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Biomedical subjects

Peng-Sheng Chen

Publications and source records attributed to Peng-Sheng Chen.

At least 37 records · Page 2Linked to original sources
PubMed2005

Electrical connections between left superior pulmonary vein, left atrium, and ligament of Marshall: implications for mechanisms of atrial fibrillation.

The importance of the ligament of Marshall (LOM) to rapid activations within the left superior pulmonary vein (LSPV) during atrial fibrillation (AF) remains poorly understood. We aimed to characterize the importance of electrical coupling between the LSPV with the left atrium (LA) and the LOM in the generation of high-frequency activations within this PV. We performed high-density mapping of the LSPV-LA-LOM junction in eight dogs, using 1,344 electrodes with a 1-mm resolution before and after posterior ostial ablation to diminish PV-LA electrical connections. A LOM potential was recordable up to 6.5 mm (SD 2.2) into the LSPV in all dogs during sinus rhythm (SR) and LA pacing. Functional LOM-LSPV electrical connections bypassing the PV-LA junction were present in five of eight dogs. Direct LOM-LSPV connections contributed to 46.5% (SD 16.0) of LSPV activations during AF, resulting in a greater propensity to develop focal activations (P < 0.05) and a higher activation rate during AF of LSPVs with direct LOM connections compared with those without (P < 0.03). Posterior LSPV ostial ablation without damaging the anterior wall or LOM slowed residual LA-PV conduction (P < 0.001). This diminished PV-LA coupling prevented the reinduction of LSPV focal activations in all dogs. However, persistent LOM focal activations in two dogs continued to activate the LSPV rapidly [cycle length 151.8 ms (SD 4.8)] via direct LOM-LSPV connections. LOM-LSPV connection forms an accessory pathway that contributes to the electrical coupling between LSPV and LA during SR and AF. This pathway may contribute to rapid activations within the LSPV during AF.

Animals↗
PubMed2005

The dynamics of cardiac fibrillation.

Reentry occurs when the electrical wave propagating through the atria or ventricles breaks locally and forms a rotor (also called a scroll wave or functional reentry). If the waves propagating outward from a rotor develop additional wavebreaks (which may form new rotors), fibrillation results. Tissue heterogeneity, exacerbated by electrical and structural remodeling from cardiac disease, has traditionally been considered the major factor promoting wavebreak and its degeneration to fibrillation. Recently, however, dynamic factors have also been recognized to play a key role. Dynamic factors refer to cellular properties of the cardiac action potential and Ca(i) cycling, which dynamically generate wave instability and wavebreak, even in tissue that is initially completely homogeneous. Although the latter situation can only be created in computer simulations, its relevance to real (heterogeneous) cardiac tissue has been unequivocally demonstrated. Dynamic factors are related to membrane voltage (Vm) and Ca(i). Vm factors include electrical restitution of action potential duration and conduction velocity, short-term cardiac memory, and electrotonic currents. Ca(i) factors are related to dynamic Ca(i) cycling properties. They act synergistically, as well as with tissue heterogeneity, to promote wavebreak and fibrillation. As global properties, rather than local electrophysiological characteristics, dynamic factors represent an attractive target for novel therapies to prevent ventricular fibrillation.

Action Potentials↗
PubMed2005

High-density mapping of pulmonary veins and left atrium during ibutilide administration in a canine model of sustained atrial fibrillation.

Ibutilide can prolong refractory period and terminate reentry. Whether ibutilide has the same effects on pulmonary vein (PV) focal discharge (FD) is unclear. We induced sustained atrial fibrillation (AF) in seven dogs by rapid left atrial (LA) pacing for 74 +/- 46 days. Ibutilide was repeatedly infused until it terminated AF (0.02 +/- 0.01 mg/kg) or when a cumulative dose was reached (0.04 mg/kg). High-resolution computerized epicardial mapping was performed. We found intermittent FD at the PVs and reentry at the PV-LA junction during AF. Ibutilide increased the cycle length of consecutive reentry from 97 +/- 13 to 112 +/- 18 ms and increased FD from 96 +/- 7 to 113 +/- 9 ms. In four dogs with both FD and reentry at the PVs, the incidence of reentry decreased from 3.5 +/- 1.9/s at baseline to 2.2 +/- 1.8/s after ibutilide administration. However, the incidence of FD remained unchanged. The conducted wave fronts between PV and LA were significantly reduced by ibutilide (10.4 +/- 2.0/s vs. 8.0 +/- 1.6/s). The ibutilide dose needed to terminate AF correlated negatively with the baseline effective refractory period of PV and LA. We conclude that ibutilide reduces reentrant wave fronts but not PV FD in a canine model of pacing-induced sustained AF. These findings suggest that the PV FD during AF is due to nonreentrant mechanisms. High doses of ibutilide may completely terminate all reentrant activity, converting AF to PV tachycardia before the resumption of sinus rhythm.

