Biomedical subjects

T J Wu

Publications and source records attributed to T J Wu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effect of N-methyl-D,L-aspartate (NMA) on gonadotropin-releasing hormone (GnRH) gene expression in male mice.

The glutamate analog N-methyl-D,L-aspartate (NMA) affects the regulation of GnRH and LH release in mammals. Several laboratories have reported a rapid and transient increase in GnRH mRNA levels of male rats after NMA injection. Studies employing the simultaneous measurements of nuclear GnRH primary transcript RNA, a reflection of gene transcription, and GnRH mRNA suggest that NMA's effect on GnRH gene expression in the rat is likely due to post-transcriptional regulation. Despite the increasingly widespread use of transgenic mice, surprisingly little is known about the regulation of GnRH gene expression in the mouse. In this study, we assessed in detail the effects of NMA on GnRH gene expression in adult male mice. In the first experiment, GnRH mRNA levels in mice killed 60-min post-NMA injection (20 mg/kg bw, ip; n=9/treatment group) were lower (P<0.05) when compared to controls (saline vehicle). In the second experiment, mice (n=7/treatment group) were administered NMA or saline vehicle and were killed at 15-, 60- and 120-min post-injection. Consistent with the first experiment, treatment with NMA resulted in a significant decrease (P<0.05) in cytoplasmic GnRH mRNA compared to control levels at 15- and 60-min but not 120-min. NMA treatment decreased the nuclear GnRH primary transcript RNA at 120-min but not at earlier time points. In summary, we have shown that regulation by NMA of GnRH gene expression in mice differs substantially from rats. This differential regulation of GnRH gene expression between rats and mice warrants further investigation.

Animals↗

PubMed2000

Vein of marshall cannulation for the analysis of electrical activity in patients with focal atrial fibrillation.

BACKGROUND: Whether or not the muscle bundle within the ligament of Marshall (LOM) can serve as the origin of focal atrial fibrillation (AF) is unknown. METHODS AND RESULTS: A total of 28 consecutive patients with paroxysmal AF underwent balloon-occlusion coronary sinus angiograms to identify the vein of Marshall (VOM). Attempts were then made to advance a 1.5-French electrophysiological catheter into the VOM via the coronary sinus orifice. In 17 of the 28 patients (10 of 17 were men aged 38+/-15 years), cannulation was successful. Double potentials were registered in 8 of these 17 patients. The first potential corresponded with local left atrial activation. The second potential was shorter and narrower than the first. The sequence of activation in the second potential in the VOM was proximal to distal. In 6 patients with direct VOM recordings, we documented that the origin of AF was in the muscle bundle within the LOM. Radiofrequency catheter ablation aimed at the insertion site of the VOM successfully terminated AF in 4 of these 6 patients. CONCLUSIONS: (1) It is possible to cannulate and to record electrical potentials from the VOM. (2) The characteristics of the double potentials within the VOM suggest that the second potential is from the muscle bundle (Marshall bundle) within the LOM. (3) The Marshall bundle may be the origin of focal AF in some patients.

Adult↗

PubMed2000

Epidemiologic study of type 2 diabetes in Taiwan.

Diabetes mellitus (DM) in adults is a global health problem, although its prevalence varies widely between different populations and the rate has generally increased worldwide. In Taiwan, the mortality rate from DM has almost doubled over the past 10 years. The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of impaired glucose tolerance (IGT) was 15.5% (men 15% and women 15.9%). The prevalence of DM and IGT increased significantly with age for both genders. The significant factors associated with newly diagnosed DM were age, BMI, family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels. The prevalence of large vessel disease (LVD) in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. Among diabetics, 15.8% had ischemic heart disease (IHD), 1.7% leg vessel disease (leg VD), and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had a significantly higher prevalence of macrovascular disease than non-diabetic subjects. The most significantly associated with the LVD was serum cholesterol levels. Serum cholesterol and HbA1(c) were significantly associated with the development of IHD. Cigarette smoking and female gender were significantly associated with the leg VD. The prevalence of diabetic retinopathy (DR) was 35.0%. (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively.) The prevalence of DR for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. From multiple logistic regression analysis, duration of DM was the most important risk factor related to DR. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In conclusion, the prevalence of DM in Taiwan was between 4.9 and 9.2%, and the prevalence of IGT was 15.5%. The possible risk factors of newly diagnosed diabetes were age, family history of DM, BMI, SBP (hypertension), physical activity and triglyceride levels. Diabetes in Chinese subjects share many characteristics similar to other Asian populations. The burden imposed by the chronic complications of diabetes is massive. In Taiwan, the mortality rates from DM have increased greatly over the past 10 years. Reduction of the modificable risk factors such as BMI, hypertenion and dyslipidemia, and increase of physical activity and good glycemic control through public health efforts may help to reduce the risk of DM and its chronic complications.

