Evaluation of the metabolic changes during hemodialysis by signal averaged ECG.

Cardiovascular diseases are frequent complications of end-stage kidney disease. The aim of the present study was to prove the arrhythmogenic effect of dialysis using signal averaged ECG. The ECG changes and laboratory parameters (sodium, potassium, urea and creatinine levels) were detected during hemodialysis treatment in 26 patients suffering from end-stage kidney disease. The tests and the ECG were performed four times, before (0. minute), during (at 15 and 90 min), and eventually after dialysis (at 240 min). The duration of the QRS complex, high-frequency low-amplitude signals (HFLA), and root-mean-square voltage of the terminal 40 ms of the filtered QRS (RMS) were determined. We considered test results to be positive when two of the three tested parameters were outside the normal range: QRS > 120 ms, RMS < 20 uV, HFLA > 39 ms. Signal averaged ECG was positive in two cases (8%) before and after the dialysis. The duration of the QRS-complex increased significantly during the dialysis (predialysis: 109 +/- 7.6 ms, postdialysis: 116 +/- 8.0 ms, p < 0.0001). Serum urea nitrogen (predialysis: 26.2 +/- 5.4, postdialysis: 11.4 +/- 3.3 mmol/l, p <0.0001) and serum creatinine levels (predialysis: 931 +/- 212, postdialysis: 434 +/- 120 micromol/I, p < 0.0001) decreased significantly during the treatment. Significant and continuous decrease in the potassium levels were detected (predialysis: 5.30 +/- 0.72, postdialysis: 3.91 +/- 0.42 mmol/I, p < 0.0001) during the dialysis. Serum sodium levels (predialysis: 139 +/- 2.7, postdialysis: 141.4 +/- 2.2 mmol/I) had not changed during the dialysis. A significant negative correlation was found between decreasing potassium levels and increasing QRS duration (r = - 0.48, p = 0.01). Our results support our primer assumption that the metabolic changes during dialysis treatment can lead to considerable risk of cardiac arrhythmias.

Characterization of human cyclooxygenase 2 gene promoter localization of a TGF-beta response element.

We characterized 2.3 kb of 5'-flanking region of the human cyclooxygenase 2 gene and analyzed its promoter activity. We localized three positive and two negative cis-acting regulatory regions and a TGF-beta response region. Basal promoter activity was located between -77 and +99 bp. Maximal promoter activity was observed from -1838 to +99 bp. A TGF-beta response region was found between -454 and -288 bp. This region included an NF-I site. Electrophoretic mobility shift assays showed that TGF-beta caused a marked change in the pattern and intensity of this NF-I like protein complex.

Prostaglandin production by type II alveolar epithelial cells.

Prostaglandin production was studied in fetal and adult type II alveolar epithelial cells. Two culture systems were employed, fetal rat lung organotypic cultures consisting of fetal type II cells and monolayer cultures of adult lung type II cells. Dexamethasone, thyroxine, prolactin and insulin, hormones which influence lung development, each reduced the production of prostaglandin E and F alpha by the organotypic cultures. The fetal cultures produced relatively large quantities of prostaglandin E and F alpha and smaller quantities of 6-keto-prostaglandin F1 alpha and thromboxane B2. However, prostaglandin E2 production was predominant. In contrast, the adult type II cells in monolayer culture produced predominantly prostacyclin (6-keto-prostaglandin F1 alpha) along with smaller quantities of prostaglandin E2 and F2 alpha. The type II cells were relatively unresponsive to prostaglandins. Exogenously added prostaglandin E, had no effect on cell growth, and only a minimal effect on cyclic AMP levels in the monolayer cultures.

Isolation and culture of two cell populations from chick calvaria by density gradient: prostaglandin synthesis by the cells in culture and coculture.

In previous studies we demonstrated that PTH stimulates production of prostaglandin E2 (PGE2) by intact chick calvaria. In the present series of experiments, two cell populations were isolated from chick calvaria by centrifugation on a 25%/55% Percoll gradient. Cells harvested from the upper band of the Percoll gradient (designated F-1) appeared large and spindle-shaped in culture. Cells harvested from the lower band of the Percoll gradient (designated F-2) were relatively small and polygonal-shaped. Both cell populations required fetal bovine serum (FBS) for attachment and proliferation. In the presence of FBS the cells formed multilayers, but they formed confluent monolayers in the presence of heat-inactivated FBS. The pattern of cAMP responses to different effectors and biochemical determinations for alkaline and acid phosphatase suggests that the F-2 fraction consists primarily of osteoblasts. No cells with osteoclastic patterns appeared in either fraction. Both cell types synthesized predominantly PGD2. PGE2 was also produced, however, in considerably smaller quantities. PG production in the presence of ionophore A23187 (1 microM) or arachidonate (10 microM) increased significantly when the F-1 and F-2 cells were cocultured at a 1:1 ratio. These results suggest that cell to cell or cell to matrix interactions normally present in intact bone influence PG synthesis.

