Biomedical subjects

Thomas Meinertz

Publications and source records attributed to Thomas Meinertz.

At least 73 records · Page 4Linked to original sources

PubMed2003

Biopanning of single-chain antibodies expressing phages reveals distinct expression patterns of angiogenic and arteriogenic vessels.

"Therapeutic angiogenesis" requires targeted delivery of growth factors for maximal benefit and limitation of potential hazards such as enhancement of tumor or plaque angiogenesis. Physiological distinctions between angiogenesis and collateral growth suggest the possibility of targeting selectively collateral endothelium. This article describes the generation of collateral-targeting single-chain antibodies (scFv). Membrane preparations of growing collateral arteries from rats were used to produce collateral-targeting antibodies (CTAs) via immunization of mice. ScFv were generated from CTA-producing hybridoma and cloned into the pV gene of M13 phages. Phages expressing collateral-targeting scFv (CT scFv) were selected via repeated exposure to activated collateral arteries followed by reamplification. CT scFv could specifically be amplified, selected, and sequenced. Phages expressing CT scFv bound selectively to proliferating collateral vessels as identified by positive Polycyclic Nuclear Antigen (PCNA) staining and homed specifically to collateral endothelium after in vivo injection but bound neither to control vessels nor to tumor vessels. This study reveals major differences between angiogenic and collateral endothelium and delivers a tool that will allow the stimulation of collateral growth without promoting tumor or plaque angiogenesis.

Amino Acid Sequence↗

PubMed2003

An approach to measure atrial and ventricular heart rate variability using pacemaker-mediated intracardiac electrograms.

Heart rate variability (HRV) measurements are usually performed from ventricular beat-to-beat intervals because of the difficulty to precisely locate the P wave fiducial point in surface ECG recordings. The aim of the study was to describe an approach to determine the atrial and ventricular HRV using pacemaker-mediated intracardiac electrograms. Twelve patients with the dual chamber pacemaker Logos were included. The atrial and ventricular intracardiac electrograms were transmitted with the high resolution telemetry channel of the pacemaker to an external recorder for 20 minutes while the patients were supine. During the measurements the patients were in sinus rhythm with intrinsic AV conduction. After computer assisted triggering of the atrial and ventricular events, the resultant intervals were used to calculate the standard deviation of all NN intervals (SDNN), the square root of the mean squared differences of successive NN intervals (RMSSD), and the percentage of successive interval differences >50 ms (pNN50). The differences between atrial and ventricular HRV-Indexes were assessed for each patient with a cut-off point of 1%. Differences >1% were analyzed in detail. A total of 15,504 heart cycles were analyzed. A manual correction due to false or not triggered atrial or ventricular events was necessary in 0.9%. The overall difference between atrial and ventricular pNN50 was-0.5%+/-2.1%and differences >1% were observed in 4 patients. The NN50 events occurred in the atrial as well as in the related ventricular interval in 84%. NN50 events occurred only in the atrium in 6% and only in the ventricle in 10%. The mean differences between atrial and ventricular SDNN and RMSSD were 0.4+/-2.1 ms and-0.1+/-3.5 ms with intra-individual differences <1%. The present study described a new method and demonstrated its feasibility to determine atrial as well as ventricular HRV from pacemakermediated intracardiac electrograms. The differences for pNN50 indicate that ventricular HRV did not reflect the changes of sinus node activity in all patients.

Aged↗

PubMed2003

[Intracoronary radiotherapy].

Intervenient cardiology is significantly more represented in attempts to solve problems of heart coronary artery disease in comparison to aortocoronary bypass procedures. Resthenoses of coronary artery blood vessel after PTCA, or PTCA and stent placement are frequent. The main causes are: neointimal hyperplasia, late contraction, and remodelling. The application of brachitherapy offers the possibility to prevent resthenosis especially stent resthenosis. Our report encompasses eight patients diseased from coronary artery occlusionn. Half of there patients had a stent resthenosis. The average degree of blood vessel occlusionn before the intervenient manipulation was 78%, and after treatment 25%-30%. Early results after recanalisation of coronary blood vessel are thus fat satisfactory, but results are to be followed carefully.