Adult↗

PubMed2000

Influence of wavefront dynamics on transmembrane potential characteristics during atrial fibrillation.

INTRODUCTION: Although computerized mapping studies have demonstrated the presence of multiple wavelets during atrial fibrillation (AF) and that action potential amplitude and duration in AF vary significantly from beat to beat, no study has correlated the single cell action potential changes with the patterns of activation during AF. METHODS AND RESULTS: We studied wavefront dynamics and single cell transmembrane potential (TMP) characteristics in 12 isolated perfused canine right atria. The endocardial surface was mapped using 477 bipolar electrodes while TMP was recorded with a standard glass microelectrode from an epicardial cell. AF was induced in the presence of acetylcholine. Successful simultaneous TMP recordings and activation maps were made during six episodes of AF and for a total of 141 activations. Large variations of TMP amplitude and duration were observed frequently; 34% of them have a low amplitude (<50% of the amplitude recorded during pacing). Low-amplitude potentials were recorded when the impaled cell was (1) in an area of random reentry (67%, n = 36); (2) within 3.2 mm of the core of organized functional reentry (22%, n = 12); (3) in the middle of two merging wavefronts (9%, n = 5); and (4) at the point of spontaneous wavebreak (2%, n = 1). CONCLUSION: Large variations of TMP are observed frequently during in vitro AF. Low-amplitude TMPs are associated with specific patterns of AF activation wavefronts.

Action Potentials↗

PubMed2000

Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats.

Leptin, the ob gene product that can decrease caloric intake and increase energy expenditure, is functionally released by insulin from adipose tissue. Adenosine is thought to be an important regulator of the action of insulin in adipose tissue. The present study investigated the role of adenosine in the release of leptin by insulin in isolated rat white adipocytes. Release of leptin, measured by radioimmunoassay, from insulin-stimulated samples was seen after 30 min. Adenosine deaminase, at concentrations sufficient to metabolize endogenous adenosine, decreased insulin-stimulated leptin release. Also, the insulin-stimulated leptin release was completely blocked by the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Mediation of endogenous adenosine in this action of insulin was further supported by the assay of adenosine released into the medium from adipocytes stimulated with insulin. In addition, activation of adenosine A1 receptors by N6-cyclopentyladenosine (CPA) induced an increase in leptin release in a concentration-dependent manner that could be blocked by antagonists, either DPCPX or 8-(p-sulfophenyl)theophylline (8-SPT). In the presence of U73312, a specific inhibitor of phospholipase C (PLC), CPA-stimulated leptin secretion from adipocytes was reduced in a concentration-dependent manner, but it was not affected by U73343, the negative control for U73312. Moreover, chelerythrine and GF 109203X diminished the CPA-stimulated leptin secretion at concentrations sufficient to inhibit protein kinase C (PKC). These results suggest that, in isolated white adipocytes, the released adenosine acts as a helper and/or a positive regulator for insulin in the release of leptin via an activation of adenosine A1 receptors that involves the PLC-PKC pathway.

Adenosine↗

PubMed2000

Current trends and new approaches in the management of diabetes mellitus.

Current trends in the management of type 2 diabetes mellitus, based on the 20-year United Kingdom Prospective Diabetic Study, include intensive treatment to control the blood glucose level and blood pressure in order to prevent or delay microvascular and cardiovascular complications. In the new millennium, type 2 diabetes will become epidemic in developing countries. If diabetes were to develop in 10% of the 1.2 billion population of China, the expense of intensive treatment would be immense. Laboratory tests are useful for detecting risk factors before the onset of the disease and convincing the general public to take preventive measures. Glucose tolerance testing is one of these tests. When glucose tolerance is impaired, 25% of beta-cell function is lost. Determining the plasma proinsulin level is another useful evaluation; impaired glucose tolerance accompanied by increased plasma proinsulin level is indicative of an enhanced risk that type 2 diabetes will develop within 5 years. Educating the public about eating a healthy diet and exercising may prevent the development of diabetes and thereby reduce the global prevalence of type 2 diabetes.

