Biomedical subjects

M R Hill

Publications and source records attributed to M R Hill.

At least 19 recordsLinked to original sources

PubMed2004

Promoter variants in tissue inhibitor of metalloproteinase-3 (TIMP-3) protect against susceptibility in pigeon breeders' disease.

BACKGROUND: Tissue inhibitors of metalloproteinases (TIMPs) play a major role in extracellular matrix turnover in the lung. However, in chronic lung disorders such as idiopathic pulmonary fibrosis (IPF) and pigeon breeders' disease (PBD), TIMPs may promote an adverse non-degradative environment. We hypothesised that polymorphisms in TIMP-3 could affect susceptibility to IPF and PBD. METHODS: Two promoter variants, -915A>G and -1296T>C, were genotyped in 323 healthy subjects, 94 subjects with IPF, 115 with PBD, and 90 exposed to avian antigen but without PBD. The severity of fibrosis in lung tissue and the clinical outcome after 1 year was determined in the PBD group. RESULTS: The variants did not influence susceptibility to IPF, but the rare alleles of both variants appeared to be protective against susceptibility to PBD (odds ratio (OR) for carriage of at least one rare allele from either variant 0.48, 95% CI 0.30 to 0.76, p = 0.002). Haplotype analysis of positions -915 and -1296 estimated four haplotypes: *A*T, *G*T, *A*C and *G*C, respectively. Their frequencies differed overall between subjects with PBD and healthy subjects (p = 0.0049) and this was attributable primarily to the *G*C haplotype (OR 0.53, 95% CI 0.36 to 0.77, p = 0.001). The severity of fibrosis correlated with poorer outcome in the PBD group (r = 0.73, p<0.01) but no relationship was seen between the *G*C haplotype and outcome or fibrosis. However, PBD subjects with the *G*C haplotype did have proportionally fewer lymphocytes in their bronchoalveolar fluid than those with the common *A*T haplotype (p = 0.029). CONCLUSIONS: TIMP-3 variants appear to contribute to susceptibility to PBD. This may be through the inflammatory reaction rather than the fibrotic reaction.

Adult↗

PubMed2002

Standardized colour coding for syringe drug labels: a national survey.

A standardised colour code for user-applied syringe labels for anaesthetic drugs exists in the USA, Australia, New Zealand and Canada. In the UK, there is none. Consequently, an assortment of colour codes for syringe labels is available in the UK. We conducted a postal survey of the 285 College Tutors of the Royal College of Anaesthetists to establish their local syringe drug labelling system and their views on a national, standardised colour code. We found that that 96% of departments currently use coloured syringe drug labels. Of these, 98% use the 'Medilabel' scheme. The College Tutors felt that a standardised colour code for labels is required (94%), that the Association of Anaesthetists or the Royal College of Anaesthetists should be involved in the choice of scheme (76%) and that the scheme chosen should be international (65%). There was a majority feeling that the opinions expressed were representative of other members of the College Tutors' departments. We conclude that a national standard for drug labels is required and that a choice will have to be made between the 'international' scheme and the currently dominant Medilabel scheme.

Anesthesiology↗

PubMed2001

Dual-site atrial pacing for atrial fibrillation in patients without bradycardia.

Atrial pacing has been shown to delay the onset of atrial fibrillation (AF) when compared with ventricular pacing in patients with sick sinus syndrome. The role for pacing in the control of AF in patients without bradycardia is uncertain. We performed a randomized, crossover, single-blinded study in 22 patients (14 women, aged 63 +/- 10 years) with paroxysmal AF refractory to treatment with oral sotalol (202 +/- 68 mg/day) and no bradycardic indication for pacing. All patients received a dual-chamber pacemaker with 2 atrial pacing leads positioned at the high right atrium and coronary sinus ostium, respectively. Patients were randomized in a crossover fashion to be paced for 12 weeks, either with high right atrial (RA) pacing at 30 beats/min ("Off") or dual-site RA pacing with an overdrive algorithm that maintained atrial pacing at a rate slightly above the sinus rate ("On"). Treatment on resulted in a significantly higher percentage of atrial pacing and a reduction in atrial ectopic frequency than the treatment off period. The time to the first clinical AF recurrence was prolonged (15 +/- 17 to 50 +/- 35 days, p = 0.006), and total AF burden was reduced (45 +/- 34% vs 22 +/- 29%, p = 0.04) in the on-treatment phase. However, there was no difference in AF checklist symptom scores or overall quality-of-life measures. Dual-site RA pacing with continued sinus overdrive prolonged the time to AF recurrence and decreased AF burden in patients with paroxysmal AF. The absence of a major impact on symptom control suggests that pacing should be used as an adjunctive therapy with other treatment modalities for AF.