Aged↗

PubMed2002

Efficacy and safety of propafenone sustained release in the prophylaxis of symptomatic paroxysmal atrial fibrillation (The European Rythmol/Rytmonorm Atrial Fibrillation Trial [ERAFT] Study).

We report a double-blind, multicenter, multinational, placebo-controlled, and well-controlled trial to prove that the sustained-release (SR) formulation of propafenone is superior to placebo in preventing symptoms of paroxysmal atrial fibrillation (AF). A total of 594 patients were enrolled in the qualifying period of the study and 293 patients were randomized at 53 centers. There were significant increases in the arrhythmia-free periods from day 5 of randomization to the first recurrence of symptomatic atrial arrhythmia in the propafenone SR 325 mg twice daily (p = 0.004) and propafenone SR 425 mg twice daily (p = 0.003) treatment groups compared with placebo. The median arrhythmia-free time was 9 days in the placebo group, 35 days in the propafenone SR 325 mg twice daily group, and 44 days in the propafenone SR 425 mg twice daily group. There was a significant reduction in average heart rate during the first recurrence of symptomatic arrhythmia after day 5 in the low-dose propafenone group compared with placebo. The median treatment failure time from day 5 (arrhythmia recurrence, adverse events, and withdrawals) was prolonged from 8 days in the placebo group to 19 days in the propafenone SR 325 mg twice daily group (p = 0.002) and to 24 days in the propafenone SR 425 mg twice daily group (p = 0.006). The percentage of patients with >/=1 serious adverse event was similar in the propafenone SR treatment groups (propafenone SR 325 mg twice daily, 10.0%; propafenone SR 425 mg twice daily, 11.2%) but lower in the placebo group (1.1%). In conclusion, the SR formulation of propafenone is superior to placebo, well-tolerated, and prevents symptoms of paroxysmal AF.

Acute Disease↗

PubMed2002

Adverse effects of nitroglycerin treatment on endothelial function, vascular nitrotyrosine levels and cGMP-dependent protein kinase activity in hyperlipidemic Watanabe rabbits.

OBJECTIVE: With the present studies we sought to determine how treatment with nitroglycerin (NTG) affects endothelial function, oxidative stress and nitric oxide (NO)-downstream signaling in Watanabe heritable hyperlipidemic rabbits (WHHL). BACKGROUND: In vitro experiments have demonstrated potent antiatherosclerotic effects of NO suggesting that treatment with NO-donors such as NTG could compensate for the diminished availability of endothelial NO. Nitric oxide may, however, not only be scavenged by reaction with endothelium-derived superoxide but also form the potent oxidant and inhibitor of vascular function, peroxynitrite (ONOO(-)). METHODS: Watanabe heritable hyperlipidemic rabbits were treated for three days with NTG patches. Normolipidemic New Zealand White rabbits (NZWR) served as controls. Endothelial function was assessed ex vivo with organ chamber experiments and vascular superoxide was quantified using lucigenin (5 and 250 microM) and CLA-enhanced chemiluminescence. Vascular ONOO(-) formation was determined using nitrotyrosine antibodies. The activity of the cGMP-dependent kinase (cGK-I) was assessed by determining the phosphorylation of vasodilator-stimulated phosphoprotein VASP (P-VASP). RESULTS: Nitroglycerin treatment caused endothelial dysfunction in NZWR and WHHL, associated with an increase in superoxide and ONOO(-) production and a substantial drop in cGK-I activity. In vivo NTG-treatment decreased lipophilic antioxidants (alpha- and beta-carotene) in NZWR and WHHL. Treatment of NZWR with NTG also decreased plasma extracellular superoxide dismutase (EC-SOD)-activity. CONCLUSIONS: Nitroglycerin treatment of WHHL with exogenous NO worsens rather than improves endothelial dysfunction secondary to increased formation of superoxide and/or peroxynitrite leading to decreased cGK-I activity. The decrease in plasma levels of alpha- and beta-carotene may be at least in part due to a decrease in EC-SOD activity.