Diabetes Mellitus, Type 2↗

PubMed1999

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↗

PubMed1999

Role of papillary muscle in the generation and maintenance of reentry during ventricular tachycardia and fibrillation in isolated swine right ventricle.

BACKGROUND: The role of papillary muscle (PM) in the generation and maintenance of reentry is unclear. METHODS AND RESULTS: Computerized mapping (477 bipolar electrodes, 1.6-mm resolution) was performed in fibrillating right ventricles (RVs) of swine in vitro. During ventricular fibrillation (VF), reentrant wave fronts often transiently anchored to the PM. Tissue mass reduction was then performed in 10 RVs until VF converted to ventricular tachycardia (VT). In an additional 6 RVs, procainamide infusion converted VF to VT. Maps showed that 77% (34 of 44) of all VT episodes were associated with a single reentrant wave front anchored to the PM. Purkinje fiber potentials preceded the local myocardial activation, and these potentials were recorded mostly around the PM. When PM was trimmed to the level of endocardium (n = 4), sustained VT was no longer inducible. Transmembrane potential recordings (n = 5) at the PM revealed full action potential during pacing, without evidence of ischemia. Computer simulation studies confirmed the role of PM as a spiral wave anchoring site that stabilized wave conduction. CONCLUSIONS: We conclude that PM is important in the generation and maintenance of reentry during VT and VF.

Animals↗

PubMed1999

Decrease of nitric oxide synthase in the cerebrocortex of streptozotocin-induced diabetic rats.

In an attempt to know the role of nitric oxide in the disease of insulin-dependent diabetic mellitus (IDDM), the present study examined the change of nitric oxide synthase (NOS) both the activity and gene expression in cerebrocortex of streptozotocin-induced diabetic rats (STZ-diabetic rats). The activity of NOS determined by conversion of [3H] L-arginine to [3H] L-citrulline was markedly decreased in STZ-diabetic rats. Northern blot showed that STZ-diabetic rats expressed a lower mRNA level of neuronal NOS (nNOS). Western blot showed a similar decrease of nNOS in STZ-diabetic rats. However, the NOS activity was increased in rats receiving repeated supply of glucose named glucose-challenged rats. Although the mRNA level of nNOS was not changed in the glucose-challenged rats, the immunoblot of nNOS was also decreased in glucose-challenged rats. These findings suggested that NOS was lowered in the brain of STZ-diabetic rats in a way unrelated to the increase of glucose.

Animals↗

PubMed1999

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↗

PubMed1999

Mechanism of procainamide-induced prevention of spontaneous wave break during ventricular fibrillation. Insight into the maintenance of fibrillation wave fronts.

BACKGROUND: Ventricular fibrillation (VF) is maintained by 2 mechanisms: first by reentry formation and second by spontaneous wave break or wave splitting. We hypothesized that spontaneous wave break results from a critical shortening of the action potential duration (APD) during VF and that its prevention by procainamide eliminates spontaneous wave break. METHODS AND RESULTS: The endocardial surfaces of 7 isolated, perfused swine right ventricles were mapped with a 3.2x3.8 cm plaque with 477 bipolar electrodes. Activation pattern during VF was visualized dynamically while simultaneously recording epicardial action potentials with a glass microelectrode. APD restitution curves were constructed during VF (dynamic) and during S(1)S(2) protocols. At baseline, VF was maintained by 5.3+/-1 wavelets. Procainamide (PA) at 10 microgram/mL decreased the number of wavelets to 3.5+/-1 (P<0.05). At baseline VF was maintained by spontaneous wave break and by new reentrant wave front formation. PA eliminated spontaneous wave break during VF while having no effect on reentry formation. PA increased the cycle length of the VF (148.5+/-41.2 ms vs 81+/-10 ms, P<0.01) and the core area of the reentry from 5.8 to 14.5 mm(2) (P<0.05). Dynamic APD restitution curve during VF showed that PA eliminated the initiation of activation with APDs shorter than 30 ms. The effects of PA on cellular properties and wave front dynamics were reversed during 60 minutes of drug-free perfusion. CONCLUSIONS: Critically short APDs during VF promote spontaneous wave break. Their elimination with PA, however, maintains VF by generating new reentrant wave front.