Animals↗
PubMed2005

Canine model of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia.

Both autonomic nerve activity and electrical remodeling are important in atrial arrhythmogenesis. Therefore, dogs with sympathetic hyperinnervation, myocardial infarction (MI), and complete atrioventricular block (CAVB) may have a high incidence of atrial arrhythmias. We studied eight dogs (experimental group) with MI, CAVB, and sympathetic hyperinnervation induced either by nerve growth factor infusion (n = 4 dogs) or subthreshold electrical stimulation (n = 4 dogs) of the left stellate ganglion. Cardiac rhythm was continuously monitored by a Data Sciences International transmitter for 48 (SD 27) days. Three normal control dogs were also monitored. Six additional normal dogs were used for histology control. Paroxysmal atrial fibrillation (PAF) and paroxysmal atrial tachycardia (PAT) were documented in all dogs in the experimental group, with an average of 3.8 (SD 3) episodes/day, including 1.3 (SD 1.6) episodes of PAF and 2.5 (SD 2.2) episodes of PAT. The duration averaged 298 (SD 745) s (range, 7-4,000 s). There was a circadian pattern of arrhythmia onset (P < 0.01). Of 576 episodes of PAF and PAT, 236 (41%) episodes occurred during either sustained or nonsustained ventricular tachycardia (VT). Among these 236 episodes, 53% started before VT, whereas 47% started after the onset of VT. Normal dogs did not have either PAF or PAT. The hearts from the experimental group had a higher density of nerve structures immunopositive (P < 0.01) for three different nerve specific markers in both right and left atria than those of the control dogs. We conclude that the induction of nerve sprouting and sympathetic hyperinnervation in dogs with CAVB and MI creates a high yield model of PAF and PAT.

Animals↗
PubMed2005

Intracellular calcium dynamics and anisotropic reentry in isolated canine pulmonary veins and left atrium.

BACKGROUND: Rapid activations due to either focal discharge or reentry are often present during atrial fibrillation (AF) in the pulmonary veins (PVs). The mechanisms of these rapid activations are unclear. METHODS AND RESULTS: We studied 7 isolated, Langendorff-perfused canine left atrial (LA) and PV preparations and used 2 cameras to map membrane potential alone (Vm, n=3) or Vm and intracellular calcium simultaneously (Ca(i), n=4). Rapid atrial pacing induced 26 episodes of focal discharge from the proximal PVs in 5 dogs. The cycle lengths were 223+/-52 ms during ryanodine infusion (n=13) and 133+/-59 ms during ryanodine plus isoproterenol infusion (n=13). The rise of Ca(i) preceded Vm activation at the sites of focal discharge in 6 episodes of 2 preparations, compatible with voltage-independent spontaneous Ca(i) release. Phase singularities during pacing-induced reentry clustered specifically at the PV-LA junction. Periodic acid-Schiff (PAS) stain identified large cells with pale cytoplasm along the endocardium of PV muscle sleeves. There were abrupt changes in myocardial fiber orientation and increased interstitial fibrosis in the PV and at the PV-LA junction. CONCLUSIONS: PV muscle sleeves may develop voltage-independent Ca(i) release, resulting in focal discharge. Focal discharge may also be facilitated by the presence of PAS-positive cells that are compatible with node-like cells. During reentry, phase singularities clustered preferentially at sites of increased anisotropy such as the PV-LA junction. These findings suggest that focal discharge caused by spontaneous calcium release and anisotropic reentry both contribute to rapid activations in the PVs during AF.

Action Potentials↗
PubMed2005

Chronic nicotine in hearts with healed ventricular myocardial infarction promotes atrial flutter that resembles typical human atrial flutter.

