[Commentary on the guidelines the diagnosis and the therapy of syncope--the European Society of Cardiology 2001 and the update 2004].
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Biomedical subjects
Publications and source records attributed to W Hartung.
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The phytohormone abscisic acid (ABA) regulates many stress-related processes in plants. In this context ABA mediates the responsiveness of plants to environmental stresses such as drought, cold or salt. In response to water stress, ABA induces stomatal closure by activating Ca2+, K+ and anion channels in guard cells. To understand the signalling pathways that regulate these turgor control elements, we studied the transcriptional control of the K+ release channel gene GORK that is expressed in guard cells, roots and vascular tissue. GORK transcription was up-regulated upon onset of drought, salt stress and cold. The wilting hormone ABA that integrates responses to these stimuli induced GORK expression in seedlings in a time- and concentration-dependent manner and this induction was dependent on extracellular Ca2+. ABA-responsive expression of GORK was impaired in the ABA-insensitive mutants abi1-1 and abi2-1, indicating that these protein phosphatases are regulators of GORK expression. Application of ABA to suspension-cultured cells for 2 min followed by a 4 h chase was sufficient to manifest transcriptional activation of the K+ channel gene. As predicted for a process involved in drought adaptation, only 12-24 h after the release of the stress hormone, GORK mRNA slowly decreased. In contrast to other tissues, GORK expression as well as K+(out) channel activity in guard cells is ABA insensitive, allowing the plant to adjust stomatal movement and water status control separately.
OBJECTIVES: To develop and test a new concept of the degradation kinetics of newly developed coronary stents consisting of magnesium alloys. METHODS: Design of a coronary stent prototype consisting of the non-commercial magnesium based alloy AE21 (containing 2% aluminium and 1% rare earths) with an expected 50% loss of mass within six months. Eleven domestic pigs underwent coronary implantation of 20 stents (overstretch injury). RESULTS: No stent caused major problems during implantation or showed signs of initial breakage in the histological evaluation. There were no thromboembolic events. Quantitative angiography at follow up showed a significant (p < 0.01) 40% loss of perfused lumen diameter between days 10 and 35, corresponding to neointima formation seen on histological analysis, and a 25% re-enlargement (p < 0.05) between days 35 and 56 caused by vascular remodelling (based on intravascular ultrasound) resulting from the loss of mechanical integrity of the stent. Inflammation (p < 0.001) and neointimal plaque area (p < 0.05) depended significantly on injury score. Planimetric degradation correlated with time (r = 0.67, p < 0.01). CONCLUSION: Vascular implants consisting of magnesium alloy degradable by biocorrosion seem to be a realistic alternative to permanent implants.
AIM: The purpose of this study was to evaluate the performance of a new VDD pacing system incorporating a high impedance, single-pass VDD lead. The new lead is a bipolar, steroid-eluting, high impedance lead with a full-ring atrial dipole. METHODS AND RESULTS: The system was implanted in 46 patients with high degree atrioventricular (AV) block. Patients were followed at pre-discharge, 6 weeks, and 3 months. The mean measured P-wave amplitude was stable, with values between 1.18 and 1.43 mV. Atrial sensing was reliable during short-term evaluation at rest and in the sitting position, with AV-synchronous stimulation between 98.79 +/- 6.90% and 99.73 +/- 1.47%. Holter recordings after 6 weeks demonstrated AV-synchronous stimulation in 99.57 1.03% of all P-waves. Lead impedance was stable during follow-up, with mean values between 1000 and 1167 Q. Mean ventricular pacing thresholds (at 0.5 ms) were 0.47 V at implant, 0.49 V at pre-discharge, 0.74 V at 6 weeks, and 0.72 V at 3 months. R-wave amplitude remained stable between 14.9 and 16.7 mV during follow-up. CONCLUSION: This new single-pass VDD lead system provided reliable atrial sensing and stable high impedance stimulation during a 3-month follow-up period.
