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Biomedical subjects

L Gellér

Publications and source records attributed to L Gellér.

At least 19 recordsLinked to original sources
PubMed2001

[Biventicular pacing in patients with severe heart failure].

According to initial clinical results biventricular pacing seems to be effective in the treatment of patients suffering from drug refractory severe heart failure combined with intraventricular conduction disturbance. Biventricular cardioverter defibrillators and biventricular pacemakers were implanted in patients suffering from drug refractory severe heart failure in 3 and in 2 cases, respectively (follow up > 6 months). NYHA III-IV functional class, low left ventricular ejection fraction (23.2 +/- 5.4%), wide QRS (> 150 ms) with left bundle branch block and lateral dyssynchrony were present in each case. The left ventricle was enlarged in each patient (end-diastolic/end-systolic diameter: 78.6 +/- 9.2/66.2 +/- 8.1 mm). The indications of cardioverter defibrillator implantations were both sustained ventricular tachycardia and ventricular fibrillation, nonsustained ventricular tachycardia combined with syncope in 2 and in 1 case, respectively. The duration of QRS decreased (190 +/- 36 vs. 134 +/- 17 ms, p = 0.012) and wall movement disorder disappeared. At the last follow up every patients were in NYHA II functional class and a decrease in left ventricular diameter could be observed (end-diastolic: 72 +/- 10.4 mm, p = 0.07; end-systolic: 62 +/- 10 mm, p = 0.09). During the follow up period (7.3 +/- 1.7 months) 18 episodes of ventricular arrhythmias could be detected in the same patient. Biventricular pacemakers and cardioverter defibrillators were implanted and applied successfully in the treatment of congestive heart failure for the first time in Hungary. The effect of biventricular pacing on morbidity and mortality, the cost-effectiveness, the exact indication and the combined use with cardioverter defibrillator have yet to be proven in future randomized trials.

Aged↗
PubMed2001

[In vitro and in vivo study of electromagnetic compatibility of cellular phones and pacemakers].

Electromagnetic compatibility (EMC) of cellular phones and pacemakers (PM) was examined in four different cellular phone system (NMT, GSM, RLL, DCS 1800 MHz) and in fifteen different PM type in-vitro and in-vivo in humans. After more than 1100 in-vitro and 130 in-vivo tests we concluded, that the electromagnetic immunity of the PMs which are implanted in Hungary is suitable with only few exceptions. The highest rate of EMC problems was observed with NMT 450 MHz cellular phones (10.5%-63%). There was no EMC disturbance observed with GSM and DCS 1800 MHz cellular phones. There was only one case when clinically significant symptom was noticed with only one PM type and with NMT system cellular phone when the distance of cellular phone was 3-4 cms, and the power was maximal. There was not any EMC disturbance observed with none of the cellular phone systems during normal talking and when the distance of the PM and cellular phone was more than 20 cms. Our study supports guidelines which suggest that PM patients should contact their physicians when using cellular phones and cellular phones and PMs should not get closer than 20 cms.

Electromagnetic Fields↗
PubMed2001

[Experience with surgical treatment of prosthetic valve endocarditis].

Prosthetic valve endocarditis (PVE) is a rare but dangerous complication that may occur after the implantation. The authors retrospectively summarize their 11-year experience in treating PVE. 2357 prosthetic valve (PV) implantations were performed over 11 years at the Department of Cardiovascular Surgery, Semmelweis University, Budapest, PVE was found to be the indication for operation in 1.8% of the cases (43/2357). 43 surgical interventions were carried out on 38 patients (mean age: 52.5 yrs, male/female ratio: 25/13). Blood cultures were positive in 86% and negative in 14% of the cases. The infected PV-s were replaced emergently (14%), urgently (79%) or electively (7%). The explanted valves were aortic in 55% and mitral 45% of the cases, 63% were mechanical and 37% biological. PVE followed the primary PV implantation in less than a year in 39.5%. Infected environment during the primary PV implantation was found to be a predisposing factor for the late endocarditis episodes. The mean age of the infected and explanted aortic bioprosthetic valves was significantly higher than that of explanted mechanical valves (p < 0.05). No such difference could be found at the mitral valves. The explanted valves were replaced by mechanical (75.5%) or biological (22.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%. Endocarditis reoccurred in 20% of the cases. Means follow-up duration was 45.5 months. Two-, five- an 10-year survival were 75%, 64% and 51% respectively. In conclusion in the surgical treatment of PVE, bioprosthetic and mechanical valves are suitable alternatives as opposed to homografts and freestyle stentless valves.