The potential of chronic nicotine exposure for atrial fibrillation (AF) and atrial flutter (AFL) in hearts with and without chronic myocardial infarction (MI) remains poorly explored. MI was created in dogs by permanent occlusion of the left anterior descending coronary artery, and dogs were administered nicotine (5 mg.kg(-1).day(-1) sc) for 1 mo using osmotic minipumps. High-resolution epicardial (1,792 bipolar electrodes) and endocardial Halo catheters were used to map activation during induced atrial rhythms. Nicotine promoted inducible sustained AFL at a mean cycle length of 134 +/- 10 ms in all MI dogs (n = 6) requiring pacing and electrical shocks for termination. No AFL could be induced in MI dogs (n = 6), control (non-MI) dogs (n = 3) not exposed to nicotine, and dogs with no MI and exposed to nicotine (n = 3). Activation maps during AFL showed a single reentrant wavefront in the right atrium that rotated either clockwise (60%) or counterclockwise (40%) around the crista terminalis and through the isthmus. Ablation of the isthmus prevented the induction of AFL. Nicotine caused a significant (P < 0.01) but highly heterogeneous increase in atrial interstitial fibrosis (2- to 10-fold increase in left and right atria, respectively) in the MI group but only a 2-fold increase in the right atrium in the non-MI group. Nicotine also flattened (P < 0.05) the slope of the epicardial monophasic action potential duration (electrical restitution) curve of both atria in the MI but not in non-MI dogs. Two-dimensional simulation in an excitable matrix containing an isthmus and nicotine's restitutional and reduced gap junctional coupling (fibrosis) parameters replicated the experiments. Chronic nicotine in hearts with MI promotes AFL that closely resembles typical human AFL. Increased atrial interstitial fibrosis and flattened electrical restitution are important substrates for the AFL.

Animals↗
PubMed2005

The perplexing complexity of cardiac arrhythmias: beyond electrical remodeling.

Cardiac arrhythmias continue to pose a major medical challenge and significant public health burden. Atrial fibrillation, the most prevalent arrhythmia, affects more than two million Americans annually and is associated with a twofold increase in mortality. In addition, more than 250,000 Americans each year suffer ventricular arrhythmias, often resulting in sudden cardiac death. Despite the high incidence and societal impact of cardiac arrhythmias, presently there are insufficient insights into the molecular mechanisms involved in arrhythmia generation, propagation, and/or maintenance or into the molecular determinants of disease risk, prognosis, and progression. In addition, present therapeutic strategies for arrhythmia abatement often are ineffective or require palliative device therapy after persistent changes in the electrical and conduction characteristics of the heart have occurred, changes that appear to increase the risk for arrhythmia progression. This article reviews our present understanding of the complexity of mechanisms that regulate cardiac membrane excitability and cardiac function and explores the role of derangements in these mechanisms that interact to induce arrhythmogenic substrates. Approaches are recommended for future investigations focused on providing new mechanistic insights and therapeutic interventions.

Arrhythmias, Cardiac↗
PubMed2005

Effects of omapatrilat on cardiac nerve sprouting and structural remodeling in experimental congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) results in decreased cardiac sympathetic innervation. OBJECTIVES: The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates cardiac neuronal remodeling in CHF. METHODS: We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n = 8) or without (CHF group, n = 10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine cardiac structure and hemodynamic parameters. Myocardial nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls. RESULTS: In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group (P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high nerve counts. OMA treatment prevented heterogeneous reduction of nerve density. The left ventricular TH-positive nerve densities were 128 +/- 170 microm(2)/mm(2), 261 +/- 185 microm(2)/mm(2), and 503 +/- 328 microm(2)/mm(2) (P < .05), and the atrial GAP43-positive nerve densities were 1,683 +/- 1,365 microm(2)/mm(2), 305 +/- 368 microm(2)/mm(2), and 1,278 +/- 1,479 microm(2)/mm(2) (P < .05) for the control, CHF, and CHF+OMA groups, respectively. CONCLUSION: CHF results in heterogeneous cardiac denervation. Long-term OMA treatment prevented the reduction of nerve density and promoted beneficial cardiac structural remodeling.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Differential beta-adrenoceptor expression induced by nerve growth factor infusion into the canine right and left stellate ganglia.

BACKGROUND: Nerve growth factor (NGF) infusion into the right stellate ganglion (RSG) is antiarrhythmic, while NGF infusion into the left stellate ganglion (LSG) is proarrhythmic in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). This functional asymmetry suggests differential neural remodeling. OBJECTIVES: To test the hypothesis that NGF infusion into the RSG and the LSG can lead to differential beta-adrenoceptor (beta-AR) expression in dogs with MI and CAVB. METHODS AND RESULTS: We performed immunostaining to quantify beta(1)-AR and beta(3)-AR immunoreactivity in six dogs with MI and CAVB, nine dogs with MI, CAVB, and NGF infusion to the LSG, six dogs with MI, CAVB, and NGF infusion to the RSG, and six normal dogs. There was significantly increased beta(3)-AR immunoreactivity in dogs with NGF infusion into the LSG and significantly decreased beta(3)-AR immunoreactivity in dogs with NGF infusion into the RSG compared with controls and with the MI and CAVB group. There were no significant differences in beta(1)-AR immunoreactivity among these four groups. To determine protein and mRNA expression of beta-ARs, we created MI and CAVB and infused NGF into the LSG in six additional dogs. The noninfarcted left ventricle free wall was harvested 1 week later. The protein level and receptor density of beta(3)-AR (but not beta(1)- or beta(2)-AR) significantly increased in these six dogs compared with normal controls. CONCLUSIONS: We conclude that NGF infusion into the RSG and the LSG in dogs with MI and CAVB induced differential beta(3)-AR expression in the left ventricular myocardium.