Glycine and serine are potential sources of nitrogen for the aquatic resurrection plant Chamaegigas intrepidus Dinter in the rock pools that provide its natural habitat. The pathways by which these amino acids might be utilized were investigated by incubating C. intrepidus roots and maize (Zea mays) root tips with [(15)N]glycine, [(15)N]serine and [2-(13)C]glycine. The metabolic fate of the label was followed using in vivo NMR spectroscopy, and the results were consistent with the involvement of the glycine decarboxylase complex (GDC) and serine hydroxymethyltransferase (SHMT) in the utilization of glycine. In contrast, the labelling patterns provided no evidence for the involvement of serine:glyoxylate aminotransferase in the metabolism of glycine by the root tissues. The key observations were: (i) the release of [(15)N]ammonium during [(15)N]-labelling experiments; and (ii) the detection of a characteristic set of serine isotopomers in the [2-(13)C]glycine experiments. The effects of aminoacetonitrile, amino-oxyacetate, and isonicotinic acid hydrazide, all of which inhibit GDC and SHMT to some extent, and of methionine sulphoximine, which inhibited the reassimilation of the ammonium, supported the conclusion that GDC and SHMT were essential for the metabolism of glycine. C. intrepidus was observed to metabolize serine more readily than the maize root tips and this may be an adaptation to its nitrogen-deficient habitat. Overall, the results support the emerging view that GDC is an essential component of glycine catabolism in non-photosynthetic tissues.
Abscisic acid (ABA) is a potent molecule that certainly modifies stomatal behaviour and plant water loss and probably acts to modify the growth of leaves. The hormone is synthesized both in the leaves and the roots of the plant and in the soil and may move freely from plant to soil and soil to plant. It can also move rapidly through the plant in both the xylem and the phloem and will partition between different compartments in different tissues largely as a function of pH. It is described here how perturbations in soil conditions around the roots and the water status of the air can modify the fluxes of ABA around the plant and its accumulation in different compartments and different tissues. These fluxes can be interpreted as signals of different stresses imposed on the plant and consideration is given to how different perturbations can exert subtle changes which are manifest as modified shoot growth rates and functioning. Most emphasis in the discussion is placed upon the plant's responses to the imposition of soil and atmospheric drought.
The exodermis (hypodermis with Casparian bands) of plant roots represents a barrier of variable resistance to the radial flow of both water and solutes and may contribute substantially to the overall resistance. The variability is a result largely of changes in structure and anatomy of developing roots. The extent and rate at which apoplastic exodermal barriers (Casparian bands and suberin lamellae) are laid down in radial transverse and tangential walls depends on the response to conditions in a given habitat such as drought, anoxia, salinity, heavy metal or nutrient stresses. As Casparian bands and suberin lamellae form in the exodermis, the permeability to water and solutes is differentially reduced. Apoplastic barriers do not function in an all-or-none fashion. Rather, they exhibit a selectivity pattern which is useful for the plant and provides an adaptive mechanism under given circumstances. This is demonstrated for the apoplastic passage of water which appears to have an unusually high mobility, ions, the apoplastic tracer PTS, and the stress hormone ABA. Results of permeation properties of apoplastic barriers are related to their chemical composition. Depending on the growth regime (e.g. stresses applied) barriers contain aliphatic and aromatic suberin and lignin in different amounts and proportion. It is concluded that, by regulating the extent of apoplastic barriers and their chemical composition, plants can effectively regulate the uptake or loss of water and solutes. Compared with the uptake by root membranes (symplastic and transcellular pathways), which is under metabolic control, this appears to be an additional or compensatory strategy of plants to acquire water and solutes.
The exodermal layers that are formed in maize roots during aeroponic culture were investigated with respect to the radial transport of cis-abscisic acid (ABA). The decrease in root hydraulic conductivity (Lp(r)) of aeroponically grown roots was stimulated 1.5-fold by ABA (500 nM), reaching Lp(r) values of roots lacking an exodermis. Similar to water, the radial flow of ABA through roots (J(ABA)) and ABA uptake into root tissue were reduced by a factor of about three as a result of the existence of an exodermis. Thus, due to the cooperation between water and solute transport the development of the ABA signal in the xylem was not affected. This resulted in unchanged reflection coeffcients for roots grown hydroponically and aeroponically. Despite the well-accepted barrier properties of exodermal layers, it is concluded that the endodermis was the more effective filter for ABA. Owing to concentration polarisation effects, ABA may accumulate in front of the endodermal layer, a process which, for both roots possessing and lacking an exodermis, would tend to increase solvent drag and hence ABA movement into the xylem sap at increased water flow (J(Vr)). This may account for the higher ABA concentrations found in the xylem at greater pressure difference.
