R Voss

Justus-Liebig-Universität Gießen, Gießen, Hesse, Germany

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Publications (50)97.46 Total impact

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    ABSTRACT: The dietary flavonoid apigenin (Api) has been demonstrated to exert multiple beneficial effects upon the vascular endothelium. The aim of this study was to examine whether Ca(2+)-activated K(+) channels (K(Ca)) are involved in endothelial nitric oxide (NO) production and antiangiogenic effects. Endothelial NO generation was monitored using a cyclic guanosine monophosphate radioimmunoassay. K(Ca) activity and changes of the intracellular Ca(2+) concentration [Ca(2+)](i) were analyzed using the fluorescent dyes bis-barbituric acid oxonol, potassium-binding benzofuran isophthalate, and fluo-3. The endothelial angiogenic parameters measured were cell proliferation, [(3)H]-thymidine incorporation, and cell migration (scratch assay). Akt phosphorylation was examined using immunohistochemistry. Api caused a concentration-dependent increase in cyclic guanosine monophosphate levels, with a maximum effect at a concentration of 1 mum. Api-induced hyperpolarization was blocked by the small and large conductance K(Ca) inhibitors apamin and iberiotoxin, respectively. Furthermore, apamin and iberiotoxin blocked the late, long-lasting plateau phase of the Api-induced biphasic increase of [Ca(2+)](i). Inhibition of Ca(2+) signaling and the K(Ca) blockade both blocked NO production. Prevention of all three (NO, Ca(2+), and K(Ca) signaling) reversed the antiangiogenic effects of Api under both basal and basic fibroblast growth factor-induced culture conditions. Basic fibroblast growth factor-induced Akt phosphorylation was also reduced by Api. Based on our experimental results we propose the following signaling cascade for the effects of Api on endothelial cell signaling. Api activates small and large conductance K(Ca), leading to a hyperpolarization that is followed by a Ca(2+) influx. The increase of [Ca(2+)](i) is responsible for an increased NO production that mediates the antiangiogenic effects of Api via Akt dephosphorylation.
    Journal of Thrombosis and Haemostasis 09/2007; 5(8):1774-81. · 6.08 Impact Factor
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    ABSTRACT: Elevated levels of Lipoprotein(a) [Lp(a)] have been linked to an increased risk of ischemic cardiovascular events. Yet the mechanism by which Lp(a) might contribute to this increased risk is not clear. To elucidate whether high plasma levels of Lp(a) contribute to the development of early atherosclerotic vessel wall changes, the intima-media thickness of the common carotid arteries [CCA-IMT] of 151 healthy young volunteers without additional relevant cardiovascular risk factors was measured by high-resolution ultrasound. Plasma concentrations of Lp(a) were quantified and other established risk factors, such as body mass index [BMI], plasma levels of cholesterol, triglycerides and homocysteine, were determined. Furthermore, the carotid arteries were examined for the presence of plaques and stenoses. Univariate analysis showed a significantly negative correlation of CCA-IMT with HDL cholesterol and positive correlations with age, BMI, total and LDL cholesterol, triglycerides and even with homocysteine, but not with Lp(a). When the study population was dichotomized according to Lp(a) levels, no statistically significant differences in CCA-IMT could be detected between persons with plasma Lp(a)<300mg/l or >or=300mg/l, respectively. Our data suggest that elevated Lp(a) levels alone do not contribute to increased cardiovascular risk by promoting early atherogenesis in vivo.
