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Biomedical subjects

Michael Gottsauner-Wolf

Publications and source records attributed to Michael Gottsauner-Wolf.

12 recordsLinked to original sources
PubMed2005

Randomized blinded clinical trial of intracoronary brachytherapy with 90Sr/Y beta-radiation for the prevention of restenosis after stent implantation in native coronary arteries in diabetic patients.

BACKGROUND: We report a double-blind, randomized clinical trial of intracoronary beta-radiation for prevention of restenosis after stent implantation in native coronary de novo lesions in diabetic patients. METHODS: After successful stent implantation in native coronary de novo lesions, 106 lesions in 89 diabetic patients were randomly allocated to treatment with beta-radiation with 18 Gy at 1 mm vessel depth (n = 53) or placebo treatment (n = 53). RESULTS: Angiographic analysis at 9 month follow-up revealed a late lumen loss of 0.7+/-0.9 mm in the radiotherapy group versus 1.2+/-0.8 mm in the control group at the injured segment (P = 0.006), 0.9+/-1.0 versus 1.3+/-0.7 mm at the radiated segment (P = 0.02), and 0.9+/-1.0 versus 1.3+/-0.7 mm at the target segment (P = 0.04) (defined as active source length plus 5mm on proximal and distal sites). Binary restenosis rates were significantly lower in the radiation group in all subsegments (injured segment: 10.9 versus 37.3%, P = 0.003; radiated segment: 21.7 versus 49.0%, P = 0.005; target segment: 23.9 versus 49.0%, P = 0.01). Target lesion revascularization for restenosis was required in nine lesions (17.6%) in the radiotherapy group versus 18 (34.0%) in the placebo group (P = 0.05). Late thrombosis occurred in four radiated patients (after premature discontinuation of antiplatelet therapy in all), resulting in a major adverse clinical event rate of 37.2% in the brachytherapy group versus 38.6% in the placebo group (P = ns). CONCLUSIONS: In diabetic patients with de novo coronary lesions, intracoronary radiation after stent implantation significantly reduced restenosis. However, this clinical benefit was reduced by the frequent occurrence of late thrombosis.

Aged↗
PubMed2005

Ultrasound thrombolysis.

Cardiovascular diseases are a major cause of mortality in the developed world. Efficacy of thrombolysis plays an important role in the management of acute myocardial infarction and cerebral insult both in the acute event and in the long-term outcome of these patients. New adjunctive strategies have been tested, therefore, to make thrombolytic therapies more effective and safer. Ultrasound Thrombolysis is a technique which showed promising results under in vitro conditions and in animal studies. Now clinical trials have to prove if it is also feasible for clinical application. This report gives an overview on different technical approaches and their current performances in the clinical setting. All original articles are chronologically ordered in tables providing detailed information on each study concerning experimental design, acoustical parameters and thrombolysis outcome.

Acoustics↗
PubMed2004

Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model.

BACKGROUND AND PURPOSE: Recently, 3 clinical trials revealed encouraging results in recanalization and clinical outcome in acute stroke patients when 2-MHz transcranial Doppler monitoring was applied. This study investigated whether a 1.8-MHz commercial diagnostic ultrasound device has the potential to facilitate thrombolysis using an in vitro stroke model. METHODS: Duplex-Doppler, continuous wave-Doppler, and pulsed wave (PW)-Doppler were compared on their impact on recombinant tissue plasminogen activator (rtPA)-mediated thrombolysis. Blood clots were transtemporally sonicated in a human stroke model. Furthermore, ultrasound attenuation of 5 temporal bones of different thickness was determined. RESULTS: In comparison, only PW-Doppler accelerated rtPA-mediated thrombolysis significantly. Without temporal bone, PW-Doppler plus rtPA showed a significant enhancement in relative clot weight loss of 23.7% when compared with clots treated with rtPA only (33.9+/-5.5% versus 27.4+/-5.2%; P<0.0005). Ultrasound attenuation measurements revealed decreases of the output intensity of 86.8% (8.8 dB) up to 99.2% (21.2 dB), depending on temporal bone thickness (1.91 to 5.01 mm). CONCLUSIONS: Without temporal bone, PW-Doppler significantly enhanced thrombolysis. However, because of a high attenuation of ultrasound by temporal bone, no thrombolytic effect was observed in our in vitro model, although Doppler imaging through the same temporal bone was still possible.

Blood Coagulation↗
PubMed2004

Adventitial response to intravascular brachytherapy in a rabbit model of restenosis.

