Interaction of phase singularities on the spiral wave tail: reconsideration of capturing the excitable gap.

The action mechanism of stimulation toward spiral waves (SWs) owing to the complex excitation patterns that occur just after point stimulation has not yet been experimentally clarified. This study sought to test our hypothesis that the effect of capturing excitable gap of SWs by stimulation can also be explained as the interaction of original phase singularity (PS) and PSs induced by the stimulation on the wave tail (WT) of the original SW. Phase variance analysis was used to quantitatively analyze the postshock PS trajectories. In a two-dimensional subepicardial layer of Langendorff-perfused rabbit hearts, optical mapping was used to record the excitation pattern during stimulation. After a SW was induced by S1-S2 shock, single biphasic point stimulation S3 was applied. In 70 of the S1-S2-S3 stimulation episodes applied on 6 hearts, the original PS was clearly observed just before the S3 point stimulation in 37 episodes. Pairwise PSs were newly induced by the S3 in 20 episodes. The original PS collided with the newly induced PSs in 16 episodes; otherwise, they did not interact with the original PS. SW shift occurred most efficiently when the S3 shock was applied at the relative refractory period, and PS shifted in the direction of the WT. In conclusion, quantitative tracking of PS clarified that stimulation in desirable conditions induces pairwise PSs on WT and that the collision of PSs causes SW shift along the WT. The results of this study indicate the importance of the interaction of shock-induced excitation with the WT for effective stimulation. NEW & NOTEWORTHY The quantitative analysis of spiral wave dynamics during stimulation clarified the action mechanism of capturing the excitable gap, i.e., the induction of pairwise phase singularities on the wave tail and spiral wave shift along the wave tail as a result of these interactions. The importance of the wave tail for effective stimulation was revealed.

Association of tricuspid regurgitation within normal range on the development of left ventricular diastolic dysfunction in patients with uncomplicated hypertension.

AIM: Tricuspid regurgitation (TR) with the maximum velocity >2.8m/s has been newly integrated into the diagnostic criteria for left ventricular (LV) diastolic dysfunction. Although the maximum velocity of TR within the normal range (TR < 2.8m/s) is frequently detected in hypertensive patients and is associated with enlarged left atrial (LA) volumes, the influence of TR < 2.8m/s on LV diastolic dysfunction remains unknown in uncomplicated hypertension. METHODS: Echocardiography was performed to assess the mitral annular velocity (e'), E/e', LV mass, and LA phasic volumes and emptying fractions (total, passive, and active) in 100 patients with uncomplicated hypertension with TR within the normal range and in 77 of those without measurable TR. Patients were defined as having normal, inclusive, or dysfunction of LV diastolic function, according to how many parameters met the cut-off levels (maximum LA volume index >34ml/mm2, e'<7 cm/s, and E/e'>15). Pulmonary artery systolic pressure (PASP) was estimated by the formula; PASP =4 (maximum velocity of TR)2 + 5 mmHg. RESULTS: The maximum velocity of TR or PASP saw a positive correlation, and LA total or passive emptying fractions saw an inverse correlation with LV diastolic dysfunction in hypertensive patients with TR < 2.8. In contrast, pulse pressure and LV mass saw positive correlation in hypertensive patients without TR. A stepwise ordinal logistic regression analysis indicated that PASP and LA passive emptying fractions were associated with LV diastolic dysfunction in hypertensive patient with TR < 2.8m/s. CONCLUSION: The presence of TR may be related to the development of LV diastolic dysfunction in hypertensive patients with TR <2.8m/s.

Ranolazine Facilitates Termination of Ventricular Tachyarrhythmia Associated With Acute Myocardial Ischemia Through Suppression of Late INa-Mediated Focal Activity.