Animals↗

PubMed2002

Functional and biochemical analysis of endothelial (dys)function and NO/cGMP signaling in human blood vessels with and without nitroglycerin pretreatment.

BACKGROUND: In experimental animal models, long-term in vivo treatment with nitroglycerin (NTG) induces both endothelial dysfunction and tolerance to nitrates. However, it is still controversial whether nitrate tolerance in humans is associated with both endothelial dysfunction and impaired vascular response to nitrovasodilator-derived NO. METHODS AND RESULTS: Patients undergoing elective bypass surgery were randomized to receive 48 hours of continuous NTG infusion (NTG group) or no nitrate therapy (control group). Segments of surgically removed arteria mammaria, vena saphena, and arteria radialis not required for the bypass procedure were used to examine (1) the vascular responsiveness to NTG and the endothelium-dependent vasodilator acetylcholine; (2) the expression of the NO target, the soluble guanylyl cyclase; (3) the expression of the soluble guanylyl cyclase/cGMP effector target, the cGMP-dependent protein kinase (cGK); and (4) the cGK activity as assessed by the phosphorylation state of its vascular substrate, the vasodilator-stimulated phosphoprotein at serine(239) (P-VASP). NTG treatment caused a marked degree of nitrate tolerance in all 3 vessel types studied and a significant cross-tolerance to the endothelium-dependent vasodilator acetylcholine in A. mammaria and A. radialis. Although soluble guanylyl cyclase, cGK-I, and VASP expression levels were not modified by NTG treatment, a marked decrease of P-VASP, a surrogate parameter for in-vivo cGK-I activity, was observed. CONCLUSIONS: We conclude that long-term NTG treatment induces endothelial dysfunction and impaired vascular NO/cGMP signaling in humans, which can be monitored by measuring P-VASP levels.

Aged↗

PubMed2002

Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling.

Angiotensin II infusion causes endothelial dysfunction by increasing NAD(P)H oxidase-mediated vascular superoxide production. However, it remains to be elucidated how in vivo angiotensin II treatment may alter the expression of the gp91(phox) isoforms and the endothelial nitric oxide synthase (NOS III) and subsequent signaling events and whether, in addition to the NAD(P)H oxidase, NOS III contributes to vascular superoxide formation. We therefore studied the influence of in vivo angiotensin II treatment (7 days) in rats on endothelial function and on the expression of the NAD(P)H oxidase subunits p22(phox), nox1, nox4, and gp91(phox) and NOS III. Further analysis included the expression of NO-downstream targets, the soluble guanylyl cyclase (sGC), the cGMP-dependent protein kinase I (cGK-I), and the expression and phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) at Ser239 (P-VASP). Angiotensin II caused endothelial dysfunction and increased vascular superoxide. Likewise, we found an increase in vascular protein kinase C (PKC) activity, in the expression of nox1 (6- to 7-fold), gp91(phox) (3-fold), p22(phox) (3-fold), NOS III mRNA, and protein. NOS-inhibition with N(G)-nitro-L-arginine decreased superoxide in vessels from angiotensin II-treated animals, compatible with NOS-uncoupling. Vascular NO assessed with electron paramagnetic resonance was markedly reduced. Likewise, a decrease in sGC-expression and P-VASP levels was found. In vivo PKC-inhibition with chelerythrine reduced angiotensin II-induced superoxide production and markedly inhibited upregulation of NAD(P)H oxidase subunits. We therefore conclude that angiotensin II-induced increases in the activity and the expression of NAD(P)H oxidase are at least in part PKC-dependent. NADPH oxidase-induced superoxide production may trigger NOS III uncoupling, leading to impaired NO/cGMP signaling and to endothelial dysfunction in this animal model. The full text of this article is available at http://www.circresaha.org.