BACKGROUND: The incidence of late major adverse cardiac events (MACE) after coronary brachytherapy is higher than in controls. Because expansive remodeling has been shown to correlate with poor clinical outcome after vascular interventions, we studied adventitial changes after intravascular irradiation in a rabbit model. METHODS: Twenty normolipidemic rabbits underwent balloon injury in both external iliac arteries. One artery was assigned for subsequent irradiation with a 90Y source (15 Gy or 30 Gy at 0.5 mm in the vessel wall). After four weeks morphometric measurements were made and cell density and collagen amount determined. Staining for Ki67 identified proliferating cells; apoptotic cells were identified by TUNEL staining. Proliferative and apoptotic indices were calculated as the number of respective positive cells/total cell count x100. RESULTS: The neointimal area decreased to 0.27 +/- 0.3 mm2 after irradiation compared with 0.55 +/- 0.2 mm2 in controls (p=0.007), whereas adventitial area increased from 0.62 +/- 0.3 mm2 to 0.87 +/- 0.3 mm2 (p=0.02). Irradiation reduced both the proliferative (0.95 +/- 2.6 vs. 3.73 +/- 4.7, p=0.026) and apoptotic (0.006 +/- 0.02 vs. 0.107 +/- 0.2, p=0.03) indices in the neointima, but not in the other arterial-wall layers. Collagen amount and arterial remodeling did not differ between the groups. There was no difference between 15 and 30 Gy in any of the parameters, although adventitial thickening was more pronounced in the high-dose group. CONCLUSIONS: In normolipidemic rabbits, intravascular beta-irradiation after balloon angioplasty is associated with an increase in neoadventitia and a reduction of neointima. It is conceivable that this phenomenon may contribute to the increased incidence of late MACE after vascular brachytherapy.

Angioplasty, Balloon↗
PubMed2004

Ultrasound affects distribution of plasminogen and tissue-type plasminogen activator in whole blood clots in vitro.

Ultrasound of 2 MHz frequency and 1.2 W/cm(2) acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% +/-6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% +/-4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 +/-2513 ng/ml vs. 2364 +/-725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 +/-2.6 microm to 21.2 +/-7.2 microm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.

Fibrinolysis↗
PubMed2003

Arterial compliance: a diagnostic marker for atherosclerotic plaque burden?

BACKGROUND: Previous studies have shown atherogenesis to be related with increased vessel stiffness. Measures of the arterial compliance can be performed noninvasively from pressure pulse contour analysis of arterial waveforms. In this prospective study we aimed to analyze to what extent vessel compliance can reflect the angiographic coronary artery status. METHODS: Large and small arterial elasticity indices (LAEI in milliliters per mm Hg x 10 and SAEI in milliliters per mm Hg x 100) were measured in 151 patients on the radial artery with the PulseWave Sensor HDI device. All patients were classified into diffuse-coronary artery disease (CAD) (defined as stenosis length >15 mm), focal-CAD (defined as stenosis length between 1 and 15 mm), or no-CAD. RESULTS: We found both LAEI and SAEI to be reduced in the diabetic group (LAEI: 11.2 +/- 2.9 v 13.4 +/- 4.5, P =.006; SAEI: 3.7 +/- 1.6 v 4.7 +/- 2.4, P =.01). Inverse association was seen between age and LAEI (r = -0.41; P <.001) and SAEI (r = -0.38; P <.001). No-CAD was found in 31 patients, focal-CAD in 64 patients, and diffuse-CAD in 56 patients. Mean LAEI were 13.8 +/- 3.5, 13.7 +/- 4.7, and 11.3 +/- 3.5 in the groups no-CAD, focal-CAD, and diffuse-CAD, respectively (P =.004), (no-CAD versus diffuse-CAD: P =.04; focal-CAD versus diffuse-CAD: P =.009). Respective SAEI values were 5.6 +/- 2.5, 5.0 +/- 2.1, and 3.1 +/- 1.6 (P <.001), (no-CAD versus diffuse-CAD: P <.001; focal-CAD versus diffuse-CAD: P <.001). Multivariate analysis revealed SAEI (P <.001), hypercholesterolemia (P =.005), systolic blood pressure (BP) (P <.001), mean arterial BP (P <.001), pulse pressure (P =.003), and male gender (P =.001) to be diagnostic markers of the type of vessel disease. CONCLUSIONS: Compliance measurements may be used for identification of patients with diffuse atherosclerotic processes of the coronary arteries.

Age Factors↗
PubMed2003

2MHz ultrasound enhances t-PA-mediated thrombolysis: comparison of continuous versus pulsed ultrasound and standing versus travelling acoustic waves.

In addition to fibrinolytic enzymes, ultrasound has the potential to enhance thrombolysis. High frequency ultrasound has the advantage that a combination of diagnostic and therapeutic ultrasound with only one device is possible. Therefore, we investigated the optimal high frequency (2 MHz) ultrasound field characteristics and application mode in vitro. Continuous ultrasound significantly enhanced rt-PA mediated thrombolysis: in a travelling wave field thrombolysis was augmented by 49.0 +/- 14.7% and in a standing wave field by 34.8 +/- 7.3%. In an intermittent application mode (1Hz, 10Hz, 100Hz, 1kHz) most efficient results were obtained for both wave fields using 1 Hz (46.4 +/- 10.7% and 39.1 +/- 6.6%, respectively). Referring to a possible in vivo application our in vitro data suggests that an intermittent application of a 2 MHz high frequency ultrasound using a travelling wave field would be the most potent application for lysing blood clots.

