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Biomedical subjects

F Horkay

Publications and source records attributed to F Horkay.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increased monophasic action potential dispersion in endothelin-1-induced ventricular arrhythmias.

The aim of this study was to investigate the changes in monophasic action potentials (MAP) from different sites in the heart and to determine MAP dispersion during endothelin-1 (ET-1) infusion. Standard ECG, left ventricular anterior, right ventricular lateral, right ventricular septal, and right ventricular apical MAPs and intra-arterial blood pressure were monitored in seven anesthetized open-chest mongrel dogs. After radiofrequency atrioventricular node ablation, ventricular pacing (70/min) was performed and intracoronary ET-1 (60 pmol/min) was administered into the left anterior descending coronary artery. Both MAPd90 and MAPd90 dispersion increased significant during ET-1 infusion. The onset of spontaneous monomorphic and polymorphic sustained ventricular tachycardias (sVT) was observed in five dogs (around 40 min), and nonsustained VTs (nsVT) developed in another two dogs. The increases in MAP and MAP dispersion lasted until the appearance of polymorphic nsVTs and sVTs, but at the time of these VTs this difference decreased. At the termination of the experiments, ventricular fibrillation occurred in six cases. In four cases third-phase early afterdepolarizations were recorded. Our results suggest that increased MAP dispersion and development of EAD contribute to the arrhythmogenic action of ET-1, and these phenomena might explain the pathogenesis of a wide variety of ventricular arrhythmias with different morphology observed in this study.

Action Potentials↗
PubMed1998

Mechanism of endothelin-induced malignant ventricular arrhythmias in dogs.

The development of ventricular tachyarrhythmias caused by low-dose intracoronary infusion of endothelin-1 (ET-1) has recently been observed in dogs. The aim of the present study was to investigate the pathomechanism of ET-1-induced ventricular arrhythmias in 32 anesthetized, open-chest mongrel dogs in group A (n = 14) without, in group B (n = 14), and in group C (n = 4 control) with atrioventricular node ablation. The coronary blood flow (CBF) was measured in the left anterior descending (LAD) coronary artery by an electromagnetic flowmeter. Standard ECG, atrial and ventricular electrograms, and in groups B and C endocardial and epicardial monophasic action potentials (MAPs) were recorded. ET-1 was administered into the LAD at a low dose (30-60 pmol/min). At the time of the appearance of premature beats, CBF was only slightly decreased. The effective ventricular refractory period did not change significantly. Onset of spontaneous polymorphic and monomorphic sustained ventricular tachycardia (sVT) was observed in five dogs without bradycardia and in nine dogs with bradycardia. VTs in dogs with complete AV block were longer and slower. In most of the cases, ventricular fibrillation occurred. ET-1 treatment resulted in a significant increase in MAP 90% duration (255 +/- 9 vs. 290 +/- 8 ms endocardial, 244 +/- 10 vs. 292 +/- 12 epicardial; p < 0.05) at 70 beats/min ventricular pacing. In eight cases (group B), third-phase early afterdepolarization could be recorded. According to our results, the mechanism of ET-1-induced arrhythmias appears to be based on prolongation of MAP duration and development of afterdepolarizations.

Action Potentials↗
PubMed1998

Electrophysiological effects of intrapericardial infusion of endothelin-1.

Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients undergoing open-heart surgery. ET-1 has been suggested to have direct arrhythmogenic effect on myocardium. The aim of the present study was to examine the putative arrhythmogenic effect of intrapericardial infusion of ET-1 in anesthetized dogs (n = 15). In preliminary experiments, ET-1 (0.125-1.0 nmol/min, n = 7) was infused into the closed pericardial sack for 40 min. ET-1 induced non-sustained and/or sustained ventricular tachyarrhythmias in all but the lowest dose. For detailed arrhythmia analysis in addition to standard ECG ventricular endocardial and epicardial monophasic action potentials (MAP) were recorded. ET-1 (0.250 nmol/min, n = 7) induced mono- and polymorphic ventricular tachycardias, which degenerated into ventricular fibrillation in two instances. Moderate if any ischemic signs could be detected before the onset of arrhythmias. The arrhythmias spontaneously disappeared in all instances with the exception when ventricular fibrillation terminated the experiment. QT interval (260 +/- 23 ms vs. 317 +/- 31 ms, P < 0.05), and endo- and epicardial MAPD90 (at 300 ms cycle length) prolonged significantly (in average 182 +/- 12 ms vs. 224 +/- 25 ms, P < 0.05). Using MAP recording afterdepolarizations were detected in three instances. In control animals (n = 3) arrhythmias were not observed and all electrophysiological parameters remained unchanged. The present results show that intrapericardial administration of ET-1 can induce ventricular arrhythmias in dogs. The arrhythmogenic effect of ET-1 may be based on prolongation of MAP duration and development of afterdepolarizations. However, the elucidation of the precise mechanism needs further investigation.

