Effect of low-density lipoprotein cholesterol on the geometry of coronary bifurcation lesions and clinical outcomes of coronary interventions in the J-REVERSE registry.

We investigated the effect of low-density lipoprotein cholesterol (LDL-C) on the geometry of coronary bifurcation lesions. A total of 300 non-left main bifurcation lesions in 298 patients from J-REVERSE registry were classified according to statin treatment status at admission (NT, non-treated; ST, statin-treated) and were further subdivided based on LDL-C levels with a cutoff of 100 mg/dL (NT-high, n = 76 lesions; NT-low, n = 46; ST-high, n = 99 and ST-low, n = 79). In addition, a group with strict control of LDL-C (< 70 mg/dL) was defined (ST-SC; n = 19). The NT-high group had higher angled bifurcations compared to that in the NT-low group (59.1° ± 21.5° vs. 50.3° ± 18.6°, p = 0.02). In the multivariate analysis, NT-high group was an independent factor contributing on generation of higher angled (> 80°) lesion (odds ratio 3.77, 95% CI 1.05-13.5, p = 0.04). The NT-low group had more men (95.6 vs. 81.6%, p = 0.03), and greater plaque volume in the distal main vessel (7.1 ± 3.2 mm3/mm vs. 5.7 ± 2.7 mm3/mm, p = 0.02), compared to those in the NT-high group. LDL-C was more likely to remain high after statin treatment in younger patients (65.3 ± 3.6 years vs. 68.6 ± 8.4 years, p = 0.02) and current smokers (36.7 vs. 16.9%, p = 0.004). The ST-SC group had limited luminal volume expansion compared to that in the ST-high group (proximal: 6.7 ± 1.4 mm3/mm vs. 7.7 ± 2.3 mm3/mm, p = 0.04; distal: 5.3 ± 1.5 mm3/mm vs. 6.5 ± 1.9 mm3/mm, p = 0.04), regardless of similar plaque volumes. Elevated LDL-C is likely to promote the generation of higher angled bifurcation lesions and multiple risk factors lead to a more progressed bifurcation lesion even in patients with lower LDL-C levels.

Impact of final kissing balloon inflation on vessel healing following drug-eluting stent implantation: Insight from the optical coherence tomography sub-study of the J-REVERSE trial.

BACKGROUND: We sought to clarify the impact of final kissing inflation (FKI) after single stenting of bifurcation lesions on vessel healing. METHODS: From the J-REVERSE registry enrolling 303 bifurcation lesions treated with provisional single stenting using sirolimus- (SES) or everolimus-eluting stent (EES), 65 lesions treated with (n=30) and without (n=35) FKI underwent 9-month follow-up optical coherence tomography. Average stent eccentricity index (SEI: minimum/maximum stent diameter) and neointimal unevenness score (NUS: maximum/average neointimal thickness of the same cross-section) for the proximal, bifurcation, and distal segments were compared between FKI and non-FKI groups. RESULTS: At the proximal segment, the FKI group demonstrated significantly larger average stent area with greater asymmetric stent expansion, and average lumen area remained significantly larger at 9-month follow-up despite a tendency toward greater neointimal proliferation. Jailed strut and thrombus incidence were also significantly lower at the side branch orifice, and NUS was significantly smaller at the bifurcation and proximal segments in the FKI group. CONCLUSIONS: Nine months after SES and EES treatment of bifurcation lesions, FKI reduced proximal-segment luminal narrowing. Considering its homogeneous neointimal distribution and fewer jailed struts, FKI may be beneficial for treating bifurcation lesions.

Efficacy of kissing balloon inflation after provisional stenting in bifurcation lesions guided by intravascular ultrasound: short and midterm results of the J-REVERSE registry.

