The effects of haemodilution with succinylated gelatin solution on coagulation in vitro as assessed by thromboelastometry and impedance (multiple electrode) aggregometry.

We investigated the in vitro viscoelastic changes of progressive haemodilution with succinylated gelatin (SG) solution compared with normal saline (NS) using rotational thromboelastometry (ROTEM®). Whole blood (WB) samples obtained from 20 healthy volunteers were diluted in vitro with SG solution or NS by 10%, 20% and 40%. Fibrinogen concentration and ROTEM (EXTEM, FIBTEM) variables including coagulation time (CT), clot formation time (CFT), α-angle, and maximum clot firmness (MCF) were measured in the undiluted sample and at each degree of haemodilution. Haemodilution with SG decreased FIBTEM MCF by 34.8% at 20% dilution (SG 20% haemodilution mean 9.1 [standard deviation, SD 2.7] mm versus WB, mean 13.9 [SD 3.4] mm) whereas this was observed only at 40% haemodilution with NS (mean 8.5 [SD 2.7] mm, 38.7% decrease). We found that 40% haemodilution with SG slowed clot formation (EXTEM CFT; SG 40%, mean 179 [SD 39] seconds versus WB mean 87.9 [SD 13.7] seconds; increased CFT by 103%), reduced clot strength by 23.5% (EXTEM MCF; SG 40% mean 47.7 [SD 3.4] mm versus WB mean 62.4 [SD 2.5] mm), and decreased fibrin formation (FIBTEM MCF; SG 40% mean 5.8 [SD 1.6] mm versus WB mean 13.9 [SD 3.4] mm); 58.4% decrease). The platelet contribution to clot strength (EXTEM MCF-FIBTEM MCF) was not changed by SG. We found that haemodilution of more than 20% with SG impaired coagulation greater than that observed with NS haemodilution in this in vitro study. This suggests that at 40% haemodilution with SG, a clinical scenario that could occur during resuscitation of a patient in grade IV haemorrhagic shock, impaired coagulation could occur. Frequent monitoring of coagulation is advised when SG solutions are administered rapidly during volume resuscitation.

Water around fullerene shape amphiphiles: A molecular dynamics simulation study of hydrophobic hydration.

Fullerene C60 sub-colloidal particle with diameter ∼1 nm represents a boundary case between small and large hydrophobic solutes on the length scale of hydrophobic hydration. In the present paper, a molecular dynamics simulation is performed to investigate this complex phenomenon for bare C60 fullerene and its amphiphilic/charged derivatives, so called shape amphiphiles. Since most of the unique properties of water originate from the pattern of hydrogen bond network and its dynamics, spatial, and orientational aspects of water in solvation shells around the solute surface having hydrophilic and hydrophobic regions are analyzed. Dynamical properties such as translational-rotational mobility, reorientational correlation and occupation time correlation functions of water molecules, and diffusion coefficients are also calculated. Slower dynamics of solvent molecules­water retardation­in the vicinity of the solutes is observed. Both the topological properties of hydrogen bond pattern and the "dangling" -OH groups that represent surface defects in water network are monitored. The fraction of such defect structures is increased near the hydrophobic cap of fullerenes. Some "dry" regions of C60 are observed which can be considered as signatures of surface dewetting. In an effort to provide molecular level insight into the thermodynamics of hydration, the free energy of solvation is determined for a family of fullerene particles using thermodynamic integration technique.

C60-dyad aggregates: self-organized structures in aqueous solutions.

Extensive full-atomistic molecular dynamics simulations are performed to study the self-organization of C60-fullerene dyad molecules in water, namely phenyl-C61-butyric acid methyl ester and fulleropyrrolidines, which have two elements of ordering, the hydrophobic fullerene cage and the hydrophilic/ionic group. While pristine fullerene or phenyl-C61-butyric acid methyl ester forms spherical droplets in order to minimize the surface tension, the amphiphilic nature of charged solute molecules leads to the formation of supramolecular assemblies having cylindrical shape driven by charge repulsion between the ionic groups located on the surface of the aggregates. We show that formation of non-spherical micelles is the geometrical consequence if the fullerene derivatives are considered as surfactants where the ionized groups are only hydrophilic unit. The agglomeration behavior of fullerenes is evaluated by determining sizes of the clusters, solvent accessible surface areas, and shape parameters. By changing the size of the counterions from chloride over iodide to perchlorate we find a thickening of the cylinder-like structures which can be explained by stronger condensation of larger ions and thus partial screening of the charge repulsion on the cluster surface. The reason for the size dependence of counterion condensation is the formation of a stronger hydration shell in case of small ions which in turn are repelled from the fullerene aggregates. Simulations are also in good agreement with the experimentally observed morphologies of decorated C60-nanoparticles.

