P4261Ticagrelor- and prasugrel-mediated platelet inhibition is not affected by mild therapeutic hypothermia generated in vitro in patients with an acute myocardial infarction

SummaryAcute myocardial infarction (AMI) is the leading cause for out-of-hospital cardiac arrest. Therapeutic hypothermia improves neurological outcome in combination with early revascularisation, but seems to affect clopidogrel responsiveness. The more potent thienopyridine prasugrel has not yet been sufficiently evaluated during therapeutic hypothermia. We investigated 23 consecutive AMI patients (61 ± 11 years) following out-of-hospital resuscitation undergoing revascularisation and therapeutic hypothermia. Prasugrel efficacy was assessed by the platelet-reactivity-index (PRI) before and 2, 4, 6, 12, 24, 48, and 72 hours(h) following a loading dose of 60 mg via a gastric tube. Mean PRI (±SD) was 70 ± 12 % prior to loading and 60 ± 16 % (2 h, ns), 52 ± 21 % (4 h, p< 0.01), 42 ± 26 % (6 h, p< 0.01), 37 ± 21 % (12 h, p< 0.01), 27 ± 23 % (24 h, p< 0.01), 18 ± 14 % (48 h, p< 0.01), and 13 ± 10 % (72 h, p< 0.01) after loading. Sufficient platelet inhibition occurred later compared to stable AMI patients (6 h vs 2 h); however, high on-treatment platelet reactivity significantly decreased over time and was non-existent after 72 h (PRI> 50 %: 2 h: 72 %, 4 h: 52 %, 6 h: 43 %, 12 h: 29 %, 24 h: 17 %, 48 h: 5 %, 72 h: 0 %). There was no relation between 30-day mortality rate (26 %) and PRI values. Prasugrel significantly reduced platelet reactivity even during vasopressor use, analgosedation and therapeutic hypothermia. Despite a significant delay compared to stable AMI patients, sufficient platelet inhibition was reached in 83 % of patients within 24 h. Therefore, prasugrel administration via gastric tube might be a useful therapeutic strategy in these patients at high risk, providing potent and effective P2Y12 inhibition.

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4034Distance from hospital as an early marker of outcomes in out of hospital cardiac arrest acute myocardial infarction survivors treated with endovascular mild therapeutic hypothermia

European Heart Journal ◽

10.1093/eurheartj/ehz745.0089 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

D Hetclova ◽

M Hutyra ◽

J Precek ◽

O Moravec ◽

T Skala ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Arrest ◽

Therapeutic Hypothermia ◽

Spontaneous Circulation ◽

Mild Therapeutic Hypothermia ◽

Circulation Time ◽

Left Ventricular Ejection ◽

Return Of Spontaneous Circulation ◽

Hospital Cardiac Arrest

Abstract Background The prediction of outcome in comatose patients after out of hospital cardiac arrest (OHCA) has major ethical and socioeconomic implications. At present, there is a lack of data comparing the predictive value from cardiac arrest localization to hospital distance in OHCA survivors treated with endovascular therapeutic hypothermia. Methods 86 patients (64±14 years, 69 men) were evaluated after OHCA due to ventricular fibrillation (VF) during an acute myocardial infarction (MI). All patients (NSTEMI 28%, STEMI 72%) were indicated for urgent coronary angiography, echocardiography for left ventricular ejection fraction (LVEF) estimation using Simpson biplane formula and treated with mild therapeutic hypothermia (MTH) using intravascular temperature management to maintain target temperature (33 °C) for 24 hours. The Cerebral Performance Categories scale (CPC) was used as the outcome measure and was assessed 3 months post admission; a CPC of 3–5 was regarded as a poor outcome (n=45), and a CPC of 1–2 (n=41) as a good outcome. Results Distance to hospital was significantly higher (p=0.0473) in patients with poor outcomes (CPC 3–5) after OHCA (37.5±4.5 km) compared with CPC 1–2 patients (27.1±4.4 km). No significant differences in return of spontaneous circulation time (21; 10.5–47.5 95th percentile vs. 23; 10.0–50.0, p=0.738), lactate (7.8; 4.5–12.4 vs. 8.4; 5.4–13.5, p=0.54), LVEF (40; 22–50 vs. 40; 21–62%, p=0.208), peak cardiac troponin T (1.5; 0.08–10.00 vs. 0.64; 0.04–5.28 μg/L, p=0.078), NSE (29.2; 15.7–54.9 vs. 25.8; 13.6–52.3 μg/L, p=0.26) and S100-B (0.17; 0.09–1.69 vs. 0.19; 0.04–1.14 μg/L, p=0.734) were found in CPC 3–5 and CPC 1–2 groups comparison. Using an optimal cut-off value ≥33 km calculated from the receiver operating characteristic curve (area under curve = 0.62; p=0.004), the sensitivity of predicting survival with poor neurological outcome was 61% and the specificity was 62%. Conclusions In patients after OHCA for VF during MI, distance from cardiac arrest localization to hospital gives reliable and on return of spontaneous circulation time independent prognostic information concerning outcome after cardiopulmonary resuscitation. Acknowledgement/Funding Grant support FNOL RIV 87-85

