Animal board invited review: Grassland-based livestock farming and biodiversity.

Grasslands dominate land cover nationally and globally, and their composition, structure and habitat value are strongly influenced by the actions of domestic and wild grazing animals that feed on them. Different pastures are characterised by varying opportunities for selective feeding by livestock; agronomically improved, sown swards generally consist of a limited range of plant species whereas longer-term leys and semi-natural grasslands are characterised by a more diverse mixture of plants. In the case of botanically diverse permanent pastures/grazing lands, the dietary preferences of different grazers have a more pronounced effect on the botanical composition of the sward in the longer term. Selection of a dominant species within the sward can give less abundant components a chance to compete, increasing community evenness and species richness. Conversely, the selection of minor components reduces sward compositional heterogeneity and hence plant species richness and evenness. Body size, gut type (foregut vs hindgut fermentation), physiological status (growing, pregnant, lactating), metabolic status (extent of body reserves) and environmental conditions all influence the nutrient requirements of a given animal and related foraging priorities. The diet selected is also strongly influenced by the availability of preferred food items, and their vertical and horizontal distribution within the sward. In general, larger animals, such as cattle and horses, are less selective grazers than smaller animals, such as sheep and goats. They are quicker to switch to consuming less-preferred sward components as the availability of preferred resources declines due to their greater forage demands, and as a result can be very effective in controlling competitive plant species consistently avoided by more selective grazers. As a result, low-intensity mixed grazing of cattle and sheep has been shown to improve the diversity and abundance of a range of taxa within grazed ecosystems. Mixed/co-species grazing with different animals exploiting different grassland resources is also associated with increased pasture use efficiency in terms of the use of different sward components and related improvements in nutritional value. In situations where cattle are not available, for example if they are not considered commercially viable, alternative species such as goats, ponies or South American camelids may offer an opportunity to diversify income streams and maintain productive and biodiverse pastures/grazing lands. Stocking rate and timing of grazing also have a considerable role in determining the impact of grazing. Regardless of the species grazing or the pasture grazed, grazing systems are dynamic since selective grazing impacts the future availability of sward components and subsequently dietary choices. New technologies under development provide opportunities to monitor plant/animal interactions more closely and in real time, which will in future support active management to deliver targeted biodiversity gains from specific sites.

Integrating Narcissus-derived galanthamine production into traditional upland farming systems.

Alzheimer's disease (AD) is a disorder associated with progressive degeneration of memory and cognitive function. Galantamine is a licenced treatment for AD but supplies of the plant alkaloid that it is produced from, galanthamine, are limited. This three-year system study tested the potential to combine Narcissus-derived galanthamine production with grassland-based ruminant production. Replicate plots of permanent pasture were prepared with and without bulbs of Narcissus pseudonarcissus sown as lines into the sward. Two different fertiliser regimes were imposed. The above-ground green biomass of N. pseudonarcissus was harvested in early spring and the galanthamine yield determined. In the second harvest year a split-plot design was implemented with lines of N. pseudonarcissus cut annually and biennially. All plots were subsequently grazed by ewes and lambs and animal performance recorded. Incorporation of N. pseudonarcissus into grazed permanent pasture had no detrimental effects on the health or performance of the sheep which subsequently grazed the pasture. There was no consistency to the effects of fertiliser rates on galanthamine yields. There was no difference in overall galanthamine yield if N. pseudonarcissus was cut biennially (1.64 vs. 1.75 kg galanthamine/ha for annual combined vs biennial cuts respectively; s.e.d = 0.117 kg galanthamine/ha; ns). This study verified the feasibility of a dual cropping approach to producing plant-derived galanthamine.

Characterization of the Microbiome along the Gastrointestinal Tract of Growing Turkeys.

