Potential benefit of Bachmann's bundle pacing on left ventricular performance in patients with cardiac resynchronized therapy.

BACKGROUND: Right atrial (RA) appendage (RAA) pacing is reported to impair hemodynamic benefits of cardiac resynchronization therapy (CRT) through a considerable delay of left atrial (LA) contraction, which compromises appropriate balance of atrioventricular (AV) and left ventricular (LV) synchrony. Potential usefulness of Bachmann's bundle (BB) pacing to solve the problem remains to be confirmed. METHODS AND RESULTS: Atrial synchrony and LV performance was investigated by echocardiography in 25 patients undergoing pacemaker implantation with preserved AV conduction and LV function (Group I), and 15 patients receiving CRT (Group II). In Group I, RAA pacing (AAI mode, n=10) increased P-wave duration (PWD) and RA-to-LA contraction delay (IAMD) compared with sinus rhythm (132±14 and 35±12 ms vs. 108±16 and 13±13 ms, P<0.001). The delayed LA contraction was associated with early interruption of LV filling, leading to an impairment of LV performance (Tei index: 0.43±0.12 vs. 0.34±0.09, P<0.01). BB pacing (AAI, n=15) did not cause such undesirable effects. In Group II, RA (BB)-paced biventricular pacing (DDD) reduced PWD and IAMD compared with RA-sensed biventricular pacing (VDD) (102±14 and -3±13 ms vs. 117±10 and 21±18 ms, P<0.001). This restoration of atrial synchrony was associated with significant improvement of LV performance (Tei index: 0.56±0.18 vs. 0.62±0.16, P<0.05). CONCLUSIONS: BB pacing preserves atrial synchrony, and might be more favorable than RAA pacing for maximizing hemodynamic efficacy of CRT.

Effects of chronic amiodarone on the electrical restitution in the human ventricle with reference to its antiarrhythmic efficacy.

INTRODUCTION: Dynamic instability of ventricular refractoriness represented by electrical restitution operates synergistically with tissue heterogeneity to increase the propensity for functional reentry leading to ventricular tachycardia/fibrillation (VT/VF). Little is known about the effect of chronic amiodarone on the electrical restitution in the human ventricle. METHODS AND RESULTS: Restitution kinetics of monophasic action potential duration (MAPD(90)) in the right ventricular outflow tract (RVOT) and apex (RVA), and of inverse of conduction time from RVOT to RVA (CT(-1)), were estimated by an S1-S2 protocol in 22 patients treated with amiodarone (180 ± 33 mg/day for 7 ± 9 months) and in 30 without treatment. In the untreated patients, the restitution kinetics of CT(-1) was steeper in the group with structural heart disease (SHD) (UNT(SHD+), n = 18) than without SHD (UNT(SHD-), n = 12), whereas MAPD(90) restitution parameters were comparable. In the amiodarone-treated patients (all with SHD), the shortest diastolic interval to produce a ventricular response (DI(min)) was increased, the maximum slope of MAPD(90) was flattened, and the magnitude of CT(-1) restitution was reduced as compared with UNT(SHD+). Sustained VT/VF was induced in 7 of 18 UNT(SHD+) (38.9%) and in 4 of 22 amiodarone-treated patients (18.2%, P = 0.07). Concomitant presence of increased CT(-1) restitution and dispersion of MAPD(90) restitution was required for the VT/VF induction. The suppression of VT/VF in the amiodarone-treated patients was associated with a smaller magnitude of CT(-1) restitution in the presence of limited dispersion of MAPD(90) restitution. CONCLUSION: Chronic amiodarone flattens restitution kinetics of MAPD(90) and CT(-1) in the human ventricle, which could be antiarrhythmic in patients with limited tissue heterogeneity.

Paroxysmal atrial fibrillation maintained by nonpulmonary vein sources can be predicted by dominant frequency analysis of atriopulmonary electrograms.

