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Biomedical subjects

M A Wood

Publications and source records attributed to M A Wood.

At least 19 recordsLinked to original sources
PubMed2000

Clinical characteristics of patients intolerant to VVIR pacing.

The incidence and clinical predictors of the development of intolerance to VVIR pacing have not been extensively studied in prospective long-term randomized trials comparing different pacing modes. The frequency and clinical factors predicting intolerance to ventricular pacing are controversial. The Pacemaker Selection in the Elderly (PASE) Trial enrolled 407 patients aged >/=65 years in a 30-month, single-blind, randomized, controlled comparison of quality of life and clinical outcomes with ventricular pacing and dual-chamber pacing in patients undergoing dual-chamber pacemaker implantation for standard clinically accepted indications. We reviewed the clinical, hemodynamic, and electrophysiologic variables at the time of pacemaker implantation in 204 patients enrolled in the PASE trial and randomized to the VVIR mode, some of whom subsequently required crossover (reprogramming) to DDDR pacing. During a median follow-up of 555 days, 53 patients (26%) crossed over from VVIR to DDDR pacing. A decrease in systolic blood pressure during ventricular pacing at the time of pacemaker implantation (p = 0.001), use of beta blockers at the time of randomization (p = 0.01), and nonischemic cardiomyopathy (p = 0.04) were the only variables that predicted crossover in the Cox multivariate regression model. After reprogramming to the dual-chamber mode, patients showed improvement in all aspects of quality of life, with significant improvements in physical and emotional role. The high incidence of crossover from VVIR to DDDR pacing along with significant improvements in quality of life after crossover to DDDR pacing strongly favors dual-chamber pacing compared with single-chamber ventricular pacing in elderly patients requiring permanent pacing.

Aged↗
PubMed2000

Clinical outcomes after ablation and pacing therapy for atrial fibrillation : a meta-analysis.

BACKGROUND: Radiofrequency ablation of the atrioventricular node and permanent pacing are used for symptomatic relief in patients with medically refractory atrial fibrillation. In this study, meta-analysis was used to clarify clinical outcomes and survival after ablation and pacing therapy using data from the published literature. METHODS AND RESULTS: We used 21 studies with a total of 1181 patients in the meta-analysis. All patients had medically refractory atrial tachyarrhythmias, primarily atrial fibrillation (97%). Nineteen measures of clinical outcome, encompassing quality of life, ventricular function, exercise duration, and healthcare use, were derived from the studies. The meta-analysis demonstrated significant improvement after ablation and pacing therapy in all outcome measures except fractional shortening, which demonstrated a trend toward improvement (P=0.08). Ejection fraction did show significant improvement (P<0.001). The calculated 1-year total and sudden death mortality rates after ablation and pacing therapy were 6.3% and 2.0%, respectively. CONCLUSIONS: Ablation and pacing therapy improves a broad range of clinical outcomes for patients with medically refractory atrial fibrillation. The calculated 1-year mortality rates after this therapy are low and comparable with medical therapy.

Aged↗
PubMed2000

Automated pacemaker function.

Pacemakers have used automated functions since the introduction of the inhibited mode more than 30 years ago. Currently, virtually all aspects of pacemaker function are subject to automated control, including automated threshold tracking and sensitivity adjustment. These features are designed to enhance patient safety and quality of life, extend battery life, and simplify pacemaker programming and follow-up for health care providers. Many of these automated algorithms are still in evolution and the clinical benefits are not clearly demonstrated for all functions. Although pacemaker function will become increasingly automated, these features should not be accepted uncritically and without demonstrating benefit to the pacemaker patient.

Algorithms↗
PubMed2000

An ATPase/helicase complex is an essential cofactor for oncogenic transformation by c-Myc.

The c-Myc transactivation domain was used to affinity purify tightly associated nuclear proteins. Two of these proteins were identified as TIP49 and a novel related protein called TIP48, both of which are highly conserved in evolution and contain ATPase/helicase motifs. TIP49 and TIP48 are complexed with c-Myc in vivo, and binding is dependent on a c-Myc domain essential for oncogenic activity. A missense mutation in the TIP49 ATPase motif acts as a dominant inhibitor of c-Myc oncogenic activity but does not inhibit normal cell growth, indicating that functional TIP49 protein is an essential mediator of c-Myc oncogenic transformation. The TIP49 and TIP48 ATPase/helicase proteins represent a novel class of cofactors recruited by transcriptional activation domains that function in diverse pathways.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2000

Left ventricular tachycardia originating near the left main coronary artery.