Angiotensin II↗

PubMed2002

Predictors of aneurysmal formation after surgical correction of aortic coarctation.

OBJECTIVES: We sought to identify the predictors of aneurysmal formation after surgical correction of aortic coarctation. BACKGROUND: In 9% of patients, aneurysms develop late after corrective surgery of coarctation of the aorta, with a 36% mortality rate if left untreated. However, the predictors of postsurgical aneurysmal formation are unknown. METHODS: Of 25 aortic aneurysms requiring corrective surgery 152 +/- 78 months after the initial coarctation repair, 8 were located in the ascending aorta (type A) and 17 at the site of previous repair (local type). Seventy-four patients without progression of the aortic diameter within 189 +/- 71 months after coarctation repair were used for categorical data analysis in an attempt to identify the predictors of postsurgical aneurysmal formation. RESULTS: Advanced age at coarctation repair (p = 0.004) and patch graft technique (p < 0.0005) independently predicted local aneurysmal formation. Type A aneurysm was univariately associated with the presence of a bicuspid aortic valve (p = 0.02), advanced age at coarctation repair (p = 0.044) and a high preoperative peak systolic pressure gradient of 74 +/- 21 mm Hg (p = 0.041). Conversely, multivariate analysis confirmed only the presence of a bicuspid aortic valve (p = 0.015) as an independent predictor of type A aneurysm. Receiver operating characteristic curve analysis revealed that 72% of patients with a postsurgical aneurysm had an operation at age 13.5 years or more, whereas 69% with no postsurgical aneurysm had an operation at a younger age. CONCLUSIONS: Use of the patch graft technique and late correction of coarctation can predict aneurysmal formation at the site of coarctation repair, although patients with a bicuspid aortic valve may be at risk for an aneurysm developing in the ascending aorta, particularly after late repair of aortic coarctation with high preoperative pressure gradients.

Adolescent↗

PubMed2002

[Prevention of arterial thromboembolisms in patients with atrial fibrillation].

BACKGROUND: Patients with atrial fibrillation have a 5% risk per year for ischemic stroke. The aim of antithrombotic therapy is to prevent arterial thromboembolic events. As anticoagulation increases the frequency of bleeding, the risk and benefits of this therapy have to be assessed for each patient. PATIENTS AT RISK: The patients can be classified as low risk (< 2% stroke/year), medium risk (2-6% stroke/year), and high-risk patients (> 6% stroke/year). Parameters for the risk stratification are the patient age and cardiac as well as non-cardiac diseases. PREVENTION: Patients with a low risk need no anticoagulation or can take aspirin. Patients with a high risk should receive oral anticoagulation with an INR range from 2.0 to 3.0. Newer guidelines recommend also for patients with intermediate level of stroke risk instead of aspirin the prescription of oral anticoagulation. Patients with a medium risk can interrupt the oral anticoagulation before surgery or invasive diagnostic procedures for 1 week, patients with a high risk should receive heparin. 3-4 weeks before and after cardioversion the standard therapy is oral anticoagulation.

Administration, Oral↗

PubMed2002

The IST registry.

Intracoronary brachytherapy has been established in Europe and the US as an evidence-based treatment of in-stent restenoses. The objective of the IST Registry is to register all patients treated in Germany with intracoronary radiation and to observe the clinical outcome for a duration of 5 years. The required set of data for each patient is kept to a minimum to encourage participation. All data are entered online. In the internet, each participating site can, at any time, check their most important parameters and compare them with those of other sites. Presently, the Novoste System is used in 58 catheter labs and the Guidant System in 16, while several sites use both. The requirements regarding radiation safety in intracoronary application of gamma radiation are very strict in Germany, so the Cordis-Gamma System is used in only one German lab. In a first analysis of 332 radiated stenoses, it was observed that late vessel occlusion could occur even after 6-month administration of clopidogrel (in addition to ASA)--without new stents being implanted within the brachytherapy session. Clopidogrel should thus be administered in addition to aspirin for at least a year. Ca. 270 patients per month receive intracoronary radiation in Germany, so the IST Registry will provide important data regarding long-term observation and a foundation for future negotiations with insurance companies potentially bearing the costs. At present, neither the physician's service nor the material costs are reimbursed. The IST Registry can furthermore be used as a comparative database regarding long-term outcome following implantation of antiproliferative-coated stents.