    Atherosclerosis 02/2007; 190(1):194-8. · 3.71 Impact Factor
  • Thrombosis Research 02/2006; 117(4):393-9. · 3.13 Impact Factor
  • A Matzdorff, R Voss
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    ABSTRACT: GP IIb/IIIa inhibitor doses high enough to inhibit platelet macroaggregation may not completely prevent formation of microaggregates. Platelets contain an internal pool of GP IIb/IIIa receptors which externalizes with activation and supports microaggregation. This study assesses microaggregation in the presence of the two GP IIb/IIIa inhibitors abciximab and tirofiban. Citrated whole blood was preincubated with abciximab (5 microg/ml), tirofiban (50 ng/ml), or saline as control and activated with TRAP (5 microM) or ADP (2 microM) at 37 degrees C under constant stirring. Microaggregate formation and receptor expression were determined with flow cytometry. Within few seconds after TRAP-activation the platelet count dropped from 266,000/microl to 20,000/microl, the number of microaggregates increased from 3700/microl to 10,100/microl and the mean number of GP IIb/IIIa receptors increased from 53,000 to 65,000/platelet. With TRAP+abciximab the platelet count dropped from 259,000 to 113,000/microl, microaggregates increased from 2500 to 9300/microl, GP IIb/IIIa receptors from 56,000 to 77,000/platelet. Platelet microaggregate formation was reversible. With TRAP and tirofiban platelet count dropped to only 190,000/microl, there was no increase in platelet microaggregates, receptors increased to 66,000/platelet. Platelet activation with ADP gave similar results. During the early phase of activation additional GP IIb/IIIa receptors externalize to the platelet surface. Abciximab does not block these new receptors sufficiently to prevent microaggregate formation. However, the number of unblocked receptors is not high enough to maintain a stable aggregate, microaggregation is reversible. With tirofiban there is no microaggregate formation, possibly because the inhibitor rapidly binds to newly externalized receptors.
    Thrombosis Research 02/2006; 117(3):307-14. · 3.13 Impact Factor
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    ABSTRACT: The primary objective of this study was to compare the inhibitory activity of tirofiban measured with the rapid platelet function assay (RPFA) and with light transmission aggregometry using two different anticoagulants (citrate versus PPACK). Twenty patients treated with tirofiban for percutaneous coronary intervention were studied at six time points during tirofiban treatment. Tirofiban was given with a bolus dose of 10 microg/kg and an infusion of 0.10 microg/kg per min (10 patients) or with a bolus dose of 15 microg/kg and an infusion of 0.15 microg/kg per min (10 patients). Inhibition of platelet function appeared highest using citrated blood and the RPFA-device and lowest when assessed by aggregometry in PPACK-anticoagulated blood. Only the higher dose of tirofiban achieved an inhibition of platelet aggregation of at least 80% in all test systems.
    Platelets 01/2006; 16(8):492-7. · 2.24 Impact Factor
  • R Voss, M Grebe
    DMW - Deutsche Medizinische Wochenschrift 10/2005; 130(39):2209-12. · 0.65 Impact Factor
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    ABSTRACT: I. The actual data base on the decision-making process of indication for revascularization reveals that angiographic severity of coronary artery disease (CAD) is the primary determinant of referral to coronary interventional procedures. Several recent studies demonstrated that after an acute myocardial infarction, women undergo cardiac catheterization to a lesser extent than men. Data of the MITI study and of the Cooperative Cardiovascular Project suggested that during acute treatment of myocardial infarction a somewhat less aggressive therapy is performed in women as compared to men. II. With respect to sex-related differences in the early and late outcome after elective PCI, the main problem is the small, limited amount of data due to the lack of randomized clinical studies including a larger number of women. The vast majority of data was obtained in patients with PTCA and stents. All the older studies and registers until 1993 revealed a three times higher periprocedural complication rate and in-hospital mortality in women. In recent studies such as BARI, after successful PCI women have an excellent long-term prognosis comparable or even better than in men. III.1. Several studies on the effect of interventional strategies in patients with unstable angina or non-ST elevation myocardial infarction NSTEMI) revealed superiority of an early invasive versus a more conservative, noninvasive approach. However, the data of the FRISC II and RITA-3 trials indicated that an early intervention strategy resulted in a beneficial effect only in men which was not seen in women. On the other hand, two studies (e.g., the TACTICS-TIMI- 18 study) showed an improved outcome of women with acute coronary syndrome after early invasive therapy. III.2. In numerous investigations, a higher early mortality after acute ST elevation myocardial infarction (STEMI) has been observed in women compared to men. Although placebo-controlled randomized trials of thrombolytic therapy have demonstrated a 25-30% reduction in early mortality, in-hospital survival has remained consistently lower for women than men after thrombolytic reperfusion. -- In our clinic, prospective studies on clinical events during the early phase (30 days) and during long-term follow-up for 4 years after direct (primary) PTCA for acute STEMI were performed in women. Data were obtained in 204 consecutive and unselected women; results in women were compared with those of 577 consecutive and unselected men who had undergone direct angiography/primary PTCA for acute STEMI in the same time span. PTCA of the infarct-related artery was equally successful in both sexes (women 95%, men 94%). In the group of patients with acute STEMI who had been treated with primary infarct PTCA, no difference of early (30 days) mortality was detected in women versus men. Total cumulative mortality during 4 years of follow-up was 12.5%, 14.5%, 18% and 23% in women, respectively, versus 9%, 10.5%, 12% and 15%, respectively, in men. The general trend for a higher postdischarge mortality in women became apparent after 3 years and reached significance after 4 years. After multivariate analysis, female gender was no independent risk factor of increased mortality. Thus, direct (primary) coronary angiography and PCI eliminate significant gender-specific differences in survival early after acute myocardial infarction. Long-term follow-up (4 years) also revealed no sex-related differences in mortality and cardiac morbidity after direct (primary) PCI for acute ST elevation myocardial infarction.