Action Potentials↗
PubMed1998

Simultaneous recordings of the monophasic action potential with silver chloride- and Ir-coated electrodes.

Ag/AgCl and Ir-coated electrodes allow the recording of the monophasic action potential (MAP) due to their electrical properties like non-polarisability. This study investigates the correlation of MAP recorded with both types of electrodes. In 20 mongrel dogs (18 +/- 6 kg) an Ag/AgCl and an Ir-coated catheter (Ir) were placed endocardially in the apex of the right ventricle. The effects of isoproterenol and verapamil were investigated during spontaneous rhythm and stimulation simultaneously recorded with both types of electrodes in 10 dogs without AV-node ablation. The correlation at different heart rates were investigated in 10 other dogs with complete AV-block. The morphology and amplitudes of MAP were comparable (AgCl: 15 +/- 7 mV; Ir: 13 +/- 8 mV). Following an i.v. bolus of 2 micrograms/kg isoproterenol the spontaneous rate increased (175 +/- 18 to 245 +/- 25 bpm). During stimulation with 250 ms cycle length the duration shortened (MAPd90: AgCl: 160 +/- 11 to 130 +/- 12 ms; Ir: 154 +/- 18 to 128 +/- 15 ms). The alterations reversed after 20 min. An i.v. bolus of 0.2 mg/kg verapamil decreased the spontaneous rate (167 +/- 11 to 104 +/- 23 bpm) and lengthened the MAPd90 (AgCl: 182 +/- 14 to 220 +/- 13 ms; Ir: 174 +/- 16 to 216 +/- 21 ms) at 300 ms stimulation. The correlation between the MAPd90 of both lead types was r = 0.98 during all measurements. Under the effect of beta-agonist and Ca(2+)-antagonist medication MAP showed a strong correlation recorded with both types of electrodes. Thus, both leads allow the recording of MAP but only the Ir-electrodes with their long-term stability are implantable and allows us to control the effects of drugs with implantable devices.

Action Potentials↗
PubMed1998

Endothelin converting-enzyme-1 mRNA expression in human cardiovascular disease.

Endothelin-1 converting-enzyme (ECE-1) cleaves the precursor, big-endothelin-1, to the active peptide endothelin-1. The aim of this study was to investigate whether ECE-1 mRNA expression is modified in human cardiovascular disease. Tissue samples from the left human atrium were analyzed for ECE-1 expression and related to different clinical parameters. A quantitative PCR assay (qPCR) with competitive and non-competitive standards was established. The ECE-1 measurements were normalized by a GAPDH qPCR. Patients who suffered from a myocardial infarction had elevated ECE-1 levels when compared to controls (5.81+/-0.76 vs. 3.20+/-0.51 fg ECE-1, ng GAPDH, p<0.05). Drug treatment with the beta-blocker metoprolol was associated with a decreased ECE-1 expression level (3.90+/-0.58 vs. 5.81+/-0.76 fg ECE-1, ng GAPDH, p<0.1). We conclude that the expression of ECE-1 is altered in the atrial tissue depending on the physiological status of the heart. This suggests a differential role of ECE-1 in cardiovascular diseases.

Adrenergic beta-Antagonists↗
PubMed1997

Characterization and stimuli for production of pericardial fluid atrial natriuretic peptide in dogs.

