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Shien-Fong Lin

Publications and source records attributed to Shien-Fong Lin.

15 recordsLinked to original sources
PubMed2003

Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart.

Cardiac ischemia causes beat-to-beat fluctuation in action potential duration (APD) alternans, which leads to T wave alternans and arrhythmias. Occurrence of APD alternans that is out of phase at two sites is especially important, but most APD alternans studies have involved rapid pacing of normal myocardium rather than ischemia. To determine the spatial features of APD alternans during ischemia, blood-perfused rabbit hearts were stained with 4-[beta-[2(di-n-butylamino)-6-napthyl]vinyl]pyridinium (di-4-ANEPPS) and imaged with a high-resolution camera. Hearts were perfused with oxygenated Tyrode solution at 37 degrees C for staining and then switched to a 50:50% blood/Tyrode mixture. Hearts were paced from the right ventricle at 3/s, and made ischemic by stopping flow for 6 min. Images of 10,000 pixels were obtained at 300 frames/s. Motion artifact was controlled by immobilization and by manual selection of undistorted single-pixel records. Upstroke propagation and conduction isochrones were displayed by computerized image processing. APD alternans was demonstrated in six of seven hearts, and was out of phase in different regions of the image in three hearts. The largest spatial variation in the onset of depolarization to 50% repolarization (APD50) was 155%. This caused beat-to-beat reversal of repolarization. An alternans map could be constructed for well-immobilized portions of the image. There were discrete regions of APD alternans separated by a boundary, as occurs with intracellular Ca2+ concentration alternans. Pixels as close together as 1.1 mm showed an APD alternans that was out of phase. The out-of-phase APD alternans was not due to conduction alternans, as shown by upstroke intervals and conduction isochrones. This contrasts with rapid pacing, where a causal relationship appears to exist. These new observations suggest distinct mechanisms for the genesis of arrhythmias during ischemia.

Action Potentials↗
PubMed2003

Synchronization of ventricular fibrillation with real-time feedback pacing: implication to low-energy defibrillation.

Wavefront synchronization is an important aspect preceding the termination of ventricular fibrillation (VF). We evaluated the defibrillation efficacy of a novel multisite pacing algorithm using optical recording-guided synchronized pacing (SyncP) in the excitable gaps. We compared the effects of SyncP with traditional overdrive pacing (ODP) at 90% of the VF cycle length (VFCL) and high-frequency pacing (HFP; 43-215 Hz) on spontaneous VF termination in isolated rabbit hearts. For SyncP, the pacing current was triggered by the activation of a reference site and was delivered when the optical potential of the pacing site was in an excitable gap. We measured VFCL and the spatial dispersion of VFCL (SDCL) from five points (3 points in the paced area and 2 points in the nonpaced area) and the distribution of phase singularities during the prepacing, pacing, and postpacing periods. The results showed that 1) the VF termination rate of SyncP (16.0%, n = 106) was higher than that of ODP (2.1%, n = 48, P < 0.01) or HFP (1.6%, n = 129, P < 0.0001); 2) energy consumption for SyncP (7.6 +/- 9.3 mJ) was significantly lower than that of ODP (14.0 +/- 14.8 mJ, P < 0.0001); and 3) SyncP, but not ODP or HFP, decreased SDCL in the paced area during the pacing (P < 0.01) and postpacing (P < 0.05) periods compared with the prepacing period. We conclude that SyncP is effective in inducing wavefront synchronization and is more effective at facilitating spontaneous VF termination than non-SyncP.

Algorithms↗
PubMed2003

Spatial distribution of phase singularities in ventricular fibrillation.

