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Background Successful restoration of epicardial coronary artery patency by primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) does not always lead to adequate reperfusion at the microvascular level. Aims This study sought to investigate the association between lipid-rich coronary plaque identified by near-infrared spectroscopy combined with intravascular ultrasound (NIRS-IVUS) and microvascular obstruction (MVO) detected by cardiac magnetic resonance imaging (MRI) after PPCI for STEMI. Methods We investigated 120 patients with STEMI undergoing PPCI. NIRS-IVUS was used to measure the maximum lipid-core burden index in 4 mm (maxLCBI4mm) in the infarct-related lesions before PPCI. Delayed contrast-enhanced cardiac MRI was performed to evaluate MVO 1 week after PPCI. Results MVO was identified in 40 (33%) patients. MaxLCBI4mm in the infarct-related lesion was significantly larger in the MVO group compared with the no-MVO group (median [interquartile range]: 745 [522-853] vs. 515 [349-698], pl0.001). Multivariable logistic regression model showed that maxLCBI4mm was an independent predictor of MVO (odds ratio: 24.7 [95% confidence interval: 2.5-248.0], p=0.006). Receiver-operating characteristic curve analysis demonstrated that maxLCBI4mm g600 was the optimal cut-off value to predict MVO (Youden index = 0.44 and area under the curve = 0.71) with a sensitivity of 75% and a specificity of 69%. Conclusions Lipid content measured by NIRS in the infarct-related lesions was associated with the occurrence of MVO after PPCI in STEMI.

We sought to investigate the differences in coronary plaque morphology on coronary computed tomography angiography (CCTA) and medical therapy between acute coronary syndrome (ACS) and stable ischemic heart disease (SIHD). We also explored the relationship between plaque morphology on CCTA at the initial phase and lesion morphology in the acute phase of ACS.In 5967 patients who underwent invasive coronary angiography, 58 ACS and 91 SIHD patients who had prior CCTA imaging of the culprit lesion and denied ischemic heart disease at CCTA scanning were enrolled.Although the prevalence of positive remodeling was not different (P = 0.27), low-attenuation plaques (LAP) on prior CCTA were significantly higher in ACS than in SIHD (52% vs. 24%, P 0.01). The frequency of coronary stenosis grading did not differ between the two groups (P = 0.14). In ACS patients, the frequencies of plaque rupture and lipid-rich plaque assessed by optical coherence tomography (OCT) were significantly higher in LAP than in non-LAP (73% vs. 23%, P 0.01; 82% and 23%, P 0.01). Multivariate regression analysis revealed that statin use and LAP on prior CCTA were predictors of future ACS events (P 0.01, and P 0.05, respectively).LAP on CCTA, not positive arterial remodeling, and lack of statin therapy were associated with ACS development. In addition, LAP more frequently led to the development of the plaque rupture type of ACS compared with non-LAP. Lipid-lowering therapy with statins might be useful to prevent plaque rupture in patients with LAP regardless of coronary stenosis.

Optical coherence tomography (OCT)-angiography coregistration during stent implantation may be useful to avoid geographical mismatch and incomplete lesion coverage. Untreated lipid-rich plaque at stent edge is associated with subsequent stent edge restenosis. The present study sought to compare the frequency of untreated lipid-rich plaque at the stent edge between OCT-guided percutaneous coronary intervention (PCI) with and without OCT-angiography coregistration. We investigated 398 patients who underwent OCT-guided stent implantation (n = 198 in the coregistration group, and n = 200 in the no coregistration group). In OCT after PCI, untreated lipid-lich plaque was identified by the maximum lipid arc > 180˚ in the 5-mm stent edge segment. The PCI-targeted lesion characteristics and stent length were not different between the coregistration group and the no coregistration group. The frequency of untreated lipid-rich plaque in either proximal or distal stent edge segment was significantly lower in the coregistration group than in the no coregistration group (16% vs. 26%, P = 0.015). The frequency of stent-edge dissection (5% vs. 6%, P = 0.516) and untreated stenosis (2% vs. 3%, P = 0.724) was low and without significant differences between the two groups. In OCT-guided PCI, the use of OCT-angiography coregistration was associated with a reduced frequency of untreated lipid-rich plaque at stent edges. OCT-angiography coregistration has a positive impact on PCI results.

We aimed to assess an impact of instantaneous wave-free ratio (iFR) on a graft failure after coronary artery bypass grafting (CABG).A total of 131 coronary arteries from 88 patients who underwent invasive coronary angiography, intracoronary pressure measurements, CABG, and scheduled follow-up coronary computed tomography angiography within one year were investigated. All studied arteries had FFR 0.80. The rate of graft failure was significantly higher in vessels with negative iFR (0.89) than in those with positive iFR (0.89) (25.7% vs. 7.3%, p = 0.012). The graft failure rates increased as the preoperative iFR values rose (iFR 0.80, 3.3%; iFR: 0.80-0.84, 5.6%; iFR: 0.85-0.89, 16.0%; iFR: 0.90-0.94, 28.0%; and iFR: 0.95-1.00, 50.0%; p = 0.002). A cut-off value of iFR to predict graft failures was determined as 0.84 by receiver-operating characteristic curve analysis with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 88%, 62%, 25%, 97%, and 66%, respectively.The risk of graft failure becomes higher, as the preoperative iFR increases. The graft failure is significantly more frequent when a bypass graft is anastomosed on vessels with negative iFR than those with positive iFR.