The cell biology of bone metabolism.

Contrary to the commonly held misconception, bone is a relatively dynamic organ that undergoes significant turnover as compared to other organs in the body. This review details how complex intercellular signalling, between the osteoprogenitor cells and mature osteoblasts, osteocytes and osteoclasts, regulates and balances activities of bone cells during remodelling and growth. Both systemic, as well as local autocrine and paracrine factors are discussed. A number of recent important advances in cell biology of bone have led to a new paradigm in understanding of the subject. In this regard, the interaction between the immune system and bone cells is of particular interest, leading to the emergence of a new discipline termed osteoimmunology. The role of lymphocytes and a number of key cytokines in the regulation of osteoclastogenesis and osteoblast function is critically examined. The intracellular signalling regulating key cellular pathways involved in cell differentiation and activity are outlined. The emerging evidence of osteocytes as mechanosensors as well as regulators of mineralisation is discussed.

Characterisation of cytosolic FK506 binding protein 12 and its role in modulating expression of Cbfa1 and osterix in ROS 17/2.8 cells.

FK506 is a commonly used immunosuppressant that mediates its action by exclusively interacting with the cytosolic immunophilin, FK506 binding protein 12 (FKBP12). Although FK506-induced acute osteoporosis is now well recognised, its precise mode of action in osteoblasts remains unclear. Therefore, in the present study we characterised FKBP12 in osteoblasts and investigated the role of FK506 in modulating osteoblast-specific transcription factors, core-binding factor alpha1 (Cbfa1) and osterix gene expression in ROS 17/2.8 cells. RT-PCR, immunolocalisation and Western blotting studies were employed to identify and characterise FKBP12 in rat primary osteoblasts and osteoblast-like osteosarcoma ROS 17/2.8 cells. Western blotting extracts of these cells revealed the 12 kDa and hitherto unreported 10 kDa FKBP isoform that were immunolocalised predominantly to the cytosol. The transient exposure of ROS 17/2.8 cells to H2O2 (100 microM) was found to elevate FKBP12 mRNA after 10 min and protein expression after 24 h. Both PTH (10(-9) M) and 1,25 (OH)2D3 (Vitamin D3) (10(-7) M) suppressed FKBP12 protein expression. FK506 in the therapeutic range (25 nmol/L) suppressed expression of Cbfa1 and osterix mRNA. The inhibition of Cbfa1 isoforms II/III expression was evident at 30 min and the extent of inhibition was sustained at 6 h. Osterix inhibition was also seen after 30 min, however, it became maximal after 6 h. The dose-dependant inhibition of osterix in these cells, carried out using 1.25, 12.5 and 125 nmol/L of FK506 was maximal at 1.25 nmol/L. Cbfa1 isoforms II/III were also maximally inhibited at 1.25 nmol/L; interestingly, the inhibition became less marked at higher concentrations of FK506. Similar dose of FK506 was found to inhibit ROS 17/2.8 cell proliferation; the inhibitory effect however was greater in insulin-stimulated cells. The results of this study suggest that immunosuppressant-induced osteoporosis, which is known to involve accelerated bone resorption by increase in osteoclastogenesis, may in fact also be accentuated by the inhibition of osteoblast differentiation and function.

Mutational and polymorphic analysis of the estradiol receptor-alpha gene in men with symptomatic vertebral fractures.

In view of the importance of estrogens in the maintenance of the skeleton in men, we have carried out mutational analysis of all the exons of the estrogen-receptor-alpha (ER-alpha) gene in 64 men (36 patients with symptomatic vertebral crush fractures and 28 control subjects). Initial screening of the ER-alpha gene, carried out by single-strand conformation polymorphism analysis followed by sequencing, showed conservative mutations in exon 4 which resulted in a single base substitutions producing GGG-->GGC transition in codon 274. We also carried out polymorphic analysis of the ER-alpha gene at the PvuII restriction site in 82 men with a range of bone density measurements (53 with symptomatic vertebral fractures and 29 controls). The frequencies of PP, Pp, and pp genotypes were 20.7%, 48.8%, and 30.5%, respectively. The distribution of the alleles was similar in the patients with symptomatic vertebral crush fractures and male control subjects. There was no association between ER-alpha genotypes and bone mineral density or arthropometric parameters. This relatively small study suggests that mutations in the ER-alpha gene are unlikely to be a common cause of osteoporosis in men with vertebral fractures. Furthermore, polymorphic variation of the ER-alpha gene appears to have little effect on the pathogenesis of osteoporosis in men.

