[show abstract][hide abstract] ABSTRACT: Elevated levels of circulating microparticles (MPs) have been reported in patients with acute myocardial infarction (AMI) and coronary artery disease. Platelet activation and inflammation have been recognized during AMI and stable angina (SA). We hypothesize that the origin and count of MPs in AMI and SA patients are related to markers of inflammation and platelet activation.
Platelet, monocytes and endothelial MPs and surface P-selectin were determined in 12 AMI patients, 10 SA patients and 9 controls by flow cytometry. Plasma P-selectin, CD40 ligand (sCD40L) and interleukin 6 (IL-6) levels were evaluated by ELISA methods.
The total MP count was compared in control subjects, AMI, and SA patients: 12,765 (8465) vs. 38,750 (11,931) vs. 29,715 (12,072) counts/μl (p = 0.01), respectively. Patients with AMI displayed higher levels of total and platelet origin- tissue factor-positive (CD42/CD142) MPs than patients with SA: 72.8 (6.2) vs. 56.2 (6.4) %, p = 0.001. Levels of soluble P-selectin were significantly elevated in patients with AMI as compared to SA patients: 146 (6.5) vs. 107 (2.7) ng/mL, p = 0.005; significant correlation between total MP count and relative number of CD34, CD51, CD42-positive MPs, and the P-selectin expression was observed in patients with AMI.
Platelet activation in AMI is associated with increased generation of MPs not only from platelets, but also monocytes and endothelial cells. It suggests that interactions between platelets, monocytes and endothelial cells play an important role in the pathogenesis of myocardial ischemia.
Archives of medical research 02/2012; 43(1):31-5. · 1.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dual antiplatelet therapy reduces the risk of thrombotic complications after primary percutaneous coronary intervention (PCI).
To assess whether inhibition of platelet function attenuates microvascular damage in patients with ST-segment elevation myocardial infarction (STEMI).
We studied 83 STEMI patients treated with primary PCI. Platelet aggregation was measured on admission (ADM) and 4 days later (D4) by light transmission aggregometry after stimulation with 0.5 mM of arachidonic acid and after stimulation with 5 and 20 μM of adenosine diphosphate (ADP) on treatment with dual antiplatelet therapy with aspirin and clopidogrel. Platelet-neutrophil aggregate (PNA) and platelet-monocyte aggregate (PMA) were analysed by flow cytometry. Contrast-enhanced magnetic resonance imaging was performed 2-4 days after STEMI to detect the area of perfusion defect at rest and to determine the size of microvascular obstruction. Microvascular obstruction was expressed as a percentage of infarct area.
Perfusion defect at rest was found in 56 (67.5%) patients whereas microvascular obstruction in 63 (75.9%) patients. Patients with perfusion defect at rest had on admission a significantly higher level of both PMA (7.0 vs. 4.5%, p = 0.004) and PNA (4.1 vs. 2.2%, p = 0.016), however there were no significant differences at D4. Platelet aggregation after stimulation with 5 μM of ADP on ADM was correlated (r = 0.37, p = 0.004) with microvascular obstruction area. Moreover, the higher the concentration of PMA(ADM) (r = 0.31, p = 0.016), PNA(ADM) (r = 0.34, p = 0.006) and PM(AD4) (r = 0.35, p = 0.005) the larger the size of microvascular obstruction. Infarct size (β = 0.43, 95% CI 0.19 to 0.67, p 〈 0.0001), TIMI < 3 after PCI (β = -0.27, 95% CI -1.90 to -0.11, p = 0.015) and PMA(D4) (β = 0.21, 95% CI 0.13 to 1.86, p = 0.032) independently influenced the size of microvascular obstruction (R2 = 0.60, p 〈 0.0001).
Excessive platelet activation during reperfusion in STEMI patients despite dual antiplatelet therapy is associated with greater microvascular impairment.
Kardiologia polska 01/2012; 70(7):677-84. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Antiplatelet properties of omega-3 polyunsaturated fatty acids (PUFA) have been demonstrated in patients with coronary artery disease (CAD). It is unknown whether omega-3 PUFA can enhance platelet inhibition on standard aspirin and clopidogrel treatment in the setting of CYP2C19 loss-of-function polymorphism.
To investigate whether omega-3 PUFA are able to modify platelet responsiveness to clopidogrel therapy in patients with CYP2C19 loss-of-function polymorphism undergoing percutaneous coronary intervention (PCI).
63 patients with stable CAD undergoing PCI (48 males, mean age 63.2 ± 9.6 years) were enrolled into an investigator- initiated, prospective, single-centre, double-blind, placebo-controlled, randomised study. Patients on standard dual antiplatelet therapy (aspirin 75 mg daily and clopidogrel 600 mg loading dose followed by 75 mg daily) were assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmittance aggregometry in response to 5 and 20 μmol/L ADP at baseline, 12 h, 3-5 days and 30 days after randomisation. CYP2C19*2 was genotyped at baseline.
