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Biomedical subjects

J J Ong

Publications and source records attributed to J J Ong.

12 recordsLinked to original sources

Mechanisms of atrial fibrillation and flutter and implications for management.

Both electrophysiologic and anatomical substrates are important in the generation and maintenance of atrial fibrillation. This review discusses the nature of re-entrant wavefronts in atrial fibrillation and the importance of anatomical structures, such as the pectinate muscles, in the generation and maintenance of re-entry. The involvement of the pectinate muscle structure on intra-atrial re-entry may have significant implications for both ablation and pharmacologic management of patients with atrial fibrillation.

Atrial Fibrillation↗

Relation between ligament of Marshall and adrenergic atrial tachyarrhythmia.

BACKGROUND: The mechanism of the adrenergic atrial tachyarrhythmia is unclear. We hypothesize that the ligament of Marshall (LOM) is sensitive to adrenergic stimulation and may serve as a source of the adrenergic atrial tachyarrhythmia. METHODS AND RESULTS: We performed computerized mapping studies in isolated-perfused canine left atrial tissues from normal dogs (n=9) and from dogs with chronic atrial fibrillation (AF) induced by 10 to 41 weeks of rapid pacing (n=3). Before isoproterenol, spontaneous activity occurred in only one normal tissue (cycle length, CL >1300 ms). During isoproterenol infusion, automatic rhythm was induced in both normal tissues (CL=578+/-172 ms) and AF tissues (CL=255+/-29 ms, P<0.05). The origin of spontaneous activity was mapped to the LOM. In the AF tissues, but not the normal tissues, we observed the transition from rapid automatic activity to multiple wavelet AF. Ablation of the LOM terminated the spontaneous activity and prevented AF. Immunocytochemical studies of the LOM revealed muscle tracts surrounded by tyrosine hydroxylase-positive (sympathetic) nerves. CONCLUSIONS: We conclude that the LOM is richly innervated by sympathetic nerves and serves as a source of isoproterenol-sensitive focal automatic activity in normal canine atrium. The sensitivity to isoproterenol is upregulated after long-term rapid pacing and may contribute to the development of AF in this model.

Animals↗

Relation between cellular repolarization characteristics and critical mass for human ventricular fibrillation.

INTRODUCTION: The critical mass for human ventricular fibrillation (VF) and its electrical determinants are unclear. The goal of this study was to evaluate the relationship between repolarization characteristics and critical mass for VF in diseased human cardiac tissues. METHODS AND RESULTS: Eight native hearts from transplant recipients were studied. The right ventricle was immediately excised, then perfused (n = 6) or superfused (n = 2) with Tyrode's solution at 36 degrees C. The action potential duration (APD) restitution curve was determined by an S1-S2 method. Programmed stimulation and burst pacing were used to induce VF. In 3 of 8 tissues, 10 microM cromakalim, an ATP-sensitive potassium channel opener, was added to the perfusate and the stimulation protocol repeated. Results show that, at baseline, VF did not occur either spontaneously or during rewarming, and it could not be induced by aggressive electrical stimulation in any tissue. The mean APD at 90% depolarization (APD90) at a cycle length of 600 msec was 227+/-49 msec, and the mean slope of the APD restitution curve was 0.22+/-0.08. Among the six tissues perfused, five were not treated with any antiarrhythmic agent. The weight of these five heart samples averaged 111+/-23 g (range 85 to 138). However, after cromakalim infusion, sustained VF (> 30 min in duration) was consistently induced. As compared with baseline in the same tissues, cromakalim shortened the APD90 from 243+/-32 msec to 55+/-18 msec (P < 0.001) and increased the maximum slope of the APD restitution curve from 0.24+/-0.11 to 1.43+/-0.10 (P < 0.01). CONCLUSION: At baseline, the critical mass for VF in diseased human hearts in vitro is > 111 g. However, the critical mass for VF can vary, as it can be reduced by shortening APD and increasing the slope of the APD restitution curve.

Action Potentials↗

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry.

OBJECTIVES: We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND: The role of increased fibrosis in reentry formation during human VF is unclear. METHODS: Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS: Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS: In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.