Adolescent↗

PubMed2000

High rate atrial tachyarrhythmia detections in implantable pulse generators: low incidence of false-positive detections. The PA Clinical Trial Investigators.

Some newer pulse generators have enhanced diagnostic features that provide information on the frequency, date, time of onset, and duration of atrial and/or ventricular tachyarrhythmias. However, the sensitivity and specificity of device-based atrial tachyarrhythmia detections may vary and depend, in part, on lead position and selected programming parameters. The prevalence of inappropriate detections of paroxysmal atrial fibrillation (PAF) was investigated in 97 patients who received a Thera DR pacemaker 3 months prior to a planned AV node ablation. Patients were randomized to no atrial or to rate adaptive atrial pacing therapy and followed for 3 months. Following a total AV node ablation, patients were randomized to DDDR versus VDD pacing and followed for 1 year. The high rate atrial episode diagnostic feature was used for detection of PAF and the diagnostic data were retrieved during follow-up visits. Criteria were developed to identify oversensing due to near-field P wave detections, far-field R wave detections, or competitive atrial pacing as causes of false-positive atrial tachyarrhythmia detections. A total of 1,636 detections of PAF were recorded in patients preablation. Only 48 episodes (2.9%) were characterized as false-positive detections; 25 episodes (1.5%) were classified as oversensing, and 23 episodes (1.4%) were classified as competitive atrial pacing. A total of 3,061 detections of PAF were recorded postablation. Only four episodes (0.1%) were classified as oversensing. Thus, the diagnostic atrial tachyarrhythmia detection feature in newer pacemakers is an effective method for evaluating the time course of PAF in patients with implantable pulse generators.

Atrial Fibrillation↗

PubMed2000

Reversal of left ventricular remodeling by synchronous biventricular pacing in heart failure.

Synchronous biventricular pacing is a new nonpharmacological supplemental treatment of advanced heart failure associated with electromechanical conduction delay. However, the role of pacing on left ventricular remodeling is unknown. Eleven patients with New York Heart Association Class III to IV heart failure, a left ventricular ejection fraction < 35%, and a QRS duration > or = 140 ms received a biventricular dual chamber pacemaker. Serial echocardiography, 6-minute hall walk, and Minnesota Living with Heart Failure quality-of-life (QOL) questionnaire were performed before and after up to 3 months of pacing. At 3 months there was a significant increase in fractional shortening (P < 0.001), ejection fraction (P < 0.001), and cardiac output (P < 0.05). The left ventricular end-diastolic volume (245 +/- 70 vs 185 +/- 37 mL, P < 0.05), end-systolic volume (209 +/- 69 vs 140 +/- 44 mL P < 0.05), and mitral regurgitation were reduced (P < 0.05), and diastolic filling time was lengthened (P < 0.05). There were also improvements in heart failure symptoms, an increase in 6-minute walk distance, and a decrease in QOL scores. Synchronous biventricular pacing for 3 months was associated with hemodynamic improvements, reversal of left ventricular remodeling, and increase in left ventricular systolic function, and a decrease in secondary mitral regurgitation.

Cardiac Pacing, Artificial↗

PubMed2000

Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2.