No significant differences were found in baseline variables, including the frequency of CYP2C19 genetic variants. At least one loss-of-function variant of CYP2C19*2 was found in 19 (30.2%) patients. In patients with CYP2C19*1/*2 and *2/*2 variants, maximal platelet aggregation induced by 5 and 20 μmol/L ADP was reduced by 21.4% (p = 0.006) and 14.3% (p = 0.041), respectively, after 1 month of treatment with omega-3 PUFA as compared to placebo. The beneficial effect of omega-3 PUFA was demonstrated in carriers of CYP2C19 loss-of-function polymorphism, whereas no differences in platelet aggregation between the omega-3 PUFA and placebo groups were found in patients with the 1*/1* variant.
The addition of omega-3 ethyl esters significantly potentiates platelet response to clopidogrel after PCI mostly in patients with CYP2C19 loss-of-function polymorphism.
Kardiologia polska 01/2012; 70(5):439-45. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: A prompt primary percutaneous coronary intervention with aspiration thrombectomy and subsequent stent implantation at the culprit lesion combined with optimal anti-platelet and anti-thrombotic pharmacotherapy is the safest and most effective reperfusion strategy. Unfortunately, this therapy does not guarantee always a good, long-term clinical outcome and left ventricular function recovery. Despite the unquestionable benefit of reperfusion, we have evidence that its initial phase leads to additional damage at the area at risk, so the final effect is the compromise between benefits and destruction, which come with the reperfusion wavefront. Experimental studies suggest that postconditioning with several very brief cycles of ischaemia alternating with reperfusion applied immediately after relief of a prolonged epicardial occlusion is associated with the infarct size limitation. The cellular protective effect of postconditioning seems to be related to prevention of mitochondrial permeability transition pore activation. We have still to wait for confirmation of the clinical effectiveness of both postconditionig as well as pharmacotherapy that mimics postconditioning effects (e.g. with cyclosporine) in a randomised, multicenter clinical trial with properly designed endpoint. To date, most clinically tested agents that induced endogenous cardioprotection such as adenosine, erythropoietin, protein kinase C-δ inhibitor, atrial natriuretic peptide, atorvastatin and nicorandil were failed to reduce infarct size. Time will tell whether postconditioning and therapy that it mimics meet expectation and find place in the recommendations concerning management of acute myocardial infarction. Kardiol Pol 2011; 69, supl. III: 67-74.
Kardiologia polska 01/2011; 69 Suppl 3:67-74. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Oxidative stress is an important causative factor in atherosclerosis. Isoprostanes are derivatives of arachidonate oxidized by reactive oxygen species (ROS). Oxidized lipids are markers of oxidative stress, important mediators of atherosclerosis, and activators of platelets. 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a stable isoprostane and reliable marker of oxidative stress in vivo.
The aim of the study was to determine the level of oxidative stress in acute coronary syndromes (ACS) and its correlations with the para meters of hemo stasis.
Fourty-nine patients aged 46 to 76 years, including 28 with ACS and 25 with stable coronary artery disease (CAD), were enrolled to the study. The levels of 8-iso-PGF2alpha, soluble CD40 ligand (sCD40L), P-selectin (P-sel), beta-thromboglobulin, and the thrombin-antithrombin complex (TAT) in the plasma of venous blood were determined. A microvascular injury model was also used to evaluate TAT generation and sCD40L levels in blood collected every 60 seconds at the site of standardized microvascular injury.
8-iso-PGF2alpha levels were significantly higher in ACS compared to CAD patients (363.2 +/-45.94 vs. 328.2 -/+31.96 pg/ml, P = 0.011) and correlated with venous plasma levels of P-sel and beta-thromboglobulin in the ACS (r = 0.66; P = 0.0005 and r = 0.62; P = 0.001, respectively) and CAD groups (r = 0.46; P = 0.02 and r = 0.49; P = 0.01, respectively). In the microvascular injury model, the maximum concentrations of sCD40L in the ACS group were associated with plasma 8-iso-PGF2alpha levels (r = 0.50, P = 0.01). No correlations between 8-iso-PGF2alpha and markers of thrombin generation in venous blood and microvascular injury model were observed.
Plasma levels of 8-iso-PGF2alpha are significantly higher in ACS compared with stable CAD and correlate with platelet activation.
