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Biomedical subjects

B D Gonska

Publications and source records attributed to B D Gonska.

At least 19 recordsLinked to original sources

Coxsackievirus genome in myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Enteroviruses are known as major infectious agents for inflammatory heart diseases such as myocarditis and dilated cardiomyopathy (DCM). Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by replacement of right ventricular myocardium by fatty and fibrous tissue. In about 65% of patients inflammatory infiltrates suggest an inflammatory or infectious etiopathogenesis. To test this hypothesis, we investigated endomyocardial biopsies of patients with ARVC, with myocarditis or DCM, and from patients with non-inflammatory cardiac disorders for the presence of enteroviral genome. Enteroviral RNA with homology to coxsackieviruses type B was detected in 3 of 8 patients with ARVC (37.5%), in 7 of 23 patients with myocarditis or DCM (30.4%), but in none of 5 patient with non-infectious myocardial diseases (p < 0.05 compared to ARVC patients). These results support earlier suggestions that coxsackievirus infection of the myocardium is possibly related to the pathogenesis of ARVC.

Adult

Mipafox differential inhibition assay for heart muscle cholinesterases: substrate specificity and inhibition of three isoenzymes by physostigmine and quinidine.

1. A differential inhibition assay was developed for the quantitative determination of cholinesterase isoenzymes acetylcholinesterase (AChE; EC 3.1.1.7), cholinesterase (BChE; EC 3.1.1.8), and atypical cholinesterase in small samples of left ventricular porcine heart muscle. 2. The assay is based on kinetic analysis of irreversible cholinesterase inhibition by the organophosphorus compound N,N'-di-isopropylphosphorodiamidic fluoride (mipafox). With acetylthiocholine (ASCh) as substrate (1.25 mM), hydrolytic activities (A) of cholinesterase isoenzymes were determined after preincubation (60 min, 25 degrees C) of heart muscle samples with either saline (total activity, A tau), 7 microM mipafox (AM1), or 0.8 mM mipafox (AM2): (BChE) = A tau-AM1, (AChE) = AM1-AM2, (Atypical ChE) = AM2. 3. The mipafox differential inhibition assay was used to determine the substrate hydrolysis patterns of myocardial cholinesterases with ASCh, acetyl-beta-methylthiocholine (A beta MSCh), propionylthiocholine (PSCh), and butyrylthiocholine (BSCh). The substrate specificities of myocardial AChE and BChE resemble those of erythrocyte AChE and serum BChE, respectively. Michaelis constants KM with ASCh were determined to be 0.15 mM for AChE and 1.4 mM for BChE. 4. Atypical cholinesterase, in respect to both substrate specificity and inhibition kinetics, differs from cholinesterase activities of vertebrate tissue and, up to now, could be identified exclusively in heart muscle. The enzyme's Michaelis constant with ASCh was determined to be 4.0 mM. 5. The reversible inhibitory effects of physostigmine (eserine) and quinidine on heart muscle cholinesterases were investigated using the differential inhibition assay. With all three isoenzymes, the inhibition kinetics of both substances were strictly competitive. The physostigmine inhibition of AChE was most pronounced (Ki = 0.22 microM). Quinidine most potently inhibited myocardial BChE (Ki = 35 microM).

Animals

Standardized assessment of psychological well-being and quality-of-life in patients with implanted defibrillators.

The ICD has become a standard treatment for patients with malignant arrhythmias. Despite its benefits it may cause additional discomfort to the patients. Thus, quality-of-life needs to be assessed in these patients. Previous studies have used only small samples or unstandardized measures of quality-of-life that do not allow comparisons with other patient groups. The present study used standardized questionnaires for a cross-sectional assessment of psychological well-being and quality-of-life in ICD patients and to compare them to a similar group of coronary artery disease (CAD) patients without ICD. Overall, quality-of-life did not differ between both groups, ICD patients being less anxious than the CAD group. With increasing numbers of ICD shocks, however, the percentage of psychologically distressed ICD patients rose from 10% to > 50%. Psychologically distressed patients had significantly worse scores on most of the quality-of-life subscales, showed less treatment satisfaction, and more negative attitudes. It is concluded that ICD patients have an acceptable mean quality-of-life and low mean anxiety. However, a relevant subgroup of about 15%, especially patients with frequent shocks, experience psychological distress and reduced quality-of-life and should receive special care.

