Rapid and inexpensive high-performance liquid chromatographic method for the quantification of flecainide in serum.
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Chromatography, High Pressure Liquid↗
Biomedical subjects
L Seipel
Publications and source records attributed to L Seipel.
[Comparison of the hemodynamics effects of D-sotalol and D,L-sotalol].
The hemodynamic effects of the class III drug D-sotalol and of the beta adrenergic receptor antagonist D,L-sotalol were compared in 16 rats (2 mg/kg i.v.). A group with NaCl-infusion served as control (n = 10). Besides measurements in the intact circulation isovolumic registrations were performed to examine the left ventricular myocardial function without interferences. D,L-sotalol significantly reduced the dp/dtmax (61%) and the peak isovolumic left ventricular pressure (64%). It lowered the heart rate by 13% and slightly increased the mean aortic pressure to 107% (p less than 0.05). D-sotalol, in contrast, caused only a very transient reduction of the dp/dtmax and was comparable to the controls already 5 min after injection. The results demonstrate, that the D-enantiomer is largely avoid of the hemodynamic effects of the racemic D,L-sotalol after intravenous injection.
Animals↗
Effect of right coronary artery occlusion during percutaneous transluminal coronary angioplasty on right ventricular performance.
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Aged↗
Accuracy of Doppler echocardiography in quantification of left to right shunts in adult patients with atrial septal defect.
In previous experimental and pediatric studies, the ratio of pulmonary to systemic flow (Qp/Qs) was accurately estimated by Doppler echocardiography in various cardiac shunt lesions. The purpose of this study was to assess the accuracy of pulsed Doppler echocardiography in determining the magnitude of shunt flow in adult patients with an ostium secundum type atrial septal defect. In 32 patients with high quality echocardiograms and excellent Doppler signals, blood flow was measured in the right and left ventricular outflow tract by Doppler echocardiography. In 16 patients without heart disease, the correlation (r) between systemic (Qs) and pulmonary (Qp) blood flow was 0.96 (SEE = 0.417 liter/min, y = 1.05x - 0.21) and the mean Qp/Qs ratio was 1.01 +/- 0.09. In 16 patients with an atrial septal defect, the Qp/Qs ration measured by oximetry ranged from 1.34 to 4.61 and by pulsed Doppler echocardiography from 1.31 to 4.46 (p = NS). In these 16 patients, the correlation between the Qp/Qs ratio determined by oximetry and pulsed Doppler echocardiography was significant (r = 0.82, SEE = 0.54). In the total group of 32 patients, the correlation was stronger (r = 0.93, SEE = 0.37). Systematic differences between the invasive and noninvasive shunt calculations did not occur. Thus, in adult patients with an atrial septal defect of the secundum type and high quality echocardiograms, the magnitude of left to right shunt can be accurately assessed by pulsed Doppler echocardiography. In the absence of pulmonary hypertension, pulsed Doppler echocardiography provides precise information for the decision to undertake conservative or operative treatment.
Adult↗
Effects of graded intensity of oxygen deficiency on function and energy metabolism in post-ischaemic myocardium.
The effect of graded ischaemic injury on post-ischaemic myocardium was examined in rat hearts after three 4 min periods of asphyxia. Systolic function under steady state conditions and during isovolumic beats, the content of high energy phosphates and glycogen, and myocardial material properties were determined. Severity of the oxygen deficiency was varied by manipulating myocardial oxygen demand (MVO2) either by rapid atrial pacing or by vagal stimulation. After 20 min of post-asphyxial recovery, steady state haemodynamics were almost normal. In the high MVO2 group (atrial pacing) the dp/dtmax was reduced to 90%(NS). The isovolumic indices of function were decreased in all post-asphyxial groups. This was most pronounced in the high MVO2 group, with a reduction in peak left ventricular systolic pressure to 85.7 (SEM 3.4)% and a decrease in peak left ventricular systolic stress to 82.3(3.9)% (p less than 0.01). The post-asphyxial myocardial performance recovered better in the low MVO2 group (vagal stimulation). Material properties were altered only in the high MVO2 group. The decreased content of ATP and glycogen were comparable in all post-asphyxial groups. A phosphocreatine overshoot phenomenon was most marked in the high MVO2 group: 11.4(2.8) mumol.g-1 v 4.7(0.9) mumol.g-1 (control), p less than 0.01. The results indicate that post-ischaemic contractile dysfunction of reversibly injured is not closely related to the previous O2 deficit or to the functional impairment. We also obtained no correlation between ATP content and material properties in modestly injured post-ischaemic myocardium.