The turkey microbiome is largely understudied, despite its relationship with bird health and growth, and the prevalence of human pathogens such as Campylobacter spp. In this study we investigated the microbiome within the small intestine (SI), caeca (C), large intestine (LI), and cloaca (CL) of turkeys at 6, 10, and 16 weeks of age. Eight turkeys were dissected within each age category and the contents of the SI, C, LI, and CL were harvested. 16S rDNA based QPCR was performed on all samples and samples for the four locations within three birds/age group were sequenced using ion torrent-based sequencing of the 16S rDNA. Sequencing data showed on a genus level, an abundance of Lactobacillus, Streptococcus, and Clostridium XI (38.2, 28.1, and 13.0% respectively) irrespective of location and age. The caeca exhibited the greatest microbiome diversity throughout the development of the turkey. PICRUSt data predicted an array of bacterial function, with most differences being apparent in the caeca of the turkeys as they matured. QPCR revealed that the caeca within 10 week old birds, contained the most Campylobacter spp. Understanding the microbial ecology of the turkey gastrointestinal tract is essential in terms of understanding production efficiency and in order to develop novel strategies for targeting Campylobacter spp.

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital.

PURPOSE: The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition. METHODS: We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO2/FiO2 <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion. RESULTS: During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH2O and 20 (7.2 %) had PaO2/FiO2 ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28. CONCLUSIONS: The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO2/FiO2 at study entry was independently associated with mortality.

Activation of natural interferon-alpha producing cells by apoptotic U937 cells combined with lupus IgG and its regulation by cytokines.

We recently demonstrated that IgG from patients with systemic lupus erythematosus (SLE) in combination with U937 cells made apoptotic by UV-irradiation, can induce interferon-alpha (IFN-alpha) production in normal peripheral blood mononuclear cells (PBMC). In the present study we show by flow cytometry that the actual IFN-alpha producing cells (IPC) among PBMC had the same phenotype (HLA-DR+, CD4+, CD11b-, CD11c-, CD14-, CD19-, CD32-, CD36+, CD40+, CD45RA+, CD68+, CD83+, CD86-, IL-3R+ and IL-10R-) and low frequency (approximately 2/10(4)PBMC) as the IPC activated by Herpes simplex virus type I. Consequently, these cells correspond to the natural IPC, also described as type 2 precursor dendritic cells. We also demonstrated that cytokines of possible importance in the pathogenesis in SLE had effects on the IFN-alpha production. Specifically, the IFN-alpha production was strongly increased by the type I IFNs, IFN-alpha and -beta, but markedly inhibited by IL-10 and also to some extent by TFN-alpha. In contrast, the cytokines IFN-gamma, IL-6, TGF-beta and GM-CSF had no clear effects. No production of IL-10 was detected in PBMC stimulated by apoptotic U937 cells and SLE IgG. These results may explain the cause of the ongoing IFN-alpha production in SLE patients and its relation to the autoimmune process.

Importance of CpG dinucleotides in activation of natural IFN-alpha-producing cells by a lupus-related oligodeoxynucleotide.

The oligodeoxyribonucleotide (ODN) 5'-TTTTCAATTCGAAGATGAAT-3' (ODN H), identified in systemic lupus erythematosus (SLE) serum, induced the production of interferon (IFN)-alpha in human peripheral blood mononuclear cells (PBMC) when combined with lipofectin. Flow cytometric analysis with staining for surface antigens and intracellular IFN-alpha, showed that the IFN-alpha-producing cells (IPC) were the natural IPC, also termed type 2 dendritic cell precursors (pDC2) or plasmacytoid monocytes. The importance of unmethylated CpG dinucleotides for the interferogenic activity of ODN was studied. Methylation of CpG impaired the activity of single-stranded (ss) ODN H, but increased that of the complementary ssODN I. Furthermore, CpG-methylated double-stranded (ds) ODN Hmet-Imet lost, but hemimethylated dsODN H-Imet retained interferogenic activity. Inversion of the CpG to GpC had no effect on the interferogenic activity of ssODN H, increased that of ssODN I, however abolished the activity of dsODN H-I. Alteration of the CpG in ODN H to ApG and in the ODN I to CpT destroyed their activity. The induction of IFN-alpha is therefore sequence-specific, but unmethylated CpGs are not always required, especially not in ssODNs. Interferogenic DNA sequences could therefore be more frequent in eukaryotic genomes than previously thought and their capacity to activate natural IPC may have implications for immune responses to microbial antigens and nuclear autoantigens.

Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies.

The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.

