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.

Autonomous influence on sinus node and AV node function in the elderly without significant heart disease: assessment with electrophysiological and autonomic tests.

Eighteen volunteers with a mean age of 63.3 years, who were asymptomatic and without significant heart disease, were investigated with standard electrophysiological tests, performed before and after inhibition of autonomous neural tone with propranolol (0.1 mg . kg-1) and atropine (0.02 mg . kg-1). In addition heart rate responses to maximal exercise, carotid sinus pressure and bolus injection of isoprenaline (0.01 microgram . kg-1) were studied to evaluate the relation between different functional qualities of the cardiac conduction system. Autonomous tone inhibition (ATI) caused significant reductions in the mean PP-interval, sinus code recovery time (SNRT) and corrected sinus node recovery time (CSNRT). Furthermore, the precision of CSNRT determinations increased after ATI. In contrast, the AV-node effective refractory period and conduction time (AH-interval) did not change after ATI. A significant correlation existed between CSNRT and heart rate after ATI, both variables reflecting sinus node automaticity, while no covariation was found between CSNRT and the response to isoprenaline stimulation. AV-node refractoriness and conduction time showed covariation after, but not before, autonomous inhibition. As elderly asymptomatic non-patients were examined the use of the presented group characteristics as reference values for diagnostic investigations is suggested. For example pre-drug CSNRT above 545 ms (mean + 2 SD) or above 505 ms after ATI, indicates impaired sinus node automaticity.

Ankylosing spondylitis: an important cause of severe disturbances of the cardiac conduction system. Prevalence among 223 pacemaker-treated men.

The cause of severe disturbances of the cardiac conduction system is seldom possible to establish clinically at pacemaker implantation, apart from cases of acute myocardial infarction or digitalis intoxication and in relatively rare cases of inflammatory disorders such as sarcoidosis and systemic sclerosis. Since cardiac manifestations, mainly conduction disturbances, occur in patients with ankylosing spondylitis, the prevalence of this disease was determined using radiologic screening for sacroiliitis in a population of 223 men who had permanently implanted pacemakers. Sacroiliitis was found in 19 men (8.5 percent), 15 of whom fulfilled the diagnostic criteria for ankylosing spondylitis. In six patients, sacroiliitis was asymptomatic and two of the patients were completely free of symptoms other than those originating from their heart manifestations. In seven of the 15 patients with ankylosing spondylitis and in the four patients with sacroiliitis without clinical criteria of ankylosing spondylitis, the diagnosis was previously unknown. Uveitis and aortic regurgitation occurred in five patients each, while peripheral arthritis was twice as common. The prevalence of sacroiliitis and ankylosing spondylitis of 8.5 and 6.7 percent, respectively, differ significantly (p less than 0.01) from the frequencies found in general Caucasian populations of 1 to 2 and 0.1 to 0.5 percent, respectively. HLA B27 was present in more than 80 percent of the patients with sacroiliitis and/or ankylosing spondylitis, compared with 8 to 10 percent in the general population. This strong association is in accordance with previous studies of patients with symptomatic sacroiliitis and/or ankylosing spondylitis. Thus sacroiliitis, diagnosed by x-ray, can be considered a marker for this relatively common rheumatic cause of severe disturbances of the cardiac conduction system.

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.

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.

Heat rate responses in patients with sinus node disease compared to controls: physiological implications and diagnostic possibilities.

The autonomic regulation of heart rate was examined in 30 patients with symptoms of sinus node disease (SND) and 18 control subjects. Heart rate, expressed as sinus cycle length, was determined after injection of isoprenaline (0.1 microgram/kg), propranolol (0.1 mg/kg), and atropine (0.02 mg/kg); heart rate was also determined at maximal exercise and during carotid sinus stimulation. In addition, heart rate responses, expressed as the absolute change in sinus cycle length, were calculated. Mean heart rates after the applied maneuvers were all significantly different in the patient group, but so was the mean spontaneous heart rate. None of the induced changes differed significantly between the groups. Thus, although all these patients had impaired sinus node automaticity no uniform decrease in responsiveness to adrenergic or cholinergic stimulation or to inhibition of autonomic influences could be detected. The response patterns were heterogeneous, indicating diversity of the underlying mechanisms. No single heart rate reaction provided a satisfying diagnostic capacity for SND. However, the combined sensitivity of the three tests--isoprenaline stimulation, carotid sinus pressure, and autonomic inhibition--was 97% with a specificity of 50%. Clinically, normal findings in all these three tests, i.e., with resulting heart rates greater than 100, 55, and 70 beats/min, respectively, strongly suggest absence of SND.

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.

Influence of heart rate and inhibition of autonomic tone on the QT interval.