Adaptation, Psychological

Inhibition of the voltage-dependent calcium current by extracellular ATP in hamster ventricular cardiomyocytes.

The modulation of the high-voltage-activated calcium current (ICa) by external ATP was examined in single ventricular cardiomyocytes of the hamster using the whole-cell configuration of the patch-clamp technique. Extracellular application of ATP (0.1-100 microM) was found to inhibit ICa reversibly. The inhibition followed a slow time course (half time approximately 25 s) and was accompanied by very small changes of the holding current and no shift in the current-voltage relationship. With 100 microM ATP, peak ICa was reduced by approximately 30%. This response was not blocked by the P1 inhibitor 8-cyclopentyl-1,3-dipropylxanthine. The nonhydrolyzable ATP analogs adenosine 5'-O-(3-thiotriphosphate) and AMP-adenosine 5'-[beta,gamma-imido]triphosphate also reduced ICa. The ATP analog alpha,beta-methylene-ATP was about equipotent with ATP at 50 microM. Internal guanosine 5'-O-(3-thiotriphosphate) (200 microM) rendered the ATP-mediated inhibition of ICa poorly reversible, whereas internal guanosine 5'-O-(2-thiodiphosphate) (200-500 microM) had no effect. Holding the intracellular adenosine 3',5'-cyclic monophosphate concentration at a constant high level did not alter the ATP response. We conclude that external ATP inhibits ICa via a P2 purinergic receptor in hamster ventricular myocytes. Our results suggest the involvement of a G protein not coupled to adenylate cyclase. The inhibition of ICa by extracellular ATP might have pathophysiological relevance under conditions of myocardial injury.

Adenosine Triphosphate

Radiofrequency catheter ablation of right ventricular tachycardia late after repair of congenital heart defects.

BACKGROUND: Ventricular arrhythmias after repair of congenital heart defects are a common finding and possibly contribute to sudden death in these patients. Optimal antiarrhythmic management has not yet been defined. METHODS AND RESULTS: The study population consisted of 16 patients in whom ventricular arrhythmias occurred 11 to 42 years after complete surgical repair of congenital heart defects. Fifteen patients had a history of symptomatic sustained or nonsustained ventricular tachycardia, and 1 had frequent nonsustained ventricular tachycardia. The diagnostic mapping procedure to identify the origin of the arrhythmia included pace mapping during sinus rhythm, activation mapping, and pacing interventions during ventricular tachycardia. Catheter ablation was carried out by means of radiofrequency energy in the temperature-controlled mode. The follow-up period was 6 to 33 months (mean, 16 months). A right ventricular origin of the tachycardia in the surgically corrected area could be determined in all patients. Catheter ablation was carried out without complications. Immediate noninducibility was achieved in 15 of the 16 patients. One patient in whom the tachycardia was again inducible at repeat stimulation 1 week later was successfully treated with amiodarone. Eleven patients were taken off antiarrhythmic drugs. During follow-up, none of them had a recurrence of the tachycardia that had been ablated. CONCLUSIONS: In patients with symptomatic or frequent ventricular tachycardia late after complete surgical repair of congenital heart defects, catheter ablation by means of radiofrequency energy is feasible and safe and thus might be taken into consideration for these patients. Short-term follow-up results are promising.

Adolescent

Enhanced detection criteria in implantable cardioverter-defibrillators to avoid inappropriate therapy.

The aim of this prospective study was to evaluate the efficacy and safety of enhanced detection criteria, stability and sudden onset, for ventricular tachycardia (VT) in the therapy of implantable cardioverter-defibrillators (ICDs). These detection enhancements ensure a high specificity in detecting VT, thereby avoiding inappropriate therapy delivery due to supraventricular tachycardia. However, delayed sensing or even undersensing of VT may lead to a problematic, even fatal, outcome. In our study, the stability detection enhancement was programmed to discriminate atrial fibrillation (AF) in 84 of 124 patients with implanted ICDs and the sudden-onset detection enhancement in 47 of the 124 patients to discriminate sinus tachycardia. Using these enhancements in 124 patients with third-generation ICDs, 13 patients (11%) had inappropriate therapy during 20 months of follow-up. AF caused shock delivery in 6 patients (5%) and antitachycardia pacing in 4 patients, atrial flutter triggered shock therapy in 1 patient, and sinus tachycardia caused shock delivery in 2 patients. In 3 of the 13 patients inappropriate therapy recurred despite reprogramming the detection enhancements. The stability parameter of 241 spontaneous VT episodes as measured by the devices was 8 +/- 7 msec. Only 10 (4%) VTs had a stability parameter >25 msec. In 46 patients a combination of both detection enhancements, stability and/or sudden onset, were programmed. The use of detection enhancements proved safe and no patient had suffered negative side effects due to prolonged detection time or therapy delay. Inappropriate shock delivery due to AF, a major complication in ICD therapy, was reduced to 5% of patients. The use of the stability enhancement is recommended for patients with intermittent or chronic AF. Selected patients profit from programming both the stability and sudden onset criteria.