Recently high immunoreactive atrial natriuretic peptide (ir-ANP) levels have been found in the pericardial fluid of patients undergoing cardiac surgery. The present study was designed to characterize pericardial fluid ANP in anesthetized dogs. Pericardial fluid ir-ANP levels were 3.4-fold higher than plasma levels and the molecular form, revealed by high performance liquid chromatography, was indistinguishable from ANP[99-126]. Elimination of [125I]ANP was 5-fold slower in the pericardial space than in plasma. Activity of the major ANP degrading enzyme, neutral endopeptidase (NEP, EC 3.4.24.11), was 15-times higher in the pericardial fluid than in plasma. Right atrial balloon distension and rapid right ventricular pacing induced maximally 2.3-fold and 1.5-fold increases of pericardial fluid ir-ANP, respectively. Pericardial fluid ir-ANP concentrations and right atrial pressure values showed significant correlation during the stimuli. Our present results show that high concentrations of ir-ANP can be found in the dog pericardial fluid even under unstimulated conditions. Slow elimination of ANP from the pericardial fluid compartment may contribute to the high peptide levels. However this slow elimination cannot be attributed to a lower NEP activity. High basal levels of ANP in the pericardial fluid could be further increased by atrial balloon stretch and rapid ventricular pacing. The increase of pericardial fluid ir-ANP appeared to be a stretch-dependent response. ANP released into the pericardial fluid may be involved in the regulation of cardiac function and coronary vascular tone.

Animals↗
PubMed1995

[Experience with a transvenous pacemaker-cardioconverter-defibrillator without subcutaneous patch].

Sudden cardiac death caused by malignant ventricular arrhythmias is one of the main causes of cardiovascular mortality. Implantation of cardioverter-defibrillators has resulted in the reduction of the incidence of sudden cardiac death caused by malignant ventricular arrhythmias from the yearly 10-30% to 1%. For the very first time in Hungary, the authors applied only transvenous lead configuration for automatic cardioverter defibrillators in three patients. The indications of the implantation were ventricular fibrillation in one case, ventricular tachycardias refractory to drug treatment in two cases. Ventricular arrhythmias were secondary to coronary heart disease in two patients, dilatative cardiomyopathy in one patient. Preoperative, intraoperative and postoperative electrophysiological studies were regularly taken. Using Biotronik Phylax 03 device with a right ventricular electrode and a superior vena cava electrode and without subcutaneous patch the intraoperative defibrillation thresholds were 6, 11 and 12 J respectively. The fractally iridium coating increases the surface of the electrodes that has a very good effect on defibrillation threshold. During a mean follow-up of six months the occurring spontaneous ventricular arrhythmias (1 ventricular fibrillation and 5 ventricular tachycardias) were terminated by Phylax 03 with cardioversion-defibrillation or overdrive stimulation. The authors' results of intraoperative testing and clinical experiences show that the Phylax 03 biphasic system due to low defibrillation thresholds without subcutaneous patch can safely be applied with only transvenous implant technique in patients with major ventricular arrhythmias to prevent sudden cardiac death and to terminate ventricular tachycardia.

Arrhythmias, Cardiac↗
PubMed1995

Ventricular tachycardias induced by intracoronary administration of endothelin-1 in dogs.

In 12 anesthetized, open-chest mongrel dogs, endothelin-1 (ET-1) was infused into the left anterior descending coronary artery through an indwelling catheter at a dose of 30 pmol.min-1 for 30 min (n = 8). In four dogs the ET-1 dose was increased to 60 pmol/min for 10 min. Programmed electrical stimulation was used for electrophysiologic studies. Coronary blood flow was reduced by 32% on average without any ischemic ECG signs. QT time (186 +/- 3 ms vs. 218 +/- 6, p < 0.05, and 225 +/- 9, p < 0.05, p < 0.05). Ventricular irritability increased in all cases; ventricular extrasystoles, and nonsustained and sustained tachycardias occurred and, in 11 cases, ventricular fibrillation terminated the experiments. In two dogs, early afterdepolarization was recorded. Therefore, ET-1 is capable of inducing fatal ventricular arrythmias at least partly independent of its vasoconstrictor effect. QT prolongation appears to have a pathophysiologic role in this arrythmogenic effect.

Action Potentials↗
PubMed1995

Human pericardial fluid contains the highest amount of endothelin-1 of all mammalian biologic fluids thus far tested.