Anti-double-stranded DNA antibodies and immunostimulatory plasmid DNA in combination mimic the endogenous IFN-alpha inducer in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have increased blood levels of IFN-alpha, which correlate to disease activity. We previously identified an IFN-alpha-inducing factor (IIF) in the blood of SLE patients that activated the natural IFN-alpha-producing cells in cultures of normal PBMC. The SLE-IIF contained DNA and IgG, possibly as small immune complexes. In our study, we demonstrated that SLE-IIF correlated to the presence of anti-dsDNA Abs in patients and contained anti-dsDNA Abs as an essential component. Purified anti-DNA Abs or SLE-IgG caused only a weak IFN-alpha production in cultures of normal PBMC in the presence of costimulatory IFN-alpha2b. However, they converted the plasmid pcDNA3, which itself induced no IFN-alpha production in PBMC, into an efficient IFN-alpha inducer. A human monoclonal anti-ss/dsDNA Ab had the same effect. This IFN-alpha-inducing activity of the plasmid was abolished by methylation, suggesting that unmethylated CpG DNA motifs were important. Like IIF in SLE serum, the combination of SLE-IgG and pcDNA3 appeared to stimulate IFN-alpha production in natural IFN-alpha-producing cells, a unique cell population resembling immature dendritic cells. The IFN-alpha production was greatly enhanced by IFN-alpha2b and IFN-beta, and for SLE-IIF it was also enhanced by GM-CSF but inhibited by IL-10. We have therefore identified a new function of DNA-anti-DNA Ab complexes, IFN-alpha induction, that might be important in the pathogenesis of SLE.

Effects of the Ikr-blocker almokalant and predictors of conversion of chronic atrial tachyarrhythmias to sinus rhythm. A prospective study.

PURPOSE: To assess the efficacy of the Ikr-blocker almokalant attempting to convert chronic atrial tachyarrhythmias, and to find predictors of conversion, to sinus rhythm. METHODS: The electrophysiological effects of a 6-hour infusion of almokalant, to a total dose of 25 +/- 4 mg, were assessed by ECG and transesophageal atrial electrograms (TAE) in 100 consecutive patients with atrial fibrillation/flutter (n = 95/5) of 8 +/- 12 months' duration (range 1 to 99 months). RESULTS: The conversion rate was 32%. The time to conversion was 3.5 +/- 2.2 hours. During infusion increases in QTtop (292 +/- 35 to 335 +/- 44 ms, p < 0.001, after 30 minutes), QT (387 +/- 40 to 446 +/- 60 ms, p < 0.001), corrected QT (425 +/- 30 to 487 +/- 44 ms, p < 0.001), and QT dispersion (21 +/- 12 to 29 +/- 31 ms, p = 0.02), were paralleled by decreases in T wave amplitude (0.31 +/- 0.19 to 0.23 +/- 0.16 mV, p < 0.001), and atrial rate (425 +/- 78 to 284 +/- 44 beats per minute (bpm) on ECG, and 396 +/- 72 to 309 +/- 44 bpm on TAE), with no differences between converters to sinus rhythm and non-converters. Patients with aberrantly conducted beats, and T wave variation, also increased. Calcium antagonists were more common among converters. A decreasing T wave amplitude predicted conversion. Four patients developed torsades de pointes. CONCLUSIONS: This study demonstrates class III action of almokalant, with a conversion rate of 32% of long-standing, chronic atrial tachyarrhytmias. An early decrease in T wave amplitude was associated with conversion to sinus rhythm.

Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells.

Patients with active SLE often have an ongoing production of IFN-alpha. We therefore searched for an endogenous IFN-alpha-inducing factor (IIF) in SLE patients and found that their sera frequently induced production of IFN-alpha in cultures of peripheral blood mononuclear cells (PBMC) from healthy blood donors, especially when the PBMC were costimulated with the cytokines IFN-alpha2b and granulocyte-macrophage colony-stimulating factor (GM-CSF). The phenotype of the IFN-alpha-producing cells (IPC) as determined by flow cytometry corresponded to that of the natural IPC, resembling immature dendritic cells. The IIF activity in SLE sera was sometimes as high as that of a virus and was present especially in patients with active disease and with measurable IFN-alpha levels in serum. The IIF had an apparent molecular weight of 300-1000 kD and appeared to consist of both immunoglobulin and DNA, possibly being immune complexes. This endogenous IFN-alpha inducer may be of pathogenic significance, since a reported occasional adverse effect of IFN-alpha therapy in patients with non-autoimmune disorders is development of anti-dsDNA antibodies and SLE.

Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha- producing cells.

Systemic lupus erythematosus (SLE) patients often have continuous production of interferon-alpha (IFN-alpha), but production of in vitro IFN-alpha by peripheral blood mononuclear cells (PBMC) may be varyingly reduced. We here report that IFN-alpha production induced by Herpes simplex virus (HSV) in PBMC resembling immature dendritic cells and designated natural IFN-alpha producing cells (NIPC), was much more affected than that induced by sendai virus (SV) in monocytes. At the cell level, the frequency of HSV-activated NIPC was reduced 70-fold, but residual NIPC produced normal amounts of IFN-alpha (1-2 U/cell). The NIPC frequency increased 10-fold in SLE-PBMC, but not in control PBMC, when co-stimulated by the combination IFN-alpha-gamma and GM- CSF. No spontaneous IFN-alpha production by PBMCs was detected in SLE patients. While no SLE serum factor inhibiting IFN-alpha production was seen, sera of four out of 11 SLE patients induced IFN-alpha production in healthy control PBMC. We propose that the number of NIPC in SLE are reduced in blood because of recruitment to tissues and activation by an endogenous IFN-alpha inducer, as well as because of lack of co-stimulatory cytokines. IFN-alpha produced in SLE could be of pathogenic significance, because autoimmune diseases develop in patients with infections or tumours during IFN-alpha therapy.

Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study.

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 +/- 114 vs 443 +/- 54 ms [mean +/- SD], P < 0.01), a larger precordial QT dispersion (50 +/- 74 vs 27 +/- 26 ms, P < 0.05), and a lower T wave amplitude (0.12 +/- 0.21 vs 0.24 +/- 0.16 mV, P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 +/- 26 vs 489 +/- 74 ms, P < 0.001), a larger QT dispersion in precordial (82 +/- 7 vs 54 +/- 52 ms, P < 0.01) and extremity leads (163 +/- 0 vs 40 +/- 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.

Detection of serum interferon-alpha by dissociation-enhanced lanthanide fluoroimmunoassay. Studies of patients with acute viral and bacterial infections.

A sensitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) was evaluated for ability to detect interferon-alpha (IFN-alpha) in serum of patients with acute infectious disease of less than one week's duration and a fever of > 38 degrees C. None of 36 patients with confirmed or probable bacterial disease was IFN-alpha positive. In contrast, 13/26 patients with viral infections had detectable levels of IFN-alpha in serum, all clearly positive (> or = 10 U/ml). The IFN-alpha positive serum samples were obtained early after onset of clinical disease, after a mean of 2.4 days. The IFN-alpha positive samples were obtained from 10 of the 12 patients with influenza or flu-like infection, and 3 of the 5 patients with varicella or herpes zoster. The IFN-alpha negative patients with viral disease (n = 9) included five patients with mononucleosis. The DELFIA should be useful in further studies of the value of IFN-alpha determinations in the identification of acute viral infections.

Sinus node recovery time assessment revisited: role of pharmacologic blockade of the autonomic nervous system.

Sinus node recovery time assessment is used to diagnose clinically significant sinus node dysfunction (SND) when Holter has failed to prove a relationship between sinus bradyarrhythmias and symptoms, but consensus has not been reached as to the value of including assessment after pharmacologic blockade of the autonomic nervous system. This issue was addressed in the present study performed on 52 patients with syncope or presyncope/dizziness (n = 48), sinus bradyarrhythmias (n = 45), or both (n = 41). Group 1 consisted of 13 patients with a proven relationship between symptoms and sinus bradyarrhythmias. Group 2 consisted of 39 patients with suspected SND. The protocol included three pacing periods at two pacing rates and was performed at baseline (n = 52), after single doses of atropine and propranolol (0.02 mg/kg and 0.1 mg/kg, respectively) (n = 41), and again after a second dose (n = 29). The sensitivity of prolonged recovery times was 77% in group 1. Among group 2 patients, 56% had prolonged recovery times at baseline (79% when including the results after the first dose of drugs). The second dose did not contribute diagnostic information, but it caused significant adverse reactions in 7 of 29 patients (P < 0.001). These 7 patients were all older than 60 years. Assessment of sinus node recovery time after pharmacologic blockade of the autonomic nervous system thus increases the sensitivity of the method in patients with suspected SND and normal baseline results. However, only 50% of the initially suggested doses of atropine and propranolol is sufficient and eliminates the risk for significant adverse reactions.