Eight patients with idiopathic ventricular tachycardia (VT) underwent mapping and radiofrequency ablation. Mapping showed VT originating in the high posterolateral left ventricular outflow tract in proximity to the left main and proximal circumflex coronary arteries. Ablation was not attempted due to this proximity to the left main and proximal circumflex coronary arteries. Ablation was not attempted due to this proximity in 2 patients and limited in 1 patient. It was successful in VT suppression in 5 of 6 patients.

Adult↗
PubMed2000

Effects of sodium channel blockade on ibutilide induced prolongation of repolarization in the isolated rabbit ventricle.

INTRODUCTION: Ibutilide fumarate is indicated for the termination of atrial fibrillation and atrial flutter. It's mechanism of action is unclear but may involve activation of a late inward Na(+) current. METHODS AND RESULTS: Twenty seven experiments were performed using an isolated perfused rabbit right ventricle preparation. In each experiment effective refractory periods (ERP) and transmembrane 90% action potential durations (APD) were measured. In 8 experiments ERP and APD were measured at baseline, in the presence of ibutilide (0. 1[emsp4 ]uM), and in the presence of both ibutilide and tetrodotoxin (TTX, 2[emsp4 ]uM). In 8 experiments lidocaine (10[emsp4 ]uM) was used in place of TTX. Measures were made at 200, 400, and 800[emsp4 ]msec paced cycle lengths under each condition. The baseline values for APD at 200, 400 and 800[emsp4 ]msec cycle lengths for the experiments treated with ibutilide and TTX were 111+/-8, 140+/-14 and 159+/-22[emsp4 ]msec, respectively. In the presence of ibutilide, APD increased to 130+/-19, 192+/-26 and 217+/-35[emsp4 ]msec at 200, 400 and 800[emsp4 ]msec cycle lengths, respectively (all p< or =0.03). After the addition of TTX there was no shortening of APD or ERP compared to treatment with ibutilide alone at any cycle length (all p> or =0.062). Similarly, in the presence of ibutilide and lidocaine there were no changes in APD or ERP compared to treatment with ibutilide alone (all p > or =0.41). In 11 control experiments, there were no changes in APD or ERP on serial measures after placebo and TTX or lidocaine. CONCLUSION: Ibutilide induced prolongation of ventricular repolarization is not affected by Na(+) channel blockade with lidocaine or TTX in the isolated rabbit heart. These findings suggest that the effects of ibutilide are not mediated by a Na(+) channel dependent late current or that this mechanism contributes minimally to its action in this model.

Action Potentials↗
PubMed2000

Influence of autothreshold sensing and sinus rate on mode switching algorithm behavior.

Mode switching is beneficial to pacemaker patients with paroxysmal atrial tachyarrhythmias. However, the optimal mode switching algorithm is still in evolution. Mode switching algorithms and atrial sensing circuitry can influence mode switching behavior. This study compared the mode switching behavior of four Medtronic, Inc. implantable devices: Thera DR model 7960 pacemaker, Kappa 700 model KDR701 pacemaker, Gem DR model 7271 dual chamber pacing defibrillator, and Jewel AF model 7250 dual chamber pacemaker atrial and ventricular defibrillator. The Thera and Gem DR use the same mean atrial rate mode switch algorithm. The Kappa and Jewel AF use four of seven short atrial intervals and an atrial fibrillation evidence counter algorithm, respectively. The Thera and Kappa devices use fixed gain sensing and the Gem DR and Jewel AF use autothreshold atrial sensing. Digitally recorded atrial electrograms from 52 episodes of human atrial fibrillation were fed into each device with differing simulated sinus rates before and after the atrial fibrillation. The percent of appropriate mode switching was highest for the Kappa 700 (94%) and lowest for the Thera (85%) (P = 0.046). The time to mode switching was significantly longer for the Thera and Gem DR compared to the Kappa 700 or Jewel AF (all P < 0.05). The time to mode switching was shorter for the Gem DR (9.0 +/- 1.6 s) using autothreshold atrial sensing than for the fixed gain Thera (11.1 +/- 2.1 s, P < 0.05). The mean atrial electrogram amplitude and cycle length were not correlated with the time to mode switching for any device. Faster sinus rates shortened the time to mode switching and prolonged the time to resynchronization in the two devices using the mean atrial interval algorithm. In conclusion, (1) mode switching function among these devices is influenced by algorithms and sensing circuitry, (2) the time to mode switching among these devices is influenced by the algorithm and use of autothreshold atrial sensing, and (3) the sinus rate before and after episodes of atrial fibrillation greatly influences the times to mode switching and resynchronization in devices using the mean atrial interval algorithm.

Algorithms↗
PubMed2000

The acute effects of biatrial pacing on atrial depolarization and repolarization.