Animals↗
[Syncope in the act of swallowing (swallowing syncope)].
In a 30-year-old female patient with recurrent syncope during swallowing, intermittent complete AV-block was documented as the underlying mechanism. This phenomenon could be provoked by inflating a balloon positioned in the lower esophagus. The His-bundle electrocardiogram, recorded simultaneously, showed a progressive increase of the normal AH-interval, up to complete block distal to the A-wave. Atropine prevented induction of the block. After implantation of a VVI pacemaker, the symptoms disappeared completely. This very rare phenomenon of swallowing syncope is probably due to a pathologic vago-vagal reflex.
Adult↗
[Flecainide-induced hepatitis].
Flecainide was given to a patient in a dose of 150 mg twice daily to convert a newly developed atrial fibrillation; concomitant therapy was unchanged. After the fourth dose the patient complained of upper abdominal pain and nausea. GOT and GPT, normal at admission to the hospital, became markedly elevated and reached a maximum of 960 IU/I (GOT) and 993 IU/I (GPT) one day later, although the enzymes which indicate cholestasis remained at a normal level or did not increase. On the assumption of a drug-induced allergic reaction, flecainide was withdrawn, after which liver enzymes rapidly returned to control values. Although neither a reexposition with flecainide nor a liver biopsy was obtained, a flecainide-induced hepatitis seems probable.
Aortic Valve Stenosis↗
[Electrophysiologic effects of betaxolol on conduction properties of the antegrade and retrograde pathway in patients with typical atrioventricular node reentry tachycardia following intravenous and oral administration].
The electrophysiologic effects of the beta-1 selective beta adrenergic blocking drug Betaxolol were investigated after intravenous (0.15 mg/kg body weight) and oral (20 mg/day) administration in 11 patients with atrioventricular-nodal reentrant tachycardia. Betaxolol significantly (p less than 0.01) prolonged cycle length, sinus node recovery time, AH-interval, as well as the antegrade functional refractory period of the slow and fast AV-nodal pathway. The effective refractory period of the fast AV-nodal pathway was also markedly increased (p less than 0.05). In only six patients could the effective refractory period of the slow AV-nodal pathway be determined; in the other patients, it was shorter than the effective refractory period of the atrium. The effective refractory period of the atrium and the ventricle was not significantly altered by Betaxolol. Intravenous administration of Betaxolol suppressed induction of tachycardia in eight patients, whereas after oral Betaxolol, tachycardia was not inducible in ten patients. Betaxolol prevented induction of tachycardia in two patients by prolonging antegrade conduction over the slow AV-nodal pathway. The retrograde fast AV-nodal pathway was blocked in eight patients. Presumably the increased effectiveness of oral Betaxolol can be attributed to higher Betaxolol plasma concentrations, reached after oral treatment (58 +/- 38 ng/ml), as compared to intravenous administration (40 +/- 40 ng/ml). There were no false positive results after intravenous testing of Betaxolol.
Administration, Oral↗
[Effect of a new class I anti-arrhythmia agent cibenzoline in patients with therapy refractory, sustained ventricular tachycardias].
