgeber Time (ZT) 2, 8, 14 and 20. Three hours after MI, animals were terminated and blood and hearts were collected to assess immunological status and damage. We observed diurnal fluctuation in leukocyte numbers in the blood, peaking during the rest-phase (ZT2 and 8) of the circadian cycle. Interestingly, the homing and infiltration of neutrophils to the injured myocardium was more pronounced during the active-phase of the mice (ZT14 and 20), at which time higher levels of Troponin-T were measured in the serum. Higher neutrophil extravasation during the active phase (especially the sleep-to-wake transition, ZT14) was also correlated to greater chemokine release in the blood and adhesion molecule expression in the heart. Conclusion The occurrence of a myocardial infarction during the early-morning hours leads to greater myocardial damage in patients. In the present study, we showed that the neutrophil response in the first hours after MI is stronger during the sleep-to-wake transition, thereby potentially playing a role in the worse clinical outcome observed during this time period. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research received funding from the EU's H2020 research and innovation programme under Marie S. Curie cofund RESCUE grant agreement No 801540.

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Troponin -T as a prognostic and diagnostic marker for myocardial infarction

GSC Biological and Pharmaceutical Sciences ◽

10.30574/gscbps.2021.14.1.0005 ◽

2021 ◽

Vol 14 (1) ◽

pp. 095-100

Author(s):

Yamini N ◽

Gopalakrishnan B ◽

Selvam R ◽

Saravanan D

Keyword(s):

Myocardial Infarction ◽

Striated Muscle ◽

Troponin T ◽

Membrane Integrity ◽

Myocardial Damage ◽

Signs And Symptoms ◽

Vital Role ◽

Coronary Syndromes ◽

Utilization Of Healthcare ◽

Contraction And Relaxation

Over the past decade, there has been a progressive evolution of cardiac marker testing in patients with acute coronary syndromes. Myocardial infarction (MI) is the leading cause of death in the developed world. Biomarkers have an vital role in analysis, risk stratification, administrative running and medical assessment making in the setting of patients presenting with signs and symptoms of MI. Cardiac troponin (cTn) rose to prominence during the 1990s and has evolved to be the cornerstone for diagnosis of MI. Cardiac troponins are released from myocytes following myocardial damage and loss of membrane integrity. Troponin T are member of a group of cardiac regulatory proteins which function to regulate the calcium mediated interaction of muscle filaments actin and myosin resulting in contraction and relaxation of striated muscle. New algorithms integrating Brain natriuretic peptide (BNP), NT-proBNP, and more sensitive cTn assays footing potential for more rapid diagnosis of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.

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Troponin T as a Marker of Infarction during Coronary Bypass Surgery

Asian Cardiovascular and Thoracic Annals ◽

10.1177/021849230000800105 ◽

2000 ◽

Vol 8 (1) ◽

pp. 19-23

Author(s):

Tarek A Abdel Aziz ◽

Mohamed A Ali ◽

Donald G Roberts ◽

Najib Al Khaja

Keyword(s):

Myocardial Infarction ◽

Creatine Kinase ◽

Troponin T ◽

Artery Bypass ◽

Myocardial Damage ◽

Perioperative Myocardial Infarction ◽

Creatine Kinase Mb ◽

Group A ◽

Electrocardiographic Changes ◽

Group B

To evaluate serum troponin T as a marker of perioperative myocardial infarction, 50 patients undergoing coronary artery bypass grafting were divided into 2 groups. Group A (14 patients) had serum creatine kinase MB-isoenzyme levels above 100 U·L−1 and electrocardiographic changes indicative of infarction. Group B (36 patients) had creatine kinase MB levels below 100 U·L−1 and no electrocardiographic changes. Blood samples were obtained preoperatively, 6 hours after aortic declamping, and on postoperative day 1, 2, and 3. Following surgery, all patients had increased levels of troponin T and creatine kinase MB. Troponin T was significantly higher in group A compared to group B at 6 hours, day 1, and day 2 postoperatively. Creatine kinase MB levels were significantly higher in group A compared to group B at 6 hours and day 1 postoperatively. The increased levels of troponin T in patients without myocardial infarction suggest that some operative myocardial damage occurred. Patients with perioperative myocardial infarction had significantly higher levels of troponin T up to postoperative day 2, whereas creatine kinase MB levels were almost normal by day 2. This suggests that troponin T may be used up to 2 days postoperatively for detection of myocardial infarction.