Southern analysis of mitochondrial DNA in cortical bone of elderly patients undergoing knee and hip arthroplasty.

The role of mitochondrial DNA deletions (dmtDNA) in involutional bone loss seen in elderly men and women has never been examined. The present investigation was carried out to determine the extent of dmtDNA in cortical bone of elderly patients undergoing knee and hip arthroplasties. The majority of earlier studies have employed the polymerase chain reaction (PCR) to detect and quantify dmtDNA in different body tissues. In the present study, Southern blotting was used to screen bone biopsies from 30 patients undergoing orthopaedic surgery (mean age+/-SD 67.5+/-9.6 years; range 49-87 years). The blotting of PvuII-digested genomic DNA, carried out using mtDNA probes covering the entire span of mtDNA, revealed high levels of deletions in six subjects (mean age+/-SD 63.0+/-10.1 years; range 49-78 years) and moderate to low levels of mutations in another 14 subjects (mean age+/-SD 64.9+/-8.9 years; range 53-87 years). The importance of this rather high prevalence of dmtDNA in the bone of the elderly is discussed in terms of possible involvement of increased production of oxygen-derived free radicals and oxidative stress, and its possible role in the accelerated bone loss leading to osteoporosis.

Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density in healthy male subjects.

OBJECTIVE: The genetic factors determining peak bone mineral density (BMD) in men are not well characterized. Recent studies have investigated the relationship between the start codon polymorphism (SCP) of the vitamin D receptor (VDR) gene and BMD in different populations. We have now examined the relationship between SCP of the VDR gene and BMD in a group of healthy Caucasian men from the north-east of England. SUBJECTS: Ninety-six healthy men (median age 50, range 40.0-77.0 years). MEASUREMENTS: Analysis of the FokI genotypes of SCP of the VDR and measurements of BMD at the femoral neck and lumbar spine were performed. RESULTS: FF, Ff and ff VDR FokI genotypes were found to have the highest, intermediate and the lowest lumbar spine BMD, respectively (Mean +/- SD, for FF 1.07 +/- 0.14, Ff 1.05 +/- 0.16 and ff 0.95 +/- 0.10 g/cm2). There was a significant difference in spine BMD between FF and ff genotypes (P < 0.05, analysis of variance [ANOVA]), but no such difference was apparent between Ff and ff (P > 0.05, ANOVA). Interestingly, there was no association between FokI polymorphism and femoral neck BMD (Mean +/- SD, for FF 0.85 +/- 0.12, Ff 0.87 +/- 0.15 and ff 0.83 +/- 0.15 g/cm2). The distribution of FokI VDR genotypes approached Hardy-Weinberg equilibrium and was similar to that reported for women from different ethnic groups, as the prevalence of FF and ff genotypes was 44% and 16%, respectively. CONCLUSION: The study shows that in this population of healthy men there is a weak association between lumbar spine bone mineral density and FokI restriction fragment length polymorphism at the translation initiation site of the vitamin D receptor gene.

Mitochondrial DNA deletion associated oxidative stress and severe male osteoporosis.