Immunoreactive endothelin-1 (ET-1) levels were measured in the pericardial fluid (PF), plasma (PL), and atrial and ventricular tissues of 16 cardiac surgical patients. ET-1 was higher in the PF (73 +/- 11 pg/ml) than in the PL/3.33 +/- 0.51 pg/ml; p < 0.05/. PF/PL ratio ranged from 8 to as high as 200. An inverse relationship was found between the NYHA stage and ET-1 concentrations in PF, whereas ET-1 in PL did not have any relation to the NYHA stage of the disease. In HPLC analysis, the total immunoreactive ET-1 in PF from five different patients co-eluted with the human ET-1 standard. The results indicate that ET-1 concentrations in human PF can be several-fold those in the PL. The source and function of the ET-1 in PF requires further investigation.

Body Fluids↗
PubMed1992

[Coronary surgery at the Cardiovascular Surgical Clinic (1976-1990)].

In the Cardiovascular Surgical Clinic of the Semmelweis Medical University of Budapest the first coronary artery bypass grafting (CABG) procedure was performed in 1975. Since that time coronary artery surgery has become a routine everyday practice representing more than half of the total workload of adult cardiac surgery. The analysis of 1347 operations performed between 1976-1990 on patients with coronary heart disease showed the followings: the first few years--so called learning curve of CABG operations is characterised by high mortality. With passing time the number of cases performed each year increased rapidly and the surgical technique has improved too. At the same time the operative mortality figures showed decreasing tendency--it was 2.1% for the last 609 cases. All observed parameters showed some progress: in 1990 the average number of grafts per patient was 3.09, internal mammary artery usage 15 percent and the mean aortic cross clamp time per anastomosis 24.5 minutes. Complete myocardial revascularisation is the key point of coronary artery surgery. In order to achieve this target in all operated cases further technical improvement is necessary.

Coronary Artery Bypass↗
PubMed1992

[Development and results of valve replacement surgery at the Városmajor Clinic 1976-1990 (retorospective clinical analysis)].

In Hungary valve replacement is still a major indication for heart surgery in adults. In the Cardiovascular Surgical Clinic of Semmelweis Medical University of Budapest from 1976 to 1990 2435 patients were operated for valve disease. Majority of the cases had single (aortic n = 856, mitral n = 912) or double (aortic + mitral n = 513) valve replacement. Over this 15 years period there have been many alterations in patients characteristics and surgical technique as well. In spite of the increasing mean age of patients the operative mortality has decreased (in the last 5 years period it was 2.7%, 5.5% and 7.9% in the three groups respectively). At the same time the number of patients requiring valve re-replacement or combined valve + coronary procedure has increased. The use of bioprosthetic valves has fallen below 10 percent from the 60--80 percent observed between 1976--1980. The analysis showes excellent surgical results in the field of valve replacement in Hungary.

Cardiac Surgical Procedures↗
PubMed1992

[Experience with the surgical management of constrictive pericarditis].

61 patients were operated on for constrictive pericarditis at the Cardiovascular Surgical Clinic of Semmelweis Medical University in the last 33 years. The average hospital mortality of the surgical pericardiectomy was 4.9%. The final conclusions of this retrospective and follow up study are as follows: pericardiectomy is the method of choice in the treatment of constrictive pericarditis, since it does not has any therapeutic alternative, its hospital mortality is low and it results excellent early and late postoperative functional effects.

Adolescent↗
PubMed1992

Response to heparinization in adults and children undergoing cardiac operations.