Synthetic human parathyroid hormone fragment stimulates prostaglandin E2 synthesis by chick calvariae.

Synthetic human PTH N-terminal 1-34 peptide [hPTH-(1-34)] stimulates prostaglandin (PG) production by chick calvariae in culture. PGE2 was the predominant PG found by both RIA and HPLC. Stimulation of PGE2 synthesis was significant at 50 ng/ml (1.2 X 10(-8) M) hPTH-(1-34) and was dose dependent at concentrations up to 0.6 microgram/ml (1.4 X 10(-7) M). Continuous exposure of calvariae to hPTH-(1-34) showed that PGE2 production increased significantly by 1 h, reached a maximum at 24 h, and then persisted over 96 h. Indomethacin at concentrations above 5 X 10(-7) M inhibited PGE2 synthesis by both control and hPTH-(1-34)-treated bones. PTH-(1-34) stimulated bone cells to convert arachidonic acid to PGE2, but did not activate the bone to release stored arachidonate. In summary, our results show that hPTH-(1-34) stimulates PGE2 synthesis by chick calvariae. This endogenous PGE2 may be involved in bone remodeling.

Alterations in prostaglandin synthesis during senescence of human lung fibroblasts.

Prostaglandin (PG) synthesis by human embryo lung fibroblasts in culture was determined with increasing population doubling. These cultures synthesized PGE2, PGF2 alpha, PGI2 (prostacyclin) and TXA2 (thromboxane A2) in response to fetal bovine serum or ascorbic acid. Changes in prostaglandin synthesis by these cells during aging were observed in response to serum or ascorbic acid. These included a shift from the synthesis of PGI2 and PGE2 to TXA2 and PGF2 alpha and finally to PGF2 alpha alone. We also observed a marked increase during aging in the release of precursor fatty acid from lipid stores upon stimulation with ascorbic acid. A parallel decrease in the ability to convert the released fatty acid to prostaglandins was detected.

Plasma membrane associated metabolic parameters and the aging of human diploid fibroblasts.

Substrate uptake, portions of the cyclic AMP system, membrane fluidity and cellular phospholipid content are some of the parameters which are structurally associated with the plasma membrane and which have been linked to the control of cell proliferation. These parameters were studied with respect to cellular aging of human embryo lung fibroblasts (HELF) in culture. We observed in late passage an increase in the rate of uridine transport and in cellular cyclic AMP levels. These results were examined in relation to the increase in cell volume which occurs in senescing HELF. We also observed an increase in Vmax of uridine transport, and a decrease in the Km of cyclic AMP phosphodiesterase (PDE) as quiescent, passage 18-25, HELF were stimulated to divide with fresh serum. A similar effect of serum occurred in late passage (p. 43) cells despite the inability of these late passage cultures to undergo further proliferation. There was no change in cAMP-PDE activity with increasing passage number suggesting that the observed alterations of the cAMP levels, basal and in response to extracellular effectors, were due to alterations in the adenyl cyclase system. We observed no change in senescent HELF in membrane fluidity or phospholipid and neutral fat content.

Prostaglandin production and cellular aging.

Prostaglandin (PG) production by human embryo lung fibroblasts (HELF) is stimulated by a number of effectors including angiotensin, thrombin, bradykinin and ascorbic acid. The types of prostaglandins produced are to a degree effector-dependent. For example, angiotensin stimulates mainly PGE2 synthesis, thrombin stimulates production of both PGE2 and prostacyclin while bradykinin and ascorbic acid stimulate production of PGE2, PGF2 alpha, prostacyclin and thromboxane A2. Upon senescence in culture, prostacyclin (PGI2) production by HELF drops dramatically in response to ascorbic or arachidonic acids. An overall drop in prostaglandin synthesis is observed with bradykinin stimulation. Prostaglandin production is also related to senescence in human skin fibroblasts (HSF). These cells produce predominantly PGI2. Prostacyclin production in response to bradykinin drops in HSF as they are obtained from individuals of increasing chronologic age. Thus our results indicate changes in prostaglandin production upon senescence, a dependency of these changes on the given stimulus and a correlation between in vivo and in culture aging with respect to prostaglandin production.