BACKGROUND: Ventricular tachycardia/fibrillation (VT/VF) associated with acute myocardial ischemia is the most common cause of sudden cardiac death, but its underlying mechanisms are incompletely understood. It is hypothesized that late Na+current (INa) contributes to arrhythmogenic activity in ischemic myocardium.Methods and Results:Langendorff-perfused rabbit hearts with regional ischemia in ventricles were optically mapped. Perfusion with ranolazine (10 µmol/L), a selective inhibitor of lateINa, significantly reduced excitation frequency and facilitated termination of VT/VF induced after occlusion of the left main coronary trunk. The activation pattern during ischemic VT/VF was characterized by breakthrough-type excitations (BEs) from multiple origins, predominantly in the ischemic border zone (BZ) and occasional short-lived rotors. Ranolazine perfusion significantly reduced the incidence of BEs in the BZ. Rotors tended to decrease with progression of ischemia and disappeared after ranolazine perfusion. During constant pacing, ranolazine attenuated ischemia-induced shortening of action potentials in the BZ without affecting conduction velocity, probably due toIKrinhibition. In intact hearts without coronary occlusion, ranolazine (10 µmol/L) terminated aconitine-induced VT by inhibiting focal arrhythmogenic activity in the injection site. CONCLUSIONS: LateINa-mediated focal arrhythmogenic activity plays important roles in the maintenance of ischemic VT/VF in isolated rabbit hearts. Suppression of lateINaby ranolazine may be a promising therapeutic strategy to reduce arrhythmic death during the acute phase of myocardial infarction.

Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles.

It has been reported that blockade of the inward rectifier K(+) current (IK1) facilitates termination of ventricular fibrillation. We hypothesized that partial IK1 blockade destabilizes spiral wave (SW) re-entry, leading to its termination. Optical action potential (AP) signals were recorded from left ventricles of Langendorff-perfused rabbit hearts with endocardial cryoablation. The dynamics of SW re-entry were analyzed during ventricular tachycardia (VT), induced by cross-field stimulation. Intercellular electrical coupling in the myocardial tissue was evaluated by the space constant. In separate experiments, AP recordings were made using the microelectrode technique from right ventricular papillary muscles of rabbit hearts. Ba(2+) (10-50 µM) caused a dose-dependent prolongation of VT cycle length and facilitated termination of VT in perfused hearts. Baseline VT was maintained by a stable rotor, where an SW rotated around an I-shaped functional block line (FBL). Ba(2+) at 10 µM prolonged I-shaped FBL and phase-singularity trajectory, whereas Ba(2+) at 50 µM transformed the SW rotation dynamics from a stable linear pattern to unstable circular/cycloidal meandering. The SW destabilization was not accompanied by SW breakup. Under constant pacing, Ba(2+) caused a dose-dependent prolongation of APs, and Ba(2+) at 50 µM decreased conduction velocity. In papillary muscles, Ba(2+) at 50 µM depolarized the resting membrane potential. The space constant was increased by 50 µM Ba(2+) Partial IK1 blockade destabilizes SW rotation dynamics through a combination of prolongation of the wave length, reduction of excitability, and enhancement of electrotonic interactions, which facilitates termination of ventricular tachyarrhythmias.

Inhibition of intercellular coupling stabilizes spiral-wave reentry, whereas enhancement of the coupling destabilizes the reentry in favor of early termination.

Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 µM) and rotigaptide (RG, 0.1 µM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36%, whereas RG increased it by 22-24% (n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV(0) - D·κ (D, diffusion coefficient; LCV(0), LCV at κ = 0). CBX decreased LCV(0) and D by 27 ± 3 and 57 ± 3%, respectively (n = 5; P < 0.01). RG increased LCV(0) and D by 18 ± 3 and 54 ± 5%, respectively (n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ~60 cm(-1). SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4% after CBX (n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6% after RG (n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.

Pharmacological blockade of IKs destabilizes spiral-wave reentry under ß-adrenergic stimulation in favor of its early termination.

We tested a hypothesis that an enhancement of I(Ks) may play a pivotal role in ventricular proarrhythmia under high sympathetic activity. A 2-dimensional ventricular muscle layer was prepared in rabbit hearts, and action potential signals were analyzed by optical mapping. During constant stimulation, isoproterenol (ISP, 0.1 µM) significantly shortened action potential duration (APD); chromanol 293B (30 µM), a selective I(Ks)-blocker, reversed the APD shortening. VTs induced in the presence of ISP lasted longer than in the control, and this was reversed by 293B. E-4031 (0.1 µM), a selective I(Kr)-blocker, did not cause such reversal. Spiral-wave (SW) reentry with ISP was characterized by more stable rotation around a shorter functional block line (FBL) than in the control. After application of 293B, SW reentry was destabilized, and rotation around a longer FBL with prominent drift reappeared. The APD abbreviation by ISP close to the rotation center was more pronounced than in the periphery, leading to an opposite APD gradient (center < periphery) compared with controls. This effect was also reversed by 293B. In conclusion, ß-adrenergic stimulation stabilizes SW reentry most likely though an enhancement of I(Ks). Blockade of I(Ks) may be a promising therapeutic modality in prevention of ventricular tachyarrhythmias under high sympathetic activity.