Selective Ik blocker almokalant exhibits class III--specific effects on the repolarization and refractoriness of the human heart: a study of healthy volunteers using right ventricular monophasic action potential recordings.

Almokalant, a recently developed potassium-channel blocker, has exhibited properties of a selective class III agent in vitro and in animal experiments. We report the first invasive study in humans in which the electrophysiological characteristics of almokalant were assessed. Thirty-four healthy males received bolus and maintenance infusions of almokalant to two of our target plasma concentrations of 20, 50, 100, and 150 nM. Electrophysiological variables were assessed during stimulation at 100 and 120 beats/min at baseline and at two consecutive targeted levels. Almokalant dose-dependently increased the duration of the monophasic action potential (MAP) above a mean plasma concentration of 60 nM. The duration at 90% repolarization significantly increased by 20% from baseline at 100 beats/min (p < 0.00005), and by 19% at 120 beats/min (p < 0.00005), at a mean plasma concentration of 116 nM. During atrial stimulation, there was a significant increase in the QT interval, amounting to 24% at 100 beats/min (p < 0.00005) and to 30% at 120 beats/min (p = 0.0006), at 124 nM. During right ventricular stimulation in the apical region, the QT interval significantly increased by 17% at 100 beats/min (p < 0.00005), and 13% at 120 beats/min (p < 0.00005). During stimulation from the right ventricular outflow tract, the QT interval increased to a lesser extent and significantly only at 120 beats/min: 9% at 100 beats/min (p = NS) and 6% at 120 beats/min (p = 0.001) at 118 nM. The effective refractory period (ERP) of the atria increased by 18% at 100 beats/min at 119 nM (p = 0.005). The right ventricular ERP increased by 16% at both heart rates (HR) (p < 0.00005) during stimulation from the apical region, and by 11% during stimulation from the outflow tract (p = 0.0001 at 100 beats/min and p = 0.0006 at 120 beats/min). There was no effect on the ERP of the atrioventricular node, (AVN) on the sinus node function or cardiac conduction. Two individuals experienced a transient metallic taste during bolus infusion aiming at 50 and 100 nM, but this side effect did not occur in the group receiving the highest doses. Pronounced T-wave/U-wave (TU) morphology changes were observed in 4 individuals. Almokalant exhibited characteristics of a pure class III agent with no effects on cardiac conduction or sinus node function when given intravenously. Although no proarrhythmias were observed, the development of TU morphology changes and increased spatial dispersion of repolarization after the highest doses warrants further studies regarding the safety profile of the drug.

Screening for sinus node dysfunction by analysis of short-term sinus cycle variations on the surface electrocardiogram.

A new noninvasive screening method for diagnosing sinus node dysfunction (SND) was evaluated. Sinus cycle variations from 1-minute electrocardiograms (ECG) were described by two variables: the variation range around the mean cycle length (percentage) and the maximal change between any two consecutive cycles (milliseconds). SND was diagnosed when both variables were increased. Part 1: Validation of this method against Holter and sinus node recovery time assessment in 69 patients with proven or possible sick sinus syndrome (SSS). Part 2: Application of the method to 60 patients with clinically significant cardiovascular and pulmonary disorders (group 3), but without any pretest suspicion of SND. Part 1: Sinus cycle variations and sinus node recovery times were abnormal in similar proportions, 55% and 63%, respectively. The sensitivities in proven SSS were 72% and 71%, respectively. Sinus node function was concordantly classified in 80% of 64 patients undergoing both tests. When sinus cycle variations were abnormal the probability of a prolonged recovery time was 89%. Part 2: Asymptomatic SND was found in 12% of patients in group 3. Thus, analysis of short-term beat-to-beat variations in the surface ECG has a sensitivity of approximately 70% and a specificity of 100% for diagnosing SND.

Haemodynamic and hormonal responses to cardiac pacing in humans: influence of different stimulation sequences and rates.