Prostaglandin production in phenotypically distinct cultured bovine pulmonary artery endothelium.

Bovine pulmonary artery endothelial cells, maintained in culture for prolonged periods, were observed to enter into a secondary growth pattern commonly referred to as sprouting. Our investigations, as well as those of other workers, indicate that these cells represent a phenotypic variant of the original endothelial cell population, rather than the proliferation of a contaminating cell type. A significant increase in prostaglandin production, particularly prostacyclin, could be correlated with the appearance of these phenotypically distinct endothelial cells in culture. We suggest that the elevation in prostacyclin synthesis is a result of endothelial cell sprouting and hypothesize that increased prostacyclin levels may account for the inhibition of platelet deposition reported in post-confluent endothelial cultures.

Comparison of prostaglandin synthesis by endothelial cells from blood vessels originating in the rat, baboon, calf and human.

The synthesis of prostaglandins (PGs) was determined in endothelial cells obtained from various vessels from baboon, human and rat both by radioimmunoassay and prelabel of the cells with [3H] arachidonate. Cells were stimulated with bradykinin, ionophore A23187 or 10 microM arachidonate. Although prostacyclin (PGI2) has proven to be the major prostaglandin product of human umbilical vein and calf pulmonary artery endothelial cells, our results show that PGI2 is frequently not the major prostaglandin product of endothelial cells from other vessels. For example baboon endothelial cells lining the large vessels, aorta and cephalic vein produce mainly PGF2a with only small amounts of PGE2 and PGI2. Human endothelial cells from saphenous vein also produce mainly PGF2a. Baboon, human and rat adipose capillary endothelial cells make predominantly PGE2 and PGI2 with rat making significant amounts of PGF2a in addition. Endothelial cells from the rat aorta produced predominantly prostacyclin.

The effect of ascorbate, hydroperoxides, and bradykinin on prostaglandin production by corneal and lens cells.

Epithelial cells from the rabbit cornea, fibroblasts from the rabbit and calf cornea, and calf lens epithelial cells were placed in individual cultures. Prostaglandin (PG) synthesis by these cell types was determined. Lens epithelial cells produced no detectable PGs under basal conditions. Corneal fibroblasts primarily produced PGE2, while epithelial cells primarily produced thromboxane A2. PG production by corneal fibroblasts was highly responsive to bradykinin, ascorbic acid, hydrogen peroxide, and t-butyl hydroperoxide, an organic peroxide. Quantitative differences in PG production between the rabbit and calf corneal fibroblasts were observed. Our results suggest that the reported therapeutic actions of ascorbic acid in the eye may, at least in part, be mediated through the PGs. Our results also support the proposed role for hydroperoxides in the control of PG synthesis.

Cardiac electrophysiologic effects of adaprolol maleate, a new beta-blocker, in closed chest dogs.

Adaprolol maleate (adaprolol) is a new beta-adrenergic receptor blocker. The cardiac electrophysiologic characteristics and the duration of action of adaprolol were studied in intact anesthetized dogs. The electrophysiologic parameters were evaluated before drug administration and 10 min after the administration of maintenance infusion of adaprolol (N = 5). The duration of action was measured during constant infusion of isoproterenol, giving the adaprolol as a single i.v. bolus in different concentrations (N = 5). Results of this study showed that adaprolol has marked electrophysiologic effects. Its major action was on sinus node; it prolonged the basic sinus cycle length and had significant effect on intrinsic automaticity as reflected by the prolonged corrected sinus node recovery time and sinuatrial conduction time. There was, also, direct effect on atrial function and AV nodal function. Adaprolol prolonged the effective refractory period of the His-Purkinje system and the ventricle. The onset of action was very rapid (within seconds) and the duration of action was relatively prolonged (3 hrs). The potency of adaprolol's electrophysiologic effects are higher compared to other widely used beta-blockers. Adaprolol appears to be a potent beta-blocker with particularly strong antiarrhythmic effect and it would be very useful in the treatment of both supraventricular and ventricular tachyarrhythmias and ectopic beats.

Minimal cardiac electrophysiological activity of alprenoxime, a site-activated ocular beta-blocker, in dogs.