Patients with acute myocardial infarction (AMI) caused by calcified nodules (CN) have worse clinical outcomes following primary percutaneous coronary intervention (PCI). This study investigated the late vascular response after everolimus-eluting stent (EES) implantation assessed by optical coherence tomography (OCT) in patients with AMI caused by CN, by comparing with plaque rupture (PR) and plaque erosion (PE).Methods and Results: Based on the OCT findings in AMI culprit lesions before PCI, a total of 141 patients were categorized into 3 groups (PR, PE, or CN), and the OCT findings immediately and 10 months after PCI were compared. The frequency of PR, PE, and CN was 85 (60%), 45 (32%), and 11 patients (8%), respectively. In the 10-month follow-up OCT, the frequency of lesions with uncovered struts and lesions with malapposed struts were highest in the CN group, followed by the PR and PE groups (82% vs. 52% vs. 40%, P=0.042 and 73% vs. 26% vs. 16%, P0.001, respectively). The incidence of intra-stent thrombus, re-appearance of CN within the stent, and target lesion revascularization were higher in the CN group compared with the PR and PE groups (36% vs. 9% vs. 7%, P=0.028; 27% vs. 0% vs. 0%, P0.001; and 18% vs. 2% vs. 2%, P=0.024, respectively).Late arterial healing response at 10 months after EES implantation in the CN was worse compared with PR and PE in patients with AMI.

BACKGROUND Optical flow ratio (OFR) is a recently developed method for functional assessment of coronary artery disease based on computational fluid dynamics of vascular anatomical data from intravascular optical coherence tomography (OCT). The purpose of this study was to investigate the relationship between OFR and fractional flow reserve (FFR) in stent-treated arteries immediately after percutaneous coronary intervention (PCI).Methods and Results:The OFR and FFR were measured in 103 coronary arteries immediately after successful PCI with a stent. An increase in the OFR and FFR values within the stent was defined as in-stent ∆OFR and ∆FFR, respectively. The values of FFR and OFR were 0.89±0.06 and 0.90±0.06, respectively. OFR was highly correlated with FFR (r=0.84, P

Background Acute myocardial infarction (AMI) is caused by coronary plaque rupture (PR), plaque erosion (PE), or calcified nodule (CN). We used optical coherence tomography (OCT) to compare stent expansion immediately after primary percutaneous coronary intervention (PCI) in patients with AMI caused by PR, PE, or CN.Methods and Results:In all, 288 AMI patients were assessed by OCT before and immediately after PCI, performed with OCT guidance according to OPINION criteria for stent sizing and optimization. The frequency of OCT-identified PR (OCT-PR), OCT-PE, and OCT-CN was 172 (60%), 82 (28%), and 34 (12%), respectively. Minimum stent area was smallest in the OCT-CN group, followed by the OCT-PE and OCT-PR groups (mean [±SD] 5.20±1.77, 5.44±1.78, and 6.44±2.2 mm2, respectively; P Conclusions Stent expansion was smallest in the OCT-CN group, followed by the OCT-PR and OCT-PE groups. Plaque morphology in AMI culprit lesions may affect stent expansion immediately after primary PCI.

Long-term safety of second generation drug-eluting stents (DES) has not yet been evaluated. We sought to evaluate the very late phase (> 3 years) vascular response after second generation everolimus-eluting stent (EES) as compared with first generation sirolimus-eluting stent (SES) by using optical coherence tomography (OCT). We examined the vascular response in 39 patients with a total of 55 DESs [31 EESs (mean 54 months after stenting) and 24 first generation SES (mean 66 months after stenting)] by OCT. The frequency of lesions with any malapposed stent struts (19% vs. 46%, p = 0.035) and evagination (6% vs. 42%, p = 0.002) was significantly lower. Segments with malapposed stent struts were significantly shorter (0.4 ± 0.9 mm vs. 1.9 ± 3.5 mm, p = 0.024), maximal malapposition area and malapposition volume were significantly smaller (0.26 ± 0.38 mm2 vs. 0.95 ± 1.54 mm2, p = 0.019, and 0.78 ± 1.35 mm3 vs. 6.22 ± 15.76 mm3, p = 0.016, respectively) in EES. Compared with first generation SES, second generation EES showed more favourable vascular responses at the very late phase.

Coregistration system of instantaneous wave-free ratio (iFR) pullback and angiography has been developed to enhance benefits of physiology oriented percutaneous coronary intervention (PCI), but its reproducibility has not yet been fully assessed.In 51 coronary arteries from 39 patients with stable coronary artery disease, iFR angio-coregistrations were repeated twice. The mean iFR values were comparable between the first and second studies (0.85 ± 0.12 vs. 0.84 ± 0.13, p = 0.97). In terms of a coronary segment with predominant iFR gradients defined by the largest segmental iFR gradients, the repeated iFR angio-coregistrations matched in 47 of 51 (92%) studies and showed good agreement (κ = 0.75) in overall vessels. When assessed only in vessels with positive iFR (≤0.89), iFR angio-coregistrations matched in 31 of 32 (97%) studies and showed an excellent agreement (κ = 0.91). The predominant iFR gradients in the repeated iFR angio-coregistrations demonstrated strong correlation (r = 0.96, p 0.0001) and an excellent agreement: mean difference was 0.0006, and the lower and upper limits (mean difference ± 1.96 standard deviation) of agreement were -0.0312 and 0.0324.iFR angio-coregistration is highly reproducible and can precisely identify a suitable target for PCI.