    Herz 09/2005; 30(5):375-89. · 0.78 Impact Factor
  • Herz 01/2005; 30(5):375-389. · 0.78 Impact Factor
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    ABSTRACT: Gadobutrol was used in coronary angiography in three patients. All three patients had a substantially increased risk of developing renal complications with iodinated contrast agents. Gadobutrol was well tolerated in all three patients without any complications. The quality of the coronary angiograms was good.
    Catheterization and Cardiovascular Interventions 12/2004; 63(3):319-22. · 2.51 Impact Factor
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    ABSTRACT: Prospective, systematic studies of the pathophysiology and prognosis of premenopausal women vs young men who suffer an acute myocardial infarction (MI) and are treated with direct angioplasty are scarce. METHODS AND RESULTS: A total of 782 consecutive and unselected patients who presented with an acute ST-elevation MI within 12 h of symptom onset underwent immediate angiography to guide direct angioplasty. Using this therapeutic approach clinical characteristics, angiographic observations, and short- and long-term prognosis were analyzed in a sub-group of 31 premenopausal women and compared to 192 young men with acute MI. Premenopausal women account for 4% of individuals with acute MI and for 15% (31/205) of all women. Men of the same age range make up 25% (192/782) of all MI patients (p<0.001). Three or more classic risk factors were present in 20/31 women. Young women presented later than men. Angiography demonstrated a coronary occlusion in 27/31 women (88%) but in 98% of young men (p<0.02). Direct PTCA was successful in all premenopausal women and in 179/185 men (97%, p=ns). Predischarge EF was 57% in women and 54% in men (p=ns). After 4 years of follow-up, all women had survived as compared to a 95% survival in young men. Major cardiac events had occurred in 50% of persons of either gender. CONCLUSION: Premenopausal women account for 4% of individuals and for 1/6 of all female patients who presented with acute MI within 12 h of onset. Hospital admittance is delayed in young women. MI was caused by (atherosclerotic) coronary occlusion in most young women and in virtually all young men. Short- and long-term survival of premenopausal women is favorable after direct PTCA for acute MI and not different than men from the same age group.
    Zeitschrift für Kardiologie 06/2003; 92(6):476-82. · 0.97 Impact Factor
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    ABSTRACT: Summary. Prospective, systematic studies of the pathophysiology and prognosis of premenopausal women vs young men who suffer an acute myocardial infarction (MI) and are treated with direct angioplasty are scarce. Methods and results: A total of 782 consecutive and unselected patients who presented with an acute ST-elevation MI within 12 h of symptom onset underwent immediate angiography to guide direct angioplasty. Using this therapeutic approach clinical characteristics, angiographic observations, and short- and long-term prognosis were analyzed in a sub-group of 31 premenopausal women and compared to 192 young men with acute MI. Premenopausal women account for 4% of individuals with acute MI and for 15% (31/205) of all women. Men of the same age range make up 25% (192/782) of all MI patients (p<0.001). Three or more classic risk factors were present in 20/31 women. Young women presented later than men. Angiography demonstrated a coronary occlusion in 27/31 women (88%) but in 98% of young men (p<0.02). Direct PTCA was successful in all premenopausal women and in 179/185 men (97%, p=ns). Predischarge EF was 57% in women and 54% in men (p=ns). After 4 years of follow-up, all women had survived as compared to a 95% survival in young men. Major cardiac events had occurred in 50% of persons of either gender. Conclusion: Premenopausal women account for 4% of individuals and for 1/6 of all female patients who presented with acute MI within 12 h of onset. Hospital admittance is delayed in young women. MI was caused by (atherosclerotic) coronary occlusion in most young women and in virtually all young men. Short- and long-term survival of premenopausal women is favorable after direct PTCA for acute MI and not different than men from the same age group.