Biocompatible Materials↗
PubMed2001

[Biatrial pacing--new possibility in the non-pharmacologic treatment of drug-resistant paroxysmal atrial fibrillation].

Biatrial pacing seems to be a possible non-pharmacological therapeutic choice in the prevention of drug-refractory, paroxysmal atrial fibrillation. Biatrial pacing using standard right atrial and coronary sinus left atrial pacing shows an antiarrhythmic effect, which mechanism is not well understood. Biatrial pacemaker was implanted in three patients suffering from drug refractory, symptomatic paroxysmal atrial fibrillation (lone and nonvalvular in 2 and in one case, respectively). Interatrial conduction disturbance (P > 120 ms) was found in three case. Bradycardia dependent arrhythmia development was not observed. Left atrial and right atrial premature beats dominated in 2 and in one case, respectively. P-wave duration was decreased by biatrial pacing in every patients. Atrial fibrillation has not been detected in two patients 1 day and 4 weeks after pacemaker implantation (follow up period: 9 and 5 months), however antiarrhythmic drugs has been withdrawn. In the number of left atrial premature beats a marked decrease was observed. Neither biatrial nor standard right atrial pacing nor combined medical and atrial pacing antiarrhythmic therapy were proven to be effective. In Hungary we were the first to implant and apply effectively biatrial pacemaker in the prevention of paroxysmal drug-refractory atrial fibrillation. However better identification the responding patients subgroup with atrial fibrillation is needed.

Aged↗
PubMed2001

Shortening the second phase duration of biphasic shocks: effects of class III antiarrhythmic drugs on defibrillation efficacy in humans.

INTRODUCTION: The specific waveform providing optimal defibrillation threshold (DFT) is unknown. We compared the defibrillation efficacy of biphasic pulses with second phases (P2) of 2 and 5 msec in a randomized prospective clinical study. METHODS AND RESULTS: Intraoperative DFTs of 62 patients (age 54 +/- 13 years; ejection fraction 43% +/- 17%; amiodarone 47%, d,l-sotalol 13%) were determined in random order using a binary search protocol. Anodal shocks of 60% tilt first phases (P1) and P2 of 2 msec/5 msec were delivered from two 100-microF capacitors between the right ventricular electrode and the test housing of a Phylax 06/XM device. Mean DFT was significantly lower using the shorter P2 (9.5 +/- 4.5 J vs 11.3 +/- 5.2 J; P < 0.0001). According to subgroup analysis, the effect of changing P2 duration was only influenced by antiarrhythmic treatment. DFT decreased markedly using the shorter P2 in patients treated with amiodarone (10.7 +/- 4.9 J vs 13.4 +/- 5.6 J; P < 0.00001) or d,l-sotalol (6.1 +/- 3.3 J vs 9.1 +/- 4.6 J; P < 0.05). The difference in patients not treated with Class III drugs was found to be insignificant. Chronic amiodarone treatment increased DFT only when the longer P2 was used. CONCLUSION: Biphasic shocks with shorter P2 should be used in patients undergoing Class III antiarrhythmic treatment.

Adult↗
PubMed2001

A new detection algorithm for implantable cardioverter defibrillator.

One of the most important subsystems of implantable cardioverter defibrillator (ICD) is the sensing stage, since it determines the sensitivity and specificity of the device to detect the heart rate and the underlying arrhythmia. This paper aims to investigate a new detection algorithm for ICD, which operates fully automatically. The algorithm ARGUS was implemented as a computer model and tested with intracardiac electrograms recorded (band-pass: 0.05 to 500 Hz; sampling rate: 1-4 kHz) under different rhythm condition like sinus rhythm (n = 18), atrial tachycardia (n = 16), and ventricular tachycardia as well as fibrillation (n = 139) during electrophysiological tests or ICD implantation. The results of the tests were visually inspected on a beat-to-beat basis. In total 31,934 events were classified by the algorithm (18,758 as long intervals (LI) with cycle length > 300 ms; 13,176 as short intervals (SI)). 195 out of the 13,176 SI and 572 out of 18,758 LI were incorrectly classified (SI: 1.48%; LI: 3.05%). In conclusion the new algorithm yield high sensitivity (99.9%) and specificity (97.0%) as known from conventional ICD algorithms but need no manual adjustments.