Using root- and cell-pressure probes, the effects of the stress hormone abscisic acid (ABA) on the water-transport properties of maize roots (Zea mays L.) were examined in order to work out dose and time responses for root hydraulic conductivity. Abscisic acid applied at concentrations of 100-1,000 nM increased the hydraulic conductivity of excised maize roots both at the organ (root Lp(r): factor of 3 4) and the root cell level (cell Lp: factor of 7-27). Effects on the root cortical cells were more pronounced than at the organ level. From the results it was concluded that ABA acts at the plasmalemma, presumably by an interaction with water channels. Abscisic acid therefore facilitated the cell-to-cell component of transport of water across the root cylinder. Effects on cell Lp were transient and highly specific for the undissociated (+)-cis-trans-ABA. The stress hormone ABA facilitates water uptake into roots as soils start drying, especially under non-transpiring conditions, when the apoplastic path of water transport is largely excluded.
UNLABELLED: Evaluation of the quality of atrial sensing is indispensable to monitor the performance of VDD single-lead systems. In addition to counters, a new VDD system offers storage of intracardiac electrograms (EGMs). The clinical contribution of stored EGMs in a VDD pacemaker was prospectively examined in a multicenter study, and the reliability of its counters was evaluated on the basis of EGM information. METHODS: A VDD system (Pulsar 870, Guidant Co.) was implanted in 46 patients with atrioventricular block. EGM storage was activated upon detection of ventricular tachycardia (VT), recurrent premature ventricular complexes (PVCs), and mode switch ("atrial tachy reaction," ATR). Stored EGMs were retrieved before discharge of the patients from the hospital, and at 6-week, 3-month, and 6-month follow-up. RESULTS: A total of 440 stored EGMs were retrieved and analyzed. Of 30 VT episodes detected, 2 (7%) were confirmed, and all others were attributable to ventricular oversensing. One postmortem interrogation documented VT as the cause of sudden death. Of 175 EGMs stored upon detection of PVCs, 43 episodes (25%) were confirmed and 124 (70%) showed intermittent atrial undersensing with spontaneous AV conduction; in 8 episodes (5%) no abnormality was observed. Of 235 episodes stored upon ATR, 82 (35%) were confirmed and 153 were due to atrial oversensing. CONCLUSIONS: (1). Stored EGMs indicated a high percentage (69%) of event misdiagnosis by the pacemaker. Thus, pacemaker counter information without the availability of stored EGMs should be interpreted with caution. (2). Misclassified events are of high clinical importance since they unmask otherwise unsuspected intermittent under- or oversensing.
Previous studies have shown that platelets are activated during atrial fibrillation (AF). However, prophylactic therapy with aspirin is not associated with a reduction of thromboembolic complications in patients with AF. Stimulation of platelet thrombin and ADP receptors causes a release of P-selectin, which is not affected by aspirin. The purpose of this study was to assess the influence of AF on platelet P-selectin expression. Blood samples from 30 patients were studied ex vivo. Nineteen patients had chronic AF (> 3 months), 11 patients were in sinus rhythm (SR). P-selectin expression was determined by flow cytometry (antibody binding capacity [BC]) at baseline and after platelet stimulation with adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP). To determine the effect of heart rate and atrial pressure (RAP), measurements were repeated after 10 minutes of ventricular pacing (120 beats/min) in patients with SR. P-selectin expression was increased in patients with AF at baseline (AF: 1329 +/- 81 BC vs SR: 968 +/- 108 BC; P < 0.05) and after stimulation with ADP (AF: 1445 +/- 101 BC vs SR: 1061 +/- 109 BC; P < 0.05) and TRAP (AF: 13,783 +/- 2442 BC vs SR: 5977 +/- 800 BC; P < 0.05). RAP (2.0 +/- 0.5 vs 6.0 +/- 0.8 mmHg; P < 0.01) and atrial rate (75 +/- 5 vs 114 +/- 5 beats/min; P < 0.001) increased during ventricular pacing. However, P-selectin levels remained stable. AF was accompanied by increased P-selectin expression. In contrast, increased ventricular rate and elevated atrial pressure alone had no effect on platelet activity. Further studies are needed to determine if platelet ADP receptor inhibitors offer a therapeutic benefit in patients with AF.
Conjugated, alkaline hydrolysable ABA (predominantly abscisic acid glucose ester, ABA-GE), which is transported in the xylem from roots to shoots of Zea mays L. plants, has its origin in the root symplast rather than from soil, although it was detectable in soil solution with concentrations up to 30 nM. External ABA glucose ester cannot be dragged with the water flow across the exodermis and the endodermis because of its hydrophobic properties. Experimental evidence is presented that enzymes in the cortical apoplast cleave ABA-GE thus releasing ABA from its conjugates. Liberated ABA can then be translocated apoplastically and symplastically to the xylem vessels. Endogenous ABA-GE can be released from isolated cortical and stelar tissues to the surrounding media, with rates that are up to 5-fold higher from stelar tissues than those from cortical tissues. Release of ABA-GE is highest under conditions of inhibited ABA-metabolism.
