European Heart Journal Advance Access published online on July 10, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn325
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention
1 Institute of Cardiology, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy
2 Department of Experimental Medicine, University ‘La Sapienza’, Rome, Italy
Received 28 November 2007; revised 27 May 2008; accepted 19 June 2008.
* Corresponding author. Tel: +39 06 301 54187, Fax: +39 06 305 5535, Email: gniccoli73{at}hotmail.it
See page 1795 for the editorial comment on this article (doi:10.1093/eurheartj/ehn281)
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Aims: Thromboxane A2 (TXA2) is a key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction. We sought to investigate whether baseline plasma levels of TXA2 are associated with coronary no-reflow after primary percutaneous coronary intervention (PPCI).
Methods and results: A total of 47 consecutive patients (age, 62.5 ± 12.7; male sex, 76.6%) admitted to our hospital for a first ST-segment elevation myocardial infarction and undergoing PPCI within 12 h of onset of symptoms were enrolled. Admission TXA2 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Angiographic no-reflow was defined as a final TIMI flow of 
2 or final TIMI flow of 3 with a myocardial blush grade of <2, whereas ST-segment resolution from baseline value of 50% was used as ECG index of no-reflow. At multivariable analysis TXA2 plasma levels, endothelin-1 (ET-1) plasma levels, and left anterior descending coronary artery (LAD) as culprit vessel were significant predictors of angiographic no-reflow (P = 0.04), whereas TXA2 and ET-1 plasma levels were the only independent predictors of lack of ST-segment resolution (P = 0.013 and 0.04, respectively). Of note, TXA2 tertiles were independent predictors of both angiographic no-reflow and lack of ST-segment resolution (OR, 3.5; 95% CI, 1.1–11; P = 0.03 and OR, 3; 95% CI, 1.3–7; P = 0.01, respectively).
Conclusion: TXA2 is an independent indicator of no-reflow that occurs after PPCI. This observation may open new therapeutic opportunity in the setting of PPCI.
Key Words: Primary percutaneous coronary intervention • Acute myocardial infarction • No-reflow • Platelets • Thromboxane A2
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
The restoration of epicardial coronary artery patency after coronary occlusion does not necessarily imply complete tissue perfusion; this phenomenon is known as ‘no-reflow’. Several studies have shown that no-reflow occurring in up to 40% of patients undergoing a successful primary percutaneous coronary intervention (PPCI) is associated with a poor prognosis. Indeed, patients with no-reflow have larger infarction, an increased incidence of heart failure, and a greater mortality.1
Several studies in animal models and in man have shown that the pathogenesis of no-reflow is multifactorial. Extravascular compression, microvascular vasoconstriction, embolization from ruptured plaque or thrombus fragmentation,2 and, more importantly, platelet and neutrophil aggregates seem to be key pathogenetic components of this phenomenon. Moreover, the role of platelets seems to be more important in the earlier stage of reperfusion while neutrophil infiltration might be more important at a later stage.3 Platelets may be implicated in no-reflow through several mechanisms: microvascular obstruction by platelet aggregates and release of platelet-derived vasoactive and chemotactic mediators.4
Because of the potential role of platelets in induction and perpetuation of no-reflow, mediators affecting platelet activation, such as thromboxane A2 (TXA2), might be involved in no-reflow. TXA2 is a key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction.5,6
The role of TXA2 in no-reflow is still unclear; therefore, in this study, we sought to investigate whether pre-PPCI plasma levels of TXA2 are associated with coronary no-reflow.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Patient population
From May 2006 to October 2006 we admitted to our hospital 65 patients with ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. STEMI was diagnosed in the presence of prolonged chest pain (>30 min) with ST-segment elevation of >0.2 mV in two or more adjacent leads on standard ECG. We enrolled in this study patients with STEMI, as first manifestation of coronary artery disease, undergoing PPCI within 12 h of pain onset. Overall, 18 patients were excluded from the study, because of rescue PCI (n = 8), late presentation (n = 7), and previous coronary artery disease (n = 3). Thus, a total of 47 patients (age, 62.5 ± 12.7; male sex, 76.6%) were included in the study. No patient was on aspirin pre-treatment.