Algorithms↗
PubMed2001

[Percutaneous angioplasty of the innominate artery in 89 patients: experience of 19 years].

PURPOSE: To assess retrospectively the success of percutaneous transluminal angioplasty (PTA) in treating innominate artery stenoses and occlusion in a large series of patients with long-term follow-up results. METHODS: In symptomatic patients with high degree (> 60%) stenosis, innominate artery PTA was performed. Long-term follow-up was undertaken by blood pressure measurements on both arms as well as subclavian, right common carotid and right vertebral duplex scan. RESULTS: Between 1981 and 1999, primary success rate of 89 innominate artery PTA (84 stenoses, 5 occlusions) was 96.4%. Complications included 1 left occipital lobe infarction (1.5%), 2 puncture-site thrombosis (2.9%), and 4 TIA (5.8%). Two patients with restenosis were successfully treated with rePTA. Cumulative primary patency was 98 +/- 2% at 6 months, 93 +/- 4% at 16 to 117 months, secondary patency was 100% at 6 months, 98 +/- 2% at 12 to 117 months; 61% of the patients became symptomless, 32% improved, 7% showed no improvement. CONCLUSION: Angioplasty of the innominate artery has been proven to be safe and effective on a large series of patients. For innominate artery stenosis and short occlusion, PTA should be the first treatment of choice.

Adult↗
PubMed2001

[Simultaneous carotid and coronary operations: experience and results of 11 years (1990-2000)].

Between 1990-2000 163 coronary + carotid procedures were performed. The mean age was 4 years higher than it was at patients underwent isolated CABG (63.4 y vs 59.8 y). Clinically proven obliterative artery diseases in other anatomical regions were also present in more than 60% of patients. The half of the procedures were performed under emergency and urgent circumstances. The cardiac status and the coronary morphology were found to be unstable in half of the patients. The "Euroscore" risk evaluation model was used for risk scoring. The mean score value was as high as 6.26. According to this the estimated surgical lethality could have been as high as 11.2%. The real surgical lethality value was far under this estimated level (7.36%). The 1, 5, 10 year survival rate were as high as 89%, 82%, 68% (Kaplan-Meier). The majority of the patients was in NYHA I-II at the end of the follow-up period. The majority of the early and late deaths were found to be myocardial in origin. The estimated surgical risk of the simultaneous procedures could be reduce by accepting of the severe surgical indications existing at this surgical field and with the availability of an experienced operating team.

Carotid Stenosis↗
PubMed2001

[Multichamber pacing--a new non-pharmacologic method for the treatment of severe heart failure].

According to initial clinical results biventricular pacing seems to be effective in the treatment of patients suffering from drug refractory severe heart failure combined with intraventricular conduction disturbance. Biventricular cardioverter defibrillators and biventricular pacemakers were implanted in patients suffering from drug refractory severe heart failure in 10 and in 15 cases, respectively. NYHA III-IV functional class, low left ventricular ejection fraction (24.2 +/- 6%), wide QRS (> 150 ms) with left bundle branch block and lateral dyssynchrony were present in each case. The left ventricle was enlarged in each patient (endodiastolic/endsystolic diameter: 78.6 +/- 9.2/68.2 +/- 8.3). The indications of cardioverter defibrillator implantations were both sustained ventricular tachycardia and ventricular fibrillation, nonsustained ventricular tachycardia combined with syncope in 7 and in 3 case, respectively. The duration of QRS decreased (187 +/- 32 vs. 136 +/- 19 ms, p = 0.012) and wall movement disorder disappeared. At the last follow up every patients were in NYHA II functional class and a decrease in left ventricular diameter could be observed (endodiastolic: 70.3 +/- 9.1 mm, p = 0.04; endosystolic: 61.9 +/- 8.8 mm, p = 0.04). During the follow up period (8.8 +/- 5.1 months) 18 episodes of ventricular arrhythmias were detected in the same patient, 2 patients died (1 arrhythmia death, 1 sudden cardiac death). Biventricular pacemakers and cardioverter defibrillators were implanted and applied successfully in the treatment of congestive heart failure for the first time in Hungary.

Cardiac Pacing, Artificial↗
PubMed2000

[Atrial fibrillation after open-heart surgery--incidence, prevention and treatment].