Whether a coronary lesion with discordant fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) causes myocardial ischemia remains unclear. This study investigates the prevalence of myocardial ischemia as assessed by myocardial perfusion scintigraphy (MPS) in coronary lesions with discordant FFR and instantaneous wave-free ratio (iFR), and, additionally, other NHPRs: resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and resting Pd/Pa.A total of 484 coronary arteries in 295 patients with stable coronary artery disease that underwent MPS and invasive physiological pressure measurements were categorized into four groups (FFR+/NHPR+, FFR+/NHPR-, FFR-/NHPR+, and FFR-/NHPR-) using the respective cut-off values of FFR ≤ 0.80, iFR ≤ 0.89, RFR ≤ 0.89, dPR 0.89, and Pd/Pa ≤ 0.92. The proportions of MPS-derived myocardial ischemia in a relevant myocardial territory were compared between the four groups.In total, 175 (36%), 61(13%), 35(7%) and 213(44%) vessels were classified into FFR+/iFR+, FFR+/iFR-, FFR-/iFR+ and FFR-/iFR- groups, respectively. The FFR+/iFR+ group had the highest proportion of MPS-derived ischemia (70%), followed by the FFR+/iFR- group (38%), the FFR-/iFR+ group (23%), and the FFR-/iFR- group (10%) (P 0.001). Similar proportions of MPS-derived ischemia were found when RFR. (70%, 34%, 24%, and 10%, P 0.001), dPR (70%, 38%, 26%, and 10%, P 0.001), and Pd/Pa (70%, 31%, 22%, and 10%, P 0.001) were used in place of iFR.The prevalence of MPS-derived myocardial ischemia in coronary lesions with discordance between FFR and NHPRs is lower than those with concordantly positive FFR and NHPRs, but higher than those with concordantly negative FFR and NHPRs.

Optical coherence tomography (OCT)-angiography coregistration during stent implantation may be useful to avoid geographical mismatch and incomplete lesion coverage. Untreated lipid-rich plaque at stent edge is associated with subsequent stent edge restenosis. The present study sought to compare the frequency of untreated lipid-rich plaque at the stent edge between OCT-guided percutaneous coronary intervention (PCI) with and without OCT-angiography coregistration. We investigated 398 patients who underwent OCT-guided stent implantation (n = 198 in the coregistration group, and n = 200 in the no coregistration group). In OCT after PCI, untreated lipid-lich plaque was identified by the maximum lipid arc 180˚ in the 5-mm stent edge segment. The PCI-targeted lesion characteristics and stent length were not different between the coregistration group and the no coregistration group. The frequency of untreated lipid-rich plaque in either proximal or distal stent edge segment was significantly lower in the coregistration group than in the no coregistration group (16% vs. 26%, P = 0.015). The frequency of stent-edge dissection (5% vs. 6%, P = 0.516) and untreated stenosis (2% vs. 3%, P = 0.724) was low and without significant differences between the two groups. In OCT-guided PCI, the use of OCT-angiography coregistration was associated with a reduced frequency of untreated lipid-rich plaque at stent edges. OCT-angiography coregistration has a positive impact on PCI results.

BACKGROUND Optical coherence tomography (OCT) provides valuable information to guide percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) regarding lesion preparation, stent sizing, and optimization. The aim of the present study was to compare lumen expansion of stent-treated lesions immediately after the procedure for ACS between OCT-guided PCI and angiography-guided PCI.Methods and Results:This study investigated stent-treated lesions immediately after PCI for ACS by using quantitative coronary angiography in 390 patients; 260 patients with OCT-guided PCI and 130 patients with angiography-guided PCI. Before stenting, the frequency of pre-dilatation and thrombus aspiration were not different between the OCT-guided and angiography-guided PCI groups. Stent diameter was significantly larger as a result of OCT-guided PCI (3.11±0.44 mm vs. 2.99±0.45 mm, P=0.011). In post-dilatation, balloon pressure-up (48% vs. 31%, P=0.001) and balloon diameter-up (33% vs. 6%, P

Background The major underlying mechanisms contributing to acute coronary syndrome are plaque rupture, plaque erosion, and calcified nodule. Artery‐to‐artery embolic myocardial infarction (AAEMI) was defined as ST‐segment–elevation myocardial infarction caused by migrating thrombus formed at the proximal ruptured plaque. The aim of this study was to investigate the prevalence and clinical features of AAEMI by using optical coherence tomography. Methods and Results This study retrospectively enrolled 297 patients with ST‐segment–elevation myocardial infarction who underwent optical coherence tomography before percutaneous coronary intervention. Patients were divided into 4 groups consisting of plaque rupture, plaque erosion, calcified nodule, and AAEMI according to optical coherence tomography findings. The prevalence of AAEMI was 3.4%. The culprit vessel in 60% of patients with AAEMI was right coronary artery. Minimum lumen area at the culprit site was larger in AAEMI compared with plaque rupture, plaque erosion, and calcified nodule (4.0 mm 2 [interquartile range (IQR), 2.2–4.9] versus 1.0 mm 2 [IQR, 0.8–1.3] versus 1.0 mm 2 [IQR, 0.8–1.2] versus 1.1 mm 2 [IQR, 0.7–1.6], P 2 [IQR, 2.5–6.7] versus 1.5 mm 2 [IQR, 1.0–2.4], P 2 (IQR, 1.0–2.1), 40% of them had nonstent strategy, and the 3‐year major adverse cardiac event rate was 0%. Conclusions AAEMI is a rare cause for ST‐segment–elevation myocardial infarction and has unique morphological features of plaque including larger lumen area at rupture site and smaller lumen area at the occlusion site.