All patients were treated with aspirin (300 mg) and clopidogrel (600 mg) on admission in the emergency room about 30 min before blood collection (median time from emergency room to catheterization laboratory). The study was approved by the Ethics Committee of the Catholic University, and all patients gave their consent to use part of their blood for scientific purposes. All patients underwent the laboratory assays planned for the study.
Percutaneous coronary intervention procedure
All PPCI procedures were performed through a femoral approach with a 6F guiding catheter. A bolus of 5000 IU of heparin was administrated. After conventional wire crossing, direct stenting implantation was performed whenever possible, preceded by balloon pre-dilatation if necessary. The use of Abciximab, followed by a 12-h continuous infusion, and a device for thrombus aspiration was left at the operator’s discretion. Intracoronary nitrates were always administered after vessel recanalization.
Angiographic analysis
Angiographic analyses included coronary TIMI flow grading and final myocardial blush grade (MBG). Angiographic assessment was always performed by two independent angiographers (G.N. and I.P.) who were blind to TXA2 levels and ECG data; final agreement was of 95% (discordances were resolved by consensus). All angiographic endpoints were evaluated before and after PPCI. TIMI flow and MBG were assessed according to previous studies.7,8 We defined angiographic no-reflow as a final TIMI flow of 2 or final TIMI flow of 3 with an MBG of <2.9 Collateral grading was done according to Rentrop grading system that ranges from 0 (no collateral filling) to 3 (complete vessel opacification by retrograde flow).10 Thrombus score was modified from Gibson et al.11
ECG assessment of ST-resolution
A 12-lead ECG was recorded before and 90 min after PPCI. All measurements were done by two independent cardiologists (S.G. and C.S.) blind to angiographic and TXA2 data. ST-segment elevation was measured 20 ms after the end of QRS complex, with TP-segment as isoelectric line. Following validated algorithms, summed ST elevation was calculated from leads V1–V6, I, and AVL for anterior acute myocardial infarction (AMI) and from leads II, III, AVF, V5, and V6 for inferior AMI. A reduction in ST elevation value of 50% (ST 50%), compared with baseline ECG, was considered as no-reflow.12
Laboratory assays
A venous peripheral blood samples for TXA2 assessment was obtained in all patients on admission. Peripheral samples were obtained immediately after puncture of the femoral artery, prior to heparin and Abciximab administration. Blood was collected using standardized tubes containing dipotassium ethylenedinitro tetraaceticacid and centrifuged at 9000 g for 1 min. Plasma aliquotes were stored at –80°C in appropriate cuvettes until assayed. TXB2, a stable metabolite of TXA2, was measured in the supernatant by a commercial ELISA kit (Cayman Chemical Company, Ann Arbor, MI, USA), according to the manufacturer's instructions with a lower limit of 0.36 pg/mL.
Serum levels of cardiac enzymes (CK and CK-MB fraction) and Troponin T (TnT) were measured every 4 h during the first day and every 24 h in the following 3 days according to hospital protocol. High-sensitivity C-reactive protein was measured by latex-nephelometry (Dade-Behring, Germany). Plasma endothelin-1 (ET-1) levels were measured by radio-immunoassay using a synthetic ET-1 (Sigma) and a highly specific antibody against synthetic ET-1 (Peninsula Laboratories, England), and 125I-ET-1 (Amersham, UK). In all patients, left ventricular ejection fraction (LVEF) was measured after the PPCI procedure by 2D echocardiography (Simpson method).
Statistical analysis
Comparisons between groups were carried out by Student's t-test or Mann–Whitney U-test (as indicated) for continuous variables and by Fisher’s exact test for discrete variables. Correlation analyses were done by Pearson test or Spearman test, as indicated.