Mast cells play a potentially important role in fibroproliferative diseases, releasing mediators including tryptase that are capable of stimulating fibroblast proliferation and procollagen synthesis. The mechanism by which tryptase stimulates fibroblast proliferation is unclear, although recent studies suggest it can activate protease-activated receptor (PAR)-2. We therefore investigated the role of PAR-2 in tryptase-induced proliferation of human fetal lung and adult lung parenchymal and airway fibroblasts and, for comparative purposes, adult dermal fibroblasts. Tryptase (0.7-70 mU/ml) induced concentration-dependent increases in proliferation of all fibroblasts studied. Antipain, bis(5-amidino-2-benzimidazolyl)methane, and benzamidine inhibited tryptase-induced fibroblast proliferation, demonstrating that proteolytic activity is required for the proliferative effects of tryptase. RT-PCR demonstrated the presence of PAR-2 mRNA, and immunohistochemical staining localized PAR-2 to the cell surface of lung fibroblasts. In addition, specific PAR-2 activating peptides, SLIGKV and SLIGRL, mimicked the proliferative effects of tryptase. In contrast, human dermal fibroblasts only weakly stained with the PAR-2 antibody, PAR-2 mRNA was almost undetectable, and fibroblasts did not respond to PAR-2 activating peptides. These results suggest that tryptase induces lung, but not dermal, fibroblast proliferation via activation of PAR-2 and are consistent with the hypothesis that the release of tryptase from activated mast cells may play an important role in the fibroproliferative response observed in asthma, chronic obstructive pulmonary disease, and patients with pulmonary fibrosis.

Adult↗

PubMed1999

Evaluation of right atrial and biatrial temporary pacing for the prevention of atrial fibrillation after coronary artery bypass surgery.

OBJECTIVES: The purpose of this study was to determine if atrial pacing is effective in reducing postoperative atrial fibrillation (AF). BACKGROUND: Atrial fibrillation after coronary artery bypass grafting (CABG) is a common problem for which medical management has been disappointing. Atrial-based pacing has become an attractive nonpharmacologic therapy for the prevention of AF. METHODS: Sixty-one post-CABG patients (mean age = 65 years) were randomized to one of three groups: no atrial pacing (NAP), right atrial pacing (RAP) or biatrial pacing (BAP). Each patient had one set of atrial wires attached to both the right and left atria, respectively, at the conclusion of surgery. Patients in the RAP and BAP groups were continuously paced at a rate of 100 pulses per minute for 96 h or until the onset of sustained AF (>10 min). All patients were monitored with Holter monitors or full disclosure telemetry to identify the onset of AF. The primary end point of the study was the first onset of sustained AF. RESULTS: There was no significant difference in the proportion of patients developing AF in the three groups (NAP = 33%; RAP = 29%; BAP = 37%; p > 0.7). However, for the subset of patients on beta-adrenergic blocking agents after CABG, there was a trend toward less AF in the paced groups. There were no serious complications related to pacing, although in three patients the pacemaker appeared to induce AF by pacing during atrial repolarization. CONCLUSIONS: Continuous right or biatrial pacing in the postoperative setting is safe and well tolerated. We did not find that post-CABG pacing prevented AF in this pilot study; however, the role of combined pacing and beta-blockade merits further study.

Adolescent↗

PubMed1999

Clinical comparability of albuterol delivered by the breath-actuated inhaler (Spiros) and albuterol by MDI in patients with asthma.

STUDY OBJECTIVE: This study compares the efficacy and safety of one and two actuations of albuterol sulfate powder delivered via a breath-actuated, effort-assisted, investigational inhaler (Spiros, Dura Pharmaceuticals, Inc) and albuterol delivered via a conventional propellant-driven metered dose inhaler (Ventolin, Glaxo, Inc). DESIGN: Randomized, double-blind, placebo-controlled, 5-way crossover study. PARTICIPANTS: Sixty patients with mild-to-moderate asthma (FEV1 59% predicted) were enrolled and 44 completed the study. MEASUREMENTS AND RESULTS: FEV1 values over 6 hours were analyzed by ANCOVA and the Finney relative potency model. The relative potency of the inhalers (albuterol MDI: albuterol DPI) was 1.132 (90% CI, 0.680 to 2.252) indicating 1.132 actuations of albuterol MDI provided the same bronchodilation as one actuation of albuterol DPI. ANCOVA analyses further indicated that there were no significant differences between the two delivery systems with respect to FEV1, FVC, FEF25-75%, or PEF. Both inhalers had similar effects on serum potassium levels, QTc interval, blood pressure, and heart rate. CONCLUSIONS: In patients with mild-to-moderate asthma in this study, the albuterol DPI was determined to be therapeutically comparable to albuterol MDI in the delivery of one and two actuations of albuterol.