AimsThe ability of optical coherence tomography (OCT) to detect plaques at high risk of developing acute coronary syndrome (ACS) remains unclear. The aim of this study was to evaluate the association between non-culprit plaques characterized as both lipid-rich plaque (LRP) and thin-cap fibroatheroma (TCFA) by OCT and the risk of subsequent ACS events at the lesion level.Methods and resultsIn 1378 patients who underwent OCT, 3533 non-culprit plaques were analysed for the presence of LRP (maximum lipid arc > 180°) and TCFA (minimum fibrous cap thickness < 65 μm). The median follow-up period was 6 years [interquartile range (IQR): 5–9 years]. Seventy-two ACS arose from non-culprit plaques imaged by baseline OCT. ACS was more often associated with lipidic plaques that were characterized as both LRP and TCFA vs. lipidic plaques that did not have these characteristics [33% vs. 2%, hazard ratio 19.14 (95% confidence interval: 11.74–31.20), P ConclusionNon-culprit plaques characterized by OCT as both LRP and TCFA were associated with an increased risk of subsequent ACS at the lesion level. Therefore, OCT might be able to detect vulnerable plaques.

The prediction of a perioperative adverse cardiovascular event (PACE) is an important clinical issue in the medical management of patients undergoing noncardiac surgery. Although several predictors have been reported, simpler and more practical predictors of PACE have been needed. The aim of this study was to investigate the predictors of PACE in noncardiac surgery. We retrospectively analyzed 723 patients who were scheduled for elective noncardiac surgery and underwent preoperative examinations including 12-lead electrocardiography, transthoracic echocardiography, and blood test. PACE was defined as cardiac death, non-fatal myocardial infarction, unstable angina, congestive heart failure, arrhythmia attack that needs emergency treatment (rapid atrial fibrillation, ventricular tachycardia, and bradycardia), acute pulmonary embolism, asystole, pulseless electrical activity, or stroke during 30 days after surgery. PACE occurred in 54 (7.5%) of 723 patients. High-risk operation (11% vs. 3%, p = 0.003) was more often seen, left ventricular ejection fraction (LVEF) (55 ± 8% vs. 60 ± 7%, p = 0.001) and preoperative hemoglobin level (11.8 ± 2.2 g/dl vs. 12.7 ± 2.0 g/dl, p = 0.001) were lower in patients with PACE compared to those without PACE. By multivariate logistic regression analysis, high-risk operation (odds ratio (OR): 7.05, 95% confidence interval (CI) 2.16–23.00, p = 0.001), LVEF (OR 1.06, every 1% decrement, 95% CI 1.03–1.09, p = 0.001), and preoperative hemoglobin level (OR 1.22, every 1 g/dl decrement, 95% CI 1.07–1.39, p = 0.003) were identified as independent predictors of PACE. Receiver operating characteristic analysis demonstrated that LVEF of 58% (sensitivity = 80%, specificity = 61%, area under the curve (AUC) = 0.723) and preoperative hemoglobin level of 12.2 g/dl (sensitivity = 63%, specificity = 64%, AUC = 0.644) were optimal cut-off values for predicting PACE. High-risk operation, reduced LVEF, and reduced preoperative hemoglobin level were independently associated with PACE in patients undergoing noncardiac surgery.

Objectives This study sought to investigate the ability of combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) to differentiate plaque rupture (PR), plaque erosion (PE), or calcified nodule (CN) in acute myocardial infarction (AMI). Background Most acute coronary syndromes occur from coronary thrombosis based on PR, PE, or CN. In vivo differentiation among PR, PE, and CN is a major challenge for intravascular imaging. Methods The study enrolled 244 patients with AMI who had a de novo culprit lesion in a native coronary artery. The culprit lesions were assessed by both NIRS-IVUS and optical coherence tomography (OCT). Maximum lipid core burden index in 4 mm (maxLCBI4mm) was measured by NIRS. Plaque cavity and convex calcium was detected by IVUS. The OCT diagnosis of PR (n = 175), PE (n = 44), and CN (n = 25) was used as a reference standard. Results In the development cohort, IVUS-detected plaque cavity showed a high specificity (100%) and intermediate sensitivity (62%) for identifying OCT-PR. IVUS-detected convex calcium showed a high sensitivity (93%) and specificity (100%) for identifying OCT-CN. NIRS-measured maxLCBI4mm was largest in OCT-PR (705 [interquartile range (IQR): 545 to 854]), followed by OCT-CN (355 [IQR: 303 to 478]) and OCT-PE (300 [IQR: 126 to 357]) (p Conclusions By evaluating plaque cavity, convex calcium, and maxLCBI4mm, NIRS-IVUS can accurately differentiate PR, PE, and CN.

