The role of age in post-cardiac arrest therapy in an elderly patient population.

AIM: We investigated the effect of age on post-cardiac arrest treatment outcomes in an elderly population, based on a local database and a systemic review of the literature. METHODS: Data were collected retrospectively from medical charts and reports. Sixty-one comatose patients, cooled to 32-34 °C for 24 h, were categorized into three groups: younger group (≤65 years), older group (66-75 years), and very old group (>75 years). Circumstances of cardiopulmonary resuscitation (CPR), patients' characteristics, post-resuscitation treatment, hemodynamic monitoring, neurologic outcome and survival were compared across age groups. Kruskal-Wallis test, Chi-square test and binary logistic regression (BLR) were applied. In addition, a literature search of PubMed/Medline database was performed to provide a background. RESULTS: Age was significantly associated with having a cardiac arrest on a monitor and a history of hypertension. No association was found between age and survival or neurologic outcome. Age did not affect hemodynamic parameter changes during target temperature management (TTM), except mean arterial pressure (MAP). Need of catecholamine administration was the highest among very old patients. During the literature review, seven papers were identified. Most studies had a retrospective design and investigated interventions and outcome, but lacked unified age categorization. All studies reported worse survival in the elderly, although old survivors showed a favorable neurologic outcome in most of the cases. CONCLUSION: There is no evidence to support the limitation of post-cardiac arrest therapy in the aging population. Furthermore, additional prospective studies are needed to investigate the characteristics and outcome of post-cardiac arrest therapy in this patient group.

Vitamin D Deficiency Predicts Poor Clinical Outcomes in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND AND AIMS: Resynchronization therapy (CRT) improves mortality and induces reverse remodeling in heart failure (HF) patients with reduced ejection fraction and wide QRS. Nonetheless, some patients do not improve despite the optimal medical therapy and right indications for device implantation. Therefore, finding biomarkers suitable for identification of those patients is crucial. Vitamin D plays a classic hormonal role in the regulation of bone metabolism and also has physiological functions in wide range of nonskeletal tissues. Based on recent studies, low levels of vitamin D seem to directly contribute to pathogenesis and worsening of HF. We planned to assess the role of vitamin D levels on clinical outcomes of HF patients undergoing CRT. METHODS AND RESULTS: We enrolled 136 HF patients undergoing CRT. Total plasma vitamin D levels were measured at baseline and 6 months later. Primary endpoint was 5-year all-cause mortality; secondary endpoint was lack of good clinical response, defined as less than 15% increase of left ventricular ejection fraction after six months. During follow-up, 58 patients reached the primary, and 45 patients reached the secondary endpoint. Vitamin D levels less than 24.13 ng/mL predicted 5-year mortality (p = 0.045) and poor clinical response (p = 0.03) after adjusting to all significant baseline predictors. CONCLUSION: Our study showed that vitamin D deficiency has a significant impact in heart failure patients; it is an independent predictor of lack of midterm clinical response and long-term mortality in patients undergoing CRT. Therefore, monitoring vitamin D status of heart failure patients could be of clinical significance.

Transseptal Leftventricular Endocardial Pacing is an Alternative Technique in Cardiac Resynchronization Therapy. One Year Experience in a High Volume Center.

INTRODUCTION: In patients receiving cardiac resynchronization therapy (CRT), failure rate to implant the left ventricular (LV) lead by the traditional trans-venous approach is 4-8%. Surgical epicardial implantation is considered as an alternative, but this technique is not without morbidity. Evidence from case documentation and from small trial batches demonstrated the viability of endocardial LV lead implantation where surgical epicardial lead placement is not applicable. MATERIAL AND METHODS: Four patients were implanted with endocardial LV lead using the transseptal atrial approach after unsuccessful transvenous implantation. Implantation of an endocardial active fixation LV leads was successful in all patients with stable electrical parameters immediately after implantation and over the follow-up period. All patients received anticoagulation therapy in order to target the international normalized ratio of 2.5-3.5 and have not experienced any thromboembolic, hemorrhagic events, or infection. RESULTS: Follow-up echocardiography indicated significant improvement of LV systolic function (24 + 4.9 to 32 + 5.1 %, P = 0.023) with a notable improvement of the functional status. CONCLUSIONS: Endocardial left ventricular lead implantation can be a valuable and safe alternative technique to enable LV stimulation in high surgical risk patients where standard coronary sinus implant is unsuccessful.

Radiofrequency ablation of focal atrial tachycardia: Benefit of electroanatomical mapping over conventional mapping.

BACKGROUND: Catheter ablation is a proven therapy of focal atrial tachycardia. However limited information is available about the additional value of electroanatomical over conventional mapping methods for this specific arrhythmia. METHODS: Consecutive catheter ablation procedures of FAT were analyzed in two cardiology centres. Only conventional mapping was used in 30 of the 60 procedures whereas additionally CARTO mapping was performed in another 30 procedures. Acute, six-month success rate, and procedural data were analyzed. RESULTS: Localization of ectopic foci is congruent with previously published data. There was no statistically significant difference between procedure time and fluoroscopy time using additionally CARTO mapping, compared to conventional mapping only. Acute success rate was higher in procedures guided by CARTO mapping than in procedures based on conventional mapping (27/30 vs. 18/30, p = 0.0081). During the 6-month follow-up period there was a better outcome (p = 0.045) in case of CARTO guided procedures (success: 11 cases, partial success: 12 cases, failure: 4 cases) compared to conventional mapping (success: 4 cases, partial success: 18 cases, failure: 7 cases). CONCLUSIONS: Catheter ablation of focal atrial tachycardias using the CARTO electroanatomical mapping system seems to provide higher acute and 6-month success rate compared to ablation using conventional mapping methods only.