Role of sphingosine-1-phosphate inß-adrenoceptor desensitization via Ca(2+) sensitization in airway smooth muscle.

BACKGROUND: The correlation between inflammatory cells and airway smooth muscle plays fundamental roles in the pathophysiology of asthma. This study was designed to determine whether pre-exposure of airway smooth muscle to sphingosine-1-phosphate (S1P), which is released from mast cells by allergic reactions, causes a deterioration of ß-adrenoceptor function. METHODS: Isometric tension and the ratio of fluorescence intensities at 340 and 380 nm (F(340)/F(380)), an indicator of intracellular Ca2+ levels, were simultaneously measured using fura-2 loaded guinea-pig tracheal tissues. Intracellular cAMP levels were also measured. RESULTS: Pre-exposure to S1P caused a reduction in the inhibitory effects of 0.3µM isoprenaline, a ß-adrenoceptor agonist, and 10µM forskolin, a direct activator of adenylyl cyclase, against 1µM methacholine-induced contraction in concentration- and time- dependent manners. In contrast, the values of F(340)/F(380) were not augmented under this experimental condition. After incubation with S1P in the presence of 0.001-1µM Y-27632, a Rho-kinase inhibitor, the reduced responsiveness to forskolin induced by S1P was reversed in a concentration-dependent manner. Moreover, pre-treatment with pertussis toxin (PTX), an inhibitor of G(i), suppressed the loss of forskolin-induced relaxation induced by S1P. Pre-exposure to S1P markedly inhibited the augmentation of cAMP accumulation induced by forskolin. However, addition of Y-27632 and pre-exposure to PTX returned forsokin-induced cAMP accumulation to the control level. CONCLUSIONS: Pre-exposure to S1P causes heterologus desensitization of ß-adrenoceptors by increasing the sensitivity of airway smooth muscle to intracellular Ca2+. Ca2+ sensitization regulated by G(i) and Rho-kinase is involved in this phenomenon.

Rotors anchored by refractory islands drive torsades de pointes in an experimental model of electrical storm.

BACKGROUND: Electrical storm (ES) is a life-threatening emergency in patients at high risk of ventricular tachycardia/ventricular fibrillation (VF), but the pathophysiology and molecular basis are poorly understood. OBJECTIVE: The purpose of this study was to explore the electrophysiological substrate for experimental ES. METHODS: A model was created by inducing chronic complete atrioventricular block in defibrillator-implanted rabbits, which recapitulates QT prolongation, torsades des pointes (TdP), and VF episodes. RESULTS: Optical mapping revealed island-like regions with action potential duration (APD) prolongation in the left ventricle, leading to increased spatial APD dispersion, in rabbits with ES (defined as ≥3 VF episodes/24 h). The maximum APD and its dispersion correlated with the total number of VF episodes in vivo. TdP was initiated by an ectopic beat that failed to enter the island and formed a reentrant wave and perpetuated by rotors whose centers swirled in the periphery of the island. Epinephrine exacerbated the island by prolonging APD and enhancing APD dispersion, which was less evident after late Na+ current blockade with 10 µM ranolazine. Nonsustained ventricular tachycardia in a non-ES rabbit heart with homogeneous APD prolongation resulted from multiple foci with an electrocardiographic morphology different from TdP driven by drifting rotors in ES rabbit hearts. The neuronal Na+-channel subunit NaV1.8 was upregulated in ES rabbit left ventricular tissues and expressed within the myocardium corresponding to the island location in optically mapped ES rabbit hearts. The NaV1.8 blocker A-803467 (10 mg/kg, intravenously) attenuated QT prolongation and suppressed epinephrine-evoked TdP. CONCLUSION: A tissue island with enhanced refractoriness contributes to the generation of drifting rotors that underlies ES in this model. NaV1.8-mediated late Na+ current merits further investigation as a contributor to the substrate for ES.

Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart.

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF (n=18) and control (n=17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs)>1,000 ms but significantly shorter at BCLs<400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17-81%), and conduction velocity was significantly decreased in CHF (by 6-20%). In both groups, high-frequency stimulation (BCLs<150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs<150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Metabolic syndrome and all-cause mortality, cardiac events, and cardiovascular events: a follow-up study in 25,471 young- and middle-aged Japanese men.

AIM: The association between subjects with metabolic syndrome (MS) who were considered not to require medication by their attending physicians and all-cause mortality, ischemic heart disease (IHD) and cardiovascular disease (CVD) remains unknown and should be clarified. METHODS AND RESULTS: This is an observational longitudinal cohort study with a median follow-up of 7.5 years performed for 25,471 Japanese men aged 20-61 years who were not on medication. We used a modified definition of MS from the Japanese Society of Internal Medicine and the NCEP ATPIII, both of which employed body mass index instead of waist circumference. MS was associated with increased rates of all-cause death (adjusted hazard ratio (HR): 4.88 [95% confidence interval, 2.96-7.66]), IHD (3.17 [1.06-7.65]), and CVD (2.63 [1.32-4.72]). In contrast, overweight subjects with no component or one component had similar rates to subjects of normal weight. Any combination of the three MS components was associated with significantly greater rates of all-cause mortality (HR: 3.18-11.2) and IHD (HR: 3.17-8.24), whereas blood pressure elevation plus dyslipidaemia was associated with a significantly higher rate of CVD (HR: 3.27). In any endpoint, MS defined by Japanese criteria had higher HRs than defined by NCEP ATP III criteria. CONCLUSION: Young and middle-aged Japanese men with MS who had been viewed as not needing medication already showed increased rates of all-cause mortality, IHD and CVD. Additionally, the event rate depended on the specific combination of metabolic syndrome components.

Smoking and smoking cessation in relation to all-cause mortality and cardiovascular events in 25,464 healthy male Japanese workers.

BACKGROUND: Smoking is still a major health problem among males in Japan. The effects of smoking and quitting on mortality and cardiovascular disease (CVD) need updating. METHODS AND RESULTS: This was a prospective cohort study with a median follow-up of 7.5 years of a total of 25,464 healthy male Japanese workers aged 20-61 years who were not on any medication. The adjusted hazard ratios (HR; 95% confidence interval) for all-cause death were 1.51 (0.73, 2.94), 1.68 (1.07, 2.70), 1.30 (0.70, 2.34), and those for total CVD events 1.91 (0.72, 4.67), 2.94 (1.65, 5.63), and 3.25 (1.69, 6.54) for light smokers (1-10 cigarettes/day), moderate smokers (11-20/day), and heavy smokers (≥ 21/day) compared to never-smokers, respectively. Total CVD events increased dose-dependently as the number of cigarettes/day increased. Acute myocardial infarction was increased at any level of smoking. Stroke was increased at a moderate level of smoking. Quitting for ≥ 4 years, compared with continuing smokers, reduced the HR for all-cause death to 0.64 (0.38, 1.01), and total CVD events to 0.34 (0.17, 0.62). CONCLUSIONS: In healthy young- and middle-aged Japanese males, a significant increase in HR for total CVD events was confirmed for a smoking level of 11-20 cigarettes/day. Quitting reduced the HR for total CVD events, with quitting for ≥ 4 years being statistically significant. A similar trend was observed for all-cause mortality.

Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling.