The activated clotting time is an unreliable index of anticoagulation status during cardiopulmonary bypass procedures. However, modern instrumentation (Hemotec Hepcon HMS) now allows the monitoring of free heparin levels via automated protamine titration. In the present study, the standard procedure of anticoagulation at Killingbeck Hospital, Leeds, was investigated. Twenty-two pediatric patients and 20 adult patients undergoing open heart procedures involving cardiopulmonary bypass were given empirical doses of heparin (3 mg/kg body weight bolus), and activated clotting time was maintained at a level greater than 450 seconds using the Hemochron Timer. Heparin neutralization was performed at the termination of the bypass period using an empirical equivalent (3 mg/kg) of protamine sulfate. Mean free heparin concentration (+/- standard deviation) fell from 2.26 (+/- 0.45) mg/kg to 1.39 (+/- 0.34) mg/kg over the period 10 to 40 minutes on bypass in children. In adults, free heparin level declined from 2.56 (+/- 0.58) mg/kg to 1.81 (+/- 0.58) mg/kg over the same period. The biological half-life for heparin was 60 minutes in adults and 35 minutes in pediatric patients. Empirical protamine dosing resulted in excess protamine administration when compared with Hepcon titrated dose requirements: for children: median (range), 80 (12 to 350) versus 33 (12 to 97) mg, p less than 0.001; and for adults: 350 (200 to 500) versus 130 (61 to 237) mg, p less than 0.001. In conclusion, empirical heparin administration (3 mg/kg) does not result in "steady-state" anticoagulation during cardiopulmonary bypass, and empirical administration of protamine takes no account of interindividual differences in heparin sensitivity and biological half-life, which may be assessed using the Hepcon HMS.

Adult↗
PubMed1992

Heparin rebound phenomenon--much ado about nothing?

Significant postoperative bleeding following open-heart surgery is often ascribed to the so-called heparin 'rebound' phenomenon and as such is treated with additional empiric doses of protamine sulphate. However, inappropriate protamine administration has been reported to be associated with acute pulmonary hypertension. The efficacy of heparin reversal was investigated in 42 patients undergoing open-heart surgery. The standard heparin bolus of 3 mg/kg body weight (4.1 IU/ml blood) administered before cardiopulmonary bypass was countered at the end of bypass using an empirical equivalent (3 mg/kg) of protamine. This regimen resulted in complete heparin neutralization (measured by the Hepcon HMS [Hemotec Inc., Englewood, CO, USA]) 15 min after protamine administration in all 42 patients, but heparin levels (0.4 IU/ml) were transiently detectable (duration less than 1 h) in six (14%) of the 42 cases 2 h later. Twenty-four hour postoperative bleeding in these patients did not differ significantly from that seen in patients who did not exhibit heparin rebound. Similarly, the thrombelastographic profiles (at 15 min and 2 h post-operation) and coagulation screen (prothrombin time, activated partial thromboplastin time, activated clotting time and platelets) did not differ significantly from those of non-rebound patients. The significance, if any, of the phenomenon of heparin rebound following cardiac surgery remains to be elucidated, and, until such time, conservative administration of protamine in response to 'rebound' is recommended.

Adolescent↗
PubMed1991

Monitoring of coagulation status using thrombelastography during paediatric open heart surgery.

Thrombelastography (TEG) has proved useful in identifying coagulopathies (via assessment of clot elasticity properties) during hepatic surgery, but its role in cardiac surgery has as yet not been defined. Twenty-two children [11M, 11F, mean age (range) 4.9 (0.1-16) years] undergoing open heart surgery were investigated [1] preoperatively, [2] 15 min post protamine, [3] 2 h and [4] 24 h postoperatively using TEG. Comparisons were made between pre- and postoperative measurements and haematological indices. The values obtained from the TEG were: R phase (indicative of thrombokinase and thrombin formation disorders), K phase (indicative of fibrinogenesis) and MA phase (providing information on clot stability and platelet function). The patients were divided into two groups based upon 24 h blood loss; Group 1 - blood loss less than 0.7 ml/kg/h and Group 2 - blood loss greater than 0.7 ml/kg/h. In Group 2 there was a highly significant correlation between post-protamine MA phase and platelet number (r = 0.93, p less than 0.001) but there was no correlation in Group 1 (p greater than 0.1). Furthermore, in Group 2 elevated postoperative blood loss was associated with a prolonged K phase (mean [SD] 12.0 [6.0] versus 6.3 [2.1] min, p less than 0.05) and diminished MA phase (37 [12.5] versus 56 [4.9] mm, p less than 0.01) relative to preoperative values. In Group 1, K and MA phase did not alter significantly (p greater than 0.5 and p greater than 0.2, respectively). TEG predicted with 100% (8/8) accuracy increased post-operative bleeding. The specificity of TEG prediction of future bleeding was 73% [8/11]. Alterations in TEG parameters merit further evaluation as markers of postoperative haemorrhage.

Blood Coagulation↗