We have screened the mitochondrial genome of 15 men with symptomatic vertebral fractures (median age 62 years, range 27-72 years) and 17 male control subjects (median age 61 years, range 40-73 years) for the presence of mitochondrial DNA (mtDNA) deletions in peripheral monocyte DNA. Polymerase chain reaction analysis provided evidence of a common age-related (4.9 kb) mtDNA deletion situated between nucleotides 8470 and 13.460 of the genomic sequence in 5 of the 17 controls (29%) and 9 of the 15 patients (60%) investigated. Southern blotting and polymerase chain reaction revealed a novel 3.7 kb deletion in 2 patients. One of the affected patients, a 27-year-old man with severe osteoporosis (lumbar spine bone mineral density (BMD) 0.381 g/cm(2); Z-score -6.45) was found to harbor deletion in almost 50% of the mitochondria. The patient had a blood lactic acid level (4.6 nM) that was over 3 times the upper reference range (0-1.3 mM), thus confirming the presence of systemic oxidative stress. Further analysis by modified primer shift polymerase chain reaction showed the 5' breakpoint to be between the nucleotides 10.63 kb and 10.80 kb of the mtDNA. The second patient harboring the 3.7 kb deletion was older (62 years) with less severe osteoporosis (lumbar spine BMD 0.727/cm(2); Z-score -2.58) and the proportion of affected mitochondria was lower (25%). The significance of these findings is discussed and the possible relation between oxidative stress and accelerated bone loss is examined.

Liver diseases.

Liver diseases in the elderly often reflect an age-associated decrease in the capacity to respond to metabolic and infectious insults. Because the geriatric population is growing rapidly, physicians can expect to encounter an increasing number of older patients with liver disease. In this article, the authors discuss the clinical manifestations of the most common liver diseases seen in the geriatric population.

Electroanatomic mapping for radiofrequency ablation of cardiac arrhythmias.

Radiofrequency catheter ablation is the current treatment of choice for several cardiac arrhythmias. The conventional approach utilizing intracardiac electrograms during sinus rhythm and during tachycardia has inherent limitations including limited two-dimensional fluoroscopic imaging and the ability to evaluate several potential sites for ablation and to go precisely to the most suitable site. Recently, a nonfluoroscopic three-dimensional electroanatomic system has been developed for mapping arrhythmias. We describe in this report the advantage of utilizing the system in facilitating a successful outcome in three patients with different arrhythmias.

Association of HLA-DRB1 alleles with giant cell tumour of bone.

AIM: To examine the possible influence of the MHC class II antigens alleles in the formation of the multinucleate aggressive giant cell tumour of bone. METHODS: HLA class II antigen alleles were investigated in eight white patients from north east England with confirmed diagnosis of giant cell tumour of bone. All had locally aggressive, immunophenotypically HLA-DR negative giant cell tumours. RESULTS: Five of the eight patients were found to be positive for HLA-DRB1*0801/3, the distribution of this allele in healthy white controls being quite low (2%). All but one of the patients possessing DRB1*080 also expressed DRB1*070. CONCLUSIONS: HLA-DRB1*080 is pre-dominant in patients with immunophenotypic HLA-DR negative giant cell tumour of bone; individuals with the genotype 070/080 are at particularly high risk of developing giant cell tumour of bone.

A mathematical model for the generation and control of a pH gradient in an immobilized enzyme system involving acid generation.

An optimal pH control technique has been developed for multistep enzymatic synthesis reactions where the optimal pH differs by several units for each step. This technique separates an acidic environment from a basic environment by the hydrolysis of urea within a thin layer of immobilized urease. With this technique, a two-step enzymatic reaction can take place simultaneously, in proximity to each other, and at their respective optimal pH. Because a reaction system involving an acid generation represents a more challenging test of this pH control technique, a number of factors that affect the generation of such a pH gradient are considered in this study. The mathematical model proposed is based on several simplifying assumptions and represents a first attempt to provide an analysis of this complex problem. The results show that, by choosing appropriate parameters, the pH control technique still can generate the desired pH gradient even if there is an acid-generating reaction in the system.

Sialyl Lewis(x) expression on IgG in rheumatoid arthritis and other arthritic conditions: a preliminary study.

Both infiltrating leukocytes and soluble immunoglobulin form aggregates in synovial fluid during the inflammatory process in rheumatoid arthritis (RA). Some of these changes are probably mediated by the adhesion molecule, E-selectin, which increases its expression with disease activity. As glycosylation changes in IgG in RA are well established, the current study was undertaken to measure the expression of the carbohydrate antigen sialyl Lewis x (sLe(x)), on IgG in RA. sLe(x) is a major ligand for E-selectin. Using a recently developed ELISA, sLe(x) expression was determined in IgG isolated from 8 healthy individuals, 20 RA sufferers (10 early and 10 with more long-standing disease) and 20 patients with other rheumatic conditions (osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus). S Le(x) expression on IgG was elevated above the reference range in all but one of the RA patients and this change was highly significant (P < 0.0006). Expression of this antigen on IgG was also significantly different from normal in the other arthritic groups (P < 0.02), but the changes were much less than that observed for RA. In early RA, sLe(x) was inversely correlated with parameters used to measure disease activity. This was not observed with the established RA, where there was weak positive association. These preliminary results indicate that a change in sLe(x) expression on IgG is an early finding in the development of RA, which may be important in the development of the disease or for predicting its outcome.

