Density enhanced phosphatase-1 down-regulates urokinase receptor surface expression in confluent endothelial cells.

VEGF(165), the major angiogenic growth factor, is known to activate various steps in proangiogenic endothelial cell behavior, such as endothelial cell migration and invasion, or endothelial cell survival. Thereby, the urokinase-type plasminogen activator (uPA) system has been shown to play an essential role not only by its proteolytic capacities, but also by induction of intracellular signal transduction. Therefore, expression of its cell surface receptor uPAR is thought to be an essential regulatory mechanism in angiogenesis. We found that uPAR expression on the surface of confluent endothelial cells was down-regulated compared with subconfluent proliferating endothelial cells. Regulation of uPAR expression was most probably affected by extracellular signal-regulated kinase 1/2 (ERK1/2) activation, a downstream signaling event of the VEGF/VEGF-receptor system. Consistently, the receptor-like protein tyrosine phosphatase DEP-1 (density enhanced phosphatase-1/CD148), which is abundantly expressed in confluent endothelial cells, inhibited the VEGF-dependent activation of ERK1/2, leading to down-regulation of uPAR expression. Overexpression of active ERK1 rescued the DEP-1 effect on uPAR. That DEP-1 plays a biologic role in angiogenic endothelial cell behavior was demonstrated in endothelial cell migration, proliferation, and capillary-like tube formation assays in vitro.

Dynamics of inflammation parameters prior to tachyarrhythmias in critically ill patients.

BACKGROUND: The aim of this study was to assess the dynamics of inflammation parameters prior to a tachyarrhythmic event in critically ill patients. We evaluated the course of inflammation parameters over 48 hours before the occurrence of tachyarrhythmias. METHODS: Prospective observational study conducted at a cardiologic medical-postoperative tertiary intensive care unit at the Vienna university hospital. Between November 1996 and July 1999 all consecutive patients (n = 756) were screened for the occurrence of arrhythmias. Patients with sustained tachyarrhythmias (n = 119) form the basis of the report. The tachyarrhythmia episodes were related to the evolution of C-reactive protein, leukocytes and fibrinogen during the 48 hours before the arrhythmic event. RESULTS: A total of 278 tachyarrhythmia episodes was identified (wide QRS complex tachycardia, n = 168; narrow QRS complex tachycardia, n = 108; ventricular fibrillation, n = 2). The body temperature on the day of arrhythmia was 37.4 +/- 1 degrees C. Overall, there was no statistically significant change in any inflammation parameter within 48 hours prior to tachyarrhythmias (C-reactive protein: 17.4 +/- 12 [-48 h], 16.2 +/- 11 [-24 h], 15.2 +/- 12 [0 h] mg/dl, p = 0.2). When stratifying for different levels of C-reactive protein on the day of arrhythmia, the trend was inhomogenous. For lower strata, values were significantly decreasing towards arrhythmias; for higher strata, an increase in C-reactive protein was observed (stratum A: 8.5 +/- 7.2 [-48 h], 6.6 +/- 4.9 [-24 h], 4.8 +/- 2.9 mg/dl [0 h], p = 0.0001; stratum B: 16.0 +/- 7.1 [-48 h], 13.8 +/- 6.0 [-24 h], 14.4 +/- 2.6 mg/dl [0 h], p = 0.09; stratum C: 21.2 +/- 7.4 [-48 h], 21.5 +/- 7.5 [-24 h], 24.9 +/- 3.0 mg/dl [0 h], p = 0.008; stratum D: 34.3 +/- 13.4 [-48 h], 35.7 +/- 9.0 [-24 h], 39.7 +/- 5.5 mg/dl [0 h], p = 0.13). CONCLUSION: In this group of critically ill patients inflammation parameters did not change significantly during the 48 hours prior to the arrhythmic event. For different levels of C-reactive protein at the time of arrhythmia, no clear dynamics of inflammatory signs were observed.

Parameters of the tissue factor pathway with coumadin/dipyridamole versus ticlopidine as adjunct antithrombotic-drug regimen in coronary artery stenting.