The effectiveness of Cibenzoline was assessed by means of programmed ventricular stimulation in 13 patients with sustained, drug refractory ventricular tachycardia. Besides Cibenzoline, an average of 3.5 antiarrhythmic drugs were tested, or were clinically ineffective. Cibenzoline was applied, i.v., in a dose of 1.5 mg/kg within 10 min. Cycle length was significantly shortened (p less than or equal to 0.05) while increases were noted for effective refractory period of the right ventricle (p less than or equal to 0.05), intranodal (AH-interval) and infranodal (HV-interval) conduction time (p less than or equal to 0.01), QRS-duration (p less than or equal to 0.001), QT-interval corrected for frequency (p less than or equal to 0.001) as well as cycle-length of the tachycardia (p less than or equal to 0.05). After i.v. Cibenzoline, induction of tachycardia was more difficult in two patients and unchanged in five patients. Spontaneous occurrence of the tachycardia was noted in three patients, and in one patient tachycardia was sustained by atrial stimulation. Cibenzoline i.v. prevented tachycardia in two patients respectively induction of tachycardia was not reproducible. It is concluded that Cibenzoline may be effective in individual patients with sustained ventricular tachycardia unresponsive to other antiarrhythmic drugs.
Adult↗
[Cardiac side effects of anti-arrhythmia agents].
Antiarrhythmic drugs have typical cardiac side effects. These effects are due to their electrophysiological action on the one hand and to the negative inotropy on the other. These electrophysiological effects can cause a depression of sinus node function and/or AV conduction leading to severe bradycardia or asystole. However, the proarrhythmic effects of these drugs are clinically more important, especially the induction of ventricular tachycardia and "torsades". The incidence of these proarrhythmic effects is at least 5% of all patients treated. Patients with reduced ventricular function, "malignant" ventricular arrhythmias, and QT prolongation are especially endangered. Proarrhythmic effects may occur after the first dose. However, in most instances the risk is increased with higher dosage. The hemodynamic effects of antiarrhythmic drugs are especially important in patients with reduced cardiac function. The negative inotropy of antiarrhythmic drugs is often counterbalanced by the simultaneous decrease in blood pressure leading to an afterload reduction. Antiarrhythmic drugs causing an increase in systemic resistance may have a more pronounced depressive effect on cardiac function. However, if the acute treatment of severely ill patients in the CCU is excluded, the negative inotropy of antiarrhythmic drugs is not such an important problem as the proarrhythmic effect. As a consequence, antiarrhythmic treatment should be restricted to severely symptomatic patients on the one hand and to those with arrhythmias of prognostic importance on the other. In addition, the patient's treatment should be carefully controlled, especially during the early phase of treatment with antiarrhythmic drugs.
Anti-Arrhythmia Agents↗
[Experimental studies of the hemodynamics of disopyramide in comparison with quinidine].
The haemodynamic effects of quinidine and disopyramide i.v. were investigated in 79 rats. Measurements were performed in the intact circulation (LVP, AoP, dp/dtmax). Myocardial function was examined independently of circulatory changes by isovolumetric registrations (peak LVP). Animals with NaCl infusion served as controls. After infusion of 5 mg/kg (10 mg/kg) quinidine, we obtained a reduction (p less than 0.05) in the left ventricular pressure to 81.6 +/- 3.1% (82.6 +/- 3.7%), in the mean aortic pressure to 70.7 +/- 3.4% (79.3 +/- 6.7%), in dp/dtmax to 73.9 +/- 5.6% (72.8 +/- 6.2%), and in the heart rate to 69.7 +/- 7.4% (69.9 +/- 5.4%). Isovolumic pressure maxima after quinidine were not different from the controls (90.7 +/- 2.4% and 93.6 +/- 1.5% respectively vs. 96.1 +/- 1.0%). 1 mg/kg disopyramide caused no significant haemodynamic changes. 2 mg/kg disopyramide led to a slight increase in dp/dtmax (107.2 +/- 5.6%, N.S.), while 4 mg/kg disopyramide had a tendency to reduce the left ventricular pressure (88.5 +/- 6.2%), mean aortic pressure (80.5 +/- 14.8%) and dp/dtmax (75.1 +/- 8.0%). After 4 mg/kg disopyramide, the isovolumic maxima were reduced. Our results indicate that the haemodynamic side effects of class-I antiarrhythmic drugs are different. Quinidine i.v. caused a reduction in pressures and heart rate, but had no influence on the isovolumic pressure maxima. Disopyramide i.v., on the other hand, had no significant haemodynamic effects in clinical doses. After high (not clinically used) doses of disopyramide (4 mg/kg), which also led to high plasma levels, myocardial performance was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Phenotypic heterogeneity of cardiac myxomas].