Angioplasty, Balloon, Coronary↗

PubMed2002

Functional disconnection of arrhythmogenic pulmonary veins in patients with paroxysmal atrial fibrillation guided by combined electroanatomical (CARTO) and conventional mapping.

BACKGROUND: Isolation of arrhythmogenic pulmonary veins (PVs) by radiofrequency current (RF) application has been introduced as a curative treatment for patients (pts) with paroxysmal atrial fibrillation (AF). The present study sought to investigate the feasibility and efficacy of this approach guided by conventional and electroanatomical mapping (CARTO). METHODS: Twenty pts (13 male; 57 +/- 8 years) with recurrent documented focally triggered idiopathic AF refractory to multiple antiarrhythmic drugs were prospectively included. Atrial premature beats were present at baseline in 9 pts and could be provoked in further 8 pts. Empirical ablation of both superior PVs was performed in 3 pts with no focal activity. After transseptal puncture selective angiography of all PVs was obtained. Thirty-six PVs (left superior: n = 18, right superior: n = 10, left inferior: n = 8) were targeted for RF ablation. A complete left atrial CARTO-map including the left atrial (LA) to pulmonary vein (PV) junction was obtained during sinus rhythm and/or coronary sinus pacing. RF was initially applied at the PV-LA junction at areas with the shortest left atrial- to PV potential interval (target 50 degrees C, max. 30 W, duration 60 sec). Isolation was confirmed by the complete disappearance of specific PV potentials. RF lesions were analyzed with respect to the number of segment-quarters covering the PV ostium. RESULTS: Functional isolation could be achieved in 35 out of 36 PVs following 10 +/- 5 RF applications for each PV. RF applications covered 2 or less quarter segments of the overall PV circumference in 29 (80%) PVs. Total session duration was 6.5 +/- 1.6 h with a mean fluoro-time of 54 +/- 18 minutes. For CARTO mapping and ablation a mean fluoro time of 34 +/- 6 min was required. During a mean follow up period of 8.3 +/- 2.5 months AF relapsed in 9 pts (46%). A second approach was performed in 5 pts. and demonstrated either new foci (n = 2) or recurrence of previously isolated PV (n = 8). The second RF ablation procedure led to stable sinus rhythm in 3 out 5 pts. Thus, the overall success rate including the second procedure was 70%. CONCLUSIONS: CARTO guided functional isolation of presumed arrhythmogenic PVs by RF lesions covering 2 or less segments of the PV ostium in most patients is feasible. However, repeat procedures are often warranted to permanently treat paroxysmal atrial fibrillation.

Adult↗

PubMed2002

Endothelin-1 mRNA and protein in vascular wall cells is increased by reactive oxygen species.

A dysregulated metabolism of oxygen-derived free radicals, nitric oxide and endothelin-1(ET-1) in conditions such as hypercholesterolaemia or hypertension may promote the development of atherosclerosis. We therefore subjected cultured human umbilical vein endothelial cells and coronary artery smooth muscle cells to oxidative stress induced by xanthine oxidase or hydrogen peroxide and observed alterations in ET-1 metabolism. Incubation with oxygen-derived free radicals increased preproET-1 promoter activity, ET-1 mRNA synthesis and big ET-1 concentrations in both cell types. This interaction of oxidative stress and ET-1 expression may be relevant in atherogenic conditions such as hypercholesterolaemia and hypertension since our data indicate that oxidative stress further aggravates the injurious effects attributed to ET-1.