A different rate and timing of subacute stent thrombosis after percutaneous coronary intervention was reported with various peri-interventional antithrombotic regimens. Next to platelet activation, coagulation triggered by tissue factor (TF) may play a key role in this process. Thirty-one consecutive patients with stable and unstable angina undergoing coronary stenting were randomly assigned to adjunct oral anticoagulation/anti-platelet therapy (coumadin, dipyridamole, aspirin and heparin; n = 16) or adjunct anti-platelet therapy with thienopyridin (ticlopidine, aspirin and heparin; n = 15). Antigen levels of plasma TF, total tissue factor pathway inhibitor (TFPI) and TFPI/ activated factor X (TFPI/FXa) complex were determined before and for up to 6 days after intervention by immunoassay. At baseline, significantly higher levels of plasma TF and TFPI/FXa were found in patients with unstable angina [TF, 161 pg/ml (126-191 pg/ml); TFPI/FXa, 7.8 ng/ml (6.1-9.6 ng/ml)] compared with stable angina [TF, 62 pg/ml (46-82 pg/ml), P < 0.0001; TFPI/FXa, 4.5 ng/ml (3-7.6 ng/ml), P= 0.003]. One hour after intervention, an increase of plasma TF and TFPI/FXa was seen in both treatment groups. In unstable angina patients, plasma levels of TF, TFPI and TFPI/FXa were more efficiently reduced by adjunct ticlopidine therapy compared with adjunct coumadin/dipyridamole. These data suggest reduced release of circulating TF by combined anti-platelet therapy with ticlopidine and aspirin after coronary artery stenting, which may-contribute to the lower incidence of subacute stent thrombosis previously observed.

[Manual compression versus mechanical compression device (FemoStop) after diagnostic coronary angiography with/without intervention]. / Manuelle Kompression versus mechanischer Kompressionshilfe (FemoStop) nach diagnostischer Koronarangiographie mit/ohne Intervention.

BACKGROUND: The aim of our study was to evaluate the practicability and the complication rates of two different forms of the post-angiographic closure of the femoral artery. METHODS: We randomized 239 patients over a time period of 4 months to either a mechanical compression system (FemoStop, 111 patients) or to conventional manual compression (128 patients). A Doppler-sonographic examination was performed if the patient reported pain of the puncture site, or if auscultation or palpation suspected a complication on the day after compression. RESULTS: After manual compression, Doppler-sonography had to be performed in 21 patients (16.4%). In the FemoStop-group only 14 patients (12.6%, p = ns) had to be referred for ultrasound examination. A complication was detected in 13 patients (10.1%) after manual compression and in 5 patients (4.5%, p = ns) after closure with the mechanical device. The incidence of a pseudo-aneurysma or of an arterio-venous fistula did not show any difference between the two groups. In 6 patients of the manual compression group a hematoma was found (p < 0.05), whereas no hematoma occurred in the FemoStop-group. None of the hematomas required the infusion of blood concentrates or surgical correction. In one patient with extreme overweight the mechanical compression device could not be applied. The mechanical compression device was used successfully in patients who had received heparin, acetyl-salicyl-acid or a glycoprotein IIb/IIIa receptor antagonist and in whom a significantly longer compression time and higher complication rate could have been expected. In addition, post-angiographic closure with the was less time consuming for the staff involved. In contrast, the higher cost of the mechanical compression device presents a disadvantage. CONCLUSION: A mechanical compression device (FemoStop) can be used successfully in routine post-angiographic management and shows a trend to lower complication rates than manual compression and increased acceptance by patients and physicians. However, the overall costs are higher for the mechanical compression device.

Idiopathic eosinophilic endomyocarditis in the absence of peripheral eosinophilia.

In this case report we present two patients with unusual manifestations of eosinophilic endomyocarditis: A 69-year-old patient with a history of heart failure and ventricular fibrillation and a 16-year-old woman with ventricular fibrillation and an ECG indicating acute myocardial infarction had both normal blood eosinophil counts at the onset of symptoms. The absence of hypereosinophilia, therefore, does not exclude the presence of eosinophilic organ infiltration. Endomyocardial biopsy may be the only diagnostic procedure to identify necrotic eosinophilic endomyocarditis in patients with unexplained heart failure or ventricular fibrillation.

Prognosis of patients who develop acute renal failure during the first 24 hours of cardiogenic shock after myocardial infarction.

PURPOSE: Acute renal failure has important prognostic implications in critically ill patients, but the effects of acute renal failure on in-hospital mortality in the subset of patients with cardiogenic shock are not known. SUBJECTS AND METHODS: All consecutive patients who presented with acute coronary syndrome at our cardiovascular intensive care unit from 1993 to 2000 and who were in cardiogenic shock were enrolled. Acute renal failure was defined as a urine volume < 20 mL/h associated with an increase in serum creatinine level > or = 0.5 mg/dL or > 50% above the baseline value. RESULTS: There were 118 patients (83 men [70%]; mean [+/- SD] age, 66 +/- 10 years), 39 (33%) of whom developed acute renal failure within 24 hours after the onset of shock. In-hospital mortality was 87% (34/39) in patients with acute renal failure and 53% (42/79) in patients without acute renal failure (odds ratio [OR] = 6.0; 95% confidence interval [CI]: 2.1 to 17; P < 0.001). Other significant univariate predictors of mortality included the peak serum lactate level, epinephrine dose, and the maximum serum creatinine level. Multivariate logistic regression analysis identified acute renal failure as the only independent predictor of mortality. CONCLUSION: Acute renal failure was common in patients with cardiogenic shock and strongly associated with in-hospital mortality.