Przemysław Prokopczuk

Coronary sinus concentrations of interleukin 6 and its soluble receptors are affected by reperfusion and may portend complications in patients with myocardial infarction

UNLABELLED Interleukin 6 (IL-6) is a pleiotropic cytokine involved in both inflammatory reaction and myocardial response to stress. Its effects largely depend on the concentration of the soluble receptors (sIL-6R and sgp130). We investigated the production of IL-6, sIL-6R and sgp130 by the heart during ischemia and reperfusion. METHODS The levels of IL-6 were determined in blood of 34 patients with first myocardial infarction (STEMI), left anterior descending (LAD) artery occlusion, otherwise normal coronaries, without significant co-morbidities and 16 comparable subjects with stable ischemic heart disease and lesion in LAD. Blood samples from coronary sinus (CS) and aorta (Ao) were drawn before percutaneous intervention (PCI), immediately after and at the end of the procedure. Venous blood from 30 healthy volunteers served as control. RESULTS STEMI patients presented high IL-6 concentrations that increased further after reperfusion when its levels in CS became significantly higher than in Ao. In both groups prior to the PCI there were significantly higher concentrations of sIL-6R in Ao than in CS. This difference disappeared immediately after reperfusion. STEMI patients who experienced cardiovascular complications had higher IL-6 concentration and higher transcardiac sIL-6R gradient than patients with event-free hospitalisation. This association was confirmed in multivariate logistic regression analysis. Myocardial infarction increases concentration of IL-6 that is further elevated by reperfusion. A transcardiac gradient of sIL-6R during ischemia may indicate that large amounts of soluble IL-6 receptors are bound to the infarcted heart and thus affect signal transduction. IL-6 and initial sIL-6R gradient may portend complications in STEMI patients.

Oxidative stress and antioxidative defense parameters early after reperfusion therapy for acute myocardial infarction

Reperfusion of ischemic myocardium evokes rapid release of free radicals in experimental models. The aim of the study was to investigate the oxidative stress and antioxidative defense during first minutes after reopening of the infarct related artery in patients treated for acute myocardial infarction. The study group consisted of 15 patients with first ST elevation myocardial infarction (STEMI) due to left anterior descending artery occlusion. The control group included ten patients with stable ischemic heart disease (IHD). Blood samples from coronary sinus were drawn before, immediately after and about 15 min after angioplasty. Activity of superoxide dysmutase (SOD), concentration of glutathione as well as the concentrations of lipid peroxides, malodialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE) were measured. There was significantly higher concentration of MDA and HNE and higher SOD activity in STEMI patients before the reperfusion, as compared to the stable IHD group. After the reperfusion concentration of HNE in erythrocytes from STEMI patients was higher than in IHD group. At the same time the activity of SOD significantly decreased in patients with impaired tissue perfusion (myocardial blush grade <2). In conclusion, there is a slightly higher concentration of oxidative stress parameters in patients with STEMI. Diminished antioxidative defense after reperfusion is associated with impaired myocardial perfusion.

Early and long-term prognosis of patients with coronary artery disease treated with percutaneous coronary interventions in 2005. Experience of single large-volume PCI center

PURPOSE The progress which has been made in interventional cardiology contributes to the gradual improvement of the results of CHD (coronary heart disease) therapy. The aim of the study was the assessment of early and long-term prognosis in all the patients with CHD treated invasively in one large-volume PCI center in 2005. MATERIAL AND METHODS 1390 consecutive patients with CHD treated with PCI in 2005 were included in the analysis. Patients with ST-elevation myocardial infarction (STEMI) accounted for 50% of cases, patients with stable angina (SA) amounted to 25%, and patients with non-ST elevation acute coronary syndromes (NSTE-ACS) constituted 25%. Mean follow-up was 738 (±237) days. RESULTS The highest mortality during the hospitalization was noted within the STEMI group(SA vs. NSTE-ACS vs. STEMI; 0% vs. 0.3% vs. 4.1%, respectively; p<0.001). The highest mortality during a 2-year follow-up was also observed in the STEMI group (SA vs. NSTE-ACS vs. STEMI, 6.3% vs. 8.5% vs. 13.8%, respectively; p<0.001). Multiple regression model showed that independent risk factors for death during the follow-up were: age, glycaemia at admission, heart rate, blood pressure, ejection fraction, STEMI, ineffective PCI (R=0.3613; F(10.131)=19.672; p<0.0001 for the model). CONCLUSIONS The highest relative increase of mortality after the discharge of patients with CHD undergoing PCI referred to the patients with NSTE-ACS. However, in the real life PCI practice STEMI patients have the worst hospital and long-term prognosis. Well recognized risk factors for death in patients with CHD are still of great importance in negative prognosis of patients undergoing PCI.

Circadian variations of interleukin 6 in coronary circulations of patients with myocardial infarction.