Animals↗
PubMed2005

Heterogeneous pulmonary vein myocardial cell repolarization implications for reentry and triggered activity.

BACKGROUND: Myocardial cells in the pulmonary veins (PVs) are thought to play a major role in the initiation and maintenance of atrial arrhythmias, including atrial fibrillation. However, systematic single-cell microelectrode recordings from different regions in intact PV-atrial tissues are lacking. OBJECTIVES: The purpose of this study was to determine the transmembrane action potential properties of myocardial cells in different regions of the PV and the left atrium (LA) and assess their arrhythmogenic potential during perfusion with isoproterenol (ISO) and rapid atrial pacing. METHODS: Glass microelectrode recordings of action potentials were made from the left PV and the LA in Langendorff-perfused young (3-4 month) male rats (Fisher344) (n = 9). RESULTS: Action potential duration (APD) of atrial and PV cells had similar duration at a pacing cycle length (CL) of 200 ms. However, shortening of the pacing CL to 100 ms led to heterogeneous repolarization of PV cells. Mid-PV cells had a significantly higher maximum slope of APD restitution than atrial or other PV sites. Intra-PV conduction block developed at rates when LA and proximal PV cells manifested 1:1 capture. Perfusion of ISO and rapid atrial pacing promoted the emergence of early afterdepolarization (EAD) and triggered beats in two out of nine tissues, causing premature atrial activation. No difference in resting potential or AP amplitude could be detected among the PV and LA cells. CONCLUSIONS: PV myocardial cells develop marked heterogeneity in repolarization, and there is a slight ease of developing EAD and triggered activity in response to rapid pacing and ISO infusion.

Animals↗
PubMed2005

Action potential duration and QT interval during pinacidil infusion in isolated rabbit hearts.

INTRODUCTION: Acute myocardial ischemia, which opens K(ATP) channel, is associated with shortened action potential duration (APD) but prolonged QT interval. This discrepancy has not been adequately explained. We hypothesize that the duration of intracellular calcium (Ca(i)) transient (DCaT) may play a role in determining QT interval. METHODS AND RESULTS: We performed simultaneous optical mapping of voltage and Ca(i) in 15 isolated rabbit hearts during a K(ATP) channel opener (pinacidil) infusion. Anterior epicardial mapping (n = 7) showed no difference of APD(90), QT interval, and the DCaT(90) at baseline. When perfused with 80 microM pinacidil, the APD(90), the QT interval, and the DCaT(90) were 105 +/- 10 msec, 199 +/- 14 msec, and 189 +/- 13 msec, respectively, during right ventricular (RV) pacing (P < 0.05). Posterior epicardial mapping (n = 4) showed that the APD(90) was significantly (P < 0.05) shorter than QT interval and DCaT(90) during pinacidil infusion. The results of the transmural mapping studies (n = 4) showed that the QT interval during RV pacing was not different than the DCaT(90) in the epicardium, midmyocardium, and endocardium, but was significantly (P < 0.01) longer than the APD(90) in epicardium, midmyocardium, and endocardium, respectively. There was a good correlation between the DCaT(90) and QT interval at baseline (r = 0.92, P < 0.0001) and during pinacidil infusion (r = 0.74, P < 0.0001). CONCLUSION: We conclude that K(ATP) channel opening shortened APD but not the QT interval. Because Ca(i) did not return to diastolic level at the end of action potential, it may have created a heterogeneous membrane potential distribution that determined the QT interval.

Action Potentials↗
PubMed2005

Intramyocardial injection of allogenic bone marrow-derived mesenchymal stem cells without immunosuppression preserves cardiac function in a porcine model of myocardial infarction.