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Complete versus simplified Selvester QRS score for infarct severity assessment in ST-elevation myocardial infarction

BMC Cardiovascular Disorders ◽

10.1186/s12872-019-1230-0 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Christina Tiller ◽

Martin Reindl ◽

Sebastian Johannes Reinstadler ◽

Magdalena Holzknecht ◽

Michael Schreinlechner ◽

...

Keyword(s):

Myocardial Infarction ◽

Troponin T ◽

Area Under The Curve ◽

Reference Method ◽

Myocardial Damage ◽

Scoring Systems ◽

St Elevation Myocardial Infarction ◽

Clinical Tool ◽

Microvascular Damage ◽

St Elevation

Abstract Background Complete and simplified Selvester QRS score have been proposed as valuable clinical tool for estimating myocardial damage in patients with ST-elevation myocardial infarction (STEMI). We sought to comprehensively compare both scoring systems for the prediction of myocardial and microvascular injury assessed by cardiac magnetic resonance (CMR) imaging in patients with acute STEMI. Methods In this prospective observational study, 201 revascularized STEMI patients were included. Electrocardiography was conducted at a median of 2 (interquartile range 1–4) days after the index event to evaluate the complete and simplified QRS scores. CMR was performed within 1 week and 4 months thereafter to determine acute and chronic infarct size (IS) as well as microvascular obstruction (MVO). Results Complete and simplified QRS score showed comparable predictive value for acute (area under the curve (AUC) = 0.64 vs. 0.67) and chronic IS (AUC = 0.63 vs. 0.68) as well as for MVO (AUC = 0.64 vs. 0.66). Peak high sensitivity cardiac troponin T (hs-cTnT) showed an AUC of 0.88 for acute IS and 0.91 for chronic IS, respectively. For the prediction of MVO, peak hs-cTnT represented an AUC of 0.81. Conclusions In reperfused STEMI, complete and simplified QRS score displayed comparable value for the prediction of acute and chronic myocardial as well as microvascular damage. However, both QRS scoring systems provided inferior predictive validity, compared to peak hs-cTnT, the clinical reference method for IS estimation.

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Recommended standards for biochemical markers of myocardial damage: All Wales Clinical Biochemistry Audit Group

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/0004563054890042 ◽

2005 ◽

Vol 42 (5) ◽

pp. 346-350 ◽

Cited By ~ 2

Author(s):

EJ Williams ◽

CJH Jones ◽

IFW McDowell ◽

JA Tovey ◽

MA Thomas ◽

...

Keyword(s):

Myocardial Infarction ◽

Clinical Biochemistry ◽

Troponin T ◽

Myocardial Damage ◽

Extensive Discussion ◽

Reference Limit ◽

Two Samples ◽

Coronary Syndromes ◽

Line Test ◽

Effective Use

The effective use of cardiac-specific troponin estimations in the diagnosis of acute myocardial infarction (AMI) is clouded by the imprecise definition surrounding the decision limits. This has led to a wide variation of criteria for the diagnosis of myocardial infarction. A survey of troponin measurements in Welsh laboratories, undertaken in 2003 under the auspices of the All Wales Clinical Biochemistry Audit Group, revealed significant variations in laboratory and clinical practice. Extensive discussion and consultation led by a working group of clinical biochemists and cardiologists in Wales culminated in recommendations concerning the use of troponin assays to establish myocardial damage. The key recommendations are: •Cardiac troponin (T or I) should be the first-line test for myocardial damage; •Two samples should be collected, at admission and 12-24 h later. The first sample is used for 'rule in' purposes, but not to 'rule out' myocardial damage; •Only one threshold (cut-off) value for troponin should be quoted on laboratory reports, values above which are indicative of myocardial damage. A study by the Wales External Quality Assurance Scheme (WEQAS) enabled the derivation of the recommended cut-off concentrations of troponin for defining myocardial damage, defined for each assay as the concentration that can be reliably distinguished, with a confidence interval of 99%, from the 99th percentile reference limit. These recommended standards provide a rationale for a uniform approach for troponin assays for patients with chest pain, working towards a standardized approach to the diagnosis and management of patients presenting with acute coronary syndromes.

