Małgorzata Pyda

New Method of Intracoronary Adenosine Injection to Prevent Microvascular Reperfusion Injury in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

The aim of our study was to examine the role of a new, simple protocol of intracoronary adenosine administration performed during primary angioplasty on the immediate angiographic results and clinical course. A prospective, single-center, randomized, placebo-controlled trial of 70 consecutive patients (64 ± 14 years, 54 men) with acute myocardial infarction with ST-segment elevation undergoing primary percutaneous coronary intervention (PCI) was conducted. Patients were randomized to 2 groups. Group 1 (n = 35) received intracoronary adenosine (1 to 2 mg) with a hand injection through the guiding catheter 2 times: immediately after crossing the lesion of the infarct-related artery with guidewire and then after the first balloon inflation. Group 2 (n = 35) received placebo. The baseline clinical and angiographic characteristics of the 2 groups were similar. Percutaneous coronary intervention resulted in Thrombolysis In Myocardial Infarction grade 3 flow after PCI in 32 patients (91.4%) in the adenosine group and 27 patients (77.1%) in the placebo group (p = 0.059). Myocardial blush grade 3 was observed at the end of PCI in 23 patients (65.7%) in the adenosine group and 13 (37.1%) in the placebo group (p < 0.05). Resolution of ST-segment elevation (> 50%) was more frequently observed in the adenosine than in the placebo group: 27 (77%) versus 15 (43%), respectively (p < 0.01). In conclusion, intracoronary adenosine administration improved the angiographic and electrocardiographic results in patients with acute myocardial infarction with ST-segment elevation undergoing PCI. Adenosine administration seemed to be associated with a more favorable clinical course.

Limitations of CA125 as an Index of Peritoneal Mesothelial Cell Mass

Background: CA125 is commonly used as an index of the mesothelial cell mass in patients treated with peritoneal dialysis. However, we have no data that show a direct relationship between the number of mesothelial cells, their functional properties, and the amount of CA125 produced in these cells. Methods: Experiments were performed on primary in vitro cultures of human peritoneal mesothelial cells obtained from 32 donors of various ages and of both sexes. Spontaneous release of CA125 from the confluent mesothelial cells was measured and correlated with the number of cells in monolayers and with their functional properties. We also studied acute effects of cytokines (IL-1β, TNF-α, and INF-γ) and the chronic effects of glucose (45 mM) on the CA125 content in mesothelial cells and the release of this antigen from their cytosol. Results: Cells from older donors released more CA125, but we found no correlation between the number of cells and the amount of CA125 released from their cytosol. The synthesis of CA125 in mesothelial cells does not correlate with the amount of monocyte chemoattractant protein 1 or interleukin-6 produced in these cells. Acute exposure to cytokines did not modify CA125 content or its release from mesothelial cells. Chronic exposure of mesothelial cells for 4 weeks to glucose (45 mM) decreased the CA125 content of their cytosol and the release of this antigen into the culture medium. Mannitol, at the same concentration and under the same conditions, did not produce these effects, namely a decrease in the CA125 content in the cytosol or its release into the cultural medium. Conclusions: The amount of CA125 released from mesothelial cells is not a good index of their number or their functional properties, because the CA125 release depends not only on the number of cells, but also on their properties. Furthermore, the process is affected by the age of the cell donor and environmental factors such as a high glucose content. The results of this study show the limitations of CA125 as an index of the mesothelial cell mass and viability.