INTRODUCTION: Increasing evidence suggests that high-frequency excitation in the pulmonary vein (PV) plays a dominant role in the maintenance of paroxysmal atrial fibrillation (AF). However, in a certain population of patients, AF remains inducible after PV isolation (PVI). We sought to clarify whether dominant frequency (DF) analysis of atriopulmonary electrograms can predict paroxysmal AF maintained by non-PV sources. METHODS AND RESULTS: Sixty-one patients with paroxysmal AF (aged 59 +/- 12 years) were studied. Before PVI, bipolar electrograms during AF were recorded simultaneously from three PV ostia, the coronary sinus (CS), and the septum and free wall of the right atrium (RA). DF was obtained by fast Fourier transform (FFT) analysis. AF was rendered noninducible after PVI in 39 of the 61 patients (noninducible group), but was still inducible in the remaining 22 (inducible group). Among the six recording sites, the highest DF was documented in the PV in all of the patients in the noninducible group; the maximum DF among the three PVs (PV-DF(max)) was higher than that among the CS and two RA sites (atrial DF(max); 7.2 +/- 1.0 Hz vs 5.8 +/- 0.7 Hz, P < 0.0001). In contrast, the highest DF was documented in the CS or RA in 45.5% of the patients in the inducible group; PV-DF(max) was comparable with atrial DF(max) (6.6 +/- 0.8 Hz vs 6.6 +/- 0.6 Hz). AF inducibility after PVI was predicted by a PV-to-atrial DF(max) gradient of <0.5 Hz, with a sensitivity of 90.9% and a specificity of 89.7%. CONCLUSION: Paroxysmal AF maintained by non-PV sources can be predicted by the PV-to-atrial DF gradient.

Opposing effects of bepridil on ventricular repolarization in humans. Inhomogeneous prolongation of the action potential duration vs flattening of its restitution kinetics.

BACKGROUND: Bepridil is highly effective in the treatment of atrial fibrillation, but its clinical usefulness is limited by a potential risk for the drug-induced Torsades de pointes (TdP) in association with its Class III action. METHODS AND RESULTS: Monophasic action potentials (MAPs) were recorded from the right ventricular outflow tract (RVOT) and apex (RVA) in 9 patients treated with bepridil (172 +/-26 mg/day) and 10 control patients. Bepridil significantly increased the steady-state MAP durations at 90% repolarization (MAPD(90S) in a rate-independent manner at pacing cycle lengths ranging from 330 to 750 ms. The bepridil-induced prolongation of the MAPD(90) was greater in RVOT (approximately 13%) than RVA (approximately 8%). Bepridil flattened the MAPD(90) restitution slope estimated by an S1-S2 protocol in both the RVOT (0.65 +/-0.22 vs 0.95 +/-0.38) and RVA (0.65 +/-0.14 vs 0.94 +/-0.29). The T(peak-end) interval in the ECG was increased by bepridil for S1 but not S2 at the shortest diastolic interval to produce a ventricular response. CONCLUSIONS: Bepridil produces an inhomogeneous prolongation of the MAPDs, but flattens their restitution kinetics in the human ventricle. The former effect would favor the functional reentry predisposing to TdP, whereas the latter one would counteract that by reducing the dynamic instability of the repolarization.

Right ventricular septal pacing preserves long-term left ventricular function via minimizing pacing-induced left ventricular dyssynchrony in patients with normal baseline QRS duration.

BACKGROUND: Right ventricular septal (RVS) pacing is an alternative to right ventricular apical (RVA) pacing, but there is limited information about its influence on long-term left ventricular (LV) synchrony and function. METHODS AND RESULTS: A total of 55 patients undergoing dual-chamber pacemaker implantation with normal QRS duration and preserved LV function at baseline were included in the study. The right ventricular lead was implanted on the septum where it would produce the shortest QRS duration possible in 40 patients and in the apex in 15. The time-to-peak systolic velocity (T(sys)) was measured in 12 segments of the LV wall by tissue Doppler imaging. After a long (approximately 4 years) follow-up period, the LV ejection fraction (LVEF) decreased significantly in patients with RVA pacing but not in those with RVS pacing. Paced QRS duration was significantly shorter during RVS than RVA pacing. T(sys) dispersion among the 12 LV segments was significantly smaller during RVS than RVA pacing. There was a positive correlation between the paced QRS duration and T(sys) dispersion (R=0.65, P<0.0001). The pacing-induced decrease in LVEF was positively correlated with the degree of T(sys) dispersion (R=0.42, P=0.008). CONCLUSIONS: RVS pacing guided by the paced QRS morphology preserves long-term LV function via minimizing LV dyssynchrony.

Efficacy of a novel trivalent inactivated vaccine against the shedding of Salmonella in a chicken challenge model.