Abscisic acid conjugate concentrations increased in barley xylem sap under salinity, whereas it remained at a low level in the intercellular washing fluid (IWF) of barley primary leaves (Hordeum vulgare cv. Gerbel). Here it is shown that IWF contains beta-glucosidase activity which releases abscisic acid (ABA) from the physiologically inactive ABA-glucose conjugate pool in the leaf apoplast. The following data support this conclusion and give the first biochemical and physiological characterization of the extracellular glucosidase activity in barley. Free ABA was released by the incubation of ABA glucose ester with IWF. The product exhibited the retention time of authentic ABA upon separation by thin layer chromatography and was identified by ABA-ELISA. p-Nitrophenol-beta-D-glucopyranoside (pNPG) was used as the substrate for beta-glucosidases. The K(M)(pNPG) was 1.8 mmol l(-1). The activity was affected by ABA glucopyranoside in a competitive type of inhibition with a K(I) of 400 micromol l(-1). Various hormone conjugates were compared with respect to their inhibitory effect on beta-glucosidase activity. Inhibition was highest for the ABA glucopyranoside and the zeatin riboside, but insignificant for ABA methyl ester and zeatin-9-beta-D-glucoside. The specific activity of the beta-glucosidase was 16-fold greater in IWF as compared to crude leaf extracts confirming its extracellular compartmentation. The activity of beta-glucosidase was strongly increased after growth in hydroponic medium supplemented with NaCl. The data support the hypothesis that the glucose conjugate is a long-distance transport form of ABA.
In order to investigate the nature of genes expressed in leaf epidermal cells of higher plants, we have identified the nucleotide sequence of a cDNA designated ltp 7a2b encoding a novel nonspecific lipid transfer protein of barley (Hordeum vulgare L. cv. Gerbel). The cDNA of 755 basepairs contains an open reading frame of 366 nucleotides coding for a 12.3-kDa polypeptide. The first 29 amino acids constitute the putative signal peptide, characteristic for targeting to the secretory pathway. Analysis of mRNA levels by Northern blotting indicated that ltp 7a2b is preferentially expressed in the leaf epidermis. Levels of mRNA decreased during ageing of leaf tissue. Expression of ltp 7a2b was stimulated by a factor of 2 - 3 when the seedlings were grown in the presence of cadmium (10 - 1600 microM). Concomitantly, the primary leaves of Cd-exposed seedlings contained elevated levels of abscisic acid and thicker was layer of the cuticle. At 100 microM Cd in the hydroponic medium, the was cover was increased by 50%. The increase in abscisic acid content, ltp 7a2b mRNA and was coverage was either not seen, or seen much less, in Ni- and Zn-stressed seedlings. The data add circumstantial evidence to the recently proposed hypothesis that nonspecific lipid transfer proteins function in transfer of cutin and/or wax monomers from the site of synthesis in the cell to the cuticle.
Pacing therapy has been recently proposed as a new non-pharmacological approach to patients suffering from congestive heart failure refractory to medical therapy (refractory CHF), but the extention and the real benefit of this method remains to be defined. Although pacing therapy for refractory CHF has been restricted to patients in sinus rhythm presenting atrial, atrioventricular or interventricular conduction disturbances, considerable conflicting results have been published. The contradictory data is most likely due to large heterogeneity of the investigated study population (ie etiology of CHF, NYHA class, duration of follow-up, end-points of the study, etc.), to difference in study methology as well as in the site and modality of acute and chronic pacing. Although several empirical data indicates, at least in some individuals, major improvement in CHF symptoms by properly coordinating the atria and the ventricles thus reducing pre-systolic mitral and/or tricuspidal regurgitation or finally, prolonging the diastolic filling time, a lack of understanding of the mechanisms responsible for acute and chronic benefit persists. In evaluating pacemaker therapy as a new supportive treatment for CHF, the clinical investigator must consider that each study protocol embodies assumptions and methodological limitations and thus provides an incomplete analysis of potential benefit. Relying solely on noninvasive measures is risky due to problems of sensitivity and repeatability.