Background A fractional flow reserve (FFR) between 0.75 and 0.80 constitutes a "gray zone" for clinical decision-making in coronary artery disease. We compared long-term outcomes of percutaneous coronary intervention (PCI) using drug-eluting stents vs. medical therapy for coronary stenosis with gray zone FFR. Methods and Results: We retrospectively investigated the clinical outcomes of 263 patients with gray zone FFR: 78 patients in the PCI group and 185 patients in the medical therapy group. During a median follow-up of 3.7 years, the frequency of target vessel failure (TVF, defined as a composite of cardiac death, myocardial infarction [MI], or ischemia-driven target vessel revascularization [TVR]) was significantly lower in the PCI group compared with the medical therapy group (6% vs. 19%, hazard ratio [HR]:0.33, 95% confidence interval [CI]: 0.13-0.84, P=0.008). The frequency of a composite of cardiac death or MI was not different between the 2 groups (1% vs. 2%, HR: 0.61, 95% CI: 0.07-5.49, P=0.645). The frequency of ischemia-driven TVR was significantly lower in the PCI group compared with the medical therapy group (5% vs. 18%, HR: 0.28, 95% CI: 0.10-0.79, P=0.005). Conclusions In patients with gray zone FFR, compared with medical therapy, PCI decreased the frequency of TVF, which was mainly driven by a reduction in the frequency of angina or myocardial ischemia without any difference in the frequency of cardiac death or MI.

Optical coherence tomography (OCT) requires intracoronary injection of contrast media to remove blood from the field of view during image acquisition. Contrast injection may cause a temporal increase in intracoronary pressure. The aim of this study was to compare the intracoronary pressure during contrast injection between OCT and coronary angiography.We measured intracoronary pressure by using a pressure guidewire during contrast injection for OCT and angiography in 30 coronary arteries (mean fractional flow reserve = 0.90 ± 0.03). Contrast media was injected into coronary artery through the guiding catheter by using a mechanical injector pump.Intracoronary pressure before contrast injection was similar between OCT and angiography (systolic pressure: 123 ± 18 mmHg vs. 122 ± 19 mmHg, p = 0.863). Intracoronary pressure was increased due to contrast injection in both OCT (systolic pressure: 123 ± 18 mmHg to 132 ± 18 mmHg, p 0.001) and angiography (systolic pressure: 122 ± 19 mmHg to 128 ± 19 mmHg, p 0.001). The increase in intracoronary pressure was slightly greater in OCT compared with angiography (absolute increase of systolic pressure: 9 ± 2 mmHg vs. 6 ± 1 mmHg, p 0.001; and relative increase of systolic pressure: 8 ± 2% vs. 5 ± 1%, p 0.001). Intracoronary pressure during contrast injection was not significantly different between OCT and angiography (systolic pressure: 132 ± 18 mmHg vs. 128 ± 19 mmHg, p = 0.831).Contrast injection for OCT induced significant but small increase in intracoronary pressure compared with that for angiography.

Very late stent thrombosis (VLST) is a quite rare but serious complication that often results myocardial infarction or cardiac death. In various causes of VLST, neoatherosclerosis with neointimal rupture has been shown to be one of major contributors to VLST. Optical coherence tomography (OCT) is

Coronary thrombosis is the most frequently final event leading to an acute coronary syndrome (ACS). The 3 most common underlying mechanisms contributing to ACS are believed to be plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN). Artery to artery embolic myocardial infarction (AAEMI

Optical coherence tomography (OCT) is a catheter-based intravascular imaging technique that uses near-infrared light to provides high-resolution images of the coronary artery. Since near-infrared light is attenuated by red blood cells, OCT requires intracoronary injection of contrast media to remove

Using β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) and β-lactamase-negative ABPC-resistant (BLNAR) nontypeable Haemophilus influenzae (NTHi) strains isolated from otological patients, colony biofilm was prepared on membrane filter substrates. Bactericidal activities of garenoxacin (GRNX), levofloxacin (LVFX), cefditoren (CDTR), and clavulanic acid/amoxicillin (CVA/AMPC) were examined by counting viable cells after drug exposure to biofilm cells for 6 and 24 h and by observation under a scanning electron microscope (SEM). After exposure of biofilm to the 100-fold MIC of GRNX or LVFX for 24 h, GRNX and LVFX showed potent bactericidal activity (∆log10 CFU/ml, ≥5.1). In this case, the drug-exposure AUC, exposure concentration × 24 μg h/ml, was 64-128 % for GRNX and 121 % for LVFX of free AUC at the clinical dosage in humans, respectively. CDTR and CVA/AMPC at 100-fold MIC exhibited little bactericidal activity against biofilm cells. Under an SEM, after exposure of BLNAS and BLNAR biofilms to GRNX or LVFX, most of the biofilm matrices were transformed. Quinolones such as GRNX show potent bactericidal activity against biofilm-forming NTHi at the usual clinical dosage.