    Zeitschrift für Kardiologie 01/2003; 92(6):476-482. · 0.97 Impact Factor
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    ABSTRACT: Long-term follow-up of 204 consecutive and unselected women vs 577 men after direct PTCA for acute myocardial infarction. Women were older, had more significant comorbidity, and had a longer prehospital phase. Direct PTCA of the infarct artery was angiographically successful in 95% of women and in 94% of men. Total cumulative mortality during 4 years of follow-up was 12.5%, 14.5% 18%, and 23% in women, respectively, vs 9%, 10.5%, 12%, and 15%, respectively, in men (p=ns through year 3, p<0.05 thereafter). After multivariate analysis, gender was no independent risk factor of increased mortality. Major cardiac events and need for target vessel revascularization were unrelated to gender. There are no gender-specific differences in mortality after direct PTCA for acute myocardial infarction.
    Zeitschrift für Kardiologie 11/2002; 91(11):921-6. · 0.97 Impact Factor
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    ABSTRACT: Proteolytic cleavage of single chain high molecular weight kininogen (HK) by kallikrein releases the short-lived vasodilator bradykinin and leaves behind two-chain high molecular weight kininogen (HKa). HKa and particularly its His-Gly-Lys-rich domain 5 have been previously reported to exert anti-adhesive properties by binding to the extracellular matrix protein vitronectin (VN). In this study the ability of HKa and domain 5 to interfere with platelet adhesion and aggregation was investigated. In a purified system HKa and particularly domain 5 but not HK inhibited the binding of VN to the alpha(IIb)beta(3) integrin, whereas the binding of fibrinogen to this integrin was not affected. The region Gly-486-Lys-502 from the carboxyl terminus of the domain 5 was identified as responsible for inhibition of the VN-alpha(IIb)beta(3)-integrin interaction, as this portion was also found to mediate kininogen binding to VN. Through these interactions, HKa, the isolated domain 5, and the peptide Gly-486-Lys-502 abrogated the alpha(IIb)beta(3)-integrin-dependent adhesion of human platelets to VN but not to fibrinogen. The codistribution of VN and HKa at sites of ex vivo platelet aggregation was demonstrated by transmission immune electron microscopy, indicating that the described interaction is likely to take place in vivo. Moreover, domain 5 and the peptide Gly-486-Lys-502 dose-dependently blocked platelet aggregation, resembling the inhibitory effect of monoclonal antibody 13H1 against multimeric VN. Finally, treatment of mice with isolated domain 5 resulted in a significantly prolonged tail bleeding time. Taken together, our data emphasize the inhibitory role of HK domain 5 on platelet adhesion and aggregation; new anti-thrombotic compounds may become available on the basis of peptide Gly-486-Lys-502 of HK domain 5.
    Journal of Biological Chemistry 07/2002; 277(26):23157-64. · 4.65 Impact Factor
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    ABSTRACT: Angiograms from consecutive and unselected patients with acute myocardial infarction were studied with respect to the prevalence as well as the significance of coronary collateral circulation to myocardium distal to the acute coronary occlusion. Coronary angiograms were obtained from 700 consecutive and unselected patients with an acute transmural infarction within 3.7 +/- 3 hours (0.5-12) of symptom onset. No patient had undergone i.v. thrombolysis prior to angiography. Complete and acute vessel occlusion was found in 626/700 patients (89%). Coronary collaterals were detected and graded using Rentrop's classification. The grade of collateral circulation was related to the clinical course after 30 days and to the global and regional left ventricular wall motion. Collaterals were found in 334 patients (69%); 242 patients (38%) had collateral flow grade 2 or 3. Collaterals were demonstrated more frequently in women vs men and in patients with multivessel disease. The prevalence of collaterals was unrelated to age and the presence of diabetes mellitus. Patients who had angiography within 3 hours of symptom onset had collaterals detected less frequently than patients who had angiography beyond 6 hours (66% vs 75%, p < 0.05). No collaterals were found in 17/37 patients (47%) in cardiogenic shock and inferior MI but in only 30/164 patients (18%, p < 0.01) without shock. Global and regional left ventricular wall motion after 2 weeks was unrelated to the degree of coronary collateral circulation during acute myocardial infarction. Collateral circulation to myocardium distal to an acutely occluded coronary artery is detected in 2/3 patients during the acute infarct phase. The absence of collaterals is related to the early occurrence of cardiogenic shock in patients with inferior MI but not to the presence of diabetes mellitus. After direct angioplasty of the infarct vessel, the protective effects of coronary collaterals on chronic LV function remain uncertain.