BACKGROUND: We investigated the efficacy of directly injected allogenic bone marrow-derived mesenchymal stem cells in improving left ventricular function in a porcine model of myocardial infarction. METHODS: Left ventricular infarction was created in 16 adult Yorkshire pigs by coil embolization and thrombotic occlusion distal to the second diagonal artery. One month after myocardial infarction was induced, the animals were randomized to either direct injection of allogenic mesenchymal stem cells or sham treatment (culture medium). Allogenic bromodeoxyuridine-labeled mesenchymal stem cells (2 +/- 0.1 x 10(8)) were directly injected into the infarct and peri-infarct areas during an open chest procedure. No immunosuppressive therapy was used. The left ventricular function was measured using serial biplane left ventricular angiography at baseline, 30, 60, and 90 days before sacrifice. Mesenchymal stem cells were localized using bromodeoxyuridine, and differentiation of mesenchymal stem cells was assessed by confocal microscopic colocalization of bromodeoxyuridine with immunofluorescent antibodies specific for cardiomyocytes (troponin I and MF-20) and endothelial cells (von Willebrand factor). RESULTS: Mesenchymal stem cells labeled with bromodeoxyuridine engrafted the peri-infarct zone and colocalized with both cardiomyocyte-specific and endothelial cell-specific immunofluorescence. No intramyocardial bromodeoxyuridine was observed in sham-treated animals. At the time of the mesenchymal stem cell injection 30 days after myocardial infarction, the left ventricular ejection fraction (LVEF) was 58% +/- 3% in mesenchymal stem cell-treated pigs and 56% +/- 2% in sham-treated pigs (P = NS). LVEF deteriorated progressively thereafter in untreated pigs (8.5% and 10.5% decline at 60 days and 90 days after myocardial infarction, respectively), but was preserved in mesenchymal stem cell-treated pigs (2.1% increase and -2.0% decline at 60 and 90 days post-MI respectively) (P < .05). CONCLUSIONS: Direct intramyocardial injection of mesenchymal stem cells results in successful intramyocardial engraftment and differentiation into cardiomyocytes and endothelial cells and preserves left ventricular function after myocardial infarction in pigs.

Animals↗
PubMed2004

Highlights of Heart Rhythm 2004, the Annual Scientific Sessions of the Heart Rhythm Society: May 19 to 22, 2004, in San Francisco, California.

Heart Rhythm 2004, the 25th Annual Scientific Sessions of the Heart Rhythm Society (formerly the North American Society of Pacing and Electrophysiology), met in San Francisco in May 2004. The meeting is the world's premier forum for the presentation of research and the exchange of state-of-the-art information in cardiac electrophysiology and pacing. Major new research findings were presented on the value of implantable cardioverter-defibrillator therapy, noninvasive methods for risk stratification, treatment of vasovagal syncope, radiofrequency ablation for atrial fibrillation, resynchronization therapy for heart failure, and new insights from basic science into the mechanisms of cardiac arrhythmias.

Arrhythmias, Cardiac↗
PubMed2004

Mother rotors and the mechanisms of D600-induced type 2 ventricular fibrillation.

BACKGROUND: Two types of ventricular fibrillation (VF) have been demonstrated in isolated rabbit hearts during D600 infusion. Type 1 VF is characterized by the presence of multiple, wandering wavelets, whereas type 2 VF shows local spatiotemporal periodicity. We hypothesized that a single mother rotor underlies type 2 VF. METHODS AND RESULTS: One (protocol I) or 2 (protocol II) cameras were used to map the epicardial ventricular activations in Langendorff-perfused rabbit hearts. Multiple episodes of type 2 VF were induced in 22 hearts by high-concentration (> or =2.5 mg/L) D600 (protocol I). During type 2 VF, a single spiral wave (n=19) and/or an epicardial breakthrough pattern (n=11) was present in 14 hearts. These spiral waves either slowly drifted or intermittently anchored on the papillary muscle (PM) of the left ventricle. Dominant-frequency (DF) analyses showed that the highest local DF was near the PM (12.5+/-1.1 Hz). There was an excellent correlation between the highest local DF of these spiral waves and breakthroughs (11.8+/-1.7 Hz) and the DF of simultaneously obtained global pseudo-ECG (11.2+/-1.8 Hz, r=0.97, P<0.0001) during type 2 VF. We also successfully reproduced the major features of type 2 VF by using the Luo-Rudy action-potential model in a simulated, 3-dimensional tissue slab, under conditions of reduced excitability and flat action-potential duration restitution. CONCLUSIONS: Either a stationary or a slowly drifting mother rotor can result in type 2 VF. Colocalization of the stationary mother rotors with the PM suggests the importance of underlying anatomic structures in mother rotor formation.

Action Potentials↗