1. To examine the effects of rate and pressure on release of vasoactive hormones, 10 healthy subjects were examined. 2. A standardized pacing protocol was used to achieve different haemodynamic responses at two predetermined heart rates. Haemodynamic variables, and plasma concentrations of atrial natriuretic peptide, arginine vasopressin, adrenaline and noradrenaline were measured. 3. Right atrioventricular pacing at a rate of 150 impulses/min resulted in disparate responses in right atrial pressure (slight decrease) and pulmonary capillary wedge pressure (increase). Change in arterial plasma concentration of atrial natriuretic peptide correlated to change in pulmonary capillary wedge pressure, and change in arterial plasma concentration of noradrenaline correlated to change in total systemic vascular resistance, whereas concentrations of adrenaline and arginine vasopressin did not alter significantly during the stimulation periods. A significant influence of rate in addition to the pressure related influence on plasma concentration of atrial natriuretic peptide was found. In contrast, an increase in rate in the absence of an increase in atrial pressures did not raise the plasma concentration of atrial natriuretic peptide. There was no significant relationship between change in atrial natriuretic peptide and noradrenaline. 4. These data support the concept of a rate dependence of atrial natriuretic peptide release in man. Increased atrial pressure and thus presumed atrial stretch seems to be a prerequisite for increased plasma concentration of atrial natriuretic peptide. In addition, these results highlight the importance of monitoring both left and right atrial pressure in clinical investigations assessing modulation of atrial natriuretic peptide release.

Atrioventricular block progression in patients with bifascicular block assessed by repeated electrocardiography and a bradycardia-detecting pacemaker.

Syncope may be due to intermittent high-degree atrioventricular (AV) block, but a cause-relation is sometimes difficult to prove. Diagnostic methods with high predictive value proven by instruments for safe and sensitive follow-up are needed. A bradycardia-detecting pacemaker was used in patients with bifascicular block, who had been the subjects of pharmacologic stress testing of the His-Purkinje system. Thirty-seven patients were included, of whom 26 had experienced at least 1 syncopal episode of suspected bradycardia origin, and 11 had previously documented transient high-degree AV block. The electrophysiologic study included injection of disopyramide 2 mg/kg (up to 150 mg) over 5 minutes. A positive test result was defined as spontaneous or pacing-induced His-Purkinje high-degree AV block after drug or a drug-induced HV prolongation of > or = 50%. Patients were followed an average 63 months with repeated electrocardiography and a diagnostic pacemaker (n = 23). Altogether, 24 patients had a significant bradycardia diagnosed by either or both methods. The sensitivity and positive predictive values were: HV interval > or = 70 ms at baseline, 47% and 88%; a positive disopyramide test result, 75% and 80%; and HV interval > or = 70 ms or a positive disopyramide test result, 93% and 74%, respectively. Thus, the diagnostic pacemaker is a safe and sensitive tool for evaluating the information obtained at electrophysiologic study, and pharmacologic stress testing with disopyramide has an informative value in patients with bifascicular block and syncope when results at baseline are inconclusive.

Choosing the stimulation rate in patients with intermittent bradycardia and a single lead pacemaker.

In order to assess the prevalence of intermittent bradycardia in a pacemaker population, we retrospectively evaluated the occurrence of intrinsic heart activity in 229 patients with ventricular pacing. Spontaneous heart activity was recorded in 60% of the patients. However, the stimulation rate had been decreased in only 40% of the patients in order to allow for longer periods of intrinsic heart activity. In the second part of the study we prospectively assessed differences in pacemaker utilization in 19 patients with intermittent bradycardia and single lead pacemakers. All patients were observed over four periods of 14 days, with the following pacing modes: 70 beats/min, 50 beats/min, hysteresis sensing 50 beats/min, and pacing 70 beats/min; and search hysteresis sensing 50 beats/min and pacing 70 beats/min. Search hysteresis pacing is a new feature that theoretically allows for a shorter time of pacing than that of hysteresis pacing. A reduction in the stimulation rate from 70 beats/min to 50 beats/min resulted in a 60% reduction in pacemaker utilization (P < 0.05). Search hysteresis decreased pacemaker utilization by 33% (P < 0.05). There was no statistical difference between conventional hysteresis and fixed rate pacing at 70 beats/min. Most patients found fixed rate pacing preferable to hysteresis pacing. In order to minimize battery consumption and to avoid unfavorable hemodynamics in patients with ventricular pacing, the stimulation mode and rate should be optimized in patients with intermittent bradycardia to allow for longer periods of intrinsic heart activity.