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Evaluation of Adjuvant Biomarkers in Acute Myocardial Infarction

International Journal of Innovative Research in Medical Science ◽

10.23958/ijirms/vol03-i02/04 ◽

2018 ◽

Vol 3 (02) ◽

Author(s):

Varghese M. V ◽

Gaikwad S. B ◽

Fawade M. M. ◽

Bhattacharya M. A.

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Serum Sodium ◽

Extracellular Enzymes ◽

Troponin T ◽

Myocardial Damage ◽

Cost Effective ◽

Control Group ◽

Cardiac Markers ◽

Time Saving

Background: Acute myocardial infarction (AMI) is one of the dreadful complications of cardiovascular disease causing increasing mortality worldwide. The alterations (increase or decrease) of intracellular and extracellular enzymes or components in developing phase of disease are called markers. Variations in biochemical markers like Cardiac Troponins - T (ctnl) creatine kinase may correlate with the extent of myocardial damage in Acute myocardial infarction (AMI). Aim and Objectives: This study was undertaken to evaluate serum sodium, potassium, urea and creatinine as adjunctive parameters along with cardiac markers, which probably help in better prognosis of AMI. Material Methods: 100 subjects were included in this study with confirmed diagnosis of recent AMI by the physicians and 100 healthy persons visiting hospital for routine checkup. Blood samples of both group were analyzed for serum urea by Diacetylmonoxime, creatinine by Jaffe's, &sodium & potassium by flamephotometry uing Bio- Lab Diagnostic Kit Methods. Whereas cardiac troponin - T was done by chemiluminescence immunoassay (CLIA) on Lumax hormone analyser and CKMB by kinetic kit method. Results: There were statistically significant decreased levels of serum sodium (P<0.0001) potassium (p<0.0001), and elevated levels of urea (p<0.0001) and creatinine (0.0001) observed in AMI. Both established cardiac markers Trop- T and CKMB were extremely statistically significantly increased (p<0.0001) as compared to control group. Conclusion: This study showed association of routine blood tests such as urea, creatinine, sodiumand potassium hence can be used as supplement information with regard to treatment and better prognosis of AMI patients or these could be cost effective time saving adjuvant markers in management of myocardial infarction.

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C-X-C motif chemokine 16, modulated by microRNA-545, aggravates myocardial damage and affects the inflammatory responses in myocardial infarction

Human Genomics ◽

10.1186/s40246-021-00314-7 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Fang-Qian Liang ◽

Jing-Yuan Gao ◽

Ji-Wei Liu

Keyword(s):

Myocardial Infarction ◽

Cell Viability ◽

Inflammatory Responses ◽

Cell Model ◽

Myocardial Damage ◽

Inhibitory Effect ◽

Luciferase Reporter ◽

Potential Candidate ◽

Human Cardiomyocytes

Abstract Background Myocardial infarction (MI), a common type of coronary heart disease, is the major cause of morbidity and mortality around the world. Chemokine-mediated inflammatory cell infiltration and local inflammatory damage response are recent research hotspots. Hence, we attempted to examine the role of C-X-C motif chemokine 16 (CXCL16) as a potential candidate in MI. Methods Human cardiomyocytes were treated with hypoxia/reoxygenation (H/R) to establish an in vitro cell model. GEO database provided the clinical data of MI patients and GSEA verified the relationship of chemokine and MI. CCK-8 and flow cytometry analyses were used to measure cell viability and apoptosis. Bioinformatics analysis and luciferase reporter assay were conducted to determine the correlation between CXCL16 and miR-545. qRT-PCR and western blot assays were performed to investigate the expression level of the indicated genes. The activity of lactate dehydrogenase (LDH) and the levels of TNF-α, IL-6, IL-1β, and IL-10 were explored using ELISA assay. Results CXCL16 was increased in MI. CXCL16 knockdown can reverse the inhibitory effect of H/R treatment on cell viability, while overexpression of CXCL16 showed the opposite trend. MiR-545 directly targeted CXCL16 and negatively regulated CXCL16 levels. MiR-545 promoted cell proliferation and inhibited apoptosis in the MI cell model, which attenuated the CXCL16-induced injury on cardiomyocytes. Conclusion These findings demonstrated that CXCL16 aggravated MI damage through being directly targeted by miR-545 and mediating inflammatory responses, thereby providing potential therapeutic targets for MI therapy.