Tertiles of TXA2 plasma levels were also calculated, and the frequency of distribution according to presence/absence of coronary no-reflow was compared by 
2 test for linear trend. Multivariable logistic regression analysis was applied to identify whether TXA2, included in turn as both continuous variable and tertiles, is independently associated with coronary no-reflow. At this scope, we included in the model, the variables showing a significant or borderline association with no-reflow at univariate analysis (P < 0.1). Furthermore, we also included in the model, the variables known to be associated in the literature with coronary no-reflow (time from chest pain onset to PPCI, thrombus aspiration, IIb–IIIa inhibitors use, and initial thrombus score). The assumption of linearity for continuous variables included in the model was confirmed by the use of restrictive cubic spline function.13 A pre-specified subgroup analysis of TXA2 plasma levels and indexes of no-reflow in patients receiving Abciximab was performed.
In order to account for the inflation of the experiment-wise type-I error owing to multiple testing, we have followed previous recommendations of reporting unadjusted P-values.14 Indeed, as Perneger15 concluded ‘simply describing what tests of significance have been performed, and why, is generally the best way of dealing with multiple comparisons’.
Owing to the exploratory nature of our study and the lack of previous studies on this topic, the estimate of sample size was based on the following consideration. We have recently found higher ET-1 levels in patients with no-reflow compared with those with reflow similar in size to that of the present study in a population of AMI patients.16 Since modulation of no-reflow is multifactorial, we designed a similar population to that enrolled in the previous study, considering a 6 month period as in that study, in order to demonstrate higher TXA2 plasma levels in patients with no-reflow compared with those with reflow.
Data are reported as mean ± standard deviation, unless otherwise indicated. A P-value of <0.05 was required for statistical significance. All tests were two-tailed, and analyses were performed using computer software packages (SPSS Italia, Florence, Italy and SAS Italy).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
Baseline features of the patients are summarized in Table 1. Our population included nearly half of patients with TIMI 0 flow on admission. Abciximab was used in about 70% of cases, whereas thrombus aspiration was performed in nearly one-third of cases. After recanalization, the incidence of angiographic no-reflow was 46.8% and that of ECG no-reflow was 44.7%. Patients with TIMI flow of <3 had higher levels of TXA2 compared with patients with TIMI flow of 3 (17.06 pg/mL, interquartile range (IQR) 11.68–29.6, vs. 4.96 pg/mL, IQR 0.44–19.49; P = 0.035, Figure 1), as well as patients with MBG of <2 had higher levels of TXA2 compared with patients with MBG of
2 (17.73 pg/mL, IQR 8.9–30.66, vs. 3.9 pg/mL, IQR 0.4–10.46; P = 0.006, Figure 1). Accordingly, patients with angiographic no-reflow had higher levels of TXA2 compared with patients without angiographic no-reflow (P = 0.005, Table 1 and Figure 1). Finally, patients with ECG no-reflow had higher levels of TXA2 compared with patients without angiographic no-reflow (P = 0.001, Table 1 and Figure 1). At univariate analysis, plasma levels of TXA2 (P = 0.005), ET-1 (P = 0.003), and TnT peak (P = 0.015) were significantly associated with angiographic no-reflow, whereas lower LVEF was of borderline statistical significance (P = 0.08, Table 1). At univariate analysis, plasma levels of TXA2 (P = 0.001), ET-1 (P = 0.02), and a lower platelet count (P = 0.02) were significantly associated with lack of ST-segment resolution (Table 1). At multivariable analysis TXA2 plasma levels (P = 0.04), ET-1 (P = 0.04), and left anterior descending coronary artery (LAD) (P = 0.09) as culprit vessel were significant predictors of angiographic no-reflow, whereas TnT peak was of borderline statistical significance (Table 2). At multivariable analysis, TXA2 and ET-1 plasma levels were the only independent predictors of lack of ST-segment resolution (P = 0.013 and 0.04, respectively, Table 2).
|
|
|
The incidence of angiographic no-reflow and lack of ST-segment resolution significantly rose with higher tertiles of TXA2 (P for trend is <0.01, Figure 2). Of note, TXA2 tertiles were independent predictors of both angiographic no-reflow and lack of ST-segment resolution (OR, 3.5; 95% CI, 1.1–11; P = 0.03 and OR, 3; 95% CI, 1.3–7; P = 0.01, respectively, Table 3).