Administration, Inhalation↗

PubMed1999

Comparison of different methods to evaluate population dose-response and relative potency: importance of interoccasion variability.

Different mixed-effects models were compared to evaluate the population dose-response and relative potency of two albuterol inhalers. Bronchodilator response was measured after ascending doses of each inhaler in 37 asthmatic patients. A linear mixed-effects model was developed based on the approach proposed by Finney for the evaluation of bioassay data. A nonlinear mixed-effects (Emax) model with interindividual and interoccasion variability (IOV) in the different pharmacodynamic parameters was also fit to the data. Both methods produced a similar estimate of relative potency. However, the estimate of relative potency was 22% lower with the nonlinear mixed-effects model if IOV was not taken into account. Monte Carlo simulations based on a similar study design demonstrated that more biased and variable estimates of ED50 and relative potency were obtained when the nonlinear mixed-effects model ignored the presence of IOV in the data. Furthermore, the linear mixed-effects model that did not account for IOV produced confidence intervals for relative potency that were too narrow and thus could lead to erroneous conclusions. These problems were avoided when the estimation model could account for IOV. Results of the simulations were consistent with those of the experimental data. Although the linear or the nonlinear mixed-effects model may be used to evaluate population dose-response and relative potency, there are important differences in the assumptions made by each method.

Administration, Inhalation↗

PubMed1999

Cardiac parasympathetic stimulation via QRS-synchronous low-energy shocks in humans.

INTRODUCTION: In patients receiving test shocks to verify lead connections at implantation, we anecdotally have observed postshock delay. The purpose of this study was to determine whether QRS-synchronous low-energy shocks delivered by implantable defibrillators result in postshock cycle length prolongation, and to determine the mechanism of this phenomenon. METHODS AND RESULTS: Twenty-five patients undergoing defibrillator testing were studied, three with epicardial patches and 22 with transvenous leads. Each patient received QRS-synchronous shocks of 0.2, 0.4, 0.6, and 2.0 J in random order. Patients were further randomized to receive either saline or 2.0 mg atropine intravenously, and then given a second sequence of shocks. At baseline, the postshock cycle length (1,035+/-245 msec) was significantly longer than the preshock cycle length (968+/-177 msec, P = 0.01). In patients with a coronary sinus (CS) or superior vena cava (SVC) lead, the mean prolongation was 91+/-160 msec, compared with 12+/-106 msec for patients without such a lead (P < 0.0001). All energy levels resulted in significant postshock prolongation compared with preshock cycle lengths (P < 0.05). Postshock prolongation before atropine was 76+/-162 msec, compared with -13+/-52 msec afterward (P < 0.00001). Biphasic shocks resulted in greater postshock prolongation than monophasic shocks of equal energy. CONCLUSION: Low-energy shocks delivered during the QRS complex cause postshock cycle length prolongation in man. This effect required the presence of a CS or SVC lead. Atropine inhibited this effect, suggesting the phenomenon was mediated by direct cardiac parasympathetic nerve stimulation by the intracardiac shock.

Adult↗

PubMed1999

Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia.

Inflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARalpha) as a potential target to modulate regulation of the immune response. Since PPARalpha activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARalpha activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARalpha wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARalpha. PPARalpha WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARalpha KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARalpha in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARalpha in vivo can be masked by other systemic effects of PPARalpha activators.

Animals↗

PubMed1999

Therapeutic equivalence of Spiros dry powder inhaler and Ventolin metered dose inhaler. A bioassay using methacholine.