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Critical difference between serial measurements of CK-MB mass to detect myocardial damage

Clinical Chemistry ◽

10.1093/clinchem/43.2.338 ◽

1997 ◽

Vol 43 (2) ◽

pp. 338-343 ◽

Cited By ~ 15

Author(s):

Robbert J de Winter ◽

Rudolph W Koster ◽

Jan P van Straalen ◽

Jozef P M C Gorgels ◽

Frans J Hoek ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Troponin T ◽

Myocardial Damage ◽

Critical Difference ◽

Blood Samples ◽

Two Samples ◽

Serial Measurements

Abstract To assess the critical difference in serial measurements of CK-MBmass and the ability of this critical difference to detect myocardial damage, we studied 110 patients in whom an acute myocardial infarction (AMI) had been ruled out. Blood samples were drawn at 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 h after onset of symptoms. With a critical difference of 72.6%, an increase of >2.0 μg/L between two CK-MBmass measurements was determined to be significant. Twenty-three of the non-AMI patients had an increase in CK-MBmass >2.0 μg/L, but five of these did not have an abnormal concentration of troponin T (i.e., not >0.1 μg/L). Also among the 110 non-AMI patients, 22 did have an abnormal troponin T value, 18 of whom (82%) also had CK-MBmassincreased by >2.0 μg/L. In 20 of the 23 patients with an increase in CK-MBmass >2.0 μg/L, this increase was detected from the values for two samples collected at 5 and 12 h after onset of symptoms. In conclusion, using the critical difference for CK-MBmassdefined as an increase >2.0 μg/L detected myocardial damage in patients without AMI.

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The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI

Mediators of Inflammation ◽

10.1155/2021/5525917 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Jostein Nordeng ◽

Hossein Schandiz ◽

Svein Solheim ◽

Sissel Åkra ◽

Pavel Hoffman ◽

...

Keyword(s):

Myocardial Infarction ◽

Signaling Pathway ◽

Troponin T ◽

Treatment Options ◽

Myocardial Damage ◽

Cross Sectional Study ◽

Receptor Protein ◽

Optimal Timing ◽

Cross Sectional ◽

Genes Encoding

Background. The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross-sectional study, we aimed to study presence, localization, and genetic expression of inflammasome- and IL-6- signaling-related proteins in coronary thrombi and circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI. Methods. Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1β (IL1-β), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT-PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses. Results. Genes encoding the 8 markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T ( r = 0.455 , p = 0.013 ), as did NLRP3 ( r = 0.468 , p = 0.024 ). Troponin T correlated with expression in circulating leukocytes of TLR4 ( r = 0.438 , p = 0.011 ), NLRP3 ( r = 0.420 , p = 0.0149 ), and IL-1β ( r = 0.394 , p = 0.023 ). IL-6R expression in thrombi correlated significantly to troponin T ( r = 0.434 , p = 0.019 ), whereas gp130 was inversely correlated ( r = − 0.398 , p = 0.050 ). IL-6 in circulating leukocytes correlated inversely to troponin T ( r = − 0.421 , p = 0.015 ). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI. Conclusions. The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti-inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822.

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The Biological Clock and Sleep in the Elderly

Zeitschrift für Gerontopsychologie & -psychiatrie ◽

10.1024/1011-6877.19.1.45 ◽

2006 ◽

Vol 19 (1) ◽

pp. 45-51 ◽

Cited By ~ 1

Author(s):

Myriam Juda ◽

Mirjam Münch ◽

Anna Wirz-Justice ◽

Martha Merrow ◽

Till Roenneberg

Keyword(s):

Circadian Rhythms ◽

Biological Clock ◽

The Elderly ◽

Early Morning ◽

Behavioral Changes ◽

Older Age ◽

Age Related ◽

Theoretical Considerations ◽

Sleep Difficulties ◽

Circadian Biology

Abstract: Among many other changes, older age is characterized by advanced sleep-wake cycles, changes in the amplitude of various circadian rhythms, as well as reduced entrainment to zeitgebers. These features reveal themselves through early morning awakenings, sleep difficulties at night, and a re-emergence of daytime napping. This review summarizes the observations concerning the biological clock and sleep in the elderly and discusses the documented and theoretical considerations behind these age-related behavioral changes, especially with respect to circadian biology.

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