|
|
Interestingly, also in the subgroup of patients receiving Abciximab, TXA2 levels were higher in patients with angiographic no-reflow compared with those with angiographic reflow (P = 0.02) and in patients with lack of ST resolution compared with those with ST resolution (P = 0.0001, Figure 3).
|
Table 3 shows correlates of TXA2 levels among main clinical, angiographic, and laboratory data. A borderline correlation was found between TXA2 plasma levels and LVEF or TnT peak (P = 0.06 and 0.07, respectively). No correlation was found between TXA2 levels and high-sensitivity C-reactive protein baseline serum levels (P = 0.35). Interestingly, the risk of both angiographic and ECG no-reflow rose when calculating the combined ORs for TXA2 and ET-1 plasma levels (OR, 2.5; 95% CI, 1.1–4; P = 0.02 and OR, 2; 95% CI, 1.1–6; P = 0.03).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
The results of our study demonstrate that higher plasma levels of TXA2 prior to PPCI are independently associated with no-reflow after PPCI, as assessed by both angiographic and ECG parameters, suggesting an important pathophysiological role of TXA2 in no-reflow.
No-reflow phenomenon occurs in up to half of patients after PPCI, and is associated with poor long-term outcome.1 A pivotal role in the pathogenesis of no-reflow is played by microvascular plugging due to a plaque fragment embolism,2 as suggested by recent studies that have shown the association between plaque characteristics and the occurrence of no-reflow, or to platelet–leucocytes and platelet–platelet aggregates.3 Of note, their degree of activation depends on the duration of coronary occlusion. Indeed, Xu et al.3 found that the transfusion of platelets from mice subjected to a prolonged coronary ischaemia exacerbate myocardial reperfusion injury in mice subjected to a brief coronary occlusion. In our study, however, time from pain onset to PPCI was not associated with no-reflow probably due to the long median delay to reperfusion in the whole population, which confer high platelet activation in most of the patients.
Although some studies suggested that the use of glycoprotein IIb/IIIa receptor inhibitors may attenuate no-reflow phenomenon, other studies have failed to demonstrate the value of these drugs in the management of this complication.17 Accordingly, in our study, we have found higher TXA2 plasma levels in patients with no-reflow compared with those with reflow, independently of the Abciximab treatment.
Along with cellular determinants of reperfusion injury, the release of vasoactive substances by platelets plays an important role in inducing sustained vasoconstriction, which further sluggish microvascular coronary flow.18 Among the different vasoconstrictive substances released by platelets, TXA2 is of particular importance. Indeed, TXA2 is a potent platelet agonist and coronary vasoconstrictor. Furthermore, it stimulates platelets–leucocytes aggregation by inducing the expression of adhesion molecules on cellular surface.5,6 TXA2 might also increase infarct size (a known predictor of no-reflow) as suggested by the correlation between TXA2 level and TnT peak observed in our study and in the study by Valles et al.19 Finally, TXA2 may activate neutrophils, whereas TXA2 antagonism has been shown to reduce neutrophil infiltration into an ischaemic zone.20 Taken together, these effects may explain the association found in our study between TXA2 levels and no-reflow. Of note, selective TXA2 antagonists have been shown to reduce infarct size and improve coronary flow after coronary occlusion in dogs, whereas in the same model aspirin treatment did not, suggesting that residual platelet activation by TXA2 may contribute to reperfusion injury also after aspirin treatment.21 This observation has been confirmed recently in man in a study by Valles et al.19, who showed a correlation between myonecrosis and TXA2 levels in aspirin-treated patients admitted for acute STEMI.19 In this study, COX-1-independent source of TXA2 were identified as potential determinants of residual TXA2 production and subsequent platelet activation. This interesting issue of extra-platelet source of TXA2, probably not affected by direct platelet antagonists, should be further investigated.
Our results are in keeping with recent studies suggesting that platelet reactivity on admission, evaluated by various indexes, may predict the occurrence of no-reflow. In particular, in a recent study by Huczek et al.21 has found that patients with higher platelet reactivity assessed through PFA-100 have a higher percentage, statistically significant, of no-reflow assessed both by angiographic and by ECG parameters. Indeed, the results of this study suggest that platelet reactivity might also provide early prognostic information about left ventricular performance and adverse clinical events after STEMI.