Cells, Cultured↗

PubMed2002

Radiofrequency catheter ablation using cooled electrodes: impact of irrigation flow rate and catheter contact pressure on lesion dimensions.

Irrigation of radiofrequency current (RF) ablation reduces the risk of thrombus formation. The aim of this study was to investigate the impact of different irrigation catheter flow rates and contact pressures from the catheter on the development of lesion dimension and thrombus formation. A thigh muscle preparation was achieved in six sheep to create a cradle that was filled and perfused with heparinized blood (250 mL/min, 37 C degrees). RF ablation (30 s, 30 W) was initially performed with three different irrigation flow rates (5 mL/min, 10 mL/min, and 20 mL/min) and a perpendicular position (0.1 N contact pressure) of the irrigated ablation catheter ("Sprinklr," Medtronic, Inc., Minneapolis, MN, USA). The next lesions were induced with constant contact pressure of 0.05 Newton (N); 0.1 N; 0.3 and 0.5 N and a parallel or perpendicular orientation of the catheter, respectively. A constant irrigation flow of 10 mL/min was maintained during these RF applications. Cross sections of the lesions were investigated with regard to maximal depth and maximal diameter at and below the surface. During high flow irrigation (20 mL/min) the surface diameter was significantly smaller (0.63 +/- 0.1 cm) compared to irrigation flowrates of 5 mL/min (0.88 +/- 0.2 cm) and 10 mL/min (1 +/- 0.1 cm). Thrombus formation was not observed during any RF application. Only in perpendicular catheter orientations with a contact pressure of 0.5 N were significantly deeper lesions (0.85 +/- 0.12 cm) induced compared to 0.05 N (0.55 +/- 0.02 cm), 0.1 N (0.7 +/- 0.01 cm) and 0.3 N (0.67 +/- 0.01 cm) contact pressure. There was no significant difference in lesion depth with different flow rates. Irrigated RF ablation even with low flow rates and high catheter contact pressure prevented thrombus formation at the electrode. Smaller lesion diameters have been created with high irrigation flow rates. The deeper lesion created with high catheter contact pressure might be caused by a greater power transmission to the tissue.

Animals↗

PubMed2002

Impact of the distribution and structure of myocardium in the pulmonary veins for radiofrequency ablation of atrial fibrillation.

Focal AF is frequently triggered by ectopic beats mostly originating from the pulmonary veins (PVs). So far, the morphological substrate for this entity is not well defined. Therefore, the distribution of myocardial cells within the PV were examined as potential target sites for RF application. The PVs (118) of 30 human autopsied hearts (age of death 63 +/- 13 years, 17 men) were dissected in their complete circumference starting 1 cm from the ostium. Tissue sections of the PV were stained with hematoxylin-eosin and with Masson's trichrome. To characterize the developmental state of the myocardial tissue in the PV, immunohistochemistry was performed with antibodies reacting with antigens which are stage specifically expressed during cardiac development (HNK1/Leu7, alpha-SMA, calponin and desmin). Furthermore, proliferative activity was assessed using antibodies against the Ki-67 antigen (MIB-1). In two hearts a left-sided common PV ostium was found. The other hearts showed four separated PV ostia. The ostium diameter of the right inferior PV (1.2 +/- 0.3 cm) was significantly smaller (P < 0.05) than remaining PV ostia (right superior 1.5 +/- 0.2, left superior, 1.5 +/- 0.3 and left inferior 1.4 +/- 0.3 cm) of the 118 specimen. There was no significant difference in the presence of myocardium in the PV 1-cm distant from the ostium comparing the right superior (78%), the right inferior (81 %), the left superior (81%), and the left inferior (81%) PV. In 54% of cases the myocardial bundles covered the complete PV circumference. In up to 38% of the small extensions of the myocardial bundles myocardial cells, characterized by distinct cross-striations and spindle shape were found. However, since these cells could not be labeled for other markers than desmin, their immature state seems unlikely. The anatomic distribution of myocardium in the PV suggests that RF applied to the entire circumference may be frequently required for its electrical isolation. Whether spindle-shaped myocytes have different electrophysiological behavior has to be further investigated.