A closed chest catheter technique was used in dogs to examine the potential cardiac effects of alprenoxime, a potent new ocular antihypertensive agent. Alprenoxime was designed to undergo metabolic activation to the beta-blocker, alprenolol, specifically within the eye using hydrolase and reductase enzymes that reside in the iris-ciliary body. Previous studies in rabbits confirmed that intraocular pressure (IOP) significantly decreased after topically instilling ophthalmic drops of alprenoxime, while heart rates remained essentially unchanged after intravenous dosing. To further explore the safety and ocular specificity of this potential antiglaucoma drug, several cardiac electrophysiologic parameters were monitored during alprenoxime infusion in anesthetized dogs. In contrast to the pharmacologically significant increases (33-144%) measured after alprenolol or other previously tested beta antagonist infusion, the identical dose of alprenoxime had no effect on sinus cycle length (SCL), conduction times through the bundle of His and atrium (H and AH), or any other monitored cardiac electrophysiologic parameter. No changes greater than 6% from baseline were detected with alprenoxime infusion. Similarly, no beta-antagonist cardiac activity could be detected in isoproterenol stimulated dogs after alprenoxime. The results demonstrate that alprenoxime has no significant cardiac activity at doses much greater than potential therapeutic levels. The study provides further support that the new agent could be safely used in treating glaucoma.

A tryptamine analog with high affinity to the heart tissues is a potential antiarrhythmic agent.

A novel tryptamine analog, 1-methyl-3-[N-(3-indolyl)ethyl]carbamoyl-1,4-dihydropyridine (T-CDS) was synthesized and converted into a stable, solid complex with 2-hydroxypropyl-beta-cyclodextrin. An aqueous solution of the complex was given intravenously to dogs and the concentration of T-CDS and its corresponding quaternary (T-Q+) forms were monitored in the blood for 50 min. The effect of the drug on vital heart parameters was monitored throughout the studies. At the end of the experiment the dogs were sacrificed and the concentration of the quaternary pyridinium form (T-Q+) was determined in the different heart tissues, as well as in the kidney, liver, lung, brain, urine and cerebrospinal fluid. The compound was found to be selectively bound to the heart muscles and showed different concentrations in different heart tissues. The T-Q+ concentrations were much higher in the heart after administration of the dihydro form (T-CDS), than after administering T-Q+ directly. The compound was found to be active on certain vital signs of the cardiovascular system and could be an effective and safe antiarrhythmic agent.

Fatty acid composition of intramuscular lipids in various muscles of Holstein-Friesian bulls slaughtered at different ages.

Holstein-Friesian bulls were slaughtered at 7, 14 and 19 months of age. Samples were collected from the psoas major, longissimus and semitendinosus muscles. The total lipids (TL) of the samples were extracted and the fatty acid compositions were analysed by gas chromatography. Both the slaughtering age and the type of muscles had significant effects on the intramuscular TL contents and fatty acid compositions. The longissimus muscle had higher intramuscular TL both at 14 and 19 months than at 7 months of age. As the bulls became older the proportion of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) increased in the TL of each muscle tested, whereas that of polyunsaturated fatty acids (PUFA) decreased. Among the muscle types, the semitendinosus had the lowest, intramuscular TL at each slaughtering age and the psoas major the highest. Except for SFA at 7 months of age, the semitendinosus showed lower levels of SFA and MUFA and higher proportions of PUFA than the other two muscles.

Complex arrhythmia analysis in uraemic haemodialysed patients.

Impulse formation and conduction disturbances of the heart were investigated in 23 uraemic patients with transvenous and oesophageal electrodes. Utilizing regular atrial pacing the sinoatrial conduction time (SACT) was obtained and sinus automaticity was evaluated by measurement of the sinus node recovery time (SNRT). The atrial effective refractory period and the Wenckebach point were also determined. The effects of regular haemodialysis treatment on impulse formation and propagation disorders caused by uraemia were observed. In 16 patients transitory or permanent cardiac stimulation had to be carried out because of 2nd and 3rd degree AV block. No complication was observed during simultaneous haemodialysis and pacemaker treatment. It is concluded that the non-invasive, simple bedside oesophageal atrial stimulation method is a good alternative and should be used in the exact diagnosis of heart conduction disturbances of haemodialysed patients.

[Management of drug-resistant supraventricular tachycardia using AV-junction radiofrequency ablation]. / Gyógyszer rezisztens supraventricularis tachycardia kezelése az AV-junctio radiofrekvenciás ablációjával.

The closed chest His bundle ablation is a worldwide accepted therapeutic method for the treatment of drug resistant supraventricular tachycardias. In the first years high-energy DC shock was applied for achieving the needed therapeutic effect. Reducing the complications caused by the DC shock, radiofrequency energy was introduced into the clinical practice. Authors describe the first successful human application of radiofrequency ablation of AV junction in Hungary.