The intriguing association between low platelet count and lack of ST-segment resolution in our study might be due to an increase in platelet consumption with more platelet aggregates and an increase of large, aggressive circulating platelet as suggested by recent studies. It has been shown that larger platelets are metabolically and enzymatically more active than small platelets. Several studies have shown that larger platelets have higher thrombotic potential, aggregate more rapidly, express more glycoprotein IIb–IIIa receptors, and are a potential source of COX-2 in conditions of accelerated platelet turnover as in inflammatory disease.22,23 Moreover, mean platelet volume on admission has recently been reported as a strong marker of impaired microvascular reperfusion and of unfavourable outcome after AMI.24
The sources of TXA2 in our patients cannot be deduced by our data. Indeed, although TXA2 is mainly produced by activated platelets, an increased production of COX-2 by inflammatory cells or newborn platelets might also occur.25
Interestingly, Kirtane et al.26 have shown that neutrophilia on admission are independently associated with larger infarct size and no-reflow in patients with AMI treated by PPCI.
Our study confirms that LAD as culprit vessel, TnT peak, and a reduced LVEF are associated with no-reflow, in keeping with previous studies which suggested that various indexes of infarct size are associated to no-reflow due to larger zones of ischaemia–reperfusion.1 Importantly, in our study, TXA2 levels predicted no-reflow independently of these established variables, suggesting that it may be an important modulator of no-reflow severity. Interestingly, ET-1 and TXA2 levels were independent predictors of no-reflow, with an increase in the combined ORs for both angiographic and ECG no-reflow suggesting a possible additive effect of the two molecules on no-reflow occurrence.
Study limitations
Our study has some limitations. First, the sample size is small, but the association between TXA2 and no-reflow was highly significant. Secondly, we did not measure urinary TXA2 metabolites levels. However, 24 h urine collection reflects global TXA2 production, including also the production of post-PCI, which was not the aim of our study focused on baseline pre-PCI TXA2 levels. Thirdly, the low use of thrombus-aspirating device, which has demonstrated to improve myocardial reperfusion in this setting of patients,27 not fully reflects the current standard treatment of AMI patients. However, TXA2 levels predicted no-reflow independently of the use of thrombus aspirating device. Finally, the results of our study should be considered hypothesis generating because of its observational nature.
|
Conclusion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
In conclusion, our study demonstrates for the first time, to the best of our knowledge, that TXA2 is an independent indicator of no-reflow after PPCI, suggesting a new clue to the interpretation of this phenomenon and to novel forms of therapies addressed to specifically block TXA2. Interestingly, terutroban, an oral specific thromboxane receptor antagonist, has been demonstrated superior to aspirin in the inhibition of thrombus formation in animals and has been able to improve endothelial dysfunction in coronary artery disease patients on chronic aspirin treatment.28,29 Finally, terutroban antagonizes the effects of TXA2 on non-platelet thromboxane receptor such as those expressed by monocytes and vascular cells, and it also inhibits the effects of other thromboxane receptor ligands such as prostacyclin and isoprostanes. Thus, it might preserve the beneficial COX-1 endothelial production of prostacyclin, leading to further inhibition of platelet aggregation and vasodilation.30,31 Taken together, all these mechanisms might be useful in the prevention/treatment of no-reflow.
Conflict of interest: none declared.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
|---|
- Rezkalla SH, Kloner RA. No-reflow phenomenon. Circulation (2002) 105:656–662.
[Free Full Text] - Kusama I, Hibi K, Kosuge M, Nozawa N, Ozaki H, Yano H, Sumita S, Tsukahara K, Okuda J, Ebina T, Umemura S, Kimura K. Impact of plaque rupture on infarct size in ST-segment elevation anterior acute myocardial infarction. J Am Coll Cardiol (2007) 50:1230–1237.