Bepridil is effective for conversion of atrial fibrillation to sinus rhythm and in the treatment of drug-refractory ventricular tachyarrhythmias. We investigated the effects of bepridil on electrophysiological properties and spiral-wave (SW) reentry in a 2-dimensional ventricular muscle layer of isolated rabbit hearts by optical mapping. Ventricular tachycardia (VT) induced in the presence of bepridil (1 µM) terminated earlier than in the control. Bepridil increased action potential duration (APD) by 5% - 8% under constant pacing and significantly increased the space constant. There was a linear relationship between the wavefront curvature (κ) and local conduction velocity: LCV = LCV0 - D·κ (D, diffusion coefficient; LCV0, LCV at κ = 0). Bepridil significantly increased D and LCV0. The regression lines with and without bepridil crossed at κ = 20 - 40 cm⁻¹, resulting in a paradoxical decrease of LCV at κ > 40 cm⁻¹. Dye transfer assay in cultured rat cardiomyocytes confirmed that bepridil increased intercellular coupling. SW reentry in the presence of bepridil was characterized by decremental conduction near the rotation center, prominent drift, and self-termination by collision with boundaries. These results indicate that bepridil causes an increase of intercellular coupling and a moderate APD prolongation, and this combination compromises wavefront propagation near the rotation center of SW reentry, leading to its drift and early termination.

Spatial phase discontinuity at the center of moving cardiac spiral waves.

BACKGROUND: Precise analysis of cardiac spiral wave (SW) dynamics is essential for effective arrhythmia treatment. Although the phase singularity (PS) point in the spatial phase map has been used to determine the cardiac SW center for decades, quantitative detection algorithms that assume PS as a point fail to trace complex and rapid PS dynamics. Through a detailed analysis of numerical simulations, we examined our hypothesis that a boundary of spatial phase discontinuity induced by a focal conduction block exists around the moving SW center in the phase map. METHOD: In a numerical simulation model of a 2D cardiac sheet, three different types of SWs (short wavelength; long wavelength; and low excitability) were induced by regulating ion channels. Discontinuities of all boundaries among adjacent cells at each instance were evaluated by calculating the phase bipolarity (PB). The total amount of phase transition (PTA) in each cell during the study period was evaluated. RESULTS: Pivoting, drifting, and shifting SWs were observed in the short-wavelength, low-excitability, and long-wavelength models, respectively. For both the drifting and shifting cases, long high-PB edges were observed on the SW trajectories. In all cases, the conduction block (CB) was observed at the same boundaries. These were also identical to the boundaries in the PTA maps. CONCLUSIONS: The analysis of the simulations revealed that the conduction block at the center of a moving SW induces discontinuous boundaries in spatial phase maps that represent a more appropriate model of the SW center than the PS point.

Acute amiodarone promotes drift and early termination of spiral wave re-entry.

Intravenous application of amiodarone is commonly used in the treatment of life-threatening arrhythmias, but the underlying mechanism is not fully understood. The purpose of the present study is to investigate the acute effects of amiodarone on spiral wave (SW) re-entry, the primary organization machinery of ventricular tachycardia/fibrillation (VT/VF), in comparison with lidocaine. A two-dimensional ventricular myocardial layer was obtained from 24 Langendorff-perfused rabbit hearts, and epicardial excitations were analyzed by high-resolution optical mapping. During basic stimulation, amiodarone (5 microM) caused prolongation of action potential duration (APD) by 5.6%-9.1%, whereas lidocaine (15 microM) caused APD shortening by 5.0%-6.4%. Amiodarone and lidocaine reduced conduction velocity similarly. Ventricular tachycardias induced by DC stimulation in the presence of amiodarone were of shorter duration (sustained-VTs >30 s/total VTs: 2/58, amiodarone vs 13/52, control), whereas those with lidocaine were of longer duration (22/73, lidocaine vs 14/58, control). Amiodarone caused prolongation of VT cycle length and destabilization of SW re-entry, which is characterized by marked prolongation of functional block lines, frequent wavefront-tail interactions near the rotation center, and considerable drift, leading to its early annihilation via collision with anatomical boundaries. Spiral wave re-entry in the presence of lidocaine was more stabilized than in control. In the anisotropic ventricular myocardium, amiodarone destabilizes SW re-entry facilitating its early termination. Lidocaine, in contrast, stabilizes SW re-entry resulting in its persistence.

Inter-arm difference of systolic blood pressure measured by automated double-cuff device is associated with arterial stiffness in patients with hypertension.