The bactericidal activity and resistance selectivity of garenoxacin against Streptococcus pneumoniae with mutations in ParC (S79F) or both GyrA (S81F) and ParC (D83Y and K137N) were investigated using in vitro pharmacokinetic models simulating plasma concentrations for a standard clinical regimen [400 mg once daily (q.d.)]. The efficacy of garenoxacin was compared with that of levofloxacin (500 mg q.d.) and moxifloxacin (400 mg q.d.). Garenoxacin showed excellent bactericidal activity against S. pneumoniae , including quinolone-resistant S. pneumoniae (QRSP), achieving ratios of area under the plasma concentration–time curve over 24 h to minimum inhibitory concentration (AUC 0–24 /MIC) ≥26.3, without emerging resistant subpopulations. The area above the killing curves was greater and the time to achieve 99.9% killing was shorter for garenoxacin than the corresponding values for levofloxacin and moxifloxacin. No resistant subpopulations and no additional substitution of amino acids in GyrA or ParC emerged following treatment with garenoxacin. On the other hand, in the parC mutant strain, levofloxacin and moxifloxacin treatment caused an increase in the frequency of the resistant population and an additional substitution of amino acids in GyrA (levofloxacin, S81Y/F/C; moxifloxacin, S81Y or E85K). In QRSP with mutations in GyrA and ParC, levofloxacin had no bactericidal activity, whilst the bactericidal activity of moxifloxacin was less than that of garenoxacin; moreover, an additional substitution of amino acids in ParC (S79Y) was noted. In conclusion, garenoxacin corresponding to an oral dose of 400 mg showed excellent bactericidal activity against S. pneumoniae , including QRSP, without the emergence of resistant mutants.

Garenoxacin showed the most potent chlamydial activity against Chlamydia trachomatis D/UW-3/Cx among three tested quinolones and azithromycin. The DNA gyrase genes, gyrA and gyrB, of C. trachomatis D/UW-3/Cx were cloned and the GyrA and GyrB subunits of DNA gyrase protein were separately expressed as histidine-tagged proteins in Escherichia coli. The mean 50% inhibitory concentration (IC(50)) of garenoxacin against the supercoiling activity of C. trachomatis D/UW-3/Cx gyrase was 2.9 ± 0.4 μg/ml, which was the most potent inhibitory activity against DNA gyrase among the quinolones tested in this study. At an extracellular concentration of 0.5 μg/ml, the cellular-to-extracellular concentration ratio of garenoxacin was 15.3 ± 1.3, equivalent to that of moxifloxacin and greater than that of levofloxacin. In a time-kill experiment, after exposure to garenoxacin at a concentration of 0.5 μg/ml at 0-6, 5-11, and 24-30 h after infection, the percentages of recoverable chlamydial inclusion-forming units were 11.1 ± 3.3, 0.6 ± 0.1, and 2.6 ± 0.5%, respectively. On transmission electron microscopy observation, after exposure to garenoxacin at 24-30 h after infection, some C. trachomatis elementary bodies remained in the inclusion body; however, the reticulate bodies were completely disrupted. In conclusion, garenoxacin is expected to be a useful quinolone in the treatment of infectious diseases caused by C. trachomatis.

The palladium-catalyzed cross-coupling reaction of 5-(tributylstannyl)isoindoline and its 1-and 3-methyl derivatives with 6-fluoro or 6-unsubstituted 7-bromo-1-cyclopropyl-8-methoxy (or difluorometh-oxy)-4-oxoquinoline-3-carboxylate afforded the corresponding 1 -cyclopropyl-7-(5-isoindolinyl)-4-oxoquinoline-3-carboxylic acids: 6-fluoro, la-7a and 6-nonfluoro, lb-7b. The in vitro antibacterial spectra of the newly synthesized quinolones were mostly characterized by excellent Gram-positive activity against Staphylococcus aureus and Streptococcus pneumoniae including quinolone-resist-ant strains, and also by significant Gram-negative activity comparable to 7-(1-piperazinyl) fluoroquinolones. Comparative examinations of the in vitro antibacterial profiles and the in vivo toxicity in terms of intravenous lethality, micronuclei-inducing potential and convulsive activity provided 6-nonfluorin-ated 1 -cyclopropyl-8-(difluoromethoxy) -7-(1-methylisoindolin-5-yl)-4-oxoquinol-ine-3-carboxylic acid [(±)-5b] as the candidate for evaluation of the stereoisomers. The enantiomers (R) -5b and (S) -5b were synthesized via the Suzuki coupling reaction of (R)- and (S)-1-methyl derivatives of 2-(triphenylmethyl)isoindolin-5-boronic acid with the corresponding 7-bromo-8-(difluoromethoxy)-4-oxoquinoli-ne-3-carboxylate. The (R)-5b stereoisomer proved to be 2- to 4-fold more active than the (S)-5b stereoisomer against the organisms tested, with the exception of an equal potency observed with S. pneumoniae IID553 and Haemophilus influenzae ATCC49247. A noticeable in vitro antibacterial profile of (R) -5b was that it is 16- and 64-fold more active than levoflox-acin (CAS 100986-85-4) and ciprofloxacin (CAS 86393-32-0), respectively, against Mycoplasma pneumoniae IID813 (MIC of 0.0313 µ g/ml), and 4-fold more active than ciprofloxacin and levofloxacin against Mycobacterium tuberculosis M-4 (MIC of 0.0313 µ g/ml). Additional studies indicate that (R)-5b (T-3811, CAS 194804-75-6) exhibits excellent antibacterial activity against a wide range of organisms including anaerobes and common respiratory pathogens, while demonstrating a high selectivity against the mammalian homolog topoisomerases. The methane-sulfonate of (R)-5b (T-3811ME, CAS 223652-90-2) is now undergoing clinical testings.

