Bolus application of a novel recombinant plasminogen activator in acute myocardial infarction patients: pharmacokinetics and effects on the hemostatic system.
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Biomedical subjects
Publications and source records attributed to V Hombach.
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The idiopathic long QT syndrome (LQTS) is an infrequently occurring disorder. Affected patients may have electrocardiographic alterations and are prone to syncope and sudden arrhythmogenic cardiac death. Adequate therapy may improve the prognosis of affected patients significantly. Therefore the early and precise diagnosis of LQTS has major prognostic impact. This study reports the diagnostic significance of standard electrocardiographic techniques and autonomic maneuvers in 14 patients with LQTS. The findings are compared with those of 14 healthy age-matched control persons. QTc duration was significantly longer in patients with LQTS during standard 12-lead electrocardiography (489 +/- 56 vs 412 +/- 30 ms, p < 0.005), exercise stress testing (490 +/- 38 vs 409 +/- 18 ms, p < 0.001), cold pressor testing (512 +/- 45 vs 407 +/- 19 ms, p < 0.001), Valsalva maneuver (497 +/- 49 vs 407 +/- 19 ms, p < 0.001), minimal heart rate during 24-hours of ambulatory electrocardiographic recording (482 +/- 69 vs 402 +/- 22 ms, p < 0.01) and maximal heart rate during Holter monitoring (460 +/- 47 vs 411 +/- 27 ms, p < 0.005). Four of 14 patients with LQTS had pathologic findings during ambulatory electrocardiographic monitoring (2 patients with short episodes of torsades de pointes tachyarrhythmia, 1 patient with intermittent sinoatrial block, and 1 patient with intermittent TU-wave alterations), whereas all control persons had normal ambulatory electrocardiographic recordings (p < 0.05). Thus, noninvasive standard electrocardiographic techniques in combination with autonomic maneuvers may contribute significant information for a precise diagnosis in patients with suspected LQTS.(ABSTRACT TRUNCATED AT 250 WORDS)
This report describes the usefulness of echocardiography in the differential diagnosis of acute cardiovascular events. In a 66-year-old patient with known aortic stenosis and mitral valve prosthesis, who suddenly deteriorated with severe dyspnea, a thrombus within the pulmonary artery could be detected with 2-D echo. Pulsed-wave Doppler disclosed the resulting flow-velocity disturbances.
Percutaneous excimer laser coronary angioplasty (ELCA) was performed in a first group of 20 patients with stable angina pectoris caused by significant coronary stenosis, and long-term follow-up was evaluated. Prototype 4 to 5.5 French multifibre catheters with 18-20 quartz fibres of 100 microns diameter, concentrically arranged around a central lumen for taking up a guide wire, were coupled to a commercial XeCl excimer laser. Energy was delivered at a wavelength of 308 nm with a pulse duration of 60 or 120 ns. Operating at a repetition rate of 20 Hz, mean energy transmission was 13.4 +/- 6.8 mJ per pulse. In all but one patient the lesion could be passed by the catheter. Percent diameter stenosis decreased from 77.1 +/- 10.8% to 53.1 +/- 11.8% after ELCA. Complications were frequently observed, intracoronary thrombus formation in eight instances, dissection in six patients and spasm in five cases, causing total vessel occlusion in five procedures. All complications could be managed efficaciously by thrombolytic and vasodilating drugs and/or balloon angioplasty. Subsequent PTCA was performed in case of complication or insufficient stenosis reduction after ELCA in 18 patients with adequate results (residual stenosis, 28.5 +/- 10.2%). Long-term follow-up angiography, which could be performed in 16 of 19 laser treatments, demonstrated significant restenosis in only three patients. Our preliminary results suggest that, using ELCA, ablation of atherosclerotic lesions is feasible in most cases. However, compared with PTCA, stenosis reduction is significantly less, and the acute complication rate is much higher. Thus, further improvements of the catheter system are necessary in order to realize the advantages of excimer laser ablation, which can be demonstrated by experimental studies.
Electrical activity can be localized by magnetocardiography (MCG) non-invasively. In this study a 37-SQUID (Super Conducting Quantum Interference Device) sensor multi-channel system (KRENIKON) was used to assess the potential of magnetocardiography to localize accessory pathways with a multichannel system. Seven WPW patients were studied by means of magnetocardiography. Prior to the MCG recordings, the site of the accessory pathway had been determined in all patients by invasive catheter mapping. MR images of the heart were used for anatomical correlation. The magnetocardiographic localization of the accessory pathway corresponded with catheter mapping within 2.1 cm on average (total range: 0-5 cm). This is thus, a promising new method for non-invasive localization of accessory pathways in WPW patients.
For the determination of the defibrillation threshold, the induction of ventricular fibrillation is mandatory. However, in severely damaged hearts it is sometimes difficult to induce ventricular fibrillation by rapid stimulation or alternating current. Only rapid nonclinical ventricular tachycardias may result, and their cardioversion threshold may be different from the defibrillation threshold. Therefore, it was the purpose of this study to test the potential of direct current (DC) application to rapidly induce ventricular fibrillation in patients with an implanted cardioverter defibrillator. The defibrillation threshold had to be determined in 13 patients (9 with coronary heart disease, 4 with dilative cardiomyopathy, ejection fraction 35%) during and 2 weeks after the implantation of a cardioverter defibrillator. DC was applied 37 times by a commercially available 9-V DC battery via a bipolar catheter for about 3 seconds. Ventricular fibrillation was induced 23 times (62%) and rapid nonclinical ventricular tachycardias were induced six times (16%). In one patient clinical ventricular tachycardia was observed. In seven instances (19%) sinus rhythm remained. In 12 of the 13 patients, ventricular fibrillation could be induced by DC. Thus, the induction of ventricular fibrillation by DC application may serve as an additional tool to induce ventricular fibrillation, determining the defibrillation threshold in implantable cardioverter defibrillator patients.