Histogenesis of cardiac myxoma is still unclear. Beside endothelial cells a variety of different cell types were detected in this benign cardiac tumor. Cryostat sections of four myxomas were analysed in the indirect immunoperoxidase technique using monoclonal antibodies (MoABs) directed against MHC class I and II antigens, as well as different surface determinants specific for endothelial cells or monocytes/macrophages. Tumor cells forming cell clusters and blood vessel like structures differed in their expression of endothelial antigens suggesting cellular heterogeneity within single and different myxomas. Like in fetal cardiac tissue vascular channels rarely carried HLA-class II antigens. Tumor cells carrying antigens of monocytes/macrophages, as well as intracellular alkaline phosphatase of endothelial cells could represent subpopulations of an early differentiation stage. This analysis further supports previous hypothesis of an endothelial origin of myxomas.
Adult↗
Determination of amiodarone and its metabolite N-desethylamiodarone in serum by high-performance liquid chromatography--comparison of different extraction procedures.
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Amiodarone↗
[Digitalis therapy in medical practice. Research on indications and dosage criteria in general practice].
Two hundred digitalized patients under nine freely practising physicians were investigated. One hundred and ninety-six patients received digoxin or one of its derivatives. Of these, 50% did not have therapeutic serum glycoside concentrations, 48% were in the mostly subtherapeutic range and 2% were in the potentially toxic range. Signs of glycoside intoxication were not found. A substantiated indication for glycoside therapy was found in the final analysis in 55% of the patients. In 128 patients, the methyldigoxin dose calculated (0.16 +/- 0.030 mg/d) was markedly in excess of that actually prescribed (0.13 +/- 0.050 mg/d; p less than 0.001), so that there were indications of a general underdigitalization. In addition, it was not possible to anchor the restrictive kidney function as a reason for reduction of digoxin dosage in the prescription behavior. In the long run, only 36% of the patients with justified indication and therapeutic serum glycoside concentration as well as (with reservations) the 3% with potentially toxic serum glycoside concentration profited from the glycoside therapy.
Atrial Fibrillation↗
[Percutaneous transluminal coronary angioplasty and aortocoronary bypass surgery in unstable angina pectoris and coronary multivessel disease].
In 113 patients demonstrating the clinical syndrome of unstable angina, acute-stage coronary angiography revealed multivessel disease. Acute PTCA of the ischaemia-related coronary artery or bypass grafting was performed depending on angiographic criteria. Of the total of 68 patients in whom PTCA was performed, 45 had two-vessel disease (2 vd) and 23 three-vessel disease (3 vd). 12 of the 45 patients with bypass operation had a left main stem stenosis, whereas 33 had three-vessel disease. The primary success rate of PTCA was 81%, 89% in patients with 2 vd and 70% in patients with 3 vd. Acute post-PTCA bypass grafting was necessary in 2 patients having 2 vd and in 5 patients suffering from 3 vd. 5 of the 68 patients treated with PTCA developed a transmural myocardial infarct and one patient died after PTCA and emergency bypass surgery. 8 of the 45 operated patients had a perioperative or postoperative myocardial infarct and 5 patients died intraoperatively or postoperatively. The overall morbidity was 11.5%, and the mortality of hospitalised patients was 5.3% (6/113). Combination of PTCA with emergency bypass grafting offers a new and effective treatment with an acceptable risk even in multivessel disease patients and in those having unstable angina pectoris. The additional use of PTCA definitely improves therapeutic management in this high-risk population.