AIMS: Our aim was to investigate the efficacy of the kissing balloon technique (KBT) in the provisional stenting of bifurcation lesions guided by intravascular ultrasound. METHODS AND RESULTS: In the J-REVERSE registry, 300 non-left main bifurcation lesions in 299 patients were divided into two groups, KBT (n=163) and non-KBT (n=137). Patient and lesion characteristics were similar except for a higher prevalence of diabetic patients in the non-KBT group. The major adverse cardiac events (MACE) incidence at nine-month follow-up, including target lesion revascularisation, myocardial infarction, stent thrombosis, and death, was 6.3% in the KBT group versus 9.1% in the non-KBT group (p=0.47). Regardless of more SB dissection (10.5% vs. 1.5%, p=0.001), the KBT group obtained a greater luminal volume in the proximal main vessel (MV) (7.8±2.3 vs. 7.0±2.0 mm3/mm, p=0.006), maintained larger minimal lumen diameter at follow-up (2.73±0.43 vs. 2.63±0.39 mm, p=0.04), and demonstrated less binary side branch (SB) restenosis (9.7% vs. 21.0%, p=0.0004), which was beneficial for both true and non-true bifurcation lesions. Multivariate analysis showed the efficacy of KBT on SB restenosis (OR 0.28, 95% CI: 0.12-0.62, p=0.002). CONCLUSIONS: Although the KBT increased SB dissection, it provided greater luminal gain in the proximal MV and SB with a similar MACE rate to non-KBT treatment up to nine-month follow-up.

Differences in Vessel Healing Between Sirolimus- and Everolimus-Eluting Stent Implantation for Bifurcation Lesions: The J-REVERSE Optical Coherence Tomography Substudy.

BACKGROUND: We aimed to clarify the differences in vessel healing after stenting of bifurcation lesions using sirolimus-eluting stents (SESs) or everolimus-eluting stents (EESs). METHODS: Japanese Registry Study in Comparison Between Everolimus-Eluting Stent and Sirolimus-Eluting Stent for the Bifurcation Lesion (J-REVERSE) is a prospective multicentre registry of 303 bifurcation lesions that were treated with provisional SES or EES with or without final kissing inflation. The first 115 lesions at selected study sites were predefined for inclusion in the optical coherence tomography (OCT) substudy, and 9-month follow-up OCT was conducted in 64 lesions (SES, n = 18; EES, n = 46). In addition to standard OCT parameters, stent eccentricity index (SEI; minimum divided by the maximum stent diameter), neointimal unevenness score (NUS; maximum neointimal thickness in the cross-section [CS] divided by the average neointimal thickness [NIT] of the same CS; uniformity of the neointima suppression) were averaged for each segment (proximal, bifurcation, and distal segments). RESULTS: Overall, the average stent and luminal area, NIT, and frequency of uncovered struts were similar. The frequency of malapposed struts and SEI were significantly lower in the EES group than in the SES group. The EES group had a significantly smaller NUS in the proximal and distal segments. CONCLUSIONS: EESs offer homogeneous vessel healing with less malapposition in the treatment of bifurcation lesions.

Comparison of Everolimus- versus Sirolimus-eluting stents in the provisional Bifurcation stenting guided by intravascular ultrasound: mid-term results of the J-REVERSE registry.

This study aimed at comparing the mid-term clinical outcome of everolimus-eluting (EES) with sirolimus-eluting (SES) stents in the provisional bifurcation stenting guided by intravascular ultrasound (IVUS). We compared the clinical outcome up to 9-month follow-up results of the prospective J-REVERSE registry of 300 non-left main bifurcation lesions in 298 patients treated with EES (n = 240) and SES (n = 60). The SB dilation with the kissing balloon technique (KBT) was performed in 54 %. The patient and lesion characteristics of the groups were similar. The incidences of SB dissections, occlusions, stenting, and slow flow were similar. A greater luminal volume gain was achieved in the proximal MV after KBT compared in non-KBT treated lesions in the EES group (7.9 ± 2.4 versus 7.0 ± 2.0 mm(3)/mm, p = 0.002), though not in the SES group. The SB diameter stenosis in the non-KBT treatment at 9 months was greater than the KBT in both groups. The incidence of target lesion revascularisation (TLR) was 5.0 % in the EES versus 8.3 % in the SES group (p = 0.35), and the incidence of major adverse cardiac events, including TLR, myocardial infarction, stent thrombosis, and death was 5.4 % in the EES versus 11.7 % in the SES group (p = 0.15). IVUS-guided provisional stenting with EES achieved a greater luminal gain after than without KBT, and similar clinical outcomes as with SES up to 9-month follow-up.

Frequency-dependent requirement for calcium store-operated mechanisms in induction of homosynaptic long-term depression at hippocampus CA1 synapses.