[Clinical cardiac electrophysiological studies in carotid sinus syndrome]. / Klinikai szív-elektrofiziológiai vizsgálatok carotis sinus syndromában szenvedö betegekben.

The aim of the present study was to evaluate the impact of electrophysiological study in the diagnosis and treatment of carotid sinus syndrome. The indications for the study include (1) attempting to exclude other cardiogenic causes of syncope; block, tachyarrhythmia, (2) diagnosing a vasodepressor response in the presence of cardioinhibitory type of carotid sinus syndrome, (3) determination of the optimal pacing mode in patients who need pacemaker implantation for treatment. 51 patients, 40 male (78%) and 11 female (22%) with an average age of 62 years suffering from carotid sinus hyperaesthesia--3000 ms ventricular asystole on carotid sinus massage--were investigated with electrophysiological study. The A-H interval in 8 patients (16%), the H-V interval in 5 pts (10%) were prolonged in the His bundle electrocardiogram. In 39 patients (76%) sinoatrial block, in 12 patients (24%) A-H block was found during carotid sinus massage. Early A-H Wenckebach block occurred in 8 patients (16%). Retrograde (V-A) conduction was present in 36 patients (70%) at a frequency of 65-85 bpm, and 22 pts (43%) at a frequency of 120-180 bpm. Sinus node disease was found in 10 patients (20%) according to the sinus node recovery time and sinoatrial conduction time. In 8 patients (16%) supraventricular and in 4 patients (8%) ventricular tachyarrhythmia was induced during study. The atrial stimulation could not prevent the occurrence of A-V block during carotid sinus massage in any of the 51 patients. In 2 patients (4%) the vasodepressor reaction with ventricular stimulation was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

[Atrioventricular block caused by tick bite--Lyme's carditis]. / Kullancs csípés okozta atrioventricularis blokk--Lyme carditis.

The authors present the case of a 44-year-old patient who was admitted to the hospital because of AV block of degree III. Six weeks earlier a tick was removed from the left foot of the patient. Two weeks later an erythema of 8 cm in diameter, spreading peripherally as well as painful inguinal lymphadenitis developed at the site of the bite with transient arthralgia and myalgia in the region of the waist and left lower limb. After the temporary use of pacemaker, steroid and atropine therapy applied because of the pronounced bradycardia the block became of degree I on the 4th day however negative T-waves appeared in leads III, aVF, V3. By the 14th day the AV time returned to normal and the pathological signs of repolarization disappeared. Serological examinations revealed increased Borrelia burgdorferi antibody level. Lyme's carditis may be prevented by starting the antibiotic therapy at the time of the chronic erythema migrans. Upon medication the patient may recover from the carditis without remaining symptoms.

[Lipid lowering treatment in secondary prevention following myocardial infarct]. / A lipidszintcsökkentó terápia helye a myocardialis infarctust követó szekunder prevencióban.

1081 patients treated with myocardial infarction between 1990-1995 were investigated retrospectively, 652 (60.3%) of the patients were male and 429 (39.7%) were female. 154 (14.2%) patients had an early, while 927 (85.5%) patients had late myocardial infarction. Of the patients with early myocardial infarction 52.3% were smokers, 45.2% had positive family history for ischaemic heart disease or acute myocardial infarction. The lipid parameters were analysed in detail, because 83.3% of the patients were hyperlipoproteinaemic. The mean cholesterol level was 6.91 +/- 1.2 mmol/l, the HDL-C level was 1.19 +/- 0.38 mmol/l, the triglyceride level was 2.66 +/- 1.8 mmol/l, the LDL-C level was 4.71 +/- 1.2 mmol/l. The serum LDL-C and the HDL-C levels of the patients with early myocardial infarction were compared to the desirable levels suggested for secondary prevention. Only 7.2% of the male patients had a cholesterol level below 5.2 mmol/l, while all female patients cholesterol levels were above 5.2 mmol/l. Of the male patients 53.6%, while 78.6% of females had lower triglyceride levels than 2.3 mmol/l 78,6% of the male patients had higher protective HDL-C level in the optimal range (> 1.1 mmol/l). 12.5 percent of the male patients had an LDL-C level lower than the value targeted by secondary prevention (3.0 mmol/l), while all of the female patients LDL-C levels were higher. The authors emphasize the importance of secondary prevention and a more widespread use of lipid lowering treatment for patients after acute myocardial infarction.