Atrial fibrillation is a common problem in the postoperative period following open-heart surgery. The pathogenesis of postoperative atrial fibrillation is likely to be multifactorial, however increased sympathetic activation may play a significant role. The aim of the study was to detect the incidence and possible reasons of atrial fibrillation in the first three postoperative days after open-heart surgery. Atrial fibrillation was detected in a total of 48 patients (mean age 64.8 +/- 8.8 years) of the 302 consecutive patients included in the study. The incidence of atrial fibrillation was 15.9%. In the history of patients with atrial fibrillation paroxysmal or persistent atrial fibrillation occurred in 18 cases. Acute ischaemia, hypopotassemia, high dose catecholamines contributed to the development of arrhythmias in 6, 4 and 4 cases, respectively. Lack of perioperative beta-blocker treatment was seen in 35 cases. Postoperative bleeding and reoperation occurred prior to the onset of atrial fibrillation in 9 instances. The applied antiarrhythmic therapy was metoprolol, amiodarone, propafenon and electrical cardioversion in 33, 21, 4 and 2 cases, respectively. Incidence of atrial fibrillation was found significantly lower in patients receiving beta-blocker premedication (13/181 [7.18%] versus 35/121 [28.9%]). There was no correlation between the incidence of atrial fibrillation and the length of the surgery, aortic-cross clamp time and the number of bypass grafts. Absence of preoperative beta-blocker treatment, previous atrial fibrillation and combined surgery were found to be strong predictors of atrial fibrillation. There was weaker association with increased age. On the basis of the outcome of our study beta-blocker premedication is suggested in most patients undergoing open-heart surgery.

Adrenergic beta-Antagonists↗
PubMed2000

Investigating the dual nature of endothelin-1: ischemia or direct arrhythmogenic effect?

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which may also elicit severe ventricular arrhythmias. The aims of our study were to compare the effects of total left anterior descending coronary artery (LAD) occlusion to intracoronary (ic.) ET-1 administration and to investigate the pathomechanism of ET-1 induced arrhythmias in 3 groups of anesthetized, open-chest mongrel dogs. In group A (n=10) a total LAD occlusion was carried out for 30 min, followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into LAD for 30 min at a rate of 30 pmol/min (n=6) and 60 pmol/min (n=8). Epi- and endocardial monophasic action potential (MAP) recordings were performed to detect electrophysiologic changes and ischemia Blood samples for lactate measurements were collected from the coronary sinus (CS) and from the femoral artery. Infrared imaging was applied to follow epimyocardial heat emission changes. At the end of the ET-1 infusion period coronary blood flow (CBF) was reduced significantly in groups B and C (deltaCBF30MIN B: 21+/-2%, p<0.05; C: 35+/-2%, p<0.05), paralleled by a significant epimyocardial temperature decrease in group C (deltaT30MIN: -0.65+/-0.29 degrees C, p<0.05). Two dogs died of ventricular fibrillation (VF) in the reperfusion period in group A. Ventricular premature contractions and non-sustained ventricular tachycardic episodes appeared in group B, whereas six dogs died of VF in group C. Significant CS lactate level elevation indicating ischemia was observed only in group A from the 30th min occlusion throughout the reperfusion period (control vs. 30 min: 1.3+/-0.29 vs. 2.2+/-0.37 mmol/l, p<0.05). Epi- and endocardial MAP durations (MAPD90) and left ventricular epicardial (LV(EPI)) upstroke velocity decreased significantly in group A in the occlusion period. ET-1 infusion significantly increased LV(EPI) MAPD90 in group B and both MAPD90-s in group C. In conclusion, ischemic MAP and CS lactate changes were observed only in group A. Although ET-1 reduced CBF significantly in groups B and C, neither MAP nor lactate indicated ischemic alterations. ET-1 induced major ventricular arrhythmias appeared before signs of myocardial ischemia developed, though reduced CBF presumably contributed to sustaining the arrhythmias.

Animals↗
PubMed2000

Ventricular arrhythmias induced by endothelin-1 or by acute ischemia: a comparative analysis using three-dimensional mapping.