Postconditioning Reduces Enzymatic Infarct Size and Improves Microvascular Reperfusion in Patients with ST-Segment Elevation Myocardial Infarction

Objectives: Postconditioning has been reported to reduce infarct size in ST-segment myocardial infarction (STEMI). However, recently, few other studies did not show any effect of postconditioning and suggested that it may be even harmful. We sought to assess whether postconditioning could reduce infarct size and improve myocardial reperfusion in early presenters with STEMI. Methods: 72 STEMI patients treated with primary percutaneous coronary intervention (PCI) were randomly assigned to either the postconditioning (n = 35) or the standard PCI group (control group; n = 37). Blood samples were obtained for creatine kinase (CK) and its MB isoform (CK-MB) within 36 h. The angiographic (myocardial blush grade, MBG) and electrocardiographic (ST-segment resolution, STR) data were evaluated and compared between groups. Results: The areas under the curve of CK and CK-MB release were significantly reduced in the postconditioning group compared with the control group (38,612.91 ± 25,028.42 vs. 60,547.30 ± 25,264.63 for CK and 5,498.23 ± 3,787.91 vs. 7,443.12 ± 3,561.13 for CK-MB, p < 0.0001). MBG was significantly better in the postconditioning group than in the control group (MBG 3: 82.3 vs. 47.1%, p = 0.0023). In the postconditioning group, STR >70% was more often observed (97.1 vs. 64.1%, p = 0.0007). Conclusions: In patients with STEMI, postconditioning could significantly reduce enzymatic infarct size and improve myocardial reperfusion.

Interpretation of elevated serum VEGF concentrations in patients with myocardial infarction

Serum has been considered an unsuitable medium for measurements of circulating vascular endothelial growth factor (VEGF) since platelets release significant quantities of VEGF during clotting. Nevertheless, the assessment of platelet-derived VEGF may be important in patients with acute coronary syndromes characterized by intraluminal thrombosis. The present study aimed at identifying the factors that impact on the interpretation of serum VEGF concentrations in patients with ST-elevation myocardial infarction (STEMI). VEGF was measured in 106 patients with STEMI and correlated with clinical and angiographic parameters. Serum VEGF levels were significantly higher in patients with STEMI than in healthy controls. Although the average number of platelets did not differ between the groups, the patients with STEMI, but not the controls, exhibited a significant correlation between serum VEGF levels and platelet counts. Stratification of patients according to different criteria revealed that VEGF concentrations were particularly elevated shortly (<3h) after the onset of chest pain in those patients who had occluding thrombi graded as large (3-4) on a TIMI scale. These data demonstrate that high levels of serum VEGF detected early in the course of STEMI may derive from activated platelets and may characterize patients with extensive intracoronary thrombosis.

Percutaneous coronary intervention for chronic total occlusion of the coronary artery with the implantation of bioresorbable everolimus-eluting scaffolds. Poznan CTO-Absorb Pilot Registry.

AIMS Data concerning the use of bioresorbable vascular scaffolds (BVS) for chronic total occlusion (CTO) lesions are limited. The aim of this study was to evaluate the early and midterm clinical outcomes of CTO stenting with BVS. METHODS AND RESULTS Forty consecutive patients (male 78%, mean age 59.9±8.3 years, diabetics 30%) with CTO treated with BVS were enrolled. Patients with a reference vessel diameter >4 mm, metallic stents, excessive calcium and tortuosity were excluded. Mean J-CTO score was 1.6. A total of 63 BVS were implanted with an average number of 1.6 per patient, and an average scaffold length of 42.4±21.5 mm. Procedural success was achieved in all patients with no device-related complications. At follow-up (median time 556 days), there were no deaths, one patient experienced subacute and late scaffold thrombosis (ST), and another one developed symptomatic in-scaffold focal restenosis treated with repeat PCI. At control angiography, performed at a median time of 329 days in 27 patients (68%), no more restenosis or vessel reocclusion was found. CONCLUSIONS CTO stenting with BVS is feasible with good acute performance, and good early and midterm clinical outcomes.