    Zeitschrift für Kardiologie 04/2002; 91(3):243-8. · 0.97 Impact Factor
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    ABSTRACT: Summary Angiograms from consecutive and unselected patients with acute myocardial infarction were studied with respect to the prevalence as well as the significance of coronary collateral circulation to myocardium distal to the acute coronary occlusion. Methods Coronary angiograms were obtained from 700 consecutive and unselected patients with an acute transmural infarction within 3.7Dž hours (0.5-12) of symptom onset. No patient had undergone iv thrombolysis prior to angiography. Complete and acute vessel occlusion was found in 626/700 patients (89%). Coronary collaterals were detected and graded using Rentrop's classification. The grade of collateral circulation was related to the clinical course after 30 days and to the global and regional left ventricular wall motion. Results Collaterals were found in 334 patients (69%); 242 patients (38%) had collateral flow grade 2 or 3. Collaterals were demonstrated more frequently in women vs men and in patients with multivessel disease. The prevalence of collaterals was unrelated to age and the presence of diabetes mellitus. Patients who had angiography within 3 hours of symptom onset had collaterals detected less frequently than patients who had angiography beyond 6 hours (66% vs 75%, p<0.05). No collaterals were found in 17/37 patients (47%) in cardiogenic shock and inferior MI but in only 30/164 patients (18%, p<0.01) without shock. Global and regional left ventricular wall motion after 2 weeks was unrelated to the degree of coronary collateral circulation during acute myocardial infarction. Conclusion Collateral circulation to myocardium distal to an acutely occluded coronary artery is detected in 2/3 patients during the acute infarct phase. The absence of collaterals is related to the early occurrence of cardiogenic shock in patients with inferior MI but not to the presence of diabetes mellitus. After direct angioplasty of the infarct vessel, the protective effects of coronary collaterals on chronic LV function remain uncertain. Zusammenfassung Um Prvalenz und klinische Bedeutung der Kollateralzirkulation zu Myokard distal eines akuten Koronarverschlusses zu untersuchen, wurden Koronarangiogramme von konsekutiven und unselektierten Patienten mit akutem Myokardinfarkt vor jeglicher Reperfusionstherapie analysiert und mit klinischen Daten korreliert. Methodik Bei 700 konsekutiven und unselektierten Patienten mit akutem ST-Hebungsinfarkt wurde im Mittel nach 3,7Dž Stunden (0,5-12) ein Koronarangiogramm ohne vorangehenden Thrombolyseversuch angefertigt. Bei 626/700 Patienten (89%) lag ein kompletter Koronargefverschluss vor. Bei diesen Patienten wurde die Kollateralzirkulation klassifiziert. Der Kollateralisierungsgrad wurde mit klinischen Befunden, dem Verlauf nach 30 Tagen und der globalen und regionalen Wandbewegung korreliert. Ergebnisse Kollateralen waren bei 334/626 Patienten (69%) nachweisbar, bei 242 Patienten (38%) ein Kollateralfluss Grad 2 oder 3. Bei Frauen gegenber Mnnern und bei Patienten mit einer Mehrgeferkrankung wurden hufiger Kollaterale gefunden. Die Prvalenz von Kollateralen war von Alter und Diabetes mellitus unabhngig. Patienten, die innerhalb von 3 Stunden nach Symptombeginn angiographiert werden konnten, hatten weniger hufig Kollateralen als nach >>;6 Stunden angiographierte Patienten (66% vs. 75%, p<0,05). Von 37 Patienten mit kardiogenem Schock bei Hinterwandinfarkt hatten 17 (46%) keine Kollateralzirkulation gegenber 30/164 Personen ohne Schock (18%, p<0,01). Die nach etwa 2Wochen angiographisch bestimmte globale und regionale LV-Funktion zeigte keine Abhngigkeit von der Kollateralisierung. Zusammenfassung Eine Kollateralzirkulation zu Myokard distal eines akuten Koronarverschlusses ist angiographisch bei etwa 2/3 der Patienten schon frh nach Infarktbeginn nachweisbar. Die Abwesenheit von Kollateralen ist bei Patienten mit Hinterwandinfarkt mit dem frhen Auftreten eines kardiogenen Schocks assoziiert, nicht aber dem Vorhandensein eines Diabetes mellitus. Ein protektiver Effekt von Kollateralen bezglich der chronischen LV-Funktion lsst sich nach direkter Angioplastie des Infarktgefsses nicht nachweisen.
