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T Szabó

Publications and source records attributed to T Szabó.

At least 19 recordsLinked to original sources

How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches.

While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.

Dermatology↗

Effect of propranolol on heart rate variability in patients with end-stage renal disease: a double-blind, placebo-controlled, randomized crossover pilot trial.

BACKGROUND: Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity. METHODS: The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 +/- 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2-9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients' HRV data were compared to that of 29 age-matched healthy controls. RESULTS: Initially, both high-(HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: AlgHFV = 0.182 (0.027 - 0.337), placebo: deltalgHFV = -0.029 (-0.128 - +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320-543) and showed an inverse relationship with the increase of IgHFV secondary to propranolol (r = -0.66, p = 0.014). CONCLUSIONS: Low HFV of ESRD patients can be improved by beta-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.

Adolescent↗

Distinct features of recombinant rat vanilloid receptor-1 expressed in various expression systems.

In this study, we expressed rat vanilloid receptor 1 (VR1) in various heterologous expression systems using different VR1-encoding vectors, and examined how the VR1 agonists capsaicin and resiniferatoxin affected intracellular calcium. Our results clearly show that the magnitude and kinetics of response as well as the extent of tachyphylaxis differ markedly between systems. Using green fluorescent protein-tagged VR1, we show that much of the VR1 is localized to intracellular membranes. Consistent with this localization, VR1 agonists are able to liberate calcium from intracellular stores in the absence of extracellular calcium. As with other parameters of response, the three expression systems differ in the degree to which, in the absence of extracellular calcium, capsaicin and resiniferatoxin can liberate calcium from the intracellular stores. Our findings emphasize the influence of the expression system on characteristics of the response of VR1 to its ligands and the need for caution in extrapolating such results to other settings.

Animals↗

Occupational and patient doses in the therapeutic cave, Tapolca (Hungary).

The radon concentration has been measured for three years in a hospital cave used for medical treatment of respiratory diseases. A mean value of the actual equilibrium factor measured in the cave in different seasons was used, different from the commonly used 0.4. The dose contribution to the patients and the staff was calculated using these data. The results of the dose assessment show that the staff in the hospital cave can receive doses up to the dose limit for occupational exposure (20 mSv y(-1)) when working 4 h per day in the cave. Patients receive 0.18-4.22 mSv committed effective dose during the treatment period depending on the exposure periods. The only solution to reduce the dose to the staff seems to be decreasing the time they spend underground, because intensive ventilation would disturb the special microclimate of the cave.

Air Pollutants, Radioactive↗

Lack of association between atopic eczema/dermatitis syndrome and polymorphisms in the promoter region of RANTES and regulatory region of MCP-1.

BACKGROUND: Chemokines play an important role in the pathophysiology of atopic eczema/dermatitis syndrome (AEDS) and allergy. Recently polymorphisms in the promoter region of RANTES (regulated on activation normal T cell expressed and secreted) and in the gene regulatory region of MCP-1 (monocyte chemoattractant protein-1) have been found, which increase the expression of these chemokines. The - 403A allele of the RANTES promoter region was found associated with AEDS in German children. We investigated whether the presence of these polymorphisms was associated with AEDS or allergy in Hungarian children. METHODS: One hundred and twenty-eight children with AEDS, 102 allergic children without AEDS and 303 children of comparable ages without allergic disorders were screened for genotype with a PCR-based assay. RESULTS: There were no significant differences in the frequency of these polymorphisms, or in the distribution of genotypes between the groups. The total IgE concentration, the white blood cell count and the blood eosinophil cell count did not differ between the genotypes. CONCLUSION: In this cohort of Hungarian children there was no association between - 28G, and - 403A alleles in the RANTES promoter, - 2518G polymorphism in the distal regulatory region of the MCP-1 and AEDS, or allergy.

Adolescent↗

[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↗

Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients.

The central role of chemokines in the pathogenesis of atherosclerosis has been made clear. Recently polymorphisms in the gene regulatory region of MCP-1 and in the promoter region of RANTES have been found, which increase the expression of these chemokines. We investigated the role of these polymorphisms together with the chemokine SDF-1-801A and the chemokine receptors CCR2-64I and CCR5Delta32 mutations in 318 patients with coronary artery disease (CAD) referred to coronary bypass surgery, comparing them with 320 healthy controls. The prevalence of the MCP-1 -2518 G/G homozygotes was significantly higher among CAD patients than among controls (P<0.005; OR=2.2 (95% CI 1.25-3.92). The Lp(a) levels of CAD patients with G/G genotype were significantly higher than those in patients with G/A or A/A genotypes. No CAD patients homozygous for the CCR5Delta32 and CCR2-64I mutations have been found. The genotype distributions of the two alleles deviated from the Hardy Weinberg equilibrium in patients, indicating that the numbers of homozygotes were significantly lower than expected. The MCP-1 -2518G variant in homozygous form appears as a genetic risk factor for severe CAD. This genotype is associated with elevated Lp(a) levels in patients. Individuals homozygous for CCR2-64I or CCR5Delta32 mutations are at reduced risk for severe CAD.