Adolescent

Catheter ablation of incessant ventricular tachycardia: acute and long-term results.

SUBJECTS: Seventeen patients with incessant ventricular tachycardia refractory to anti-arrhythmic therapy underwent catheter ablation between 1987 and 1993. Fifteen patients had coronary heart disease and two had dilated cardiomyopathy. The mean age of the patients was 65 +/- 8 and the mean left ventricular ejection fraction was 31 +/- 9%. METHODS: Ablation sites were selected on the basis of endocardial activation mapping, concealed entrainment or bundle branch mapping. Catheter ablation was performed with direct current in nine patients and with radiofrequency energy in eight patients. Incessant ventricular tachycardia was terminated by catheter ablation in all 17 patients. RESULTS: One patient died after the ablation procedure due to pericardial tamponade. During electrophysiological testing 5-14 days later, 7 of 16 patients (44%) had inducible sustained or non-sustained ventricular tachycardia. Five of them underwent implantation of an automatic cardioverter/defibrillator, and three of these experienced discharges of the device during a mean follow-up of 30 +/- 12 months. another patient underwent implantation of a cardioverter/defibrillator after spontaneous recurrence of ventricular tachycardia. Out of the nine patients without inducible ventricular tachycardia, one died as a result of sudden cardiac death, and another had spontaneous ventricular tachycardia. Thus, ventricular tachycardia recurred clinically in 6 of 16 patients (38%), in whom ventricular tachycardia with the same morphology as that of the ablated ventricular tachycardia could be determined only in one patient. CONCLUSION: Catheter ablation is the method of choice for the emergency treatment of patients with incessant ventricular tachycardia. Due to the high risk of recurrence, additional anti-arrhythmic management, such as the implantation of a cardioverter/defibrillator, has to be considered.

Aged

Implantable cardioverter defibrillator detection during radiofrequency catheter ablation of ventricular tachycardia.

Right ventricular radiofrequency catheter ablation was performed in an ICD patient with frequent ventricular tachycardia without prior inactivation of the device. The registrations of intracardiac ECG and marker channel were excellent during energy delivery: the surface ECG was affected. The device did not show dysfunction during and after energy delivery.

Catheter Ablation

[Transient pacemaker dysfunction and spontaneous arrhythmias in symptomatic and asymptomatic patients with ventricular demand pacemakers].

This prospective cross-sectional study include 100 consecutive patients (56 males, 44 females, 29 to 86 (mean = 67.5 +/- 12.2) years) with ventricular inhibited demand pacemakers 0.1 to 94.7 (mean 23.3 +/- 25.4) months after pacemaker implantation. Fifty-two patients were free of symptoms, whereas 48 patients were still complaining of syncope, dizziness, or palpitations. After history, physical examination, and 12-lead standard ECG all patients underwent 24-h Holter monitoring. A computer-aided analysis of spontaneous arrhythmias was done first. In a second run computed-aided analysis of transient pacemaker dysfunctions was performed with a specially designed pacemaker module. There were no significant differences between asymptomatic and symptomatic patients with regard to the incidence of transient pacemaker dysfunctions, with regard to defined types of pacemaker dysfunctions, spontaneous ventricular arrhythmias, and with regard to supraventricular tachycardias. A significant difference between asymptomatic and symptomatic patients was found, however, regarding the Lown classification of ventricular arrhythmias, because asymptomatic patients showed class 0 and I/II arrhythmias more frequently (p < 0.025). In the 100 patients a total of 6609 pacemaker dysfunctions were observed, 5104 failures to sense and 1505 inappropriate inhibitions. Most patients showed up to 240 pacemaker dysfunctions per 24 h. There were no failures to capture. Different types of pacemaker dysfunctions were found with different clinical implications. Due to the Holter findings in nine patients pacemakers were reprogrammed or replaced. After pacemaker implantation the number of patients with severe symptoms significantly decreased compared to the number of patients before pacemaker implantation. Nonetheless, there was a number of patients still complaining of symptoms after pacemaker implantation. In only a few patients did pacemaker implantation worsen symptoms . Our data show that with use of long-term ECG transient pacemaker dysfunctions and spontaneous arrhythmias are more frequent than patients' history and common standard techniques in the pacemaker clinic may suggest Holter monitoring, therefore, is a useful diagnostic tool, not only in symptomatic, but also in asymptomatic pacemaker patients. It allows to obtain a reliable survey of the real amount of transient pacemaker dysfunctions in the individual patient, which is the base for further therapeutic decisions.