    Zeitschrift für Kardiologie 02/2002; 91(3):243-248. · 0.97 Impact Factor
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    ABSTRACT: Methodik: Analyse der Langzeitergebnisse der direkten PTCA bei 204 konsekutiven und unselektierten Frauen und 577 Männern mit akutem Myokardinfarkt. Ergebnisse: Frauen waren im Durchschnitt älter, hatten eine bedeutsamere Komorbidität und hatten eine längere Prähospitalphase als Männer. Die PTCA des Infarktgefäßes war erfolgreich bei 95% der Frauen und 94% der Männer. Die kumulative Gesamtmortalität während der ersten 4 Jahre war 12,5%, 14,5% 18% und 23% bei Frauen und 9%, 10,5%, 12% und 15% bei Männern (p=ns bis Jahr 3, p<0,05 ab dem 4. Jahr). Bei multivariater Analyse war das Geschlecht kein unabhängiger Risikofaktor. Kardiale Ereignisse und erneute Interventionen (Re-PTCA) waren in beiden Geschlechtern nicht unterschiedlich. Schlussfolgerung: Nach primärer Angioplastie des Infarktgefäßes bestehen keine geschlechtsspezifischen Unterschiede bezüglich der Mortalität und kardialen Morbidität. Methods: Long-term follow-up of 204 consecutive and unselected women vs 577 men after direct PTCA for acute myocardial infarction. Results: Women were older, had more significant comorbidity, and had a longer prehospital phase. Direct PTCA of the infarct artery was angiographically successful in 95% of women and in 94% of men. Total cumulative mortality during 4 years of follow-up was 12.5%, 14.5% 18%, and 23% in women, respectively, vs 9%, 10.5%, 12%, and 15%, respectively, in men (p=ns through year 3, p<0.05 thereafter). After multivariate analysis, gender was no independent risk factor of increased mortality. Major cardiac events and need for target vessel revascularization were unrelated to gender. Conclusions: There are no gender-specific differences in mortality after direct PTCA for acute myocardial infarction. Schlüsselwörter–Myokardinfarkt–Frauen–Angioplastie–PrognoseKey words–Myocardial infarction–women–angioplasty–prognosis
    Zeitschrift für Kardiologie 01/2002; 91(11):921-926. · 0.97 Impact Factor
  • The American Journal of Cardiology 12/2001; 88(10):1194-7. · 3.21 Impact Factor
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    ABSTRACT: GP IIb/IIIa inhibitors have primarily been used short-term e.g., during PTCA. They failed to show clinical benefit during long-term therapy. One reason might be the absence of a method to monitor inhibitor activity. This study compared platelet aggregometry, the rapid platelet function analyzer (RPFA) test, single platelet counting, and flow cytometric determination of receptor occupancy to measure GP IIb/IIIa-receptor inhibitor activity. Increasing doses of abciximab, tirofiban, and eptifibatide were added to whole blood in vitro. Whole blood was used for the RPFA, for single platelet counting and flow cytometry. Platelet rich plasma was prepared for aggregometry. The correlation between aggregometry and RPFA results was linear for abciximab and eptifibatide. Tirofiban was a stronger inhibitor with the RPFA (IC(50) 7.7nM) than with aggregometry (IC(50) 19.6nM). The single platelet counting technique showed that even supratherapeutic concentrations of all three inhibitors could not completely suppress microaggregation. Abciximab concentrations that were equipotent to tirofiban with aggregometry were less potent with regards to the inhibition of microaggregation. This difference was more pronounced with TRAP induced microaggregation than with ADP. The flow cytometric receptor occupancy test showed that occupancy was 95% with 5 microg/ml abciximab and almost 97% with 10 microg/ml. Tirofiban reached a maximum receptor occupancy of 56%, eptifibatide 64%. While aggregometry is time consuming the RPFA provides results fast and with little variability. There is still a discrepancy between aggregometry and RPFA results for tirofiban. The single platelet counting technique detects the inhibition of microaggregation the relevance of which for the clinical outcome is not known. The flow cytometric receptor occupancy assay is best suited for abciximab.