OBJECTIVES: To analyze three-dimensional activation patterns of ventricular arrhythmias induced by endothelin-1 in comparison with ischemia-induced tachycardias. METHODS: Following AV node ablation, sixty pin electrodes containing four bipoles each were inserted into both ventricles of ten foxhounds. Using a computerized mapping system, this would allow to simultaneously record 240 endo-, epi- and midmyocardial electrograms for reconstruction of the three-dimensional activation pattern. In five dogs, endothelin-1 was infused into the LAD at 60 pmol/min. In another five animals, the LAD was ligated. During the following 40 min, all ventricular arrhythmias were recorded for subsequent analysis. Furthermore, left ventricular conduction times during constant pacing and local effective refractory periods at eight left ventricular sites were determined before and after either intervention. RESULTS: Endothelin-1 had no significant effect on conduction time and refractoriness, whereas ligation prolonged both parameters significantly. Endothelin-1 as well as ligation induced multiple mono- and polymorphic nonsustained ventricular tachycardias. Endothelin-1-induced arrhythmias were exclusively based on focal mechanisms, whereas during ligation, macroreentrant mechanisms were involved in the maintenance of tachycardias in 29% of episodes. CONCLUSION: The differences in the effects of endothelin-1 and LAD ligation on electrophysiologic properties and the difference in the mechanism of induced ventricular tachycardias support the hypothesis that, apart from vasoconstrictive properties, endothelin-1 exerts an intrinsic arrhythmogenic effect.

Animals↗
PubMed2000

Fundamental electrophysiological differences between low-dose intracoronary endothelin-1 infusion and myocardial ischemia revealed by multiple monophasic action potential recording.

The supposed direct arrhythmogenic property of endothelin-1 (ET-1) has not yet been clearly proven. Our study aimed to characterize the electrophysiological changes during left anterior descending artery (LAD) occlusion and intracoronary (i.c.) ET-1 infusion, and to differentiate between the supposed direct and ischemic arrhythmogenic actions of ET-1 in a canine model. Changes of monophasic action potential duration (MAPD90) and upstroke velocity (UV) are capable of detecting local ischemic changes. Left and right ventricular endo- (LVEND, RVEND) and epicardial (LVEP, RVEP) monophasic action potentials were recorded. MAPD90, monophasic action potential dispersion (MAPDISP) and UV were determined. In group A (n = 8) 30 min LAD occlusion was followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into the LAD at rates of 30 (n = 8) and 60 pmol/min (n = 10), respectively. In group A after the LAD occlusion both MAPD90 and UV decreased significantly in the LAD region (LVEP and LVEND 18 +/- 3% and 10 +/- 1%, p < 0.05, and 65 +/- 4% and 52 +/- 8%, respectively, p < 0.05; control and 30 min values in all groups), whereas the increase in MAPDISP remained unchanged. No severe arrhythmias were noticed in this group. In group B, both MAPD90 and MAPDISP increased significantly (LVEP and LVEND 11 +/- 4% and 18 +/- 3%, p < 0.05; MAPDISP 200 +/- 40%, p < 0.05), whereas UV remained unchanged at the end of the infusion. Early afterdepolarizations (EADs) were present in three instances. In group C both MAPD90 and MAPDISP increased significantly (LVEP and LVEND 12 +/- 5% and 26 +/- 8%, respectively, p < 0.05; MAPDISP 215 +/- 30%, p < 0.05) and UV decreased slightly in the LAD region. EADs were observed in five instances. Severe arrhythmias were observed in both groups B and C. We concluded that MAP prolongation, increased MAP dispersion and development of EADs all contribute to the arrhythmogenic action of ET-1. The lack of the almost prompt decrease of UV and MAPD90 which was observed in group A in groups B and C strongly supports the probability of a direct arrhythmogenic effect of ET-1.

Action Potentials↗
PubMed2000

The selective endothelin-A-receptor antagonist LU 135.252 inhibits the direct arrhythmogenic action of endothelin-1.