The safety and efficacy of a novel trivalent inactivated Salmonella vaccine consisting of Salmonella Enteritidis (SE), Salmonella Typhimurium (ST), and Salmonella Infantis (SI) was evaluated with chickens. Chickens were injected subcutaneously with 0.5 ml per dose of the vaccine with an oil adjuvant. To assess the efficacy of the vaccine, vaccinated and unvaccinated chickens were challenged by oral inoculation of SE, ST, SI, and Salmonella Heidelberg (SH) virulent strains 4 wk after vaccination. The vaccinated chickens showed no clinical abnormalities, and the body weight gain after vaccination was comparable to that of unvaccinated chickens. The shedding of SE from the vaccinated chickens at 4, 7, 10, and 14 days postchallenge were significantly reduced in comparison with those of the unvaccinated chickens. The efficacy of the vaccine against ST and SI was comparable to that against SE. The shedding of SH at 4, 7, 10, and 14 days postchallenge was also significantly reduced in the vaccinated chickens compared with those in the unvaccinated suggesting that the vaccine could be effective against different serotype strains having O antigens homologous to those of the vaccine strains. These results suggest that the novel trivalent inactivated vaccine can be an effective tool for controlling the Salmonella infections of O4, O7, and O9 groups in chicken farms.

Raman imaging of carious lesions using a hollow optical fiber probe.

Raman spectroscopy using a hollow optical fiber probe with a glass ball lens at the distal end is proposed for detection of early caries lesions. Raman spectroscopy on carious lesions of extracted teeth showed that the probe enables measurement with a high signal-to-noise ratio when combined with a ball lens with a high refractive index. The proposed probe and lens combination detects changes in Raman spectra caused by morphological differences between sound and carious enamel. We also obtained a high-contrast image of an early carious lesion by scanning the tooth surface with the probe.

A case of short-coupled variant of torsade de pointes characterized by spatial heterogeneity of action potential duration and its restitution kinetics.

A 21-year-old male experienced frequent episodes of polymorphic ventricular tachycardia (PVT) initiated by a closely coupled premature ventricular complex (PVC) in the absence of QT prolongation and structural heart disease. Programmed stimulation at right ventricular apex (RVA), but not at the outflow tract (RVOT), provoked PVT degenerating into ventricular fibrillation (VF). Monophasic action potential duration (MAPD) was significantly shorter at RVA than RVOT. The maximum slope of MAPD restitution was much steeper at RVA than RVOT (1.91 versus 0.50). Such spatial heterogeneities of MAPD and its restitution may facilitate wavebreak and functional reentry predisposing to PVT and VF.

Effects of yokukansan on behavioral and psychological symptoms of vascular dementia: an open-label trial.

Previous clinical trials suggest that the traditional Japanese medicine yokukansan has beneficial effects on the behavioral and psychological symptoms of dementia (BPSD). The present study was conducted to elucidate the efficacy of yokukansan on BPSD in patients with vascular dementia. Thirteen Japanese patients (9 men and 4 women) who were diagnosed as having vascular dementia (VaD) according to the diagnostic criteria of NINDS-AIREN were subjected to the open-label clinical trial in which yokukansan (7.5g/day) has been given for 4 weeks. Their mean age was 71.2±6.5 years. The BPSD was evaluated using the Neuropsychiatric Inventory (NPI), cognitive function was evaluated by the Mini-Mental State Examination (MMSE), the activities of daily living was evaluated by Barthel index (BI) and Disability Assessment for Dementia (DAD), and the extrapyramidal signs were evaluated by United Parkinson's Disease Rating Scale (UPDRS). The mean NPI was 33.0±17.3 and 23.6±13.9 for the baseline and after treatment, respectively. It was significantly improved after treatment (p<0.05). In the NPI-subcategories, there was a significant improvement in agitation and disinhibition after the treatment. There was no significant change in MMSE, BI, DAD or UPDRS before and after the treatment. There was no adverse effect during the treatment period. The present results suggest that yokukansan is beneficial for the treatment of BPSD in VaD patients.

Irrelevance between the induction of anti-Campylobacter humoral response by a bacterin and the lack of protection against homologous challenge in Japanese Jidori chickens.

