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Biomedical subjects

Lajos Papp

Publications and source records attributed to Lajos Papp.

15 recordsLinked to original sources

Human heart mitochondria do not produce physiologically relevant quantities of nitric oxide.

Previous studies raised the possibility that nitric oxide synthase is present in heart mitochondria (mtNOS) and the existence of such an enzyme became generally accepted. However, original experimental evidence is rather scarce and positive identification of the enzyme is lacking. We aimed to detect an NOS protein in human and mouse heart mitochondria and to measure the level of NO released from the organelles. Western blotting with 7 different anti-NOS antibodies failed to detect a NOS-like protein in mitochondria. Immunoprecipitation or substrate-affinity purification of the samples concentrated NOS in control preparations but not in mitochondria. Release of NO from live respiring human mitochondria was below 2 ppb after 45 min of incubation. In a bioassay system, mitochondrial suspension failed to cause vasodilation of human mammary artery segments. These results indicate that mitochondria do not produce physiologically relevant quantities of NO in the heart and are unlikely to have any physiological importance as NO donors, nor do they contain a recognizable mtNOS enzyme.

Animals↗

[Ruptured and reruptured sinus of Valsalva aneurysm].

Aneurysm of the sinus of Valsalva (SVA) is a rare condition of the aorta. It progrediates slowly and can be hidden for a long time, but during its development it may cause various symptoms due to compression. Rupture of the aneurysm can result in acute heart failure necessitating an urgent operative treatment. We operated on a patient with symptoms of acute heart failure, grade III-IV tricuspid insufficiency, loud systolo-diastolic murmur and an extremely high calculated right ventricular pressure. The echocardiography discovered the rupture of the non-coronary sinus of Valsalva shunting to the right ventricle. During the operation we removed the aneurysm sac, and closed the hole directly with running sutures. The involved non-coronary cusp ruptured in the early postoperative course, so an acute reoperation was performed, during which we decided to replace the valve. We must take into account the rupture of SVA in the presence of above symptoms and consider valve replacement instead of repair regarding to the delicate valve apparatus.

Adult↗

[The importance of the knowledge of acute coronary syndrome].

The acute coronary syndrome is not only a new phrase in the every day medical practice. It has basically changed not only our knowledge but our way of thinking. In the background of these changes is the understanding of the common origin of the different forms of acute ischemic heart diseases. Although acute coronary syndrome is one of the hot topic of today's cardiology and interventional cardiology, this review was not made for only interventional cardiologist, much rather for real world practitioner to help understanding the treatment of acute coronary syndrome, which is one of the real challenge of the every day practice.

Acute Disease↗

[Cardiac surgery--2005].

The demand of the patients and the society, the results of basic sciences and industrial developments besides the judgement of the surgeon determine the evolution of cardiac surgery. The authors review the actual questions of the main disciplines in cardiac surgery. Outcomes of coronary artery surgery are detailed, on what the new interventional techniques have enormous influence. In the valvular surgery the spreading of plastic surgical procedures and stentless valve implantation is to be expected. According to the international surveys the amount of heart transplantation stagnates. The usage of long- and short-term mechanical support devices is neccessitated. The minimally invasive techniques associated with less operative injury can be performed safely with appropriate experience in selected patients. The prevention of perioperative brain damage is also considered an important issue, and several refinements are tested. Actually we are in the phase of acquiring experience; however, it can be compared to "shooting a moving target" due to the continuous developments.

Atrial Fibrillation↗

Pulmonary embolization as primary manifestation of hepatocellular carcinoma with intracardiac penetration: a case report.

Intracardiac manifestation of hepatocellular carcinoma (HCC) is a rare condition and an uncommon finding even at autopsy. Pulmonary tumor embolism as a presenting feature of HCC has been published only twice previously. In our case report, a 63-year-old man presented with high fever and six episodes of recurrent pneumonias during the last half year. Echocardiography was performed, a solid mass was found in the right atrium. Transesophageal echocardiography proved a tumor mass in the inferior vena cava (IVC) extending into the right atrium, abdominal ultrasound revealed tumor mass in the IVC and a solid tumor in the liver. Combined liver and heart surgery was attempted in order to remove the tumor mass from both the liver and the right atrium. Acute cor pulmonale occurred during tumor removal from the right atrium and the patient expired. In addition to local factors the possibility of embolization should arise in the background of recurrent pneumonia. Occult carcinoma must be included in possible causes of recurrent pulmonary embolism. Searching for primary malignancy should include HCC as frequent cause of hypercoagulability. In case of HCC, echocardiography is suggested because of the possibility of expansion in IVC or right atrium and tumor-embolization.