UNLABELLED We hypothesize that higher morbidity of patients with ST-segment elevation myocardial infarction (STEMI) in the out-of-office hours differences in outcome after myocardial infarction may depend on the concentrations of inflammatory cytokines. The aim of the study was to determine the relation between the time of percutaneous coronary intervention (PCI) and local concentration of interleukin 6 (IL-6) and its soluble receptors (sIL-6R and sgp130) in patients with STEMI. METHODS AND RESULTS The study included 32 patients with invasively treated left anterior descending artery occlusion and no significant co-morbidities. Blood samples were drawn from coronary sinus and aorta before and after intervention. Patients admitted in the afternoon (13-20) presented significantly higher mean IL-6 levels in all samples than patients admitted in the morning. There was a positive correlation between time of intervention and concentrations of IL-6 in all samplings, but also with transcardiac IL-6 gradient at the end of procedure and IL-6 increase during PCI. We did not find any significant association between time of PCI and concentrations of sIL-6R and sgp130, time from pain to balloon, angiographic parameters or medical history. CONCLUSIONS Coronary concentration of IL-6 in patients with STEMI is significantly higher in the afternoon than in the morning. This might be involved in increased morbidity of those patients.

Safety and Feasibility of a Novel Dosing Regimen of Tirofiban Administered in Patients with Acute Myocardial Infarction with ST Elevation Before Primary Coronary Angioplasty: A Pilot Study

AbstractBackground: Intravenous glycoprotein GP IIb/IIIa receptor antagonists administered to patients with acute coronary syndromes limit platelet-dependent thrombus formation and vasoconstriction and lower the complication rate of PCI. The efficacy of glycoprotein IIb/IIIa inhibitors critically depends on appropriate suppression of platelet aggregation. A growing body of evidence indicates that regimen of tirofiban used in several recent trials may be suboptimal. We investigated if a novel regimen of dosage of tirofiban administered to patients with acute myocardial infarction with ST elevation (STEMI) before primary angioplasty is safe, feasible and whether such treatment improves coronary flow in infarct-related artery. Methods: It was an open-label, non-randomized, prospective observational study. 253 consecutive patients with STEMI, qualified to PCI were included. 104 of patients (group 1) received heparin plus tirofiban at a novel regimen (10 μg/kg bolus, followed by 0.4 μg/kg/min for 30 min and then 0.1 μg/kg/min for 12–24 hours) and the remaining 149 of the patients (group 2) received a standard dose of heparin prior to PCI. Bleeding complications were recorded. The primary end point of the study was combined TIMI 1 + 2 + 3 grade flow at the time of first contrast medium injection during angiography for primary PCI. Results: Heparin was administered 50.3 ± 58.1 minutes (group 1) or 62.3 ± 67.3 minutes (group 2) (p = 0.205). Tirofiban was administered for an average of 14.5 ± 14.4 minutes before TIMI assessment (group 1). In patients treated with heparin + tirofiban the rate of combined TIMI 1 + 2 + 3 coronary flow was higher (38.4% vs. 24.8%,p = 0.020) as compared to patients treated with heparin alone. The difference in the rate of TIMI ≥ 2 coronary blood flow between the groups 1 and 2 (24.0% vs. 20.1%) has not reached statistical significance (p = 0.459). At the same time the significant difference in the rate of TIMI 1 coronary blood flow between the groups 1 and 2 was noted (14.4 vs. 4.7%,p = 0.007). In hospital mortality in the groups 1 and 2 was similar (5.3 vs. 4.8%,p = 0.838). Significant difference was noted between the groups 1 and 2 with regard to minor bleeding complications (17.3 vs. 8.7%,p = 0.041). Conclusion: In patients undergoing primary angioplasty for acute myocardial infarction the novel regimen of tirofiban is well tolerated and feasible, and is associated with improvement in coronary blood flow in the infarct related artery. Larger studies assessing the effects of tirofiban on clinical outcomes of patients with AMI undergoing primary angioplasty seem worthwhile.

Percutaneous Coronary Interventions Affect Concentrations of Interleukin 6 and Its Soluble Receptors in Coronary Sinus Blood in Patients With Stable Angina

Coronary stenting may create local inflammatory reaction. Interleukin 6 effects depend on the presence of soluble receptors (sIL-6R and sgp130) that facilitate or impede interleukin 6 signal transduction. Concentrations of interleukin 6 and its soluble receptors were assessed in aorta and coronary sinus after stenting in optimally treated stable angina patients scheduled for elective stenting. Baseline levels of interleukin 6 and its soluble receptors in patients did not differ from healthy controls. Initial levels of sIL-6R in aorta were significantly higher than in coronary sinus but this difference disappeared after intervention. Stenting caused interleukin 6 concentration increase to a similar extent both in coronary sinus and in aorta. Moreover, there was significantly higher sgp130 concentration in coronary sinus than in aorta. Coronary intervention increases concentration of interleukin 6 in patients with stable angina. It affects the cardiac level of interleukin 6 soluble receptors what may influence the local inflammatory reaction.