As an active surface can be a nucleation site for some reactions, the possibility of iron and carbon acting as a catalyst for methane hydrate formation has been examined in the previous study. If iron oxide and carbon can be used as a catalyst, they would have a low environmental influence and a relatively low cost. It has previously been shown that carbon and iron oxide can be used as a catalyst under weak stirring conditions. In the present study, experiments involving intense stirring were conducted for the establishment of the basis for a high production system. The proposed reaction model consisted of the mass transfers of CH4 in the liquid films both at the gas-liquid and the liquid-solid interfaces and the diffusion in liquid water, and a chemical reaction at the liquid-solid interface. The kinetic analysis was performed using the model and the following results were obtained. The reaction was a mixed control between the mass transfer and the chemical reaction at 277 K, which was closed to the maximum temperature of methane hydrate formation thermodynamically. While in the lower temperature region lower than 275 K, the mass transfer including the diffusion of CH4 and the apparent mass transfers in the liquid films, k 0 was dominant. The addition of catalysts (hematite, graphite and its mixture) had acceleration effects on hydrate formation, but to varying degrees. The catalyst ‘‘Mix’’ (mixture of hematite and graphite) had the largest effect on hydrate formation over the whole stirring range. From the results of kinetic analysis, the existence of catalyst had a relatively large influence on the chemical reaction of the formation of methane hydrate. [doi:10.2320/matertrans.M2009369]

We performed quantum spin dynamics in anisotropic electron-spin systems to clarify the mechanism in single molecular magnets (SMM) theoretically. Usually, SMMs have large negative anisotropic D value and the large total spin angular moment (Stotal). The splitting ground spin states in one SMM molecule are usually caused by the anisotropic terms (D and E), which become more important as well as isotropic term (J). In order to examine the effects of such anisotropic magnetic terms, model systems with large spin multiplicity of the ground state (Stotal = 5 and 2) were treated. First, energy diagram in external magnetic field is shown, since negative D terms are responsible to the zero-field magnetic moment. Next, the quantum Liouvile approach is used for our spin dynamics simulation involving the relaxation processes of the system. Our simulations in Stotal = 5 system successfully reproduced magnetic quantum tunneling (MQT) behavior in DC-external magnetic field. Moreover, in Stotal = 2 system under AC-external magnetic field, frequency dependence of real (χ′) and imaginary (χ″) parts of χ can be shown with Fourier transformation. Our theoretically drawn half circles in Cole-Cole plot (χ′ versus χ″) will give information to many experimental studies.

We compared the antibacterial effects and the emergence of resistance to tosufloxacin or levofloxacin for Streptococcus pneumoniae by simulating the serum concentration according to the Japanese clinical regimens using an in vitro pharmacokinetic-pharmacodynamic model. For quinolone-susceptible strain ATCC49619, tosufloxacin showed bactericidal activity, given that both the AUC(0-24h)/MIC ratios at the dosage of 150 mg t.i.d. and 300 mg b.i.d. of tosufloxacin tosilate were 138 and 193, and the C(max)/MIC ranges were 7.93-10.2 and 15.9-17.6, respectively, which were greater than those of levofloxacin (100 mg t.i.d. and 200 mg b.i.d.). The greater area above the killing curves (AAKCs) or shorter time to achieve 99.9% killing (99.9% KT) in both models of tosufloxacin than those of levofloxacin was related to their larger AUC(0-24h)/MIC and C(max)/MIC. Exposure of only 100 mg t.i.d. of levofloxacin led to outgrowth of the parC mutants, which were twofold less susceptible to levofloxacin than the parent strain. Neither of the tosufloxacin tosilate regimens resulted in isolation of resistant mutants of this strain. For the parC mutant strain D-3197, both the AUC(0-24h)/MIC and C(max)/MIC ratios of tosufloxacin were greater than those of levofloxacin, which resulted in comparable or better bactericidal activity as compared to those of levofloxacin. However, both fluoroquinolones and both regimens led to outgrowth of resistant mutants, which possessed a mutation in gyrA in addition to parC. In conclusion, tosufloxacin is superior to levofloxacin in bactericidal activity against S. pneumoniae in the Japanese clinical regimens, especially in the quinolone-susceptible strain, without emergence of resistant subpopulations.

A master equation approach involving the effect of the interaction between spins and phonons is formulated in the Markov approximation in order to perform a dynamics for a spin aggregate which have the novel fractal architectures. Such a dynamics is important for elucidating the relation between the dynamical features and the architectures of spin aggregates.

The directional energy transport, i.e. exciton migration, in nanostar dendritic systems composed of two-state monomer units is studied using a quantum master equation approach. We examine the effects of the variation in the excitation energy of the monomer in the core region (core monomer) on the multistep exciton migration from the periphery to the core based on the relaxation factors among exciton states originating in weak exciton–phonon coupling. It turns out that when the core monomer possesses both an excitation energy slightly lower than that of the first generation and a partial exciton overlap with the first generation, more efficient and rapid exciton migration to the core is expected as compared with other core monomer cases with the energy level closer to or much lower than that of the first generation.