To evaluate whether heart-rate-induced changes of the QT interval are dependent on autonomic tone, we studied 13 healthy subjects, mean age 67.5 years. The maximal uncorrected QT from leads I, II, V1 and V6 was determined during atrial pacing at 90 beats/min and 130 beats/min before and after i.v. administration of propranolol, 0.1 mg/kg, and atropine, 0.02 mg/kg. Significant reductions (p less than 0.01) of QT were induced by the paced increases in heart rate before drugs (10%), after propranolol (10%) and after the combination of atropine and propranolol (9%). Propranolol caused no significant change in the QT interval when heart rate was held constant by pacing. In contrast, atropine produced rate-independent reductions of QT interval (5%) in subjects with beta-adrenergic blockade (p less than 0.05). Bazett's formula for heart-rate correction of the QT interval (QTc) was not applicable for atrial overdrive pacing, as it gave proportionately longer QTc values at higher heart rates. These results show that heart rate is a major determinant of the duration of the QT interval and that paced changes in heart rate induce QT-interval responses that are essentially uninfluenced by autonomic tone. The rate-dependent effect of the QT interval produced by elimination of cholinergic tone suggests a direct influence of cholinergic activity on the repolarization of ventricular myocardium.

Associated conduction disturbances in patients with symptomatic sinus node disease.

Electrophysiological investigations were performed in 30 patients with symptomatic sinus node disease (SND) to assess the extent and distribution of associated functional disturbances in the conduction system. The tests were performed before and after inhibition of autonomous tone with propranolol, 0.1 mg/kg, and atropine, 0.02 mg/kg. Surface ECG had shown bundle branch blocks (BBB) in 5 patients and fascicular blocks in 2. AV block I had been recorded in 4 patients, while none had shown high-degree AV block. Malfunction was most often detected in the AV junction, 17 patients showing a prolonged conduction time or an abnormal effective AV node refractory period. Intraventricular conduction delay was present in 7 patients, with a prolonged HV interval in 3 and a complete permanent BBB in the others. Rate-dependent BBBs were demonstrated in a further 4 patients. Long cardiac arrests following interruption of atrial pacing, suggesting impaired automaticity also of subsidiary escape pacemakers, were seen in 11 patients. Only 6 patients, 20%, showed no signs of associated malfunction of the conduction system. Thus, detailed electrophysiological assessment demonstrated associated conduction abnormalities in the majority of these SND patients. The results agree with histopathological studies and show that sinus node malfunction is often the clinically apparent manifestation of a widespread degenerative process in the cardiac conduction system.

Advanced heart block aggravated by carbamazepine.

This report presents a serious adverse reaction to the anticonvulsant compound carbamazepine. A woman was admitted to hospital for recurrent attacks of syncope. She suffered from atrioventricular block of the Mobitz type II. Carbamazepine suppressed the conduction in her already defective Purkinje fibres and induced ventricular stand-still with subsequent Adams-Stokes attacks.

Complete heart block in HLA B27 associated disease. Electrophysiological and clinical characteristics.

A genetic predisposition associated with HLA B27 for developing complete heart block with or without clinical or radiological signs of associated rheumatic disease has recently been found. In this electrophysiological study of 12 patients with spontaneous complete heart block and HLA B27 associated disease, of whom eight had ankylosing spondylitis, 10 had suprahisian second or third degree atrioventricular block (eight spontaneously and two during atrial pacing at rates below 90 impulses per minute) and one infrahisian block. One patient with narrow QRS complexes during complete heart block three months earlier had normal findings. Three patients also had sinus node malfunction and six had fascicular or bundle branch block. In HLA B27 associated disease the atrioventricular block seems to be preferentially located in the atrioventricular node, although the conduction system may be widely affected. The findings in this study indicate a further cause of high degree atrioventricular block with a predominantly suprahisian location in addition to acute inferior myocardial infarction, digitalis intoxication, and "congenital" heart block.

Clinical and electrophysiologic course of sinus node disease: five-year follow-up study.

Thirty patients with symptomatic sinus node disease (SND) who 5 years previously had undergone a clinical investigation including intracardiac electrophysiologic studies with pharmacologic inhibition of autonomic tone were followed up with respect to development of arrhythmias and cardiac conduction abnormalities. In 17 of these patients a reinvestigation, including a second intracardiac study, was performed. Stable atrial fibrillation developed in five patients, paroxysmal supraventricular tachycardia occurred in one patient, and complete heart block appeared in another patient. Paroxysmal atrial arrhythmias and radiographic atrial enlargement were more common at the initial investigation in patients who during follow-up developed either stable atrial fibrillation or paroxysmal supraventricular tachycardia. Development of complete heart block was associated with signs of severe conduction defects at the initial study. General progression of conduction dysfunction as evaluated by intracardiac techniques was not a finding in this study. Conduction abnormalities limited to the atrioventricular (AV) node did not in this context predict a clinically important progression. The results indicate that those patients with SND who are predisposed to develop high-grade AV block and atrial arrhythmias can be identified by Holter monitoring, chest x-ray examination, and an intracardiac electrophysiologic study. These possibilities improve the selection of patients suitable for pacing modes preserving atrial transport.