Adolescent↗

Induction of meandering functional reentrant wave front in isolated human atrial tissues.

BACKGROUND: The purpose of this study was to test the hypothesis that a single meandering functional reentrant wave front can result in rapid and irregular electrogram activity in human atrial tissues. METHODS AND RESULTS: The study used the explanted hearts of five human cardiac transplant recipients. Three right and two left atrial tissue samples, 3.4+/-0.3 mm thick, were excised and trimmed to 3.5x3.0 cm. The isolated atrium was placed endocardial surface down in a chamber with a 477 bipolar recording electrode array built into the bottom of the tissue bath. The interelectrode distance was 1.6 mm. The tissue was constantly superfused with 36.5 degrees C oxygenated Tyrode's solution at a rate of 10 mL/min. After eight baseline stimuli (S1) delivered at 400- or 600-ms cycle length from the edge of the tissue, a single premature stimulus (S2) was given at the center of the tissue to induce reentry. A total of nine episodes of reentry were induced with S1-S2 coupling intervals of 232+/-29 ms (range, 190 to 290 ms) and an S2 strength of 10+/-3 mA (range, 5 to 15 mA). In all samples, a single meandering reentrant wave front was induced, causing irregular and rapid bipolar electrogram activity. These wave fronts had a mean cycle length of 229+/-45 ms (160 to 290 ms) and persisted for 1.1+/-0.3 seconds (0.6 seconds to 2.5 seconds), or 5.2+/-1.4 (3 to 9) cycles, before spontaneous termination. CONCLUSIONS: A single meandering functional reentrant wave front can be induced in human atrial tissues and produce rapid and irregular electrical activity.

Adult↗

Prevalence of retrograde accessory pathway conduction during atrial fibrillation.

INTRODUCTION: Although atrial fibrillation occurs frequently in patients with the preexcitation syndrome, its pathogenesis remains controversial. The purpose of this study was to test the hypothesis that retrograde conduction over the accessory pathway occurs during atrial fibrillation and can serve as an important source of new wavefronts in atrial fibrillation. METHODS AND RESULTS: Eight patients undergoing surgical division of their accessory pathway(s) were studied. A plaque electrode array containing 56 (7 x 8) bipolar electrodes (5-mm resolution) was placed epicardially at the AV junction over the accessory pathway and atrial fibrillation was electrically induced. Excluding one patient who had only preexcited QRS complexes during atrial fibrillation and another whose accessory pathway was outside the mapped region, 4 of the 6 patients studied showed retrograde conduction over the accessory pathway during atrial fibrillation (mean atrial cycle length 157 +/- 59 msec). In these patients, 186 atrial wavefronts near the accessory pathway were analyzed. Among 67 wavefronts immediately following nonpreexcited QRS complexes, 17 originated from retrograde conduction. This constituted 9% (17/186) of total atrial wavefronts near the accessory pathway. Estimated atrial refractory period during atrial fibrillation ranged from 81 to 165 msec. CONCLUSIONS: (1) In patients with the preexcitation syndrome and atrial fibrillation, retrograde conduction over the accessory pathway contributed up to 9% of total atrial wavefronts near the accessory pathway. (2) The presence of an excitable gap in human atrial fibrillation was suggested by atrial preexcitation during retrograde conduction.

Atrial Fibrillation↗

Arrhythmias after cardioverter-defibrillator implantation: comparison of epicardial and transvenous systems.