Because chlorofluorocarbons (CFCs) contribute to depletion of stratospheric ozone, CFC-containing metered-dose inhalers (MDIs) such as Ventolin and Proventil are being phased out of production. In terms of delivery of albuterol to the lungs, we compared an alternative delivery system, the Spiros dry-powder inhaler (DPI), with Ventolin, using a methacholine challenge-based clinical bioassay. Twenty-four adults and adolescents with asthma completed this double-blind, four-period crossover study. Doses evaluated were one and three actuations each of Spiros and Ventolin (90- and 270-microgram albuterol base). A methacholine challenge (Cockcroft method) was initiated 3 h before and 0.25 h after albuterol. Predose PC(20)FEV(1) values were not significantly different between study days. Postdose PC(20)FEV(1) results met standard bioassay study validity criteria: i.e., a significant dose-response relationship was present (p = 0.0002); tests for deviation from parallelism and overlap of dose-response curves were nonsignificant (p = 0.08, 0.69). By using Finney 2-by-2 bioassay analysis, we estimate that each Spiros actuation delivers 1.12 times as much albuterol to the airways as one Ventolin actuation (90% confidence interval, 0.68 to 1.94). There were no significant differences in markers of systemic effects (vital signs, potassium, and blood glucose concentrations). We conclude that Spiros and Ventolin inhalers deliver comparable quantities of albuterol to the airways.

Adolescent↗

PubMed1999

Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma.

STUDY OBJECTIVE: To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System (Dura Pharmaceuticals; San Diego, CA) dry powder inhaler (DPI) and albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) administration using a metered-dose inhaler (MDI) in patients with asthma. MATERIALS AND METHODS: This was a phase III, 12-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 283 adolescent and adult patients with mild to moderate asthma. The patients were randomized into one of three treatment groups: the Spiros group, who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base; the MDI group, who were given 90 microg/actuation of albuterol; and the placebo group. RESULTS: Over the length of the study, the Spiros and MDI groups were comparable in all FEV1 parameters. Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits. With the exception of differences at treatment week 0 for the maximum percent change in the FEV1, the duration of effect, and the area under the curve at baseline, there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters. Using a repeated-measures analysis, the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4, 8, and 12. The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline (weeks 4, 8, and 12) and duration of effect. Adverse events and changes in clinical laboratory values, vital signs, ECG results, and physical examinations were reported with similar incidence in each of the three treatment groups. CONCLUSION: Both active treatments were superior to the placebo treatment. The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma.

Administration, Inhalation↗

PubMed1998

Bradycardia induced by intravascular versus direct stimulation of the vagus nerve.

BACKGROUND: Electrical stimulation of the parasympathetic nervous system results in slowing of the heart. We sought to determine whether cardiac vagal efferent axons can be stimulated adequately to induce bradycardia without disturbing the integrity of the thorax. METHODS: Cardiodepressor effects elicited by direct stimulation of a vagus nerve in anesthetized dogs and pigs were compared with those generated when the same nerve was stimulated indirectly through bipolar electrodes placed in the adjacent superior vena cava. RESULTS: The heart rate of dogs decreased by about 80% when electrical stimuli were delivered to the right thoracic vagus at the level of the thoracic outlet through bipolar electrodes placed either in the adjacent superior vena cava (intravascular method) or directly on the nerve (direct method). Maximal responses were achieved with 10-V, 5-ms, and 20-Hz stimuli. In anesthetized pigs, similar bradycardia occurred when the right cervical vagus or the right cranial thoracic vagus was stimulated either directly or indirectly through the intravascular method. Atrial dysrhythmias occurred when the stimulating electrodes were placed by either method within 1 cm of the right atrium in both animal models. CONCLUSIONS: Controlled bradycardia can be induced during operation without the risk of generating cardiac dysrhythmias using electrical stimuli (10 V, 5 ms, and 10 to 20 Hz) delivered to the right cervical vagus nerve or the right cranial thoracic vagus nerve through adjacent intravascular electrodes.