PURPOSE: Inter-arm differences of SBP ≧5 mmHg have been associated with all-cause and cardiovascular mortalities in hypertensive subjects. Inter-arm differences of SBP appears to be mediated by arterial stiffness. We hypothesized inter-arm differences of SBP ≧5 mmHg may be related to higher pulse pressure/stroke volume index, a surrogate marker of arterial stiffness. MATERIALS AND METHODS: To obtain inter-arm differences of SBP (the absolute difference of right and left arm) and ankle-brachial index, bilateral blood pressures were measured simultaneously at the four limbs using an automated oscillometric device in patients with treated hypertension (n = 234) and in normotensive subjects (n = 40). Pulse pressure was calculated as SBP-DBP. Stroke volume was obtained by time-velocity integral method using echocardiography. Left ventricular mass and relative wall thickness were calculated by the conventional methods. RESULTS: All hypertensive patients were medically treated and had average blood pressure levels of 135/85 mmHg. Inter-arm differences of SBP ≧5 mmHg was detected in 26.5% of hypertensive patients. Hypertensive patients with inter-arm differences of SBP ≧5 mmHg had higher pulse pressure/stroke volume index, lower ankle-brachial index, higher BMI, and higher relative wall thickness, higher prevalence of female than those with inter-arm differences of SBP <5 mmHg. Multiple linear regression analysis confirmed inter-arm differences of SBP ≧5 mmHg was associated with higher pulse pressure/stroke volume index, higher relative wall thickness, and lower ankle-brachial index. CONCLUSION: Inter-arm difference of SBP measured by automated double-cuff device was related to large artery stiffness in patients with hypertension.

Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit.

The aim of the study was to identify ion channel transcripts expressed in the sinoatrial node (SAN), the pacemaker of the heart. Functionally, the SAN can be divided into central and peripheral regions (center is adapted for pacemaking only, whereas periphery is adapted to protect center and drive atrial muscle as well as pacemaking) and the aim was to study expression in both regions. In rabbit tissue, the abundance of 30 transcripts (including transcripts for connexin, Na(+), Ca(2+), hyperpolarization-activated cation and K(+) channels, and related Ca(2+) handling proteins) was measured using quantitative PCR and the distribution of selected transcripts was visualized using in situ hybridization. Quantification of individual transcripts (quantitative PCR) showed that there are significant differences in the abundance of 63% of the transcripts studied between the SAN and atrial muscle, and cluster analysis showed that the transcript profile of the SAN is significantly different from that of atrial muscle. There are apparent isoform switches on moving from atrial muscle to the SAN center: RYR2 to RYR3, Na(v)1.5 to Na(v)1.1, Ca(v)1.2 to Ca(v)1.3 and K(v)1.4 to K(v)4.2. The transcript profile of the SAN periphery is intermediate between that of the SAN center and atrial muscle. For example, Na(v)1.5 messenger RNA is expressed in the SAN periphery (as it is in atrial muscle), but not in the SAN center, and this is probably related to the need of the SAN periphery to drive the surrounding atrial muscle.

Scale-invariant competitive growth of side branches in a dendritic crystal.

We experimentally investigated statistical properties of side branches of quasi-two-dimensional NH(4)Cl dendritic crystals. The height distributions of the side branches and their number density exhibit scale-invariant power laws. The results are in good agreement with the results of numerical simulations and theories of diffusion-limited needle growth. Our scaling exponents are independent of supersaturation and the statistical properties are universal in dendrites.

Modulation of spiral wave reentry by K(+) channel blockade.

It is well established that spiral wave reentry is the primary mechanism of ventricular tachyarrhythmias (ventricular fibrillation/tachycardia, VF/VT), but information is still limited concerning pharmacological modification of spiral waves by ion channel blockers. In this brief review, the antiarrhythmic and proarrhythmic actions of K(+)-channel blockade (I(Kr) and I (K1)) are discussed in terms of spiral wave dynamics, primarily based on recent experimental findings in ventricular preparations perfused in vitro with the aid of high-resolution optical mapping, as well as their related theoretical studies using computer simulation.

Simple model for competitive dynamics among dendritic sidebranches.

We study competitive dynamics among sidebranches in the crystal growth of dendrites. Numerical simulations are performed with a coupled map lattice to investigate the competitive dynamics among dendritic branches. A simple form of interaction via a diffusion field is estimated from the numerical simulations of the coupled map lattice. We propose a needle model on the basis of the competitive interaction, and perform numerical simulations of it. The size distribution of the dendritic branches exhibits a power law in the needle model.