Carcinoma, Hepatocellular↗

[Correlation of B-type natriuretic peptide (NT-proBNP) levels and conventional and tissue Doppler echocardiographic parameters of left ventricular diastolic function in patients with hypertrophic cardiomyopathy].

INTRODUCTION: Preload-independent pulsed tissue Doppler echocardiography (TDI) and conventional pulsed Doppler echocardiography were used to assess the global left ventricular diastolic function in patients with hypertrophic cardiomyopathy (HCM). Levels of B-type natriuretic peptide (BNP) could be elevated in patients with isolated left ventricular diastolic dysfunction. AIM: The study was to investigate the correlation between BNP levels and the parameters measured by conventional echocardiography and TDI in patients with HCM. PATIENTS: 32 consecutive patients with HCM (21 male, 11 female, mean age 47 +/- 14 years) were studied. Inclusion criteria were: normal sinus rhythm; ejection fraction > or = 50%; absence of moderate to severe mitral regurgitation or prosthetic mitral valve. METHODS: In addition to the conventional transmitral flow patterns (E, A, E/A, DT, IVRT) myocardial early (Ea) and late diastolic (Aa) velocities were measured at the lateral and septal border of the mitral annulus by ATL HDI 5000 ultrasound system. Ea/Aa and E/Ea ratios were calculated. NT-proBNP levels were measured by Roche-Elecsys test (immunoassay). Because the distribution of BNP values did not appear to be normal, the values were transformed into a natural logarithm (InBNP). RESULTS: Mean BNP level was 543 +/- 845 pg/ml. BNP levels negatively correlated with lateral Aa values (r = -0.59, p < 0.001). No significant relationship was observed between BNP levels and other echocardiographic parameters. By stepwise multiple linear regression analysis the only significant predictor of InBNP was lateral Aa value, too (r = -0.467, p < 0.05). CONCLUSION: Significant correlation was found between BNP levels and a single TDI parameter characterizing left atrial systolic function, but there was no significant correlation between BNP levels and global left ventricular diastolic function characterized by either conventional echocardiographic or TDI parameters.

Adult↗

[Data of the morbidity and mortality index of the acute coronary syndrome in the South Trans-Danubian Region between 1999 and 2002].

Data of the morbidity and mortality index of the acute coronary heart disease in the South Trans-Danubian Region between 1999 and 2002. South Trans-Danubian Regional Acute Coronary Registry. Based on GYOGYINFOK database, the authors' purpose was to monitor the morbidity and mortality of acute coronary heart diseases (acute coronary syndrome, acute myocardial infarction) in the approximately one million people inhabiting the South Trans Danubian Region. Data were obtained using the financing data sheets reported to GYOGYINFOK by 15 in-patient health care institutions located in the region. The regional data were compared nation-wide ones as well. The observed diagnoses correspond to diseases the codes of which range from I 20.00 to I 22.90, according to BNO classification. The data of years 1999, 2000, 2001 and 2002 have already been processed and categorized by gender and age-groups. Hospital mortality, therapeutical procedures (thrombolysis, GP IIb/IIIa receptor blocker) as well as the parameters of progressive care have all been evaluated. Of the processed 4 years, the data of 8431 patients are already recorded in the registry. The rate of the thrombolytic therapy reached patients was decreased from 26.01% (which was detailed in 1999) to 7.39% into 2002 in our region, but the rate was nearly constant 16.1% in 1999 and 13.28% in 2002 in the country. The rate of the GP IIb/IIIa therapy reached patients was increased from 2.15% to 6.66% in our region, while it was increased from 0.66% to 3.96% between 2000 and 2002 in the country. Mortality in the hospitals decreased in the case of male from 14.44% to 8.7% in the region, and from 20.28% to 16.18% in the female. At the same time the hospital mortality was constant in the country, in males it was 14.39% in 1999, and 13.11% in 2002, and in females it was 20.00% in 1999, and 18.81 in 2002. As regards the therapeutical procedures--based on the data processed up to the present--it can be observed that classic thrombolytic therapy becomes de-emphasized while treatments with GP IIb/IIIa receptor blockers as well as the intervention coupled to these gain ground. The authors consider the creation of this registry a very important beginning step in building the cardiological map of the region.

Acute Disease↗

Mitogen-activated protein kinases p38 and ERK 1/2 mediate the wall stress-induced activation of GATA-4 binding in adult heart.