For induction of long-term depression (LTD), mechanisms dependent on N-methyl-D-aspartate receptors (NMDARs) and on intracellular calcium stores have been separately known. How these two mechanisms coexist at the same synapses is not clear. Here, induction of LTD at hippocampal Schaffer collateral-to-CA1 pyramidal cell synapses was shown to depend on NMDARs throughout the theoretically predicted activation range for LTD induction. With stimulation at 1 Hz, the largest LTD was induced in a store-independent manner. With stimulation at 0.5 and 2.0 Hz the induced LTD was much smaller, and dependence on calcium stores appeared. Under caffeine application, an enlarged LTD was induced with 0.5 Hz stimulation. Postsynaptic blockade of ryanodine receptors prevented this caffeine-induced enhancement of LTD. It is therefore suggested that calcium release from calcium stores facilitated by caffeine contributed to the LTD enhancement, and that the caffeine effect was exerted on the postsynaptic side. Induction of this enhanced LTD was resistant to NMDAR blockade. We thus propose that the store-dependent mechanism for LTD induction is dormant at the centre of the theoretically predicted activation range for LTD induction, but operates at the fringes of this activation range, with its contribution more emphasized when ample calcium release occurs.

Small-conductance Ca2+-dependent K+ channels are the target of spike-induced Ca2+ release in a feedback regulation of pyramidal cell excitability.

Cooperative regulation of inosiol-1,4,5-trisphosphate receptors (IP(3)Rs) by Ca(2+) and IP(3) has been increasingly recognized, although its functional significance is not clear. The present experiments first confirmed that depolarization-induced Ca(2+) influx triggers an outward current in visual cortex pyramidal cells in normal medium, which was mediated by apamin-sensitive, small-conductance Ca(2+)-dependent K(+) channels (SK channels). With IP(3)-mobilizing neurotransmitters bath-applied, a delayed outward current was evoked in addition to the initial outward current and was mediated again by SK channels. Calcium turnover underlying this biphasic SK channel activation was investigated. By voltage-clamp recording, Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs) was shown to be responsible for activating the initial SK current, whereas the IP(3)R blocker heparin abolished the delayed component. High-speed Ca(2+) imaging revealed that a biphasic Ca(2+) elevation indeed underlays this dual activation of SK channels. The first Ca(2+) elevation originated from VDCCs, whereas the delayed phase was attributed to calcium release from IP(3)Rs. Such enhanced SK currents, activated dually by incoming and released calcium, were shown to intensify spike-frequency adaptation. We propose that spike-induced calcium release from IP(3)Rs leads to SK channel activation, thereby fine tuning membrane excitability in central neurons.

[Voiding function and sexual activity in patients following Hautmann neobladder construction].

PURPOSE: We retrospectively evaluated the outcome of Hautmann neobladder reconstruction in terms of complications, lower urinary tract symptoms, and sexual function in a large group of patients who underwent radical cystectomy. METHODS: We reviewed the medical records of 118 patients (105 men and 13 women) who underwent radical cystectomy and Hautmann neobladder construction at the Gifu University Hospital or one of its affiliate hospitals between Jan 1993 and Dec 1999. The 118 patients were asked to complete a questionnaire regarding lower urinary tract symptoms and sexual activity, and the data was compiled. RESULTS: The mean follow-up period was 50.4 months (range, 6.8-88.2). Early complications comprised wound infection (in 17.8% of patients) and ileus (in 10.1% of patients). Late complications comprised ileus, pyelonephritis, stone, and stricture of the pouch-urethral anastomosis, each of which occurred in 3.4% of patients. Eighty-one (73 men and 8 women, 72.9%) of 90 surviving patients replied to the questionnaire. Seventy-seven (95.1%) of these patients reported spontaneous micturition, whereas 4 (4.9%) patients required intermittent self-catheterization. The mean total I-PSS was 11.6 points. Twenty-five percent of patients experienced interrupted voiding almost always; 38% of patients did not experience this at all. Approximately 26% of patients experienced weak urinary streams; 36% did not. Daytime continence was achieved in 97.3% of patients; nighttime incontinence was present in 61.3%. Preoperatively, 79.7% of the men were capable of sexual intercourse. Postoperatively, 63.6% of men who underwent radical cystectomy with the nerve-sparing procedure were capable of sexual intercourse, whereas only 14.8% of men who underwent radical cystectomy without the nerve-sparing procedure were. CONCLUSIONS: Morbidity rates were acceptable and functional outcome was excellent in this rather large group of patients who underwent Hautmann neobladder construction. Some problems have not been fully overcome, however, i.e., nocturnal incontinence and sexual dysfunction.