Polskie archiwum medycyny wewnȩtrznej 01/2010; 120(1-2):19-24. · 1.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Area at risk, infarct area, the size of no-reflow phenomenon and finally left ventricular function determine immediate and long-term outcome in patients with acute myocardial infarction (AMI). Cardiac magnetic resonance imaging is a gold standard technique for evaluation of left ventricular volumes and function and therefore has evolved into an important diagnostic tool in the assessment of patients with AMI. Increased free water content in the infracted myocardium prolongs the T2-relaxation time. Differences in T2-relaxation time are clinically useful for detection of area of risk whereas first-pass technique is useful for the assessment of areas with perfusion deficit at rest. Myocardial necrosis appears hyper-enhanced in comparison to the normal myocardium after contrast injection with delayed enhancement (DE) technique. Experimental and clinical studies indicate that extent of DE closely correlates with infarct size and predicts functional recovery of postinfarcted myocardium. The hypo-enhanced zone usually located in the core of hyper-enhanced region indicates microvascular obstruction (MVO) and corresponds with the area of no-reflow as defined by histopathology. The presence of MVO is associated with impaired functional recovery after AMI.
Kardiologia polska 01/2010; 68 Suppl 5:S441-7. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Stable angina is associated with unfavorable fibrin structure/function. It is not known how acute coronary syndromes (ACS) affect fibrin architecture.
We investigated fibrin clot properties and their determinants in ACS patients.
Clot permeability, turbidity and fibrinolysis were assessed in 40 patients with ACS versus 40 controls with stable angina matched for age, sex, and risk factors.
Patients with ACS had lower clot permeability (p=0.001), faster fibrin polymerization (p=0.008), and prolonged fibrinolysis time (p<0.0001) than controls. C-reactive protein (CRP) and 8-epi-prostaglandin F(2alpha), a marker of oxidative stress, were the only independent predictors of clot permeability (R(2)=-0.74; p<0.0001 and R(2)=-0.65; p<0.0001, respectively) and fibrinolysis time in ACS patients (R(2)=0.60; p<0.0001 and R(2)=0.59; p=0.0002, respectively). In angina patients, fibrinogen and CRP predicted permeability (R(2)=-0.71; p<0.0001 and R(2)=-0.62; p<0.0001), and D-dimer predicted lysis time (R(2)=0.54; p=0.0005). In regression analysis models incorporating all patients, the only independent predictor of all clot variables was being an ACS patient (R(2) 0.51 to 0.85; p<0.001).
This first study of clot properties in patients during an ACS demonstrated that compared with stable angina patients, their clots are composed of dense networks that are more resistant to lysis and these features are correlated with raised CRP and oxidative stress.
[show abstract][hide abstract] ABSTRACT: Recent evidence shows poor efficacy of over-the-wire balloon catheter (OTW) coronary occlusive technique adopted widely for intracoronary bone marrow stem cell (BMSC) delivery. The waterfall effect of OTW-balloon inflation/deflation with reactive > or = 2-fold flow velocity increase might be partly responsible for poor BMSC retention.
To evaluate the safety, feasibility and tolerability of perfusion-infusion BMSC delivery with the facilitation of cell rolling in contact with the coronary endothelium (a pre-requisite for downstream transmigration).
We randomly assigned 11 patients (age 41-72 years) with first anterior myocardial infarction treated with PTCA+stent and LVEF < or =45% at 6-9 days to OTW in-stent occlusive (3 x 3 min.) BMSC delivery or cell infusion via a perfusion catheter with multiple side holes (SH-PC).
OTW and SH-PC patients had a similar infarct size (mean peak CK 4361 vs 4717 U/L), LVEF (41.2% vs 40.3%), infused mononuclear cell number (2.99 x 108 range 0.61-7.48 x 108 vs 3.28 x 108 range 1.64-4.39 x 108), CD 34(+) number (1.79 x 106 vs 1.62 x 106), cell viability (91.5% vs 91.8%) and clonogenicity (CFU assay). None of the SH-PC, but 67% of OTW patients, had ST-segment elevation with chest pain (and nsVT in one) that limited OTW occlusion tolerance to 50-110 sec. At 6 months DLVEF in the OTW vs SH-PC patients was +4.2% (2-6) vs +8.8% (5-16) by MRI and +4.8 (2-7) vs +13.8% (2-24) by SPECT.
Our work indicates that the SH-PC technique can be used safely for intracoronary BMSC transplantation. Further research is needed to determine whether the putative advantages of physiological SH-PC delivery translate into enhanced BMSC homing.
Kardiologia polska 05/2006; 64(5):489-98; discussion 499. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tissue perfusion during acute myocardial infarction (AMI) may be assessed by means of the angiographic method -- TIMI myocardial perfusion (TMP). We hypothesised that TMP grade (TMPG) after primary coronary angioplasty (PCI) implicates immediate and long-term clinical outcomes.