Permanent biatrial and/or multisite atrial pacing may prevent atrial fibrillation (AF), but the effects on atrial electrophysiology remain incompletely understood. Acute biatrial pacing was studied in 20 patients with and 28 without (controls) a history of atrial fibrillation and/or flutter. Twelve-lead electrocardiograms were recorded during pacing from the high right atrium (RA), from the distal coronary sinus (LA), and biatrial pacing. P wave duration was measured in each lead and the difference between maximum and minimum P duration was termed P wave dispersion. Effective refractory periods (ERPs) were measured during each pacing mode. The dispersion of P wave duration was 35 +/- 14 ms in controls and 40 +/- 29 ms in AF patients (P = 0.17). Compared to RA pacing, LA pacing shortened P duration in controls (127 +/- 18 to 107 +/- 16 ms, P < 0.05) and biatrial pacing markedly shortened P duration in controls (127 +/- 18 to 93 +/- 14 ms, P < 0.05) and AF patients (114 +/- 43 to 97 +/- 21 ms, P < 0.05). P wave dispersion was unaffected. In controls, the LA ERP was longer than the RA ERP. This phenomenon was not present in AF patients, whose LA ERP was shorter than that of controls. Biatrial pacing had no effect on atrial ERPs or the dispersion of atrial refractoriness. In conclusion, acute biatrial pacing does not affect atrial repolarization but it does cause a marked shortening of global biatrial depolarization. Distal coronary sinus pacing produces a shorter P wave than RA pacing. There is substantial dispersion in the surface P wave of the electrocardiogram, the significance of which awaits further study.

Atrial Fibrillation↗
PubMed2000

A prospective randomized-controlled trial of ventricular fibrillation detection time in a DDDR ventricular defibrillator. Ventak AV II DR Study Investigators.

Implantable cardioverter defibrillators (ICDs) with dual chamber and dual chamber rate responsive pacing may offer hemodynamic advantages for some ICD patients. Separate ICDs and DDDR pacemakers can result in device to device interactions, inappropriate shocks, and underdetection of ventricular fibrillation (VF). The objectives of this study were to compare the VF detection times between the Ventak AV II DR and the Ventak AV during high rate DDDR and DDD pacing and to test the safety of dynamic ventricular refractory period shortening. Patients receiving an ICD were randomized in a paired comparison to pacing at 150 beats/min (DDD pacing) or 175 beats/min (DDDR pacing) during ICD threshold testing to create a "worst case scenario" for VF detection. The VF detection rate was set to 180 beats/min, and VF was induced during high rate pacing with alternating current. The device was then allowed to detect and treat VF. The induction was repeated for each patient at each programmed setting so that all patients were tested at both programmed settings. Paired analysis was performed. Patient characteristics were a mean age of 69 +/- 11 years, 78% were men, coronary artery disease was present in 85%, and a mean left ventricular ejection fraction of 0.34 +/- 0.11. Fifty-two episodes of VF were induced in 26 patients. Despite the high pacing rate, all VF episodes were appropriately detected. The mean VF detection time was 2.4 +/- 1.0 seconds during DDD pacing and 2.9 +/- 1.9 seconds during DDDR pacing (P = NS). DDD and DDDR programming resulted in appropriate detection of all episodes of VF with similar detection times despite the "worst case scenario" tested. Delays in detection may be seen with long programmed ventricular refractory periods which shorten the VF sensing window and may be avoided with dynamic ventricular refractory period shortening.

Aged↗
PubMed2000

The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc.

The c-Myc protein functions as a transcription factor to facilitate oncogenic transformation; however, the biochemical and genetic pathways leading to transformation remain undefined. We demonstrate here that the recently described c-Myc cofactor TRRAP recruits histone acetylase activity, which is catalyzed by the human GCN5 protein. Since c-Myc function is inhibited by recruitment of histone deacetylase activity through Mad family proteins, these opposing biochemical activities are likely to be responsible for the antagonistic biological effects of c-Myc and Mad on target genes and ultimately on cellular transformation.

Acetyltransferases↗
PubMed1999

Diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in patients with unexplained syncope.