Atrial Fibrillation↗

PubMed2002

Atrial premature beats in patients with focal atrial fibrillation: incidence at baseline and impact of provocative maneuvers.

This study evaluated the incidence of atrial premature beats (APBs) and the impact of various provocative maneuvers in patients with focally initiated AF. Fifty patients (39 men, 57 +/- 0.4 years) with focally initiated, paroxysmal AF underwent Holter recording and a standardized protocol of provocative maneuvers: vagomechanical stimulation, adenosine 12 mg i.v., esmolol 500 ng/kg i.v., orciprenaline i.v. 5 mg/50 mL saline 0.9%, and atropine 0.01 mg/kg i.v. A surface ECG was recorded for 20 minutes at baseline and following each part of the protocol. High focal activity was defined as > or = 1 APB/minute. During Holter ECG, 29 (58%) patients had an amount of < 200 APBs, 12 (24%) patients < 700 > or = 200, and 9 (18%) patients > or = 700 APBs. Less than 1 hour of high focal activity was observed in 34 (68%) of the 50 patients. Before starting provocative maneuvers 15 (30%) patients had high focal activity whereas 35 (70%) presented < 1 APB/minute. In 29 (58%) patients APBs increased by > or = 1/min during provocative maneuvers: by vagomechanical stimulation in 11 patients, after adenosine in 15, esmolol in 12, orciprenaline in 15, and after atropine in 9 patients. In all patients with > or = 1 APB/min at baseline, focal activity decreased or disappeared during some single provocative maneuvers. AF occurred in eight patients under provocative maneuvers. No predictive factors of a successful provocative maneuver were detected with regard to the baseline patients characteristics and Holter results. In conclusion, patients with focally initiated AF have a low incidence of spontaneous APBs. Various provocative maneuvers successfully increase APBs in more than half of the patients; orciprenaline had the highest efficacy. Some provocative maneuvers may suppress APBs in the setting of high focal activity at baseline.

Adenosine↗

PubMed2002

A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test.

The aim of this study was to assess the efficacy of lipophilic beta-blockers in preventing recurrent neurocardiogenic syncope and the value of head-up tilt test (HUT) in predicting response to therapy. The efficacy of beta-blockers in recurrent syncope is controversial. The value of HUT in predicting efficacy of therapy has not been investigated. Fifty-six patients (44+/-18 years, 36 women) with recurrent syncope (> 1 event in the last 6 months) of suspected neurocardiogenic origin were included in the study. Independent of the response to HUT, patients were randomized to receive metoprolol or propanolol at the maximal tolerated dose (28 patients, group A, 86+/-23 vs 98+/-29 mg/d) or no pharmacological therapy (28 patients, group B). The primary endpoint was the first recurrence of syncope. During the 1-year of follow-up, 20 patients of group A and 8 of group B had no recurrence. In group A, of 20 patients without recurrences 12 had a positive and 8 a negative HUT result while of 8 patients with recurrences 5 had a positive and 3 a negative response to HUT. In the group B, of 20 patients with recurrences 10 had a positive and 10 a negative HUT result while of 8 patients without recurrences 4 had a positive and 4 a negative response to HUT. In a multivariate Cox-regression analysis, medical therapy was the only independent factor for predicting recurrence of syncope (P = 0.004); HUT had no influence in this regard (P = 0.773). In conclusion, lipophilic beta-blockers appear efficacious in preventing recurrent syncope of suspected neurocardiogenic origin. The efficacy of therapy seems to be not predicted by HUT.

Adrenergic beta-Antagonists↗

PubMed2002

Low settings of the ventricular pacing output in patients dependent on a pacemaker: are they really safe?