Angina Pectoris↗
Phosphocreatine and adenine nucleotides in postasphyxial hearts with normal basal function and normal oxygen demand.
We investigated whether there is a relationship between the prolonged dysfunction after myocardial ischaemia and the postischaemic phosphocreatine overshoot phenomenon. In 16 open-chest rats 3 periods of 4 minutes of oxygen deficiency were performed and basal haemodynamic variables and the myocardial oxygen demand were determined during the recovery period. At the end of the 20 minutes recovery period, left ventricular pressure, dp/dtmax, ejection fraction, and myocardial oxygen demand were completely recovered. High energy phosphate levels, however, were still altered. The sum of adeninenucleotides was decreased to 78 +/- 4% of control (mean +/- SEM, p less than 0.05). The level of phosphocreatine was markedly elevated to 162 +/- 14 (mean +/- SEM). The persistence of the phosphocreatine overshoot phenomenon, while basal function was already normalized, indicates that a reduced function and thus a reduced energy demand of the contractile apparatus are not the cause of the phosphocreatine overshoot. We found no close relationship between high energy levels and basal function or oxygen demand in myocardium after mild oxygen deficiency.
Adenine Nucleotides↗
Changes in haemodynamics and left ventricular function during intravenous nifedipine infusion with and without additional propranolol in patients with coronary artery disease. A randomized, placebo controlled trial.
The haemodynamic effects of a combined intravenous treatment of nifedipine and propranolol in ten patients with coronary artery disease compared to a single treatment with nifedipine or placebo were investigated. Nifedipine infusion resulted in a reduction of left ventricular (LV) afterload and LV volumes with an increase in heart rate and EF and no change of the double product, coronary sinus flow, LV diastolic parameters and dp/dtmax. Addition of propranolol lowers myocardial oxygen demand by reducing heart rate and dp/dtmax together with a sustained afterload reduction with no change in LV volumes and EF. The vasodilatatory action of nifedipine pretreatment balanced the negative effects of acute beta-receptor blockade on LV function and allows the reduction of myocardial oxygen demand without a deterioration of LV function.
Angiography↗
Influence of sampling site and flow area on cardiac output measurements by Doppler echocardiography.
In 40 patients cardiac output was simultaneously determined by pulsed Doppler echocardiography and thermodilution (range 4.0 to 10.2 liters/min). The sample volume was located in the center of the mitral anulus, at the tips of the mitral leaflets and in the center of the aortic anulus. Circular cross-sectional areas of the mitral anulus, aortic anulus and aortic bulbus were calculated from M-mode and two-dimensional echocardiographic diameters. The varying short axis of the elliptical mitral opening area was obtained from the diastolic leaflet separation in the M-mode, and the long axis was derived from the maximal mitral orifice area or mitral anulus diameter. Cardiac output was calculated by multiplying time-velocity integrals with the different areas and heart rate. Doppler flow measurements correlated significantly with the thermodilution method (r = 0.79 to 0.93). Flow measurements at the aortic anulus were most accurate (r = 0.93, SEE = 0.589 liter/min) if the annular area was derived from the M-mode tracing. Measurement of the anulus in the apical five chamber view yielded a significant underestimation and the area of the aortic bulbus provided an overestimation of cardiac output. Left ventricular inflow was underestimated at the mitral leaflet tips and overestimated at the mitral anulus. The accuracy of pulsed Doppler cardiac output measurements strongly depends on the assumed flow area and sampling site. Both should be determined at the same level in the inflow or outflow tract of the left ventricle. Measurement of cardiac output in the center of the aortic anulus provided the highest accuracy.
Adolescent↗