BACKGROUND: Catheter ablation with radiofrequency energy is feasible in a limited subset of patients with ventricular tachycardia. The purpose of this study was to evaluate a technique for mapping and ablation of ventricular myocardium with the use of transcatheter subendocardial infusion. METHODS AND RESULTS: A needle-tipped deflectable electrode catheter was used to deliver reagents to endocardial target sites. This was equipped with two central lumens to allow sequential administration of mapping and ablation injectants with minimal admixture. The mapping injectant consisted of a mixture of lidocaine, iohexal, and glycerin; the ablation injectant contained ethanol, iohexal, and glycerin. Infusion of the mapping injectant (1 cm3 over 3 or 5 seconds, n = 14) produced a stain on fluoroscopy and increased local capture threshold by 61%. No lesions resulted from mapping infusions. Infusion of the ethanol-containing injectant (n = 48) produced discrete lesions, with a mean volume ranging from 0.6 to 1.5 cm3. There was a direct relationship between infusion volume, infusion duration, and resultant lesion volume. Fibrosis in a region of healed myocardial infarction did not impair diffusion of the injectant or affect lesion dimensions. Microscopic analysis of chronic lesions showed a sharply demarcated border zone between fibrotic and normal myocardium. CONCLUSIONS: Transcatheter subendocardial infusion can be used to reversibly impair local excitability and mark an injection site fluoroscopically. Subendocardial injection of ethanol can predictably ablate a large volume of ventricular myocardium. Additional study of this system in an arrhythmia model will help to define its potential for mapping and ablation of hypotensive ventricular tachycardia.
A major problem in patients with cardioverter-defibrillators is to determine reliably the mechanism for spontaneous implantable cardioverter-defibrillator (ICD) discharges. Electrogram storage in ICD devices is comparable to that in permanent Holter monitors. Stored bipolar electrograms obtained from the sensing or shocking lead system contain a wide variety of different information. Intracardiac electrograms (EGMs) recorded from pace/sense electrodes (or "near-field" EGMs) show bipolar signals that have a distinct absence of any atrial activity during ventricular tachycardia or sinus rhythm. In contrast, the EGMs recording from the shocking electrodes, integrating a much larger area of myocardium, provide a more global visualization of electrical activity, which includes both atrial and ventricular deflections. Improved diagnostic capabilities available in the new generation ICD devices, in particular the stored intracardiac EGMs, facilitate sensing error diagnosis, permit a better evaluation of device function and ICD detection algorithms, and are helpful for reprogramming in order to overcome or prevent errors. In addition, EGMs give us a unique opportunity to gather information about the arrhythmic mechanism of the sudden cardiac death syndrome. Information such as the day and time of the episode, the preceding heart rate, the influence of the coupling interval of preceding premature beats, and their morphology can be gained from the analysis of stored EGM recordings. Although the availability of stored intracardiac EGMs are of enormous value in troubleshooting of ICD problems, they are occasionally not conclusive and must be complemented by additional techniques in order to complete the diagnosis. The information obtained by the analysis of stored intracardiac EGMs together with a database of EGMs can be of great importance for further improvements in future devices and may provide insights as to which patients are likely to benefit most from ICD therapy.
The conversion of the submerged form of Riccia fluitans to the landform either by transfer to a moist solid surface or by treatment with abscisic acid (ABA), is accompanied by the formation of a set of new polypeptides and concomitant down-regulation of other polypeptides. Changes in gene expression were analyzed by two-dimensional separations of proteins and differential screening of a cDNA library. One of the landform-specific proteins might depend on the expression of the newly discovered Ric 1 gene. The deduced amino acid sequence of the isolated Ric 1 cDNA clone codes for a protein with a molecular mass of 30.1 kDa. This polypeptide possesses two amino acid sequences which are repeated five times each and it is largely hydrophilic with the exception of a hydrophobic carboxyl-terminal region. Under ABA treatment the expression of the Ric 1 mRNA had already reached its maximum after 1 h of incubation. Transferring submerged thalli onto an agar surface resulted in a slower induction. The Ric 1 gene product shows homology to an embryo-specific polypeptide of carrot seeds and to the group 3 of late-embryogenesis-abundant (LEA) proteins. Interestingly, ABA treatment improved the desiccation tolerance of the submerged thalli. Additionally, ABA stimulated the synthesis of a protein which is immunologically related to a tonoplast protein. This finding, together with the fact that the ABA-induced landform exhibits an increased activity of several vacuolar enzymes, may indicate a special role of the tonoplast and the vacuole during ABA-induced conversion of the thallus from the submerged to the terrestrial form.