The zinc finger transcription factor GATA-4 has been implicated as a critical regulator of inducible cardiac gene expression and as a potential mediator of the hypertrophic program. However, the precise intracellular mechanisms that regulate the DNA-binding activity of GATA-4 are not fully understood. The aim of the present study was to examine the role of mitogen-activated protein kinases (p38 kinase, extracellular signal-regulated protein kinase, and c-Jun N-terminal protein kinase) in the left ventricular wall stress-induced activation of GATA-4 DNA binding in adult heart. Isolated perfused rat hearts were subjected to increased left ventricular wall stress by inflating a balloon in the ventricle. Gel mobility shift assays were used to analyze the transacting factors that interact with the GATA motifs of the B-type natriuretic peptide promoter. The left ventricular wall stress rapidly activated GATA-4 DNA binding and significantly increased the levels of phosphorylated p38 kinase, extracellular signal-regulated protein kinase, and c-Jun N-terminal protein kinase. The wall stress-induced increase in the DNA-binding activity of GATA-4 was abolished both in the presence of the p38 inhibitor SB239063 and MEK1/2 inhibitor U0126. In contrast, the inhibition of c-Jun N-terminal protein kinase by CEP11004 had no effect on the baseline or stretch-induced GATA-4 DNA binding. Moreover, GATA-4 DNA binding was up-regulated by mechanical stretch in the isolated rat atria via p38 and extracellular signal-regulated protein kinase. In conclusion, the present study demonstrates that both p38 and extracellular signal-regulated protein kinase are required for the stretch-induced GATA-4 binding in intact heart.

Amino Acid Motifs↗

[Experiences in the invasive treatment of acute coronary syndrome].

INTRODUCTION: Primer percutaneous coronary intervention is a very powerful tool in the treatment of acute coronary syndrome. The aim of the authors was to work out and analyse the methods of making the upto-date percutaneous coronary intervention available for patients living far from the Heart Institute. PATIENT AND INTERVENTIONS: Between 1st January 2000 and 31st October 2002, 221 patients with acute coronary syndrome were sent to intensive treatment from Kaposvár to the Heart Institute in Pécs partly by helicopter. The average age of patients was 54 years. 103 of them with acute myocardial infarction and 118 others with unstable angina were catheterised. Revascularization was achieved in 133 cases, and coronary operation in 63 cases. Primary intensive therapy was applied on 34 patients with infarction. RESULTS: No lethal complications arose during transport or operation. Mortality rate coming from cardial complications was only 4% during the first two years. These results are based on well organised cooperation between the Department of Internal Medicine Kaposvár and Heart Institute Pécs. CONCLUSION: Given suitable logistic background and adequate indication the risk of transporting patients can be taken. The percutaneous coronary intervention proved to be successful.

Acute Disease↗

[Facilitated revascularisation in myocardial infarction with ST-segment elevation].

AIMS: The authors performed urgent coronarography and revascularisation after administering a combined half dose of alteplase (tissue plazminogen activator) and eptifibatide (glycoprotein II/bIIIa receptor blocking agent) to patients suffering from acute coronary syndromes with persistent ST-segment elevation. METHODS: During the period between 01 April to 15 December, 2001. 20 patients (16 men and 4 women, mean age: 55.6 years) were treated. The localization of infarction on the basis of ST-segment elevation was: 9 cases inferior, 10 cases anterior and patient with left bundle branch block in 1 cases. The mean time between the infarct related angina and hospital admission was 158 (30-600) minutes. The combined medical therapy was initiated after 34 (15-150) minutes on the average admission, and 123 (71-210) minutes later the patients were in the catheter laboratory. RESULTS: Coronarography showed TIMI-0 flow in 4 cases, TIMI-2 flow in 3 cases and TIMI-3 flow in 13 cases. Acute percutan coronary intervention was done in 14 cases, aorto-coronary bypass surgery was performed in 4 cases (2 of them were emergency operations, the other 2 were done electively). Besides postpunctional haematomas, hemorrhagic complications in the form of haematemesis were observed in 2 cases, but there was no need for transfusion. The mean CK-MB release (between 14 patients) was 230.4 (30-1176) U/l. One patient died after the emergency bypass surgery. CONCLUSIONS: On the basis of initial results the authors emphasize the importance of working out the optimal revascularisation strategy for acute coronary syndrome patients with ST-segment elevation in every Hungarian catheter centre. The authors find this method--in their case the catheter laboratory is 60 kms away, time of transport is approximately 70-90 minutes--an effective and safe alternative therapy in patients under the age of 75 years with acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

[Combined treatment of acute ischemic syndrome].

Lots of changes has been made on the treatment of ischaemic heart disease (especially the acute ischaemic syndrome) during the last few years. Large scale, multicentre trials provided clinical evidences the novel therapeutical approach of acute coronary syndrome (ACS). In order to suit this great challenge and to treat the patients with ACS successfully, all efforts should be addressed to open the occluded coronary artery, and to restore coronary circulation as soon as possible. During this process the first mandatory step is to perform acute coronarography, in order to reveal the exact pathomorphology, and to make a plan for the optimal treatment. Patients with acute ischaemic syndrome should be transferred to the haemodynamic laboratory within 2-6 hours from the development of the first clinical symptoms, to perform a primary coronary intervention and/or pharmacological treatment when required. A well-established, local/regional system is suitable to organize different levels of medical treatment from the family medicine to the regional heart center, and enables to transfer patients to the appropriate place without delay, and gives an equal chance for every patient with acute ischaemic syndrome.