    Journal of Thrombosis and Thrombolysis 11/2001; 12(2):129-39. · 1.99 Impact Factor
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    ABSTRACT: Flow cytometry can detect platelet activation (CD62p), aggregate formation, microparticle formation, and glycoprotein IIb/IIIa (GP IIb/IIIa) receptor occupancy in one sample at the level of single particles. We studied the effect of GP IIb/IIIa inhibitors on platelet activation with flow cytometry in vitro. Citrated whole blood was incubated with increasing concentrations of three different GP IIb/IIIa inhibitors (c7E3, DMP728, XJ757), then thrombin or adenosine diphosphate (ADP) was added, and after 1 minute the sample was fixed. Samples with thrombin but without c7E3 had a decrease in platelet count, from a mean of 260,000 platelets/microl to 56,000 platelets/microL, and aggregates increased. Samples with concentrations of c7E3 that resulted in 80% or more receptor blockade had no decrease in platelet count, and no aggregates were formed, but the number of CD62p-positive single platelets increased from 1200 to 7400 platelets/microL. The two other inhibitors (DMP 725, XJ757) or ADP instead of thrombin gave similar results. Microparticle formation did not change with platelet activation in the presence of a GP IIb/IIIa inhibitor. With small inhibitor doses resulting in <80% receptor blockade, the number of aggregates did not change or was even higher than that in samples without inhibitor. GP IIb/IIIa inhibitors do prevent aggregate formation but they do not prevent activation of platelets. With GP IIb/IIIa inhibition, more activated single platelets remain in the blood. One may expect an increasing number of circulating, activated platelets with the use of GP IIb/IIIa inhibitors.
    Journal of Laboratory and Clinical Medicine 03/2000; 135(3):247-55. · 2.62 Impact Factor
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    ABSTRACT: Mortality in diabetic patients with acute myocardial infarction (MI) is high. The significance of the pretreatment coronary status in type 2 diabetic patients with acute MI, as well as the effect of mechanical revascularization using percutaneous transluminal coronary angioplasty (PTCA), has not been established. All patients with type 2 diabetes and acute MI (n = 54) were prospectively enrolled into a study of immediate coronary angiography to guide PTCA of the occluded infarct vessel. Hospital and long-term course were assessed and compared with an unselected control group of nondiabetic patients (n = 358) who were enrolled in the same study. Angiography showed that sites of occlusion and acute coronary flow were similar in both groups. Multivessel disease and shock were more common in type 2 diabetic versus nondiabetic patients: 69 vs. 51% and 21 vs. 10% (P < 0.02), respectively. Direct PTCA was successful in > 90% in both groups. Mortality after 30 days was 13% in type 2 diabetic patients versus 5% in patients without diabetes (P < 0.04). Left ventricular (LV) ejection fraction before discharge was lower in diabetic patients (48 +/- 17 vs. 55 +/- 15%, P < 0.05). Mortality 1 year after discharge was 11 vs. 4% in diabetic versus nondiabetic patients (P < 0.02). Multivariate analysis identified type 2 diabetes as an independent risk factor for acute, but not for late, mortality. Direct PTCA is safe and effective in type 2 diabetic patients with acute MI. Mortality after 30 days in unselected diabetic patients is < 15% with this approach. Advanced disease and shock contribute to an increased mortality in type 2 diabetic patients with acute MI versus nondiabetic patients.
    Diabetes Care 11/1999; 22(11):1832-8. · 7.74 Impact Factor