Action Potentials↗

PubMed1999

The association of metalloendopeptidase EC 3.4.24.15 at the extracellular surface of the AtT-20 cell plasma membrane.

Endopeptidase EC 3.4.24.15 (EP24.15) is a soluble, neuropeptide-degrading metalloenzyme, widely expressed in the brain, pituitary and gonads. For the physiological metabolism of neuropeptides, the enzyme should be located extracellularly, either associated with the plasma membrane or in the extracellular milieu. Western immunoblot analyses of crude cytosolic and post-nuclear membrane fractions prepared by differential centrifugation revealed a slightly smaller molecular mass ( approximately 2 kDa) for EP24.15 in the post-nuclear membrane fraction. This smaller EP24.15 species was also present in an enriched fraction of plasma membrane prepared by Percoll gradient centrifugation. To ascertain whether EP24.15 is associated with the extracellular surface of plasma membrane, two sets of experiments were carried out. First, Western immunoblot analysis of AtT-20 cells treated with the membrane-impermeable, thiol-cleavable cross-linker, 3, 3'-dithio-bis(sulpho-succinimidyl-propionate) (DTSSP), indicated an extracellular membrane association. After cross-linking and thiol-reduction, a distinct band corresponding to EP24.15 was significantly diminished under non-reducing conditions. Second, immunocytochemical studies performed at 4 degrees C on non-permeabilized AtT-20 cells (i.e., non-fixed to prevent antibody internalization), indicated that EP24.15 was expressed on the surface of the AtT-20 cells. We furthermore determined that EP24.15 enzymatic activity is present on the extracellular surface of the cell discernable from the secreted enzyme. These results suggest that the EP24.15 is associated with the extracellular surface of the AtT-20 cell plasma membrane and is enzymatically active. Taken together, the results are consistent with a putative role in the degradation of neuropeptides acting at the external cell surface.

Animals↗

PubMed1999

Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing: importance of cardiac restitution properties.

The mechanism by which rapid pacing induces ventricular fibrillation (VF) is unclear. We performed computerized epicardial mapping studies in 10 dogs, using 19-beat pacing trains. The pacing interval (PI) of the first train was 300 ms and then was progressively shortened until VF was induced. For each PI, we constructed restitution curves for the effective refractory period (ERP). When the PI was long, the activation cycle length (CL) was constant throughout the mapped region. However, as the PI shortened, there was an increase in the spatiotemporal complexity of the CL variations and an increase in the slope of the ERP restitution curve. In 5 dogs, we documented the initiation of VF by wavebreak at the site of long-short CL variations. Computer simulation studies using the Luo-Rudy I ventricular action potential model in simulated 2-dimensional tissue reproduced the experimental results when normal ERP and conduction velocity (CV) restitution properties were intact. By altering CV and ERP restitutions in this model, we found that CV restitution creates spatial CL variations, whereas ERP restitution underlies temporal, beat-to-beat variations in refractoriness during rapid pacing. Together, the interaction of CV and ERP restitutions produces spatiotemporal oscillations in cardiac activation that increase in amplitude as the PI decreases, ultimately causing wavebreak at the site of intrinsic heterogeneity. This initial wavebreak then leads to the formation of spiral waves and VF. These findings support a key role for both CV and ERP restitutions in the initiation of VF by rapid pacing.

Action Potentials↗

PubMed1999

Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance.

To determine the function of VGF, a secreted polypeptide that is synthesized by neurons, is abundant in the hypothalamus, and is regulated in the brain by electrical activity, injury, and the circadian clock, we generated knockout mice lacking Vgf. Homozygous mutants are small, hypermetabolic, hyperactive, and infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AGRP) expression. Furthermore, VGF mRNA synthesis is induced in the hypothalamic arcuate nuclei of fasted normal mice. VGF therefore plays a critical role in the regulation of energy homeostasis, suggesting that the study of lean VGF mutant mice may provide insight into wasting disorders and, moreover, that pharmacological antagonism of VGF action(s) might constitute the basis for treatment of obesity.

Aggression↗

PubMed1999

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↗

PubMed1998

Transmembrane potential properties at the core of functional reentrant wave fronts in isolated canine right atria.