Diagnostic capacity of sinus node recovery time after inhibition of autonomous neural tone.

Symptomatic arrhythmias often occur intermittently in patients with sinus node dysfunction. A diagnostic test with ability to reveal latent sinus disease has therefore been much sought for. Determinations of sinus node recovery time (SNRT) and corrected sinus node recovery time (CSNRT) have been attempted but limitations in their diagnostic power are well recognized. To eliminate a possible masking effect of autonomous neural tone, propranolol 0.1 mg/kg and atropine 0.02 mg/kg was administered to 30 patients with established symptomatic sinus bradydysrhythmias (SSBD) and to a control group of 18 age-matched healthy volunteers. In addition the same procedure was applied to 9 patients with symptoms suggesting SSBD in whom, however, this cause was later excluded. The upper normal limit of CSNRT defined by the control group was 545 msec before and 505 msec after drugs. In the SSBD group, CSNRT was falsely negative in 8 of the 30 patients. Repeated testing after drug inhibition reduced this number to 2 patients. Thus, the sensitivity increased from 73% to 93%. CSNRT determinations were normal in the non-SSBD patients, specificity remaining at 100%. Thus, the discriminative power of electrophysiologic testing for sinus node disease was found to be high when CSNRT determinations were performed both before and after drug inhibition of autonomous neural tone.

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.

Left main stem coronary artery disease. Retrospective review of 26 patients treated surgically or medically.

The clinical, angiographic, exercise testing, operative, and follow-up data of 26 patients found at angiography to have left main stem coronary artery stenosis, defined as a reduction in the lumen diameter of 50% or more, are reviewed. There was a high incidence of significant proximal stenosis in the branches of the left main stem. No clinical features were found to distinguish patients with left main stem stenosis. All patients were considered for saphenous vein bypass grafting, selection being based upon the severity of symptoms, left ventricular function, and suitability of the coronary vessels for grafting. Two patients died within 24 hours of coronary angiography. Nine patients were operated on with no mortality. There has been one late cardiac death during a mean follow-up time of 13 months. All patients were symptomatically improved with a significant (P less than 0-01) increase in exercise ability postoperatively. Fifteen patients were not operated on. Six of these patients were regarded as operable but surgery was deferred; five have died at a mean time of 7-2 months. Five of the nine patients regarded as inoperable have died at a mean follow-up time of 14-8 months. The five non-surgical survivors remain symptomatic with no significant change in exercise ability. Recently reported surgical and medical series of patients with left main stem stenosis are reviewed.

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.

Disopyramide induced second and third degree atrioventricular block in patients with bifascicular block. An acute stress test to predict atrioventricular block progression.

Syncopal attacks in patients with bifascicular block may be due to both ventricular tachyarrhythmias and intermittent atrioventricular block in addition to non-cardiac causes and lead to antiarrhythmic treatment with drugs or pacemaker or both. The acute electrophysiological effect of intravenous disopyramide 2 mg/kg body weight given over five minutes on the His-Purkinje system was assessed in 27 patients with chronic bifascicular block undergoing evaluation for permanent pacemaker treatment. The predictive value of this pharmacological stress test as regards the development of atrioventricular block during follow up was analysed. The HV interval increased (mean 43%) and the QRS duration was prolonged (mean 24%). Intrahisian or infrahisian second or third degree atrioventricular block occurred in 14 patients after disopyramide administration, requiring temporary pacing in four of them. Before the electrophysiological study 15 of the 27 patients had had at least two syncopal attacks of suspected cardiac origin but no evidence of second or third degree atrioventricular block. Second or third degree atrioventricular block was subsequently recorded in five of these 15 patients during a mean of two years follow up. The sensitivity, specificity, and predictive value of second or third degree atrioventricular block produced by disopyramide administration including subsequent atrial pacing--a positive disopyramide test--as regards later development of atrioventricular block were 80%, 90%, and 80% respectively. Intravenous administration of disopyramide to patients with bifascicular block and syncopal attacks of suspected cardiac origin may provoke atrioventricular block and asystole requiring immediate temporary pacing. Furthermore, a positive disopyramide test seems to have a significant value in predicting the later development of atrioventricular block.