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Pharmacokinetics and Haemostatic Status During Consecutive Infusions of Recom binant Tissue-Type Plasminogen Activator in Patients with Acute Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646622 ◽

1989 ◽

Vol 61 (03) ◽

pp. 497-501 ◽

Cited By ~ 47

Author(s):

E Seifried ◽

P Tanswell ◽

D Ellbrück ◽

W Haerer ◽

A Schmidt

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Plasminogen Activator ◽

Peak Plasma ◽

Peak Plasma Concentration ◽

Tissue Type ◽

Tissue Type Plasminogen Activator ◽

Precise Control ◽

Type Plasminogen Activator

SummaryPharmacokinetics and systemic effects of recombinant tissue type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean ±SD) of 3310±950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of. 2210±470 nglml and 930±200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380±74 ml/min, t,½α was 3.6±0.9 min and t,½β was 16±5.4 min.After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, α2-antiplasmin to 25%, α2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 μg/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.

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Neutrophil extracellular traps induce MCP-1 release from endothelial cells at the plaque rupture site in acute myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.3834 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Ondracek ◽

T.M Hofbauer ◽

A Mangold ◽

T Scherz ◽

V Seidl ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Endothelial Cells ◽

Plaque Rupture ◽

Ex Vivo ◽

Coronary Intervention ◽

Neutrophil Extracellular Traps ◽

Funding Source ◽

Extracellular Traps

Abstract Introduction Leukocyte-mediated inflammation is crucial in acute myocardial infarction (AMI). We recently observed that neutrophil extracellular traps (NETs) are increased at the culprit site, promoting activation and differentiation of fibrocytes, cells with mesenchymal and leukocytic properties. Fibrocyte migration is mediated by monocyte chemoattractant protein (MCP)-1 and C-C chemokine receptor type 2 (CCR2). We investigated the interplay between NETs, fibrocyte function, and MCP-1 in AMI. Methods Culprit site and femoral blood of AMI patients was drawn during percutaneous coronary intervention. We characterized CCR2 expression of fibrocytes by flow cytometry. MCP-1 and the NET marker citrullinated histone H3 (citH3) were measured by ELISA. Fibrocytes were treated in vitro with MCP-1. Human coronary arterial endothelial cells (hCAECs) were stimulated with isolated NETs, and MCP-1 was measured by ELISA and qPCR. The influence of MCP-1 on NET formation in vitro was assessed using isolated neutrophils. Results We have included 50 consecutive AMI patients into the study. NETs and concentrations of MCP-1 were increased at the CLS. NET stimulation of hCAECs induced MCP-1 on mRNA and protein level. Increasing MCP-1 gradient was associated with fibrocyte accumulation at the site of occlusion. In the presence of higher MCP-1 these fibrocytes expressed proportionally less CCR2 than peripheral fibrocytes. In vitro, MCP-1 dose-dependently decreased fibrocyte CCR2 and reduced ex vivo NET release of healthy donor neutrophils. Conclusions NETs induce endothelial MCP-1 release, presumably promoting a chemotactic gradient for leukocyte and fibrocyte migration. MCP-1 mediated inhibition of NET formation could point to a negative feedback loop. These data will shed light on vascular healing. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund

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