On-farm vaccination of chickens against Campylobacter jejuni is considered a potentially effective countermeasure to decrease campylobacteriosis via consumption of contaminated chicken meat, but is not yet available. In this study, 2 groups of Jidori chicks were immunized subcutaneously with a formalin-killed C. jejuni with 2 different adjuvants. Other chicks served as the unvaccinated control group. Both vaccines induced high levels of anti-Campylobacter IgG but did not decrease bacterial excretion in cecal droppings and bacterial load in the liver and spleen after oral challenge with 10(5) CFU of the homologous strain. Further study is needed to address the observed irrelevance and to develop a novel effective vaccine against C. jejuni.

Verapamil eliminates the hierarchical nature of activation frequencies from the pulmonary veins to the atria during paroxysmal atrial fibrillation.

BACKGROUND: There is evidence that verapamil promotes the persistence of paroxysmal atrial fibrillation (AF). Little is known about the underlying mechanisms. OBJECTIVE: The purpose of this study was to determine the effect of verapamil on dominant frequencies (DFs) in the pulmonary veins (PVs) and atria during paroxysmal AF with reference to its potential arrhythmogenicity. METHODS: Forty-three patients with paroxysmal AF were studied. Bipolar electrograms were recorded simultaneously during AF from the right atrial free wall (RAFW), coronary sinus (CS) and three PVs, or two PVs and the left atrial appendage (LAA). The DFs were obtained by fast Fourier transform analysis before and after infusion of verapamil (0.1 mg/kg, intravenously). RESULTS: At baseline, the maximum DF among the PVs (6.9 +/- 0.9 Hz) was significantly higher than the DF in the RAFW (6.2 +/- 0.7 Hz), CS (5.7 +/- 0.5 Hz), or LAA (5.9 +/- 0.7 Hz) (P<.01); there was a substantial PV-to-atrial DF gradient (RAFW 0.7 +/- 0.9, CS 1.1 +/- 0.7, LAA 0.7 +/- 0.9 Hz). Verapamil increased the atrial DF to 6.9 +/- 0.8, 6.6 +/- 0.7, and 7.2 +/- 1.0 Hz in the RAFW, CS, and LAA, respectively (P<.0001) but did not affect the maximum PV DF (7.1 +/- 0.7 Hz). The PV-to-atrial DF gradient was eliminated after verapamil (RAFW 0.2 +/- 0.8, CS 0.5 +/- 0.6, LAA -0.4 +/- 0.8 Hz; P<.01 vs. baseline). CONCLUSION: Verapamil increases the activation frequency in the atria but not in the PVs, eliminating the PV-to-atrial DF gradient during paroxysmal AF.

Action potential characteristics in the sinus venosa of patients with and without atrial flutter.

BACKGROUND: A functional line of conduction block is often observed in the sinus venosa (SV) during typical atrial flutter (AFL). Little information, however, is available as to the action potential characteristics in the SV with respect to the functional block. METHODS AND RESULTS: Monophasic action potentials (MAPs) from the SV and lateral wall of the right atrium were recorded in 7 patients with paroxysmal AFL and 11 control patients. For both the control and AFL patients, the MAP duration at 90% repolarization (MAPD90) in the SV was longer, and the MAPD90 restitution slope was less steep than in the lateral wall. The MAPD90 in the SV in the AFL patients was slightly longer than that in the controls at the shortest cycle length (CL) tested (300 ms). However, the MAPD90s at longer CLs (350-700 ms), as well as the MAPD90 restitution slopes in the SV were comparable between the 2 groups. CONCLUSIONS: The MAPs in the SV are characterized by a long duration and flat restitution kinetics in humans. MAP properties to facilitate the development of conduction block in the SV are not appreciable in patients with paroxysmal typical AFL.

Biventricular pacing has an advantage over left ventricular epicardial pacing alone to minimize proarrhythmic perturbation of repolarization.