5-CT or DOI augments TRH analog-induced gastric acid secretion at the dorsal vagal complex.

Serotonin (5-HT) interacts with thyrotropin-releasing hormone (TRH) at the dorsal vagal complex (DVC) to augment TRH-induced stimulation of gastric acid secretion. To investigate the 5-HT receptor family involved in the augmentation response, prototypical 5-HT receptor-selective agonists (146 pmol) were coinjected with the TRH analog RX-77368 (RX; 12 pmol) into the rat DVC in a 30-nl volume. The DVC coordinates were 0.2 mm anterior, 0.2 mm right, 0.6 mm ventral with respect to the calamus scriptorius. Coinjection of RX with the 5-HT agonists 5-carboxyamidotryptamine (5-CT) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 5-HT2 agonist) produced a 183 or 103% increase in gastric acid output compared with the RX injection alone. In contrast, coinjection of 2-methyl-5-HT (5-HT3 agonist) with RX produced no effect on RX-induced increase in gastric acid secretion. Moreover, coinjection of SC-53116 (5-HT4 agonist) decreased the gastric acid output by 45% compared with the RX response itself. Examination of the RX/5-HT agonist coinjection response in more rostral regions of the DVC using the same doses (5-CT/RX or DOI/RX) revealed that only 5-CT was effective in producing the augmented response to TRH analog. The results suggest that activation of 5-CT- or DOI-sensitive receptors augments, and of 5-HT4 receptors inhibits, the gastric acid response to TRH analog injected into the DVC. Thus the integrated response to several serotonin receptor subtypes may mediate changes to the TRH response induced by 5-HT at the DVC.

Risk stratification and clinical outcome of minimally symptomatic and asymptomatic patients with nonsustained ventricular tachycardia and coronary disease: a prospective single-center study.

The Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed improved survival with defibrillator therapy but was restricted to coronary artery disease patients with nonsustained ventricular tachycardia (NSVT) and inducible nonsupressible VT. The outcome of patients without inducible VT or inducible but suppressed VT still remains unclear. We performed risk stratification at electrophysiologic (EP) study in 111 consecutive unselected patients with nonsustained VT and coronary artery disease and randomized them to drug or device therapy. Follow-up on selected therapy was 1-71 (mean 27 +/- 20) months. Of 111 patients, 39 patients (35%) had inducible sustained VT at baseline EP study and were stratified to a "higher" risk group (group 1) for sudden death. In 9 of these patients (group 1A), sustained VT was suppressed with class IA antiarrhythmic drugs; in the remaining 30 patients (group 1B) sustained VT was not suppressed with class IA antiarrhythmic drugs. The other 72 of 111 patients (65%) had no inducible sustained VT at EP study and were stratified to a "lower"-risk group (group 2) for sudden death. Mean LVEF in group 1 was 30 +/- 10% versus 37 +/- 9% in group 2 (p = 0.001). Selected therapy in group 1 was an implantable cardioverter defibrillator (16 patients) or guided drug therapy (electrophysiologically guided class I antiarrhythmic drugs = 7 patients; Holter-guided class III antiarrhythmic drugs = 16 patients). In group 2, empiric drug therapy included beta blockers in 29 patients or Holter-guided class III antiarrhythmic drugs in 17 patients, with no antiarrhythmic drug therapy being administered in 26 patients. Mean LVEF tended to be lower in patients receiving class III antiarrhythmic drug therapy (34 +/- 12%) than in patients receiving beta blockers (40 +/- 10%, p = 0.06). Three-year total survival was comparable in group 1 (70%) and in group 2 (81%), but sudden cardiac death mortality tended to be lower in group 1 versus group 2 (0 vs 9%, p = 0.09). Patients receiving class III antiarrhythmic therapy had significantly higher 3-year all cause (40%, p = 0.04) and sudden death (25%, p = 0.06) mortality than patients receiving beta blockers (17% and 8% respectively) or no antiarrhythmic drug therapy (4% and 0%, respectively). The following conclusions can be drawn from this analysis: (1) Electrophysiologically guided drug therapy and implantable defibrillators can minimize the risk of sudden cardiac death in patients with coronary artery disease and inducible sustained VT stratified to higher risk of sudden death. A comparable outcome with respect to sudden death prevention in drug-suppressed or drug-refractory patients suggests limited prognostic benefit of class IA drug testing. (2) Lower-risk patients with severely depressed LVEF and minimal or no symptoms do not have a favorable outcome with respect to sudden and all-cause mortality on Holter-guided class III drug therapy. However, asymptomatic patients with mildly depressed left ventricular function have low sudden death event rates on beta blocker or no antiarrhythmic drug therapy.