We studied 588 consecutive patients (mean age 58.7+/-10.8 years) with ST-segment elevation AMI treated with PCI. Infarct-related TMPG was evaluated before and after PCI. Myocardial injury was expressed as an area under the curve (AUC) of CK-MB release in the first 48 hours of reperfusion. Left ventricular ejection fraction (LVEF) was assessed by 2-dimensional echocardiography one day after PCI. Clinical end-points during a 12-month follow-up included death, recurrent MI and repeated revascularisation or hospitalisation. At the end of the follow-up, NYHA functional class was evaluated in all patients.
Before PCI, TMPG -3, -2 and -0/1 values were observed in 52 (8.8%), 77 (13.1%) and 459 (78.1%) patients, respectively. After PCI, TMPG-3, -2 and -0/1 were achieved in 196 (33.3%), 174 (29.6%) and 218 (37.1%) patients, respectively. Patients with TMPG-3, -2, and -0/1 had AUC of 10341+/-1194, 12330+/-1272 and 16718+/-1860 (U/l x h) (p<0.01) and LVEF of 53.6+/-8.6%, 45.5+/-9.5% and 41.7+/-10.4% (p<0.001), respectively. In-hospital mortality rate in patients with TMPG-3, -2 and -0/1 was 0%, 4% and 11.9%, respectively (p<0.001), and after 12-months - 2%, 6.3% and 16.5%, respectively (p<0.001). The event-free survival rate after 1-year was 83.2%, 74.1% and 65.1% respectively (p<0.001). The percentage of patients in NYHA class > or =2 was 10.2%, 16.1% and 20.6% (p=0.003), respectively.
The TIMI myocardial perfusion grade after primary coronary angioplasty in acute myocardial infarction effects left ventricular injury and function as well as early and long-term clinical outcome.
Kardiologia polska 10/2004; 61(10):316-27; discussion 327-8. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Microvasculature damage after myocardial infarction (MI), known as "no-reflow" phenomenon, may occur in some patients with acute MI in spite of invasive treatment and opened infarct-related coronary artery. There are several non-invasive and invasive methods used for the coronary flow assessment at the tissue level.
To compare the value of intravenous contrast echocardiography (MCE) in detecting myocardial perfusion defects in patients with acute MI with (99m)Tc MIBI SPECT study.
Sixteen patients (11 males, 5 females, mean age 55.4+/-10.2 years) underwent primary coronary angioplasty or facilitated angioplasty (with reduced dose of a fibrinolytic drug and glycoprotein IIb/IIIa inhibitor) (PCI) for acute anterior MI. TIMI grade flow, TIMI Myocardial Perfusion Grade (TMPG), corrected TIMI frame count (cTFC), wall motion score index (WMSI) and segmental perfusion by myocardial contrast echocardiography (MCE) were estimated in real time before and immediately after PCI. MCE was repeated on the third day after PCI. All patients underwent (99m)Tc MIBI SPECT study (SPECT) while at rest on the third day after PCI. The area at risk was defined as the number of segments with no perfusion before angioplasty. Reflow was defined as an increase in contrast score in the same segments after angioplasty.
Baseline MCE showed 95 segments with perfusion defects. Immediately after PCI, 77 segments were found with perfusion defect; in 10 patients improvement of myocardial perfusion was observed whereas in 6 patients perfusion defect remained unchanged. On the third day further improvement was observed in 8 patients. The number of segments with perfusion defect decreased to 53. SPECT detected perfusion defect in 54 segments. The agreement between MCE and SPECT for detecting perfusion abnormality was 98% (kappa 0.94).
MCE is a safe technique for detecting myocardial perfusion in patients with acute MI. MCE proves that both primary and facilitated angioplasty improve myocardial perfusion in two thirds of patients with acute MI. Serial MCE allows identification of patients with both early and late improvement of myocardial perfusion. There is a very strong correlation between MCE and SPECT in the assessment of perfusion defects.
Kardiologia polska 02/2004; 60(1):27-38. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Almost one in five patient has reperfusion abnormalities despite the type of percutaneous interventional procedure after acute myocardial infarction. It has been shown with myocardial contrast echocardiographic and coronary angiographic studies that infarct related artery patency does not always correlate with the presence of adequate myocardial perfusion in the infarct related artery territory. Therefore, it is necessary to obtain further diagnostic and evaluation tools to assess coronary microcirculation and reperfusion failure. ST segment resolution time, TIMI flow grade, TIMI Frame Count and TIMI Myocardial Perfusion Grade (blush score) are helpful tools to assess myocardial perfusion and diagnosis of reperfusion abnormalities.