Acute Disease↗

Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents.

Reactive oxygen and nitrogen species are overproduced in the cardiovascular system during circulatory shock. Oxidant-induced cell injury involves the activation of poly(ADP-ribose) polymerase (PARP). Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the new potent phenanthridinone PARP inhibitor PJ34 [the hydrochloride salt of N-(oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide], we studied whether the impaired cardiac function in endotoxic shock is dependent upon the PARP pathway. Escherichia coli endotoxin (lipopolysaccharide, LPS) at 55 mg/kg, i.p., induced a severe depression of the systolic and diastolic contractile function, tachycardia, and a reduction in mean arterial blood pressure in both rats and mice. Treatment with PJ34 significantly improved cardiac function and increased the survival of rodents. In addition, LPS-induced depression of left ventricular performance was significantly less pronounced in PARP-1 knockout mice (PARP(-/-)) as compared with their wild-type littermates (PARP(+/+)). Thus, PARP activation in the cardiovascular system is an important contributory factor to the cardiac collapse and death associated with endotoxin shock.

Animals↗

Endothelial function studies in pulmonary vascular disease: determination of angiotensin converting enzyme activity in humans (review).

Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme. The majority of ACE has been found on the pulmonary capillary endothelium (PCE). Pulmonary capillary endothelium-bound (PCEB)-ACE has been extensively studied by means of indicator dilution techniques in animals and man. We have recently developed and applied methodologies for assaying pulmonary capillary endothelium-bound (PCEB) angiotensin converting enzyme (ACE) activity in man. This article provides a summary of our studies in human subjects utilizing similar methodology. Trace amounts of the specific ACE substrate, (3)H-benzoyl-Phe-Ala-Pro ((3)H-BPAP; 40 microCi or 2 nmol), was injected as a bolus into the subclavian vein of patients and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product ((3)H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage. To investigate the PCE in this manner we tested the hypothesis that PCEB-ACE is depressed in patients diagnosed with acute lung injury and estimated interaction of an ACE inhibitor (enalaprilat) with PCE in human subjects. An inverse correlation was found between the pulmonary endothelium-bound ACE activity (v) and the lung injury score (r=0.379; p<0.01). Similarly, an inverse correlation was found between the pulmonary capillary perfusion index (CPI) and the lung injury score (r=0.284, p<0.05). PCEB-ACE activity in the group of patients with mild lung injury was significantly different from the group of control patients (0.44 +/- 0.048 vs. 1.15 +/- 0.05; p<0.01). Trace amounts (1.5 microg/kg) of enalaprilat had no significant effect on mean arterial pressure (91 +/- 6 vs. 84 +/- 7 vs. 88 +/- 6 mmHg for T(1), T(2) and T(3), respectively), but significantly decreased PCEB-ACE activities. When normalized to pre-drug (T(1)) activity levels, enalaprilat inhibited PCEB and SE ACE activity at T(2) by 74 +/- 6 and 68 +/- 6%, respectively. PCEB-ACE measurements can be used in clinical practice for estimating PCE functions and can provide new insight into the physiology of the pulmonary circulation.

Angiotensin-Converting Enzyme Inhibitors↗

Accumulation of Hg(II) Ions in Mouse Adrenal Gland.

Female BALBc mice were administered HgCl2 at a single dose of 4 mg/kg i.p. The acute intoxication with Hg(II) salts (2 hr) caused accumulation of Hg(II) ions in the adrenal gland in general, and in the medulla, in particular. Based on data obtained with atomic absorption spectroscopy and quantitative cytochemistry, we determined the amount of mercury (II) in the adrenal glands and found it to be 14.2 ng Hg(II) (3.5 mg/kg wet weight of the adrenals). An uneven distribution of Hg(II) was found within the adrenal gland, not only between the medulla and cortex, but also within the cortex. The applied autometallographic method revealed that the cortex was negative except the zona glomerulosa, whereas the medulla showed a strong reaction localised to the chromaffin granules of the secretory cells. Both adrenaline and noradrenaline producing cells reacted. The comparison of the density of silver grains by scanning densitometry in the medulla and cortex revealed a significantly higher Hg(II) concentration in the medulla compared to the cortex (10 mg/kg vs 2 mg/kg, respectively). The results presented here suggest that there may be a connection between the symptoms of acute Hg(II) intoxication and its adrenal accumulation.

Journal Article↗