Acoustics↗
PubMed2003

Inhibition of interleukin-1beta convertase is associated with decrease of neointimal hyperplasia after coronary artery stenting in pigs.

Inhibition of IL-1beta convertase has been shown to decrease inflammation and apoptosis, which are features of the neointimal development after vascular interventions. The aim of our study was to reduce neointimal proliferation after stenting of the porcine coronary artery, using the irreversible IL-1beta convertase and caspase-1 inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethyl-ketone (Ac-YVAD-cmk). Before coronary stent implantation, 8 pigs received an intracoronary infusion of 50 mg Ac-YVAD-cmk into the left coronary artery (group 1, n = 8), while 8 animals served as untreated controls (group 2). After 4 weeks, coronary angiography and intracoronary ultrasound (IVUS) with 3D measurements were performed. IVUS revealed a smaller in-stent intimal volume (27.3 +/- 11.6 vs. 75.8 +/- 18.4 mm3, p < 0.005) and a decreased maximal percentage area stenosis (36.1 +/- 8.5 vs. 69.0 +/- 8.2%, p < 0.001) in group 1 vs. group 2. A smaller maximal neointimal thickness (0.63 +/- 0.28 vs. 1.75 +/- 0.94 mm, p < 0.005) and a decreased maximal neointimal area (2.14 +/- 1.29 vs. 5.03 +/- 1.92 mm2, p < 0.005), assessed by computerized planimetry, were found in group 1 vs. group 2. Lower apoptotic indices of the neointimal cells were observed in the treated animals (3.0 vs. 13.4% of total intimal cells, p < 0.05). The coronary arterial tissue IL-1beta level was significantly decreased in the animals treated with Ac-YVAD-cmk (0.254 +/- 0.162 vs. 0.463 +/- 0.307 pg/mg protein, p < 0.05), and exhibited a positive linear correlation (r = 0.581, p = 0.013) with the in-stent plaque volume. In conclusion, intracoronary administration of Ac-YVAD-cmk before coronary artery stenting results in significantly decreased neointimal hyperplasia due to the inhibition of local IL-1beta production and decreased neointimal apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed2002

[Manual compression versus mechanical compression device (FemoStop) after diagnostic coronary angiography with/without 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.

Age Factors↗
PubMed2002

Vascular morphometric changes after radioactive stent implantation: a dose-response analysis.

OBJECTIVES: The goal of this study was to evaluate the dose-dependency of morphometric changes in the coronary arterial wall after radioactive stenting. BACKGROUND: Radioactive stents have been found to reduce intrastent intimal hyperplasia (IIH) but lead to a characteristic type of restenosis occurring predominantly at the stent edges. METHODS: Fifteen patients underwent intravascular ultrasound (IVUS) examination after implantation of a P-32 radioactive stent and at the six-month follow-up. The post-stent IVUS measurements on seven predefined locations of each lesion were subjected to a computer algorithm for the development of dose-volume histograms (DVH). Thus, we derived the radiation doses delivered to at least 10% and 90% of the adventitia (DV10, DV90). The IIH and vascular remodeling at follow-up were correlated with the doses in each segment. RESULTS: The IIH was most pronounced at the stent edges and lowest in the stent-body, whereas we detected a significant expansive remodeling within the stent body. The delivered doses correlated with a decreased IIH (r = 0.52, p < 0.001 for DV10 and r = 0.62, p < 0.001 for DV90) and with expansive remodeling (r = 0.48, p = 0.009 for DV10 and r = 0.50, p = 0.006 for DV90). A DV10 >90 Gy or a DV90 >15 Gy reduced IIH and induced expansive remodeling. Plaque growth was not reduced by radioactive stents. CONCLUSIONS: The DVH analysis reveals a dose-dependent increase of external elastic lamina area behind radioactive stents, whereas plaque growth is not reduced but inverted into an outward direction from the stent. A DV10 >90 Gy or a DV90 >15 Gy results in a beneficial long-term outcome after radioactive stenting.

Arteries↗
PubMed2002

In vitro thrombolysis enhanced by standing and travelling ultrasound wave fields.

Success of thrombolytic therapy depends on penetration of recombinant tissue plasminogen activator (rt-PA) into clots. Ultrasound (US) of therapeutic quality accelerates thrombolysis in vitro. As yet, only the effects of travelling acoustic waves on thrombolysis have been investigated, and the impact of standing acoustic waves has been neglected. In the present study, we examined the effects of standing and travelling US wave fields applied continuously for 1 h (frequency 2 MHz, acoustic intensity 1.2 W/cm(2)) on thrombolysis enhancement by measuring clot weight reduction and concentration of fibrin degradation product D-dimer (FDP-DD) produced from clots subjected to rt-PA. The level of FDP-DD was 1.8 times greater in travelling than in standing acoustic waves. Thrombolysis enhancement was 46.0 +/- 20.8% in standing and 116.8 +/- 23.1% in travelling acoustic waves. Travelling waves enhanced thrombolysis significantly more (p < 0.0001) than did standing waves.

Culture Techniques↗