Besides being a strong vasoconstrictor, endothelin-1 (ET-1) also causes severe ventricular arrhythmias. The aim of our study was to differentiate between the vasoconstrictor and arrhythmogenic actions of ET-1 by using the selective endothelin-A-(ETA) receptor antagonist LU 135.252 (LU). A bolus injection of 5 mg/kg LU was administered to 10 anesthetized mongrel dogs in group A. The 30 min intracoronary ET-1 infusion was started 20 min after the LU bolus at a rate of 60 pmol/min. In the control group (group B, n = 8) only ET-1 was administered (60 pmol/min). The left anterior descending coronary artery blood flow (CBF), cardiac output, electrocardiograph (ECG) and arterial blood pressure were monitored. Two monophasic action potential duration (MAPD) catheters were placed onto the left ventricular epicardium (LVEP) and into the right ventricular endocardium (RVEND) to follow electrophysiologic changes. No significant changes were observed in blood pressure (0 min vs 30 min: group A, 99.0 +/- 4.5 vs 90.0 +/- 5.2 mmHg, p = NS; group B, 103 +/- 6 vs 104 +/- 3 mmHg, p = NS), cardiac output (0 min vs 30 min: group A, 3.5 +/- 0.7 vs 3.2 +/- 0.8 l/min, p = NS; group B, 3.6 +/- 0.4 vs 3.3 +/- 0.3 l/min, p = NS), and MAPD90 (0 min vs 30 min: group A, LVEP, 241 +/- 11 vs 260 +/- 14 ms; RVEND, 233 +/- 5 vs 239 +/- 8 ms, p = NS), whereas a significant decrease was observed in CBF (deltaCBF 30 min: group A, -28 +/- 2%, p < 0.05; group B, -32 +/- 3%, p < 0.05). In group A ventricular fibrillation (VF) occurred once. Ventricular premature contractions (VPCs) and short, nonsustained ventricular tachycardias (nsVTs) were observed in seven cases. Early after depolarizations and a MAPD90 increase were observed in the control group B (0 min vs 30 min: LVEP, 244 +/- 10 vs 292 +/- 12 ms; RVEND, 255 +/- 9 vs 290 +/- 8 ms) accompanied by VPCs, incessant nsVTs. Sustained VT and VF were evident in seven cases. Our results indicate, that the applied single bolus injection of LU effectively prevents ET-1-induced major ventricular arrhythmias, whereas it has no effect on coronary vasoconstriction. These data support the notion that ET-1 possesses a direct arrhythmogenic action.

Animals↗
PubMed2000

Endothelin-A-receptor antagonist LU 135.252 inhibits the formation of ventricular arrhythmias caused by intrapericardial infusion of endothelin-1.

Intrapericardial endothelin-1 (ET-1) infusion causes dose-dependent severe ventricular arrhythmias. We examined the effects of the endothelin-A- (ETA) receptor antagonist LU 135.252 (LU) on ET-1-induced arrhythmias on six open-chest mongrel dogs. Ten minutes after an intravenous bolus of LU (5 mg/kg), ET- 1 (33 pmol/kg/min) was given into the pericardial space for 30 min (LU group). Six dogs received ET-1 infusion without LU treatment (control group). Mean arterial blood pressure (MAP), cardiac output, electrocardiograph (ECG), right ventricular endocardial and epicardial (RVEND, RVEP), and left ventricular endocardial and epicardial (LVEND, LVEP) monophasic action potential durations (MAPDs) were recorded. No significant changes were observed in MAP and cardiac output. MAPD90s did not change significantly in the LU group (basic vs ET 20min: RVEP, 186 +/-7 vs 190 +/- 7; LVEP, 189 +/- 8 vs 201 +/- 11; RVEND, 191 +/- 10 vs 192 +/- 9; LVEND, 199 +/- 11 vs 203 +/- 11 ms), while significant MAPD90 prolongation was found in all investigated regions of the control group (ET start vs ET 20 min: LVEP, 174 +/- 3 vs 208 +/- 10*; RVEND, 206 +/- 9 vs 241 +/- 12* ms, *p < 0.05). No early after depolarization (EAD) was observed in the LU group, while EADs occurred in three controls. In the LU group, we have not found any significant arrhythmias except nonsustained ventricular tachycardias (nsVTs) in one animal. In the control group incessant nsVTs were observed in six, sustained VTs (sVTs) in four and ventricular fibrillation (VF) in two instances. Significant ST-elevation was observed in all animals in the LU and control groups (LU: 6.7 +/- 2.1 mV; control: 10.1 +/- 2.0 mV, p = NS). In conclusion, the arrhythmogenic action and the main electrophysiological effects of pericardial ET-1 infusion, MAPD prolongation and EAD formation, are inhibited by LU. However, LU could not prevent the ischemic changes resulting from ET-1 infusion.

Action Potentials↗
PubMed2000

Bosentan the mixed endothelin-A- and -B-receptor antagonist suppresses intrapericardial endothelin-1-induced ventricular arrhythmias.