OBJECTIVES: The purpose of the present study was to systematically evaluate the diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in a consecutive series of patients with recurrent unexplained syncope. BACKGROUND: Carotid sinus hypersensitivity (CSH) is an infrequently recognized cause of recurrent unexplained syncope usually diagnosed by carotid sinus massage (CSM) in the supine position. The diagnostic utility of systematic assessment of mechanical, pharmacological and orthostatic stimulation of the carotid sinus has not been clearly established. METHODS: Eighty consecutive patients (63 +/- 12 years) with a history of recurrent unexplained syncope (mean episodes: 6 +/- 3); 30 age-matched controls (65 +/- 14 years) and 16 patients (59 +/- 12 years) with syncope not related to CSH were studied. Pharmacological stimulation of the carotid sinus was achieved by randomly administering bolus injections of nitroprusside and phenylephrine. Mechanical stimulation of the carotid sinus was performed by CSM applied for 5 s in the supine position and after 2 min at 60 degrees. A 60 degree low-dose isoproterenol head-up tilt test (HUTT) was also performed for a total duration of 30 min. RESULTS: Carotid sinus hypersensitivity was elicited by CSM in the supine position in seven (8.7%) patients, two (6.6%) controls and one (6.3%) patient with syncope unrelated to CSH, compared with 48 (60%) patients, two (6.6%) controls and one (6.3%) syncope unrelated to CSH patient after 60 degree HUTT, increasing the diagnostic yield by 51%. Baroreceptor gain was significantly reduced in the CSH group. Head-up tilt test was positive in 12 (25%) patients with CSH, two (6.6%) controls and two (12%) with documented syncope but not positive in any of the patients in which syncope remained unexplained. Diagnostic accuracy was enhanced by 38% (31% supine vs. 69% upright) when CSM was performed at 60 degrees. CONCLUSIONS: CSH was documented in 68% of patients, 8.7% in the supine position and 60% in the upright position. Sensitivity was increased by 51%, and diagnostic accuracy was enhanced by 38% by performing CSM in the upright position. Decreased baroreceptor gain was documented and may play a role in the pathophysiology of CSH.

Aged↗
PubMed1999

Survival of DDD pacing mode after atrioventricular junction ablation and pacing for refractory atrial fibrillation.

BACKGROUND: Patients with recurrent forms of atrial fibrillation may receive dual-chamber pacemakers after atrioventricular junction ablation for refractory symptoms. These patients are at risk for chronic atrial fibrillation, which would negate the benefits of dual-chamber pacing. The purpose of this study was to examine the survival of dual-chamber pacing modes in patients undergoing ablate and pace therapy. METHODS AND RESULTS: One hundred fifty-six patients underwent ablate and pace therapy for medically refractory chronic (70 patients) or recurrent (86 patients) atrial fibrillation. Seventy-eight percent of patients had structural heart disease. The mean age was 66 +/- 11 years, with an average ejection fraction of 48% +/- 18%. The choice of pacing mode and programming were at the discretion of the investigators. At implantation, 91 patients (58%) were programmed to VVI mode, 47 (30%) were programmed to DDD mode, and 18 (12%) were programmed to DDI mode. After 1 year of follow-up, 10 DDD patients were reprogrammed to VVI mode (7 patients) or DDI mode (3 patients), most frequently for chronic atrial fibrillation (7 patients). Two patients with DDI mode were reprogrammed to VVI and DDD modes (1 patient each). Survival of the DDD mode was 76% at 1 year by Kaplan-Meier analysis. Reprogramming from DDD mode was not associated with patient age, left ventricular ejection fraction, discontinuation of antiarrhythmic drugs, or the duration of atrial fibrillation symptoms before ablation. CONCLUSIONS: Seventy-six percent of patients with recurrent atrial fibrillation who are initially programmed to DDD mode remain in DDD mode 1 year after ablation and pacing therapy. The modest rate of progression to chronic atrial fibrillation supports the use of dual-chamber pacing in this setting.

Aged↗
PubMed1999

Induction of ventricular fibrillation by T wave shocks: observations from monophasic action potential recordings.

INTRODUCTION: Shocks given during the vulnerable period of cardiac repolarization may induce ventricular fibrillation (VF). However, the relationship of the vulnerable period and the monophasic action potential (MAP) has not yet been reported in humans. The purpose of this study was, therefore, to determine how the monophasic action potential recorded from the right ventricle correlates with inducibility of VF using T wave shocks during ventricular pacing. METHODS: Eleven patients undergoing implantable cardioverter defibrillator (ICD) implantation had a MAP catheter positioned in the right ventricle (RV). The local monophasic action potential duration at 90% repolarization (MAP90) duration was measured during pacing at 400 ms. VF induction was attempted by pacing at 400 ms for 10 cycles and then giving a 1.0 joule monophasic T wave shock at varying coupling intervals (CI) to the last paced stimulus. The maximum and minimum CI that induced VF were determined and mapped in relation to the MAP90 recording. RESULTS: The average paced MAP duration was 275 +/- 20 ms. The minimum and maximum CI to induce VF were 255 +/- 24 ms and 325 +/- 36 ms respectively. This ranged from 93% to 118% of the MAP90 duration but because of delay in conduction time to the MAP catheter, shocks that induced ventricular fibrillation occurred between 74% and 99% of local repolarization time. CONCLUSION: VF is inducible with low energy T wave shocks falling during the last 25% of the right ventricular MAP90 recording. This corresponds with VF initiation during phase III repolarization.

Action Potentials↗