[Abstract/Free Full Text] - Xu Y, Huo Y, Toufektsian MC, Ramos SI, Ma Y, Tejani AD, French BA, Yang Z. Activated platelets contribute importantly to myocardial reperfusion injury. Am J Physiol Heart Circ Physiol (2006) 290:H692–H699.
[Abstract/Free Full Text] - Heindl B, Zahler S, Welsch U, Becker BF. Disparate effects of adhesion and degranulation of platelets on myocardial and coronary function in postischaemic hearts. Cardiovasc Res (1998) 38:383–394.
[Abstract/Free Full Text] - Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med (2005) 353:2373–2383.
[Free Full Text] - FitzGerald GA. Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Am J Cardiol (1991) 68:11B–15B.[CrossRef][Medline]
- TIMI Study Group. The thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group. N Engl J Med (1985) 312:932–936.[Medline]
- Van’t Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Myocardial Infarction Study Group. Circulation (1998) 97:2302–2306.
[Abstract/Free Full Text] - Gibson CM, Murphy SA, Morrow DA, Aroesty JM, Gibbons RJ, Gourlay SG, Barron HV, Giugliano RP, Antman EM, Braunwald E. Angiographic perfusion score: an angiographic variable that integrates both epicardial and tissue level perfusion before and after facilitated percutaneous coronary intervention in acute myocardial infarction. Am Heart J (2004) 148:336–340.[CrossRef][Web of Science][Medline]
- Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol (1985) 5:587–592.[Abstract]
- Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, Antman EM, Braunwald E, TIMI Study Group. Combination therapy with abcixamab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation (2001) 103:2550–2554.
[Abstract/Free Full Text] - Schröder R, Dissmann R, Brüggemann T, Wegscheider K, Linderer T, Tebbe U, Neuhaus KL. Extent of early ST-segmental elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction. J Am Coll Cardiol (1994) 24:384–391.[Abstract]
- Harrell FE Jr. Predicting Outcomes: Applied Survival Analysis and Logistic Regression (1997) Charlottesville: University of Virginia.
- Rigby AS. Statistical methods in epidemiology: I. Statistical errors in hypothesis testing. Disabil Rehabil (1998) 20:121–126.[Web of Science][Medline]
- Perneger TV. What’s wrong with Bonferroni adjustments. Br Med J (1998) 316:1236–1238.
[Free Full Text] - Niccoli G, Lanza GA, Shaw S, Romagnoli E, Gioia D, Burzotta F, Trani C, Mazzari MA, Mongiardo R, De Vita M, Rebuzzi AG, Lüscher TF, Crea F. Endothelin-1 and acute myocardial infarction: a no-reflow mediator after successful percutaneous myocardial revascularization. Eur Heart J (2006) 27:1793–1798.
[Abstract/Free Full Text] - Chaitman B, Lim B. No reflow and the quest to achieve optimal perfusion during the acute phase of myocardial infarction. J Am Coll Cardiol (2004) 44:313–315.
[Free Full Text] - Frossard M, Fuchs I, Leitner JM, Hsieh K, Vlcek M, Losert H, Domanovits H, Schreiber W, Laggner AN, Jilma B. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation (2004) 110:1392–1397.
[Abstract/Free Full Text] - Valles J, Santos MT, Fuset MP, Moscardo A, Ruano M, Perez F, Piñon M, Breña S, Aznar J. Partial Inhibition to platelet thromboxane A2 synthesis by aspirin is associated with myonecrosis in patients with ST-segment elevation myocardial infarction. Am J Cardiol (2007) 99:19–25.[CrossRef][Web of Science][Medline]
- Smith EF 3rd, Griswold DE, Egan JW, Hillegass LM, DiMartino MJ. Reduction of myocardial damage and polymorphonuclear leukocyte accumulation following coronary artery occlusion and reperfusion by the thromboxane receptor antagonist BM 13.505. J Cardiovasc Pharmacol (1989) 13:715–722.[Web of Science][Medline]
- Huczek Z, Filipiak KJ, Kochman J, Piatkowski R, Grabowski M, Roik M, Malek LA, Jaworski P, Opolski G. Baseline platelet reactivity in acute myocardial infarction treated with prymari angioplasty- influence on myocardial reperfusion, left ventricular performance, and clinical events. Am Heart J (2007) 154:62–70.[CrossRef][Web of Science][Medline]
- Campo G, Valgimigli M, Gemmati D, Percoco G, Tognazzo S, Cicchitelli G, Catozzi L, Malagutti P, Anselmi M, Vassanelli C, Scapoli G, Ferrari R. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention. J Am Coll Cardiol (2006) 48:2178–2185.