BACKGROUND: Multiple excitation wavelets are present during ventricular fibrillation (VF). The underlying wavelet organization of VF is unclear. Phase singularities (PSs)-locations of ambiguous activation state-underlie reentry and wavelet splitting and represent the sources of VF. Understanding the mechanisms of PS formation might be important in the development of effective therapies for sudden death. METHODS AND RESULTS: We performed voltage, phase, and PS mapping in fibrillating ventricles, applying an automated PS detection algorithm to optically recorded fibrillation signals. PS clustering was noted along epicardial vessels, ridges of endocardial trabeculae, and papillary muscle insertions. Microscopically, these locations correlated with areas of apposition of fibers with different angulations and intramural vessels. A total of 83.2% of PSs were formed at and meandered about these anatomic structures, which acted as stabilizers: PSs colocalizing at anatomic substrates had longer life spans than nonanatomic PS (82.46+/-60.8 versus 40.5+/-31.9 ms, P<0.01). The RV endocardium had a higher PS incidence than the epicardium (42.3+/-9.2 versus 23.5+/-11.6 PS/s, P<0.01). Autocorrelation showed that irregular behavior was spatially restricted to anatomic heterogeneities compared with other areas, which had nearly periodic behaviors. Simple spatial PS distributions underlay complex and variable activation patterns attributable to variable PS behaviors, life spans, and inter-PS interactions. CONCLUSIONS: PSs occur in a nonrandom spatial distribution and colocalize with normal anatomic heterogeneities. Varying PS behaviors and life spans but stable PS spatial distributions cause ever-changing activation patterns that characterize VF.

Animals↗
PubMed2003

Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits.

Whether hypercholesterolemia (HC) can induce proarrhythmic neural and electrophysiological remodeling is unclear. We fed rabbits with either high cholesterol (HC, n=10) or standard (S, n=10) chows for 12 weeks (protocol 1), and with HC (n=12) or S (n=10) chows for 8 weeks (protocol 2). In protocol 3, 10 rabbits were fed with various protocols to observe the effects of different serum cholesterol levels. Results showed that the serum cholesterol levels were 2097+/-288 mg/dL in HC group and 59+/-9 mg/dL in S group for protocol 1 and were 1889+/-577 mg/dL in HC group and 50+/-21 mg/dL in S group for protocol 2. Density of growth-associated protein 43- (GAP43) and tyrosine hydroxylase- (TH) positive nerves in the heart was significantly higher in HC than S in protocol 1. Compared with S, HC rabbits had longer QTc intervals, more QTc dispersion, longer action potential duration, increased heterogeneity of repolarization and higher peak calcium current (ICa) density (14.0+/-3.1 versus 9.1+/-3.4 pA/pF; P<0.01) in protocol 1 and 2. Ventricular fibrillation was either induced or occurred spontaneously in 9/12 of hearts of HC group and 2/10 of hearts in S group in protocol 2. Protocol 3 showed a strong correlation between serum cholesterol level and nerve density for GAP43 (R2=0.94; P<0.001) and TH (R2=0.91; P<0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased ICa. The neural and electrophysiological remodeling was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased ventricular vulnerability to fibrillation.

Action Potentials↗
PubMed2002

Two types of ventricular fibrillation in isolated rabbit hearts: importance of excitability and action potential duration restitution.

BACKGROUND: The combined effects of excitability and action potential duration (APD) restitution on wavefront dynamics remain unclear. METHODS AND RESULTS: We used optical mapping techniques to study Langendorff-perfused rabbit hearts. In protocol IA (n=10), D600 at increasing concentrations was infused during ventricular fibrillation (VF). With concentration increased to 0.5 mg/L, fast VF (dominant frequency, 19.1+/-1.8 Hz) was consistently converted to ventricular tachycardia (VT). However, increasing D600 further to 2.5 or 5.0 mg/L converted VT to slow VF (11.9+/-2.3 Hz, P=0.0011). In an additional 4 hearts (protocol IB), tetrodotoxin converted a preexisting VT to slow VF (11.0+/-1.4 Hz). Optical maps show wandering wavelets in fast VF, organized reentry in VT, and spatiotemporal periodicity in slow VF. In protocol II, we determined APD and conduction time(-1) (CT(-1)) restitutions during D600 infusion. CT(-1) was used as an estimate of excitability. At 0.1 mg/L, APD and CT(-1) restitutions were steep and flat, respectively. APD restitution became flattened when D600 increased to 0.5 mg/L, converting fast VF to VT. Further increasing D600 to 2.5 or 5.0 mg/L steepened CT(-1) restitution and widened the range of S(1) pacing cycle lengths over which CT(-1) decreased, converting VT to slow VF. CONCLUSIONS: Two types of VF exist in isolated rabbit hearts. Fast (type I) VF is associated with a steep APD restitution, a flat CT(-1) restitution, and wandering wavelets. Slow (type II) VF is associated with a flat APD restitution, a steep CT(-1) restitution, and spatiotemporal periodicity. Both excitability and APD restitution are important in VF maintenance.