Surgery for implantable cardioverter-defibrillators can cause postoperative exacerbation of ventricular and atrial arrhythmias. It is not known whether the techniques of electrode implantation (epicardial vs transvenous) influence the incidence of arrhythmia exacerbation. We reviewed the postoperative course of 229 consecutive patients who received either epicardial (n = 119) or transvenous (n = 110) implantations from 1984 to 1994. Exacerbation of ventricular tachycardia (VT) was defined as an increase in the number of sustained VTs during the postoperative versus the preoperative 2 weeks. Of the entire cohort, 18 patients (8%) developed exacerbation of VT after operation, which was more frequent in patients with epicardial than with transvenous implantations (12% vs 4%, p < 0.03, odds ratio 3.5, 95% confidence interval 1.0 to 13.2). New-onset atrial fibrillation occurred in 15% of patients with epicardial versus 1% of those with transvenous implantations (p = 0.00005, odds ratio 19.4, 95% confidence interval 2.7 to 86.7). These differences persisted after excluding patients with concurrent cardiac surgery. Preoperative occurrence of arrhythmias was the strongest independent predictor for postoperative occurrence (p < 0.01 for VT, p < 0.0001 for atrial fibrillation). Epicardial implantation (p = 0.03) and a history of myocardial infarction (p = 0.04) were independent predictors for postoperative VT exacerbation, whereas epicardial implantation (p < 0.05) and concurrent coronary bypass surgery (p = 0.0001) were independent predictors for postoperative new atrial fibrillation. Perioperative discontinuation of antiarrhythmic drugs did not influence postoperative VT exacerbation. Epicardial implantation was associated with longer length of hospital stay than transvenous implantation (p = 0.0005), independent of age, left ventricular ejection fraction, and concurrent cardiac surgery.

Aged↗

The relation between atrial fibrillation wavefront characteristics and accessory pathway conduction.

Although the source-sink relationship for impulse propagation in cardiac tissues has been demonstrated in vitro, there has been no verification of this hypothesis in humans. Accordingly, eight patients undergoing surgical division of their accessory pathways were studied. A 56-channel (7 x 8) bipolar plaque electrode array was placed over the atrioventricular groove on the accessory pathway and atrial fibrillation electrically induced. 10 episodes of QRS transition from consecutively preexcited to nonpreexcited complexes were analyzed. This showed that consecutively preexcited QRS complexes were always associated with uniform large atrial wavefronts. Immediately prior to QRS transition, four general types of changes were observed: (a) premature invasion by secondary wavefronts creating local conduction block (n = 5); (b) wavefront collision leading to wavefront curvature (n = 2); (c) transition from a uniform large atrial wavefront to multiple fractionated small wavefronts (n = 1); and (d) uniform atrial wavefronts "marching" into the accessory pathway refractory period (n = 2). We conclude that local atrial wavefront characteristics are important factors influencing impulse propagation through the accessory pathway. The findings that local wavefront collision, curvature, or fractionation often precede loss of accessory pathway conduction support the notion that source-sink relationship is an important determinant of the safety factor for impulse propagation in the human heart.

Adolescent↗

Circadian rhythmicity of heart rate and QTc interval in diabetic autonomic neuropathy: implications for the mechanism of sudden death.

Patients with diabetic autonomic neuropathy (DAN) exhibit decreased heart rate variability (HRV) and are prone to sudden death. When HRV was used as an index of DAN, the circadian rhythmicity of heart rate and QT intervals was studied in 17 patients with diabetes who had varying degrees of DAN and 13 healthy control subjects. Heart rate and QT and QTc intervals for all subjects were found to exhibit a significant circadian periodicity. Heart rate was lowest and QT and QTc intervals were longest between midnight and 6:00 AM; heart rate increased and QT and QTc intervals shortened in the hours after waking. The diabetic group with more severe autonomic neuropathy (DAN+, HRV = 76 +/- 20 msec, n = 7) had significantly higher heart rate and shorter QT and QTc intervals compared with the diabetic group without autonomic neuropathy (DAN-, HRV = 120 +/- 13 msec, n = 10) or healthy control subjects (CT, HRV = 119 +/- 26 msec, n = 13). Twenty-four-hour mean heart rate was 90 +/- 7 beats/min (range, 79 to 98 beats/min) for DAN+, 77 +/- 8 beats/min (range, 64 to 86 beats/min) for DAN- (DAN+ vs DAN-; p = 0.005), and 74 +/- 7 beats/min (range, 64 to 80 beats/min) for CT (DAN+ vs CT; p = 0.0004). Mean 24-hour QTc was 391 +/- 13 msec (range, 387 to 399) msec for DAN+, 417 +/- 19 msec (range, 413 to 425 msec) for DAN- (DAN+ vs DAN-; p = 0.01), and 412 +/- 28 msec (range, 408 to 419 msec) for CT (DAN+ vs CT; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System Diseases↗