[Abstract/Free Full Text] - Martin JF, Bath PM, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet (1991) 338:1409–1411.[CrossRef][Web of Science][Medline]
- Huczek Z, Kochman J, Filipiak KJ, Horszczaruk GJ, Grabowski M, Piatkowski R, Wilczynska J, Zielinski A, Meier B, Opolski G. Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. J Am Coll Cardiol (2005) 46:284–290.
[Abstract/Free Full Text] - Rocca B, Secchiero P, Ciabattoni G, Ranelletti FO, Catani L, Guidotti L, Melloni E, Maggiano N, Zauli G, Patrono C. Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Proc Natl Acad Sci USA (2002) 99:7634–7639.
[Abstract/Free Full Text] - Kirtane AJ, Bui A, Murphy SA, Barron HV, Gibson CM. Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction. Am J Cardiol (2004) 93:532–536.[CrossRef][Web of Science][Medline]
- Svilaas T, Vlaar PJ, van der Horst IC, Diercks GF, de Smet BJ, van den Heuvel AF, Anthonio RL, Jessurun GA, Tan ES, Suurmeijer AJ, Zijlstra F. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med (2008) 358:557–567.
[Abstract/Free Full Text] - Osende JI, Shimbo D, Fuster V, Dubar M, Badimon JJ. Antithrombotic effects of S 18886, a novel orally active thromboxane A2 receptor antagonist. J Thromb Haemost (2004) 2:492–498.[CrossRef][Web of Science][Medline]
- Belhassen L, Pelle G, Dubois-Rande JL, Adnot S. Improved endothelial function by the thromboxane A2 receptor antagonist S 18886 in patients with coronary artery disease treated with aspirin. J Am Coll Cardiol (2003) 41:1198–1204.
[Abstract/Free Full Text] - Fiddler GI, Lumley P. Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review. Circulation (1990) 81(Suppl. 1):169–178.
- Grover GJ, Schumaker WA. Effect of the thromboxane A2 receptor antagonist SQ 30, 741 on ultimate myocardial infarct size, reperfusion injury and coronary flow reserve. J Pharmacol Exp Ther (1989) 248:484–491.
[Abstract/Free Full Text]
-
The above article uses a new reference style being piloted by the EHJ that shall soon be used for all articles.
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in EHJ:
- No-reflow: the next challenge in treatment of ST-elevation acute myocardial infarction
- Antonio Abbate, Michael C. Kontos, and Giuseppe G.L. Biondi-Zoccai
EHJ 2008 29: 1795-1797.[Extract] [FREE Full Text]
This article has been cited by other articles:
|
|
 |
|
  G. Niccoli, F. Burzotta, L. Galiuto, and F. Crea Myocardial no-reflow in humans. J. Am. Coll. Cardiol., July 21, 2009; 54(4): 281 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Niccoli, N. Cosentino, and F. Crea Letter by Niccoli et al Regarding Article, "Presence of Older Thrombus Is an Independent Predictor of Long-Term Mortality in Patients With ST-Elevation Myocardial Infarction Treated With Thrombus Aspiration During Primary Percutaneous Coronary Intervention" Circulation, July 7, 2009; 120(1): e4 - e4. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rivera, M. L. Lozano, L. Navarro-Nunez, and V. Vicente Platelet receptors and signaling in the dynamics of thrombus formation Haematologica, May 1, 2009; 94(5): 700 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Abbate, M. C. Kontos, and G. G.L. Biondi-Zoccai No-reflow: the next challenge in treatment of ST-elevation acute myocardial infarction Eur. Heart J., August 1, 2008; 29(15): 1795 - 1797. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||