Adult

Obstructive sleep apnoea and signal averaged electrocardiogram.

Patients with obstructive sleep apnoea demonstrate an increased rate of ventricular arrhythmias. The present study was designed in order to investigate whether these arrhythmias may be related to myocardial injury, since myocardial injury of various aetiologies has been observed to change the signal averaged electrocardiogram (ECG). Signal averaged ECG was registered in 23 patients with obstructive sleep apnoea diagnosed by polysomnography (apnoea index 43 +/- 20 events.h-1, age 55 +/- 10 yrs). QRS duration, root mean square voltage of the last 40 ms of QRS, and low amplitude (< 40 mV) signal duration were determined from the vector magnitude of the QRS, high-pass filtered at 40 Hz. Patients with coronary heart disease or bundle branch block were excluded. No patient showed an abnormal signal averaged ECG. Mean duration of the filtered QRS complex was 96 +/- 9 ms, root mean square voltage 38 +/- 18 microV and low amplitude signal duration 26 +/- 8 ms. These results were not significantly different from 14 snoring subjects with an apnoea/hypopnoea index < 10. Four patients showed no ventricular arrhythmias and six patients had Lown III or IVa in the Holter ECG. Echocardiography revealed increased left atrial (43.7 +/- 4.1 mm) and interventricular septal diameters (11.3 +/- 1.4 mm). In conclusion, obstructive sleep apnoea does not generate a substrate for late potentials in the signal averaged ECG.

Arrhythmias, Cardiac

[Bacterial endocarditis of the transvenous lead of an implantable cardioverter/defibrillator].

A 27-year-old patient carrying a transvenous ICD developed infective endocarditis more than 1 year after surgery. Staphylococcus aureus was isolated from blood cultures. A transesophageal echocardiogram revealed a mobile vegetation on a thrombus attached to the ICD lead in the right atrium. The ICD lead was removed by right anterolateral thoracotomy. This raises the issue of the risk of thrombus formation in patients with intravenous ICD leads and the associated susceptibility to infective endocarditis.

Adult

Catheter ablation of ventricular tachycardia in 136 patients with coronary artery disease: results and long-term follow-up.

OBJECTIVES: This study attempted to determine the feasibility and long-term efficacy of catheter ablation by means of either radiofrequency or direct current energy in a selected group of patients with coronary artery disease. BACKGROUND: Catheter ablation of ventricular tachycardia has proved to be highly effective in patients with idiopathic and bundle branch reentrant ventricular tachycardia. In patients with coronary artery disease and recurrent sustained ventricular tachycardia resistant to medical antiarrhythmic management, the value of catheter ablation has not yet been established. METHODS: One hundred thirty-six patients with coronary artery disease and one configuration of monomorphic sustained ventricular tachycardia underwent radiofrequency (72 patients) or direct current catheter ablation (64 patients). The mapping procedure to localize an adequate site for ablation included pace mapping during sinus rhythm, endocardial activation mapping, identification of isolated mid-diastolic potentials and pacing interventions during ventricular tachycardia. RESULTS: Primary success was achieved in 102 (75%) of 136 patients (74% of 72 undergoing radiofrequency and 77% of 64 with direct current ablation). Complications were noted in 12% of patients. During a mean (+/- SD) follow-up period of 24 +/- 13 months (range 3 to 68), ventricular tachycardia recurred in 16% of patients. CONCLUSIONS: Catheter ablation of ventricular tachycardia in coronary artery disease is feasible in patients with one configuration of monomorphic sustained ventricular tachycardia. There is no significant difference with respect to the type of energy applied. The follow-up data show that in a selected group of patients with coronary artery disease, catheter ablation offers a therapy alternative.

Adult