Janusz Korecki

Oxidative stress and neutrophil activation—the two keystones of ischemia/reperfusion injury

The widespread introduction of fibrinolytics and recently also PTCA in the treatment of myocardial infarction has changed the picture of modern cardiology. But this therapy also raises new problems and challenges. One of them is the occurrence of extensive tissue injury caused by reperfusion. Reinstitution of oxygen to the ischemic tissues initiates various processes leading to generation of reactive oxygen species (ROSs). Acting on the plasma membrane ROS damage its organization and release various proinflammatory agents. Different proteins, including receptors, ionic channels, transporters or components of transduction pathways are substrates of oxidation by ROSs. Their changed structure results in altered functioning and disruption of vital cellular processes. Another key factor of reperfusion injury is activation and infiltration of infarcted area by polymorphonuclear leukocytes (PMNs). Multiple studies identified consecutive stages of PMN activation and substances being involved in it. Main interest lies in cellular adhesion molecules, particularly selectins and beta2 integrins, as their antagonists were repeatedly found to diminish neutrophil activation and infarct size. Nevertheless new publications strike at the foundations of the established order and confront the relation between neutrophil infiltration and infarct size. PMNs are linked by close ties to other cells involved in inflammatory response. Seemingly also in cardiac ischemia-reperfusion injury, the activity of neutrophils is modulated by lymphocytes and macrophages. The article describes mutual interactions between different factors involved in the reperfusion injury that may enable preparing new treatments, hopefully as effective and successful as reperfusion therapy.

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.

The association between type 2 diabetes mellitus and A1/A2 polymorphism of glycoprotein IIIa gene.

Glycoprotein IIIa (GpIIIa) is a membrane receptor, found in various tissues, that has two alleles: A1 and A2. Signalling cascade of GpIIIa is modulated by enzymes called calpains, proteases that may also influence glucose metabolism. There is one small study that shows a high association of A1/A2 polymorphism with type 2 diabetes mellitus. In our research we planned to evaluate the association of A1/A2 polymorphism with type 2 diabetes in a population of patients with ST elevation acute myocardial infarction (STEMI). The study comprised 352 individuals. From the cohort of patients hospitalised for STEMI we chose 113 patients with diagnosed diabetes (diabetic group) and 118 patients with STEMI and normal glucose metabolism (non-diabetic group). The population group consisted of 121 persons. Genotyping was performed by the restriction fragments length polymorphism (RFLP) method. The frequency of alleles in all groups was in Hardy-Weinberg equilibrium. The percentage of A2 allele carriers was comparable among all groups : 20.4% (diabetic patients), 23.7% (nondiabetic) and 21.5% (control group) (p>0.05). There was no significant difference in frequency of A2 allele among the groups. We have not observed any association between GpIIIa polymorphism with either type 2 diabetes or STEMI.

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.

Supraventricular tachycardia and pulmonary hypertension at the presentation of Hodgkin's disease.

A 27-year-old pregnant woman was admitted with supraventricular tachycardia (SVT) and symptoms of heart failure. Echocardiography revealed pulmonary hypertension due to a tumour infiltrating the left atrium and compressing the pulmonary veins. After delivery by Caesarean section, the paroxysmal SVT was controlled by amiodarone.Thoracic CT scan showed mediastinal masses compressing the pulmonary arteries and veins, and a preliminary diagnosis of Hodgkin’s disease was later confirmed by mediastinoscopy and lymph node biopsy. Following two courses of chemotherapy the masses diminished. The lumen of the left atrium increased, pulmonary hypertension and SVTs receded.