Effect of Haluronan-Supplemented Dialysate on in vitro Function of Human Peritoneal Mesothelial Cells

Background: Addition of hyaluronan (HA) to the dialysis solution has been suggested as a means to protect the peritoneum from injury during peritoneal dialysis (PD). Methods: Concentrations of inflammatory mediators were determined in dialysate samples obtained from PD patients after 6-hour dwells with glucose-based (13.6 g/l) solution containing 0.1 and 0.5 g/l of exogenous high-molecular-weight HA. We additionally evaluated the effect of HA-supplemented dialysate, drained after dwell in PD patients, on function of human peritoneal mesothelial cells (MC) in in vitro culture. Results: Concentration of nitrites was significantly higher in HA 0.5 g/l supplemented dialysate (+43%, p < 0.05) as compared to control. Levels of monocyte chemoattractant protein (MCP-1), soluble intercellular adhesive molecule (s-ICAM), vascular endothelial growth factor (VEGF) and fibronectin were comparable in all the studied groups. However, when MC were exposed in in vitro conditions for 24 h to the studied dialysates, we observed that HA containing fluids inhibited the synthesis of MCP-1, s-ICAM, VEGF and fibronectin in these cells. HA-supplemented dialysate accelerated growth rate of in vitro proliferating MC. Conclusion: High-molecular-weight HA added to the dialysis fluid exerts anti-inflammatory and antifibrotic actions on the in vitro cultured MC and accelerates their growth rate what may be important for peritoneal healing during PD.

QT Interval Dispersion as a New Marker of Restenosis after Percutaneous Transluminal Coronary Angioplasty of Isolated Single-Vessel Coronary Artery Stenosis

Background: There are no reliable non-invasive markers of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The aim of our study was to measure changes in QT interval dispersion after PTCA and to determine whether restenosis subsequently affects QT interval dispersion. Methods and Results: Fifty-six consecutive patients – 41 men and 15 women (mean age: 56.2 ±8.3 years) – with isolated stenosis of the left anterior descending artery who underwent successful PTCA were studied. A symptom-limited treadmill exercise test was performed within 7 days after PTCA and then again before repeated angiography. Repeated coronary angiography revealed restenosis in 15 patients (26.8%) and no signs of significant stenosis in 41 patients (73.2%). QT interval dispersion in the group of patients with restenosis measured before exercise increased from baseline 34 ± 7 to 49 ± 15 ms after 6 months (p < 0.01) and QT interval dispersion measured immediately after exercise increased from baseline 38 ± 4 to 68 ± 21 ms after 6 months (p < 0.001). In contrast, patients without restenosis showed no significant changes in QT interval dispersion measured before (baseline: 34 ± 9 ms; after 6 months 33 ± 12 ms; p = NS) and immediately after exercise (baseline: 34 ± 12 ms; after 6 months: 33 ± 10; p = NS). When QT interval dispersion ≧60 ms (measured 6 months after PTCA procedure) was considered as a potential marker of restenosis, this indicator had very high sensitivity and specificity when measured immediately after exercise (80 and 95% respectively). Conclusions: QT interval dispersion significantly increases in the group of patients with documented restenosis and may be a simple, non-invasive marker of restenosis. However, further studies are needed to confirm this observation.

Hemodialysis-induced changes in the blood composition affect function of the endothelium

Hemodialysis induces oxidative stress causing intravascular inflammation, which may cause endothelial dysfunction. We evaluated how hemodialysis‐induced changes in blood affect the function of endothelial cells in in vitro culture. Serum samples were collected from 42 uremic patients treated with hemodialysis, one before the start of dialysis and the other one at the end of session. All patients were dialysed with polysulfone dialyzer. Concentrations of the inflammatory molecules carbonyl protein and metabolites of NO synthesis were measured in blood. Additionally, the effect of the serum obtained before and after dialysis on the function of endothelial cells in in vitro culture was studied. Hemodialysis caused increase of monocyte chemoattractant protein (MCP)‐1 (+17%), hepatocyte growth factor (+91%), and pentraxin‐3 (+30%) concentration in serum. Concentration of carbonyl protein was decreased by 30%. Decrease of blood level of asymmetric dimethylarginine (−25%) and nitrate/nitrites (−62%) was observed. Serum obtained after hemodialysis stimulated proliferation of endothelial cells (+10%) and synthesis of MCP‐1(+11%) in these cells. Hemodialysis‐induced intravascular inflammation changes the function of endothelial cells, which may lead to acceleration of atherosclerosis.