Animals↗

PubMed1998

Design and implementation of the Dual Site Atrial Pacing to Prevent Atrial Fibrillation (DAPPAF) clinical trial. DAPPAF Phase 1 Investigators.

The Dual Site Atrial Pacing to Prevent Atrial Fibrillation (DAPPAF) study compares dual site, single site and support pacing modalities in the prevention of atrial fibrillation (AF) in patients with a history of paroxysmal AF (PAF) and a bradyarrhythmic indication for pacing. The trial is a randomized crossover comparison of dual site atrial pacing, single site atrial pacing, and a support pacing control period (DDI at 50 ppm or VDI) done in six month intervals. Patient inclusion requires at least 2 documented AF episodes in the three months prior to enrollment. The patients can be on concurrent antiarrhythmic drug regimens but this regimen must remain constant throughout the protocol. Patients with AV nodal ablation are excluded from this study. The primary endpoints of the study compare the time to first recurrence of clinically significant symptomatic AF with ECG verification, and quality of life among the three treatment modes. Secondary endpoints include time to first recurrence of all AF episodes as monitored by the pacemaker, the measurement of echocardiographic parameters, and symptoms logged by the patients. This trial was designed after pilot studies showed dual site pacing to be safe, feasible and preliminary results suggested increased maintenance of sinus rhythm with atrial pacing.

Adult↗

PubMed1998

Quantification of house-dust-mite populations.

Since the proposal that allergen from the mite Dermatophagoides pteronyssinus is identical to the house-dust allergen supposed to cause asthma and allergy, interest in the abundance, species diversity, and frequency of mites in the home has expanded. Surveys and ecologic studies have confirmed the ubiquity of mites in house dust, especially mites of the family Pyroglyphidae, but most do not give an accurate estimate of population size or mite exposure. These are still important issues today in attempts to quantify the exposure to house-dust mite that constitutes a risk, to assess mite-eradication trials, and to determine fluctuations in mite population. The problems encountered with common methods of house-dust sampling. mite extraction, and measuring house-dust allergen are discussed.

Allergens↗

PubMed1998

Nuclear hormone receptors and adipogenesis.

Adipocytes provide a model cell system for exploring the complexities of nuclear hormone receptor transcriptional regulation. Adipocytes produce lipid and cholesterol metabolites which can serve as activating ligands for many of the classic and "orphan" nuclear hormone receptors. At the same time, nuclear hormone receptors directly control adipocyte commitment. The recently described nuclear hormone receptor coactivators and corepressors provide an additional level of complexity to this system. This review emphasizes available in vitro and in vivo models and discusses them in the context of current controversies and future experimental directions.

Adipose Tissue↗

PubMed1998

Randomized prospective pilot study of long-term dual-site atrial pacing for prevention of atrial fibrillation.

OBJECTIVE: To determine whether dual-site atrial pacing is feasible, safe, and effective. DESIGN: We undertook a randomized prospective single-blind crossover study. MATERIAL AND METHODS: Nine patients with at least two episodes per month of symptomatic paroxysmal atrial fibrillation participated in a randomized crossover study involving three separate 3-month blocks of single-site atrial pacing, dual-site atrial pacing, and control (support-only) pacing. RESULTS: Dual-site atrial pacing resulted in shorter P wave duration (81 +/- 14 ms) than did single-site pacing (111 +/- 12 ms) or control sinus rhythm (123 +/- 9 ms) (P<0.0001) and in fewer premature atrial complexes on Holter monitoring (P = 0.06). The arrhythmia-free interval was longer with dual-site pacing (67 +/- 17 days) than with single-site (62 +/- 30 days) or support-only (49 +/- 34 days) pacing (P = 0.10). This pilot study was not statistically powered to detect a difference between pacing modes. CONCLUSION: (1) Dual-site atrial pacing is feasible and safe; (2) it shortens the P wave duration and tends to decrease premature atrial complexes on Holter monitoring; (3) any atrial pacing tends to prolong the arrhythmia-free interval; and (4) this pilot study enrolled too few patients to determine whether a significant difference in pacing modes exists and supports the need for a larger study.

Adult↗