Presence of functional, autoreactive human milk-specific IgE in infants with cow's milk allergy.

BACKGROUND: Occasionally, exclusively breastfed infants with cow's milk allergy (CMA) remain symptomatic despite strict maternal milk avoidance. OBJECTIVE: To determine whether or not persistence of symptoms could be due to sensitization against endogenous human milk proteins with a high degree of similarity to bovine allergens. METHODS: Ten peptides representing known bovine milk IgE-binding epitopes [α-lactalbumin (ALA), ß- and κ-casein] and the corresponding, highly homologous human milk peptides were labelled with sera from 15 breastfed infants with CMA, aged 3 weeks to 12 months, and peptide (epitope)-specific IgE antibodies were assessed. Nine of the 15 breastfed infants became asymptomatic during strict maternal avoidance of milk and other major food allergens; six infants remained symptomatic until weaned. Ten older children, aged 5-15 years, with CMA were also assessed. The functional capacity of specific IgE antibodies was assessed by measuring ß-hexosaminidase release from rat basophilic leukaemia cells passively sensitized and stimulated with human and bovine ALA. RESULTS: A minimum of one human milk peptide was recognized by IgE antibodies from 9 of 15 (60%) milk-allergic infants, and the majority of older children with CMA. Genuine sensitization to human milk peptides in the absence of IgE to bovine milk was occasionally seen. There was a trend towards specific IgE being detected to more human milk peptides in those infants who did not respond to the maternal milk elimination diet than in those who did (P = 0.099). Functional IgE antibody to human ALA was only detected in infants not responding to the maternal diet. CONCLUSIONS AND CLINICAL RELEVANCE: Endogenous human milk epitopes are recognized by specific IgE from the majority of infants and children with CMA. Such autoreactive, human milk-specific IgE antibodies appear to have functional properties in vitro. Their role in provoking allergic symptoms in infants exclusively breastfed by mothers strictly avoiding dietary milk remains unclear.

[In vitro and in vivo study of electromagnetic compatibility of cellular phones and pacemakers]. / Rádiótelefonok és pacemakerek elektromágneses kompatibilitásának vizsgálata.

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.

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.

[Experience with surgical treatment of prosthetic valve endocarditis]. / Múbillentyú-endocarditis sebészi kezelésével szerzett tapasztalataink.

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.

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.

[Biatrial pacing--new possibility in the non-pharmacologic treatment of drug-resistant paroxysmal atrial fibrillation]. / Biatrialis ingerlés--a gyógyszerrezisztens paroxizmális pitvarfibrilláció nonfarmakológiás kezelésének újabb lehetósége.

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.

PCR candidate region mismatch scanning: adaptation to quantitative, high-throughput genotyping.

Linkage and association analyses were performed to identify loci affecting disease susceptibility by scoring previously characterized sequence variations such as microsatellites and single nucleotide polymorphisms. Lack of markers in regions of interest, as well as difficulty in adapting various methods to high-throughput settings, often limits the effectiveness of the analyses. We have adapted the Escherichia coli mismatch detection system, employing the factors MutS, MutL and MutH, for use in PCR-based, automated, high-throughput genotyping and mutation detection of genomic DNA. Optimal sensitivity and signal-to-noise ratios were obtained in a straightforward fashion because the detection reaction proved to be principally dependent upon monovalent cation concentration and MutL concentration. Quantitative relationships of the optimal values of these parameters with length of the DNA test fragment were demonstrated, in support of the translocation model for the mechanism of action of these enzymes, rather than the molecular switch model. Thus, rapid, sequence-independent optimization was possible for each new genomic target region. Other factors potentially limiting the flexibility of mismatch scanning, such as positioning of dam recognition sites within the target fragment, have also been investigated. We developed several strategies, which can be easily adapted to automation, for limiting the analysis to intersample heteroduplexes. Thus, the principal barriers to the use of this methodology, which we have designated PCR candidate region mismatch scanning, in cost-effective, high-throughput settings have been removed.

[Percutaneous angioplasty of the innominate artery in 89 patients: experience of 19 years]. / Az arteria anonyma percutan angioplasztikás kezelése: 19 év tapasztalata 89 betegen.

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.

[Simultaneous carotid and coronary operations: experience and results of 11 years (1990-2000)]. / Szimultán végzett carotis-coronaria mútétek: 11 év tapasztalatai és eredményei (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.

[Multichamber pacing--a new non-pharmacologic method for the treatment of severe heart failure]. / Többüregú ingerlés--a súlyos szívelégtelenség kezelésének új nonfarmakológiás módszere.

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.

[Biventicular pacing in patients with severe heart failure]. / Súlyos szívelégtelenség kezelése biventricularis ingerléssel.

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.

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.

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.

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.

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.