BACKGROUND: It is generally acknowledged that pacemaker output must be adjusted with a 100% voltage safety margin above the pacing threshold to avoid ineffective pacing, especially in patients dependent on pacemakers. AIMS: The aim of this prospective crossover study was to assess the beat-to-beat safety of low outputs in patients who are dependent on a pacemaker between 2 follow-up examinations. METHODS: The study included 12 patients who had received a DDD pacemaker with an automatic beat-to-beat capture verification function. The ventricular output at 0.4 milliseconds pulse duration was programmed independently of the actual pacing threshold in a crossover randomization to 1.0 V, 1.5 V, and 2.5 V for 6 weeks each. At each follow-up, the diagnostic counters were interrogated and the pacing threshold at 0.4 milliseconds was determined in 0.1-V steps. The diagnostic pacemaker counters depict the frequency of back-up pulses delivered because of a loss of capture. During the randomization to 1.0-V output, we evaluated whether the adjustment of the output under consideration of the >100% voltage safety margin reduced the frequency of back-up pulses. RESULTS: Pacing thresholds at the randomization to 1.0-V, 1.5-V, and 2.5-V output were not significantly different, with 0.7 +/- 0.3 V at 2.5-V output, 0.6 +/- 0.2 V at 1.5-V output, and 0.6 +/- 0.2 V at 1.0-V output. The frequency of back-up pulses was similar at 2.5-V and 1.5-V output, 2.2% +/- 1.9% and 2.0% +/- 2.0%, respectively. The frequency of back-up pulses significantly increased at 1.0-V output to 5.8% +/- 6.4% (P <.05). Back-up pulses >5% of the time between the 2 follow-ups were observed in no patient at 2.5 V, in 1 patient at 1.5 V, and in 5 patients at 1.0 V. At the randomization to the 1.0-V output, 6 patients had pacing thresholds of 0.5 V or less, and 6 patients had pacing thresholds >0.5 V. The frequency of back-up pulses in the 2 groups was not significantly different, 6.4% +/- 8.6% and 5.7% +/- 2.6%. CONCLUSIONS: The frequency of back-up pulses was significantly higher at 1.0-V output than at 1.5-V and 2.5-V output. This also applied to patients with pacing thresholds of < or =0.5 V. Fixed low outputs seem not to be absolutely safe between 2 follow-ups in patients who are dependent on a pacemaker, even when the output has a 100% voltage safety margin above the pacing threshold. When patients with pacemakers programmed to a low ventricular output have symptoms of ineffective pacing, an intermittent increase of the pacing threshold should be carefully ruled out.

Aged↗

PubMed2002

Influence of heparin coating of coronary stents and ex vivo efficacy of different doses of acetylsalicylic acid and ticlopidine in a pulsed floating model of recirculating human plasma.

Acute occlusion of stented coronary vessels still occurs in up to 3%. Activated platelets have been found to play a major role in the pathogenesis of these complications. We therefore analyzed the efficacy of a heparin coating of coronary stents and investigated the ex vivo efficacy of different antiplatelet drugs. Each of seven healthy volunteers was treated with each of the following medications for 7 days: ASA 100 mg/day, ASA 300 mg/day, ticlopidine 250 mg/day, and ticlopidine 500 mg/day. Three standardized in vitro silicon tubing models, one of them containing an uncoated stent, one a heparin-coated stent, and one without a stent (control) were filled with PRP and circulation was started. TOS in systems with heparin-coated stents was 2.4-times longer compared to systems with uncoated stents (P<0.001), and 1.5-times longer compared to the control (P<0.01). The increase of CD62p expression within the first 5 min was 2.5-times higher in systems with uncoated stents and 1.7-times higher in the control than in systems with heparin-coated stents (P<0.05). Aggregometry revealed significant medication- and dose-dependent inhibition of platelet aggregability for all medications. Heparin-coating of coronary stents reduces their thrombogenicity significantly. ASA and ticlopidine effectively reduce platelet activation ex vivo. The used in vitro system facilitates a reproducible method to estimate the thrombogenicity of coronary stents prior to in vivo trials.

Angioplasty, Balloon, Coronary↗