BACKGROUND: The characteristics of transmembrane potential (TMP) at the core of functional reentry in the atrium are not well understood. METHODS AND RESULTS: In protocol 1 (11 dogs), isolated perfused canine right atria were mapped from the endocardial surface while simultaneous TMPs were recorded from the epicardial surface. Episodes of reentry (n=64) were induced in the presence of 1 to 5 micromol/L acetylcholine. Successful simultaneous TMP recordings and activation maps were made in 8 episodes. The TMP was "near the core" if it was within 3.2 mm of the core; otherwise, it was considered to be "in the periphery." The mean cycle length of reentry was 110+/-35 ms. The TMP amplitude, duration (90% repolarization), and (dV/dt)max near the core (n=106) were 58+/-22 mV, 46+/-14 ms, and 33+/-20 V/s, respectively, significantly less than those in the periphery (n=241): 70+/-8 mV, 94+/-32 ms, and 55+/-10 V/s (P<0.001 for all). In 2 episodes of reentry, the cell at the core remained unexcited at its resting membrane potential. In protocol 2 (2 dogs), we performed simultaneous high-density mapping in 4 episodes of reentry and showed synchronous activation patterns on both surfaces with similar locations of the core. CONCLUSIONS: During meandering functional reentry in isolated canine right atria, (1) TMPs of cells near the core have a reduced amplitude, duration, and (dV/dt)max, and (2) cells at the core may remain unexcited at their resting membrane potential. These findings are compatible with the spiral wave concept of functional reentry in the atrium.

Acetylcholine↗

PubMed1998

Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2.

A series of nonpeptide somatostatin agonists which bind selectively and with high affinity to somatostatin receptor subtype 2 (sst2) have been synthesized. One of these compounds, L-054,522, binds to human sst2 with an apparent dissociation constant of 0.01 nM and at least 3,000-fold selectivity when evaluated against the other somatostatin receptors. L-054,522 is a full agonist based on its inhibition of forskolin-stimulated adenylate cyclase activity in Chinese hamster ovary-K1 cells stably expressing sst2. L-054,522 has a potent inhibitory effect on growth hormone release from rat primary pituitary cells and glucagon release from isolated mouse pancreatic islets. Intravenous infusion of L-054,522 to rats at 50 microgram/kg per hr causes a rapid and sustained reduction in growth hormone to basal levels. The high potency and selectivity of L-054, 522 for sst2 will make it a useful tool to further characterize the physiological functions of this receptor subtype.

Animals↗

PubMed1998

Role of pectinate muscle bundles in the generation and maintenance of intra-atrial reentry: potential implications for the mechanism of conversion between atrial fibrillation and atrial flutter.

To determine the role of pectinate muscle (PM) bundles in the formation of intra-atrial reentry, 10 isolated canine right atrial tissues were perfused with Tyrode's solution containing 1 to 2.5 micromol/L acetylcholine (ACh). The endocardium was mapped using 477 bipolar electrodes with 1.6-mm resolution. Reentry was induced by a premature stimulus (S2). Computer simulation studies were used to investigate the importance of regional myocardial thickness in reentry formation. A total of 40 episodes of reentry were induced; 28 episodes were stationary, and the remaining 12 were nonstationary. The stationary reentry was induced either immediately after the S2 stimuli (n=9) or after an initial period of irregular activations that lasted 1460+/-1077 ms (n= 19). Of 28 episodes, 20 were initiated by conduction block along large PM ridges, leading to wave break and the initiation of reentry. The reentrant wave fronts remained stationary and rotated around these ridges as anchoring sites. During the transition from the initial irregular activations to stationary reentry, the electrogram morphology converted from "fibrillation-like" to "flutter-like" activity. In 8 episodes, initially stationary reentry converted to irregular activations because of interference with outside wave fronts (n=5) or spontaneous separation of waves from the ridges (n=3). Compared with stationary reentry, nonstationary reentry always occurred over an area without large PMs, and the mean life span was much shorter (102+/-151 versus 3.8+/-1.1 rotations, P<0.001). Computer simulation studies showed that a critical ridge thickness is needed for reentry to anchor, thereby converting fibrillation to flutter. We conclude that PM ridge forms an area where wave break occurs, allowing the initiation of reentry. It also provides a natural anchor to the reentrant wave front, lengthening the life span of reentry. The attachment and detachment of the reentrant wave front to and from the ridge determine "flutter-like" or "fibrillation-like" activity.

Animals↗