Adult↗

Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity.

BACKGROUND: Chemokines play an important role in the pathophysiology of asthma and allergy. Recently, polymorphisms in the gene regulatory region of monocyte chemoattractant protein 1 (MCP-1) and in the promoter region of RANTES have been found; these polymorphisms increase the expression of the chemokines. OBJECTIVE: We investigated whether the presence of the polymorphisms was associated with atopy or asthma and whether these alleles influenced the severity of asthma in affected individuals. METHODS: Three groups of subjects-160 children with asthma (disease severity being classified according to the Global Initiative for Asthma guidelines, modified for children), 151 children with nonasthmatic but allergic phenotype, and 303 children without allergic or asthmatic disorders-were screened with a PCR-based assay for genotyping. RESULTS: The frequency of the -2518G polymorphism in the gene regulatory region of MCP-1 was significantly higher in asthmatic children than in controls (P <.001; odds ratio [OR] = 2.0 [1.4-2.6]) and nonasthmatic atopic children (P <.001; OR = 2.0 [1.4-2.9]). The MCP-1 G/G genotype correlated with asthma severity. In asthmatic children, the MCP-1 -2518G allele was also associated with an increased blood eosinophil level. The promoter polymorphisms in the RANTES gene did not have a detectable effect on the susceptibility to asthma or allergy or on the blood eosinophil count. CONCLUSION: In this cohort of children, there are associations between carrying G at -2518 of the MCP-1 gene regulatory region and the presence of asthma as well as between asthma severity and homozygosity for the G allele. In asthmatic children, the MCP-1 -2518G polymorphism correlated with increased eosinophil levels. This variant of MCP-1 might belong to the predictor gene set for asthma.

Adolescent↗

Acute postnatal increase of extracellular antioxidant defence of neonates: the role of iron metabolism.

UNLABELLED: In this study we investigated the extracellular antioxidant capacity of neonates during the first two postnatal days and its association with iron metabolism. Cord blood and blood samples at 47+/-6 postnatal hours were taken from 10 healthy neonates and their antioxidant capacity was determined using Randox Antioxidant kits and the heme-specific antioxidant activity (HSAA). Randox indicates the chain-breaking antioxidant capacity; HSAA corresponds to the ability to limit lipid peroxidation. Iron, ferritin and transferrin levels were also measured. Randox and HSAA values were 30% higher, ferritin was 100% higher and iron was 60% lower postnatally. The amount of change in HSAA values correlated with the change in ferritin level (r= 0.67, p < 0.05). CONCLUSION: These results suggest that extracellular antioxidant capacity (both chain-breaking and heme-specific antioxidant activities) increases shortly after birth. Lower iron and higher ferritin levels could also be responsible for this phenomenon.

Age Factors↗

Hyperhomocysteinaemia and MTHFR C677T gene polymorphism in renal transplant recipients.

AIM: To study the effect of folate treatment on hyperhomocysteinaemia and the effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on total homocysteine and folate concentrations after renal transplantation. METHODS: A total of 30 transplanted children and adolescents were investigated for total homocysteine and folate serum concentrations before and after folate treatment, as well as for the presence of the MTHFR C677T polymorphism. RESULTS: The allele frequency of C677T polymorphism in the MTHFR gene in the study population (0.33) was not different to that in controls (0.38). Before folate treatment the homocysteine concentration was raised in all groups; following folate supplementation it was significantly decreased in the CC and CT groups, but not in the TT group. In patients with CC genotype, serum homocysteine correlated with serum creatinine and cholesterol, and time since transplantation before treatment. CONCLUSION: Folate supplementation appears to be an effective strategy to normalise total homocysteine concentration in renal transplanted children and adolescents.

Adolescent↗

[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↗

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↗

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↗

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↗

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↗

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↗

Determination of H+/K+-ATPase activity in human gastric biopsy specimens.

The aim of our work was to develop a method to determine the the H+/K+-ATPase activity of human gastric biopsy samples. Our method is based on the phosphatase activity and the K+-inducible property of the enzyme. K+-inducible pNPPase activity was determined from homogenated corpus and antrum biopsy samples. H+/K+-ase activity was calculated as the difference between the corpus and antrum K+-inducible pNPPase activities. Quality control measurements were done during 20 successive days from pooled homogenates. The total, between-day and between-run, within-day and within-run coefficients of variations were between 10 and 16%. The healthy mean and reference range of K+-inducible pNPPase activity in the corpus was 95.8 (95% CI: 83.4-108.2 mU/mg protein); in the antrum it was 28.3 (21.6-35.0) mU/mg protein. The calculated H+/K+-ATPase activity was 67.2 (56.9-77.5) mU/mg protein. The measured activities were independent of the age and gender. Summarizing our results we have concluded, that our novel method might be a potential tool to gather data about the functional acid producing capability of human gastric mucosa.

Adolescent↗