Postconditioning attenuates early ventricular arrhythmias in patients with high-risk ST-segment elevation myocardial infarction

BACKGROUND It has been demonstrated that postconditioning (postcon), brief episodes of ischemia during reperfusion period, in patients with ST-segment elevation myocardial infarction (STEMI) confers protection against ischemia-reperfusion injury and as a result, postcon might reduce infarct size. However, whether postcon may exert its beneficial effect on STEMI patients by reducing the occurrence of early malignant ventricular arrhythmias (VA) is still unknown. The aim of the study was to evaluate the influence of postcon on the presence of VA in early presenters with high-risk STEMI treated with primary coronary intervention (PCI). METHODS Seventy-five STEMI patients treated with primary PCI within 6h from symptoms onset were randomly assigned to postcon group (n=37) or conventional PCI group (n=38) in 1:1 ratio. Postcon was performed immediately after restoration of coronary flow as follows: the angioplasty balloon was inflated 4× 1min with low-pressure inflations, each separated by 1min of deflation. After that the patients were continuously monitored electrographically for 48h. The end-point of the study was the occurrence of VA (ventricular fibrillation-VF, sustained ventricular tachycardia-sVT, non-sustained ventricular tachycardia-nsVT) within 48h after the procedure. RESULTS In the postcon group, the occurrence of VAs was significantly lower: VF-3, sVT-0, nsVT-15, i.e. (18 patients - 48.6%) in comparison to control group: VF-2, sVT-4, nsVT-23 (29 patients - 76.3%); p=0.013. The occurrence of accelerated idioventricular rhythm varied insignificantly between both groups (postcon - 45.9% vs control - 34.2%; p=NS). CONCLUSIONS Postcon may reduce the occurrence of malignant VA in patients with STEMI treated with primary PCI.

Endothelial cell growth response to stimulation with serum from patients with acute ST-elevation myocardial infarction.

Acute ST-elevation myocardial infarction (STEMI) is associated with increased levels of angiogenic mediators [1,2] thought to derive both from the ischemic myocardium [3] and from activated platelets within intra-luminal thrombi [4]. Since their impact on the endothelium in vivo is poorly defined, we have attempted to mimic the diseased environment by incubating endothelial cells in vitro in the presence of serum from patients with STEMI (Fig. 1). Such an approach has previously been used in studies on inflammatory bowel disease [5], colorectal cancer [6], and ageing [7]. We measured the endothelial cell growth index in culture and then related it – without any assumptions – to a number of demographic, clinical, laboratory, and angiographic criteria. Subsequent post-hoc analyses formed a basis of this hypothesis-generating investigation. The study protocol was approved by the institutional ethics committee. All patients with STEMI underwent primary percutaneous coronary intervention (PCI) within 12 hours after the onset of chest pain. Only patientswith bare-metal stents, without prior statin therapy, and without co-existing neoplastic or inflammatory diseases were included in the analysis. Healthy regular blood donors with no prior treatment with statins served as the controls. Endothelial cell proliferation was found to be significantly greater following exposure to serum from patients with STEMI (n=106; median age 57, 71% men) than from healthy blood donors (n=50; median age 48 years, 84% men). The growth response clearly discriminated the two populations (Fig. 2). The difference was not related to a higher proportion of youngermen in the controls since the sub-analysis of 47 individuals from each group carefully matched for age and sex revealed exactly the same pattern and similar level of significance (not shown). Theproliferation index in STEMIpatients appeared to bemorewidely distributed than in control subjects. As a result, a number of patients had the proliferation index as low as the controls. In order to determine whether the magnitude of growth response differentiated the STEMI patients in any way, they were categorised into two groups according to whether their proliferation index was below or above the 25th percentile. This cut-off point was selected so that the patients with significant overlappingwith the interquartile range of the controls were classified as thosewith lowproliferation index (Fig. 2). All the remaining