INTRODUCTION: Cardiac resynchronization therapy (CRT) by simultaneous biventricular pacing is now widely accepted as a new therapeutic option for patients with severe congestive heart failure (CHF). Recent studies have shown comparable hemodynamic benefits of left ventricular (LV) pacing alone. The clinical usefulness of CRT, however, might be compromised by potential exaggeration of arrhythmogenic substrates through a modification of ventricular repolarization. METHODS AND RESULTS: We compared ECG parameters during sinus rhythm (SR), atrioventricular synchronous pacing at the right ventricular apex (RV(end)P), at LV epicardium (LV(epi)P), and at both sites (BiVP) in acute homodynamic studies of 14 CHF patients scheduled for CRT (QRS duration = 144 +/- 23 msec, LVEF = 27 +/- 10%). The maximum rate of increase in LV pressure (LVdp/dt(max)) was decreased significantly during RV(end)P, whereas it was increased similarly during LV(epi)P and BiVP compared with SR. QTc was increased during RV(end)P (by 10.2%) and LV(epi)P (by 26.1%). QTc dispersion (QTc(max)-QTc(min) in the six precordial leads) was also increased during LV(epi)P (by 66.5%). These parameters were unaffected during BiVP. JTc was unchanged, and the interval from the peak to the end of the T wave (Tc(peak-end)) was increased slightly (by 19.3%) during RV(end)P. Both JTc and Tc(peak-end) were increased dramatically during LV(epi)P (by 18.2% and 55.4%, respectively), but increased only modestly during BiVP (by 6.6% and 15.8%, respectively). CONCLUSIONS: LV(epi)P causes much greater increase in spatial dispersion of ventricular repolarization than BiVP in CHF patients. BiVP may have a substantial advantage over LV(epi)P to minimize the proarrhythmic perturbation of ventricular repolarization in association with CRT.

Acute effects of cigarette smoking on global cerebral blood flow in overnight abstinent tobacco smokers.

We examined whether cerebral vascular reactivity to 5% CO2/95% O2 would be a useful, independent measure of effects of tobacco smoking on global cerebral blood flow (gCBF). The acute effects during smoking one's favorite brand of cigarettes were determined after overnight tobacco abstinence. Positron emission tomography was used to quantitatively measure gCBF using H(2)15O in 10 right-handed young-adult male volunteer tobacco smokers. After a 12-hr abstinence, gCBF measurements were repeated six times at 15-min intervals: First baseline, 5% CO2/95% O2 inhalation, first cigarette smoking, second baseline, 5% CO2/95% O2 inhalation, and second cigarette smoking. Surprisingly, no significant change was seen in mean gCBF during smoking compared with baseline. However, the increase in arterial plasma concentration of nicotine correlated inversely with gCBF. Out of 19 smoking sessions, gCBF increased in 7, decreased in 7, and was unchanged in 5 sessions. The gCBF increased during smoking when baseline gCBF was relatively low, whereas gCBF decreased when baseline gCBF was relatively high. Both vascular reactivity and estimated gCBF plus arterial nicotine concentrations were useful measures to predict the changes in measured gCBF. These individual differences result in important bimodal effects of smoking on the brains of different young adult tobacco smokers.

Sotalol reverses remodeled action potential in patients with chronic atrial fibrillation but does not prevent arrhythmia recurrence.

INTRODUCTION: Recurrence of atrial fibrillation (AF) may be related to AF-induced electrical remodeling characterized by shortening of the atrial action potential duration (APD) and loss of its rate adaptation. We investigated the effects of pretreatment with oral d,l-sotalol on rate-dependent changes in atrial monophasic action potential (MAP) duration after cardioversion of chronic AF with reference to the efficacy in preventing the arrhythmia recurrence. METHODS AND RESULTS: MAPs were recorded from the right atrium at six pacing cycle lengths (CLs) from 300 to 750 ms in 19 chronic AF patients after electrical cardioversion; 9 had been pretreated with oral d,l-sotalol (196 +/- 42 mg/day) for 7 days and 10 were untreated. MAP duration at 90% repolarization (MAPD90) in 11 control patients increased progressively with increases in CLs from 209 +/- 19 ms at CL = 300 ms to 264 +/- 28 ms at CL = 750 ms. In AF patients without sotalol, the CL-MAPD relation was shifted downward and flattened at longer CLs; MAPD90 values were 206 +/- 11 ms and 227 +/- 16 ms at CLs of 300 and 750 ms, respectively. MAPD90 values at CLs > or =500 ms in AF were significantly shorter than controls. In AF patients with sotalol, the normal CL-MAPD relation was preserved; MAPD90 increased from 226 +/- 19 ms to 282 +/- 46 ms in the CL range. AF recurred within 2 weeks after cardioversion in 14 of 24 patients pretreated with d,l-sotalol (216 +/- 51 mg/day) despite of continuation of sotalol treatment. CONCLUSION: Sotalol reverses AF-induced decrease in MAPD adaptation to rate in the atria of chronic AF patients, but this effect does not lead to prevention of AF recurrence.