Helicobacter pylori survival in gastric mucosa by generation of a pH gradient.

Helicobacter pylori has been established as the major causative agent of human active gastritis and is an essential factor in peptic ulcer disease and gastric cancer. The mechanism that has been proposed for H. pylori to control its inhospitable microenvironment happens to coincide with the pH control technique developed by us. This technique was developed to separate an acidic environment from a basic environment for a sequential enzymatic reaction by the hydrolysis of urea within a thin layer of immobilized urease. In this paper, a mathematical model is presented to consider how H. pylori survives the gastric acidity. The computed results explain well the experimental data available involving H. pylori.

Demonstration of pH control in a commercial immobilized glucose isomerase.

The synthesis of a variety of important biochemicals involves multistep enzyme-catalyzed reactions. In many cases, the optimal operating pH is much different for the individual enzymatic steps of such synthesis reactions. Yet, it may be beneficial if such reaction steps are combined or paired, allowing them to occur simultaneously, in proximity to one another, and at their respective optimal pH. This can be achieved by separating the micro-environments of the two steps of a reaction pathway using a thin urease layer that catalyzes an ammonia-forming reaction. In this article, the pH control system in a commercial immobilized glucose (xylose) isomerase pellet, which has an optimal pH of 7.5, is demonstrated. This system allows the glucose isomerase to have near its optimal pH activity when immersed in a bulk solution of pH 4.6. A theoretical analysis is also given for the effective fraction of the immobilized glucose isomerase, which remains active when the bulk pH is at 4.6 in the presence of 20 mM urea versus when the bulk pH is at its optimal pH of 7.5. Both theoretical and experimental results show that this pH control system works well in this case. (c) 1996 John Wiley & Sons, Inc.

Clinical efficacy and safety of atrial defibrillation using biphasic shocks and current nonthoracotomy endocardial lead configurations.

We undertook a prospective randomized clinical trial evaluating efficacy and safety of internal atrial defibrillation in patients with drug-refractory atrial fibrillation (AF). Consecutive patients with paroxysmal or chronic AF were randomly tested with 3 internal atrial defibrillation lead configurations and biphasic shocks. Patients with implanted cardiac pacemakers were tested with the right atrium (RA) and left pulmonary artery or coronary sinus (CS) configuration. Shocks were initially delivered without anesthesia to assess patient tolerance. The need for backup ventricular defibrillation and pacing support was evaluated. Eighteen patients with (n = 15) or without (n = 3) structural heart disease, mean left ventricular ejection fraction 36 +/- 14%, and mean left atrial diameter 4.5 +/- 0.6 cm were studied. The mean defibrillation threshold in the best randomized lead configuration was 9.9 +/- 7.7 J. Mean defibrillation threshold for the right ventricle (RV) and superior vena cava configuration was 13.3 +/- 5 J, which was significantly lower than the RA and axilla configuration (20.1 +/- 7.4 J, p < 0.04) but not the RV to RA configuration (16.5 +/- 11 J, p > 0.2). The mean defibrillation threshold using the RA-left pulmonary artery/CS configuration was 8.9 +/- 9 J (p > 0.2 vs RV-superior vena cava). There was a bimodal distribution of defibrillation thresholds. Low atrial defibrillation thresholds correlated with absence of heart disease, higher ejection fraction, and smaller left ventricular end-diastolic diameter. Shocks were hemodynamically well tolerated, but 2 of 18 patients (11%) had nonsustained ventricular tachycardia after shock delivery. Six of 18 patients (33%) had postshock bradyarrhythmias. Fourteen of 16 patients perceived shocks > or = 3 J as intolerable.(ABSTRACT TRUNCATED AT 250 WORDS) [corrected]