Action Potentials↗
PubMed2002

Frequency analysis of ventricular fibrillation in Swine ventricles.

It has been suggested from frequency analysis that cardiac fibrillation is driven by stable intramural reentry, with wavebreak occurring due to failure of 1:1 propagation. We tested this hypothesis with a combined experimental and theoretical approach. Optical mapping was performed on epicardial, endocardial, and transmural cut surfaces of fibrillating swine ventricles. Wavelets were characterized, the frequency content of optical signals analyzed, and space-time plots (STPs) constructed to detect Wenckebach-like conduction. The findings were compared with simulations in 2D and 3D cardiac tissue using the Luo-Rudy action potential model. The incidence of reentry in the cut transmural surface (11.8% in right ventricle, 14.3% in left ventricle) was similar to that on the endocardial surface (13.1%, P=NS) but greater than on the epicardial surface (7.7%, P<0.01). Frequency spectra of optically recorded membrane voltage were organized into spatial domains with the same dominant frequency, but these domains were nonstationary. In STPs, pseudo-2:1 conduction block was caused by double potentials arising when reentry occurred on the recording site rather than true Wenckebach conduction. The latter was observed in 11 of 166 STPs but did not occur at borders of high-to-low frequency domains. In simulations, similar findings were obtained when action potential duration (APD) restitution slope was steep. Stationary dominant frequency domains with Wenckebach conduction patterns were observed only in the presence of shallow APD restitution slope and marked nonuniform tissue heterogeneity. In conclusion, stable intramural reentry as the engine of fibrillation was not observed. Our findings support the idea that dynamic wavebreak plays a fundamental role in the generation and maintenance of ventricular fibrillation.

Action Potentials↗
PubMed2002

Aging-related increase to inducible atrial fibrillation in the rat model.

INTRODUCTION: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF. METHODS AND RESULTS: Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2-3 months) and 12 old (22-24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 microM were studied in both groups. Heptanol 2 to 5 microM promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 microM, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 microM. In the old rats, AF could still be induced during perfusion of 2 microM heptanol. However, when its concentration was raised to 5 and 10 microM, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous. CONCLUSION: The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model.

Age Factors↗
PubMed2002

Demonstration of electrical and anatomic connections between Marshall bundles and left atrium in dogs: implications on the generation of P waves on surface electrocardiogram.

INTRODUCTION: The muscle bundles within the ligament of Marshall (LOM) are electrically active. The importance of these muscle bundles (Marshall bundle [MB]) to atrial activation and the generation of the ECG P wave is unclear. METHODS AND RESULTS: We used optical mapping techniques to study epicardial activation patterns in isolated perfused left atrium in four dogs. In another seven dogs, P waves were studied before and after in vivo radiofrequency (RF) ablation of the connection between coronary sinus (CS) and the LOM. Computerized mapping was performed before and after RF ablation. Optical mapping studies showed that CS pacing resulted in broad wavefronts propagating from the middle and distal LOM directly to the adjacent left atrium (LA). Serial sections showed direct connection between MB and LA near the orifice of the left superior pulmonary vein in two dogs. In vivo studies showed that MB potentials were recorded in three dogs. After ablation, the duration of P waves remained unchanged. In the other four dogs, MB potentials were not recorded. Computerized mapping showed that LA wavefronts propagated to the MB region via LA-MB connection and then excited the CS. After ablation, the activation of CS muscle sleeves is delayed, and P wave duration increased from 65.3 +/- 14.9 msec to 70.5 +/- 17.2 msec (P = 0.025). CONCLUSION: In about half of the normal dogs, MB provides an electrical conduit between LA free wall and CS. Severing MB alters the atrial activation and lengthens the P wave. MB contributes to generation of the P wave on surface ECG.