In earlier studies severe ventricular arrhythmias developed during intrapericardial (i.p.) endothelin-1 (ET-1) infusion. Monophasic action potential duration (MAPD90) increase and significant ST segment elevation preceded the onset of arrhythmias. The aim of this study was to test the antiarrhythmic and anti-ischemic efficacy of the mixed endothelin-A- and -B- (ETA/B) receptor antagonist bosentan (BOS) on ET-1-induced arrhythmias on six mongrel dogs. Ten minutes after an intravenous bolus dose of BOS (10 mg/kg), ET-1 (33 pmol/kg/min) was given into the pericardial space for 30min (BOS group). Six control dogs received only ET-1 infusion (control group). Mean arterial blood pressure (MAP), cardiac output, electrocardiograph (ECG), right and left ventricular endo- and epicardial (RVEND, RVEP, LVEND, LVEP) MAPD90s were recorded. MAP and cardiac output did not change significantly in the BOS group. Significant MAPD90 prolongation was found in all investigated regions of the control group (ET start vs ET 20 min: LVEP, 174 +/- 3 vs 208 +/- 10*; RVEND, 206 +/- 9 vs 241 +/- 12* ms, *p < 0.05), while significant MAPD90 alterations were not observed in the BOS group (basic vs ET 20 min: RVEP, 189 +/- 5 vs 196 +/- 5; LVEP, 199 +/- 5 vs 199 +/- 4; RVEND, 194 +/- 5 vs 195 +/- 6; LVEND, 209 +/- 3 vs 213 +/- 5 ms). Early after depolarizations (EADs) were observed in three control dogs. Severe ventricular arrhythmias [incessant nonsustained ventricular tachycardias (nsVTs) in all cases, sustained VTs (sVTs) in four, ventricular fibrillation (VF) in two instances] were present in the control group, whereas nsVTs were observed only in two dogs in the BOS group. ST segment elevation was more pronounced in the control group than in the BOS group (1.01 +/- 0.2 vs 0.41 +/- 0.07 mV, p < 0.05). In summary, bosentan effectively inhibits intrapericardial ET- 1-induced ventricular arrhythmias, moreover it may have a protective effect against epimyocardial ischemia.

Action Potentials↗
PubMed1998

Intrapericardial infusion of endothelin-1 induces ventricular arrhythmias in dogs.

OBJECTIVES: Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients with heart disease; however, the pathophysiological importance of this finding is not known. The present study was designed to characterize ET-1 levels in canine pericardial fluid and to investigate the effects of local high concentrations of exogenous ET-1 in vivo. METHODS: In anesthetized, open-chest dogs ET-1 (Groups 1 and 2: 11 and 33 pmol.kg-1.min-1; n = 6 and 6, respectively) or physiological saline (Group 3, n = 5) were infused into the closed pericardial sac for 40 min. In serial pericardial fluid and aortic blood plasma samples, ET-1 levels were measured by radioimmunoassay, and analysed by high-performance liquid chromatography (HPLC). Systemic arterial blood pressure, heart rate, cardiac output (CO), standard ECG and right ventricular endocardial monophasic action potentials (MAPs) were recorded. RESULTS: Basal pericardial fluid ET-1 levels were significantly higher than respective plasma levels (342 +/- 210 vs. 8.0 +/- 5.2 pmol.l-1, n = 14, P < 0.001. In HPLC analysis pericardial fluid ET-1 was indistinguishable from ET-1(1-21). Infusion of exogenous ET-1 into the pericardial space induced ventricular arrhythmias in all instances, which were associated with 9.7-fold increase in pericardial fluid ET-1 levels. Ventricular tachycardias developed in 9 of 12 animals. The arrhythmogenic effect of ET-1 was more apparent in dogs with the larger dose. Before the onset of arrhythmias, intrapericardial infusion of ET-1 increased QT time (Group 1: 207 +/- 18 to 230 +/- 23 ms, P < 0.01; Group 2: 220 +/- 12 to 277 +/- 17 ms, P < 0.01) and MAP duration at 90% repolarization (at 300 ms cycle length) (Group 1: 192 +/- 9 to 216 +/- 9 ms, P < 0.01; Group 2: 205 +/- 9 to 255 +/- 9 ms, P < 0.001). Hemodynamic variables did not change significantly prior to the onset of ventricular tachyarrhythmias. In Group 3, arrhythmias were not observed and all electrophysiological and hemodynamic parameters remained unchanged. CONCLUSIONS: Administration of exogenous ET-1 into the pericardial space induces ventricular arrhythmias associated with prolongation of QT time and MAP duration. Whether pericardial fluid ET-1 under pathophysiological conditions can ever reach sufficiently high levels to induce ventricular arrhythmias remains to be elucidated.

Action Potentials↗