The idiopathic long QT syndrome (LQTS) is an infrequently occurring disorder. It has major clinical impact as patients are prone to syncope, ventricular tachyarrhythmias and sudden arrhythmogenic cardiac death. This paper reports the value of ambulatory electrocardiogram (ECG) monitoring as a diagnostic tool to establish the diagnosis of LQTS. 14 patient with idiopathic LQTS were studied. The results were compared to those of 14 age- and sex-matched healthy control individuals. A 24-hour ambulatory ECG tracing was obtained in each individual. 5/14 patients with LQTS had pathological findings during ambulatory ECG monitoring (2 patients with episodes of torsade de pointes tachycardia, 2 patients with T-wave alternans and 1 patient with bradycardia due to an intermittent SA block), whereas all control persons had normal ambulatory ECG recordings (p < 0.03). Thus, ambulatory ECG recordings may contribute significant diagnostic information in patients with suspected LQTS.
BACKGROUND: Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies. METHODS AND RESULTS: We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin. CONCLUSIONS: We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.
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The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia.
As part of a randomized, single-blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemorheologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and deformability, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (less than or equal to 25 mg/dL) high-density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp(a) levels (greater than 25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low-density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated.
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Cardiac arrhythmias represent a common diagnostic and a frequent therapeutic problem (table 1). They occur both in cordially sound people and in patients with a basic cardiac disease, their clinical significance reaching, therefore, from harmless to life-threatening episodes. For this reason, a documentation and characterization of the different arrhythmias is necessary in clinical practice in order to be able to initiate an adequate therapy in symptomatic and particularly in prognostically relevant cardiac arrhythmias.
The present study was undertaken to measure normal aortic blood velocity profiles by means of continuous wave Doppler echocardiography from apical and suprasternal positions in 40 healthy adults. The profiles in the ascending aorta were measured from both positions, whereas the profiles in the descending aorta were measured only from the suprasternal position. The highest values for the maximal flow velocities were found in the ascending aorta from the suprasternal position (1.28 +/- 0.18 m/s), the lowest values for the maximal flow velocities were found in the descending aorta (1.17 +/- 0.22 m/s). This trend was also found for the mean velocity values. As to the time parameters, a longer acceleration time for the descending aorta was remarkable (106 +/- 24 ms), whereby the mean values for the ejection time for the descending aorta (308 +/- 25 ms, suprasternal: 320 +/- 30 ms). The highest values for the acceleration were found in the ascending aorta (suprasternal: 1526 +/- 531 cm/s2, apical: 1422 +/- 330 cm/s2) and the lowest values in the descending aorta (1208 +/- 378 cm/s2). Regarding the maximal velocity index there was no significant difference for the maximal values between the different transducer positions. The results of the regression analysis showed only a weak correlation of the maximal velocity values in the different transducer positions. This means that for follow-up examinations only those values should be used that were obtained from the same transducer position.
In 40 patients (pts) (ages 34-83 years) the severity of tricuspid regurgitation (TR) was graded by pulsed Doppler echocardiographic determination of regurgitant jet extension. Mild TR was assessed in seven pts (group I), mode-rate TR in 20 pts (group II), and severe TR in 13 pts (group III). The enddiastolic diameter of the left ventricle as measured by M-mode-echocardiography was 55 +/- 16 mm in group I, 48 +/- 6 mm in group II, and 50 +/- 10 mm in group III. The regurgitant index (RI), i.e., the ratio of left-to-right-ventricular stroke counts (normal range 0.89-1.97) and the time-activity curve over the liver area were measured by equilibrium radionuclide ventriculography (RNV). The RI differed significantly between group I (1.6 +/- 0.5), II (1.0 +/- 0.3), and III (0.8 +/- 0.3) (p less than 0.01). An RI-value below 0.89 as an index of right-ventricular volume overload was found in 14% (group I), 45%, (group II) and 77% (group III). The time-activity curve over the liver area, as graded by count variation in phase with the right atrium from 1 (no count variation) to 4 (typical count variation) showed all grades in groups I and II, but only grade 2 to 4 in group III. The RI resp. the time-activity curve over the liver is a sensitive parameter for the detection of moderate to severe TR. If TR is ascertained, severe regurgitation can be differentiated from mild regurgitation by RNV-derived RI as an index of right-ventricular volume overload.
A series of 45 patients with congestive heart failure due to coronary disease had semisupine bicycle exercise tests (ramp protocol, 10 W/min) on two occasions separated by 3 to 7 days in order to determine the short-term reproducibility of gas exchange measurements during symptom-limited exercise. The percentage difference (PD) between each pair of measurements (m1, m2; PD = 100%.(m2-m1): m1) were calculated. The mean PD values (+/- 1 sigma) and the single determination standard deviations (SDSD) for exercise tolerance (ET, W), peak heart rate (pHR, 1/min), peak oxygen uptake (pVO2, ml/min/kg), peak carbon dioxide output (pVCO2, ml/min/kg), and peak minute ventilation (pVE, l/min) were as follows: [table: see text] No patient reached a plateau of oxygen uptake during the last portion of the ramp exercise test. Thus, pVO2 is not an objective endpoint. The single determination standard deviations show that exercise tolerance and peak oxygen uptake do not differ as to their reproducibility. The absolute values of PD were not a function of exercise tolerance for any of the parameters studied. The PD values for ET and pVO2 were normally distributed. The data suggest that a change in ET and pVO2 must exceed 27% and 28% between two sequential studies in an individual patient in order to be significant at the 5% level, respectively. For the one-tailed test situation, the changes in ET or pVO2 must be greater than 23% in order to be significant.