Animals↗
PubMed2002

Effects of amiodarone on wave front dynamics during ventricular fibrillation in isolated swine right ventricle.

The effects of acute amiodarone infusion on dynamics of ventricular fibrillation (VF) are unclear. Six isolated swine right ventricles (RVs) were studied in vitro. Activation patterns during VF were mapped optically, whereas action potentials were recorded with a glass microelectrode. At baseline, VF was associated with frequent spontaneous wave breaks. Amiodarone (2.5 microg/ml) reduced spontaneous wave breaks and increased the cycle length (CL) of VF from 83.3 +/- 17.8 ms at baseline to 118.4 +/- 25.8 ms during infusion (P < 0.05). Amiodarone increased the reentrant wave front CL (114.4 +/- 15.5 vs. 78.2 +/- 19.0 ms, P < 0.05) and central core area (4.1 +/- 3.8 vs. 0.9 +/- 0.3 mm2, P < 0.05). Within 30 min of infusion, VF terminated (n = 1), converted to ventricular tachycardia (VT) (n = 1) or continued at a slower rate (n = 4). Amiodarone flattened the APD restitution curves. We conclude that amiodarone reduced spontaneous wave breaks. It might terminate VF or convert VF to VT. These effects were associated with the flattening of APD restitution slope and increased core size of reentrant wave fronts.

Action Potentials↗
PubMed2002

Action potential duration restitution and ventricular fibrillation due to rapid focal excitation.

The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 microg) into normal isolated perfused swine right ventricles (RVs) stained with 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 +/- 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 +/- 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10-20 mM, n = 6), bretylium (10-20 microg/ml, n = 3), and verapamil (2-4 microg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the "aconitine" site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.

Aconitine↗
PubMed2002

The role of approximate entropy in predicting ventricular defibrillation threshold.

BACKGROUND: The role of myocardial tissue mass on ventricular defibrillation threshold (DFT) is unclear. We hypothesized that changes in tissue mass modulate DFT by changing ventricular fibrillation (VF) wavefront regularity (entropy). METHODS AND RESULTS: The right ventricles (RV) of seven farm pigs were isolated, superfused and perfused through the right coronary artery with oxygenated Tyrode's solution at 37 degrees C. The epicardial surface was stained with the voltage sensitive dye, di-4-ANEPPS, and activation wavefront numbers (AWN) during VF were determined from the optical maps using a CCD camera (96 x 96 pixels over a 3.5 x 3.5 cm area). The RV mass was progressively reduced by sequential cutting of 1 to 2 g of tissue (approximately 12 cuts in total) distal to the perfusion site. After each cut, VF was reinduced, optical maps obtained, and the 50% probability of successful DFT(50) determined using an up-down algorithm. After each cut, the approximate entropy (ApEn) was also computed using 5 seconds of VF data obtained with a bipolar electrode and a pseudo-electrocardiogram. Tissue mass reduction of up to one third of the RV mass (ie, from 48.4 +/- 4.25 g to 34 +/- 4.7 g) caused little or no change in the DFT, ApEn or AWN. However, further progressive reduction of the RV mass near the critical mass of VF resulted in a significant (P < 0.05) progressive decrease in all three measured parameters. DFT energy was reduced by 27% (1.47 +/- 0.34 J vs. 1.02 +/- 0.14 J). There was a significant (P < 0.01) correlation between the DFT and ApEn, which significantly further increased (P < 0.001) near the critical mass. In a separate series of 6 isolated RVs, the ApEn correlated well with the Kolmogorov-Sinai (K-S) entropy, the standard method of calculating entropy. CONCLUSION: Tissue mass reduction significantly reduces DFT when the mass reduction increases VF wavefront regularity.

Animals↗