We perform spin dynamics in strongly correlated electron-spin systems to clarify the relationship between the phase relaxation and the structure of the spin systems. The interaction among spins is considered to be Heisenberg-type exchange. The quantum Liouville approach is used for the dynamics involving the relaxation processes of the systems, which is considered to originate in spin-phonon and electron spin-nuclear spin interactions. As a first step of our study, to examine the effects of the structures on the phase relaxation, we consider the phenomenological relaxation parameters for the relaxation terms of quantum Liouville equation, and perform the spin dynamics in four types of four electron-spin systems that have linear, square, star (dendritic structure), and tetrahedral structures. The results of our calculation indicated the possibility for the control of the phase relaxation by the change of the structure in spin clusters. Possible implications of our results are related to the single-molecule magnets, ESR-STM detection of spins, and related spin-transition phenomena (decoherence and population relaxation). © 2005 Wiley Periodicals, Inc. Int J Quantum Chem 105: 615- 627, 2005

In a previous paper, we investigated static second hyperpolarizabilities (γ) of 1,4-phenylendiamine (PDA) and 4,4′-diaminodiphenylamine (DADPA), which is considered to be the simplest model for extended dendrimers including linking nitrogen (N) atoms, using the ab initio molecular orbital (MO) methods.1 The γ value was shown to be drastically changed by linking via a N atom and/or the introduction of positive charges. In this study, we investigate the applicability of the density functional (DF) methods to the calculation of γ. It is found that although the DF methods can reproduce γ value and their nonlinear enhancement for neutral state at the CCSD(T) level, they are insufficient to reproduce reliable γ values of their charged states.

We investigated static second hyperpolarizabilities (γ) of 1,4-phenylendiamine (PDA) and 4,4‘-diaminodiphenylamine (DADPA) by using the ab initio molecular orbital (MO) methods. The DADPA molecule ...

The quantum master equation approach involving a weak exciton-phonon coupling is applied to the exciton migration dynamics of dendritic molecular aggregates modeled after a phenylacetylene dendrimer, D25, which exhibits an efficient light-harvesting property. The mechanism of efficient exciton migration from the periphery to the core is studied by analyzing relaxation terms among the exciton states originating in weak exciton-phonon coupling. Partial overlaps of exciton distributions between neighboring exciton states are found to be important for realizing the unique migration behavior by step-by-step transfer from the periphery to the core via multi-step exciton states. The same calculation method is applied to the exciton dynamics of a larger dendritic aggregate model, D127, modeled after the largest synthesized phenylacetylene dendrimer D127 in order to examine the dependencies of the exciton migration on the strength of the intermolecular interaction and the temperature of phonon bath. In the case of the relatively weak dipole-dipole coupling, exciton is not observed to migrate efficiently from the periphery to the core, while the largest exciton population is found to remain in the intermediate generations. This is ascribed to the fact that the thermal excitation to the higher exciton states significantly contributes to the exciton distribution in the equilibrium state when the weak intermolecular interaction reduces the energy difference between exciton states. This indicates that the intermolecular interaction is important not only for the overlaps of the exciton distributions between the exciton states, but also the relation between the exciton energy differences and thermal excitations, which spoil the distinct concentration of exciton distribution in the core generation. In the case of a low temperature, even if the intermolecular interaction is weak, the exciton population in the core region is found to be the largest in all the generations. This suggests that exciton tends to efficiently migrate from the periphery to the core when the temperature is sufficiently low. Implications of these theoretical results are discussed in relation to design of magneto-optical materials and other technological applications.

We investigate the intermolecular-interaction effects on the longitudinal second hyperpolarizabilities (γ) for π−π stacking dimers of π-conjugated cation monomers, C5H7+. Three types of geometrical configurations are examined to elucidate the relation between the longitudinal γ and the π−π orbital interaction in the perpendicular direction to the monomer plane. The γ values are calculated by the finite-field (FF) approach using several ab initio molecular orbital (MO) and density functional (DF) methods. The spatial contributions of electrons to γ are analyzed using the plots of the second hyperpolarizability (γ) densities, which are described by the third-order derivatives of the charge densities with respect to the applied electric fields. It is found that the relative phase relation between interacting upper and lower π-orbitals is closely related to the intermolecular-interaction effects on γ of a dimer. Namely, in-phase (bonding-like) π−π orbital interactions in the HOMO and HOMO−1 levels of a dimer ...

Discoveries of superconductivity of MgB2 by Akimitsu et al. and high-Tc cupurate superconductors by Bednorz and Muller have raised great interest for elucidation of the superconducting mechanism from both experimental and theoretical grounds. The transition temperature (Tc) was found to be 40 K for MgB2, while the very high-Tc over 130 K was reported for doped copper oxides with layer structures. A crucial role of the electron–phonon (EP) interaction was pointed out as a common mechanism of the superconductivity of both materials. However, such high-Tc superconductivity may indicate the possibility of cooperative mechanism of the EP interaction with others such as electron correlation (EC) and multiband (MB) effects discussed in part I (Int J Quantum Chem 1990, 37, 167) of this series. Here, as a continuation of part I, theoretical backgrounds are briefly described to select active orbital space for superconductivity and elucidate the nature of EP, EC, and MB effects for cooperative mechanisms. Next, molecular orbital calculations of MgmBn and cage-type carbon cluster are carried out to elucidate contributions of the EP interaction using McMillan equation. The relative contributions of the EP and EC interactions are also discussed in relation to the screening of the Coulomb repulsion. Pair binding energies are calculated for cage-type carbon clusters. Finally, the cooperative mechanisms of the EP, EC, and MB effects are discussed to realize the high-Tc superconductivity in molecule-based materials such as cage compounds and nanotubes. Several possible candidates are proposed on both experimental and theoretical grounds. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003

The two-exciton dynamics in a dendritic molecular aggregate composed of monomers coupled with each other by the dipole- dipole interaction is performed to investigate the effect of two-exciton states on the exciton migration using the master equation approach. Although the spatial unique feature of exciton migration from the periphery to the core in the one-exciton model is also observed in the two- exciton model, about 36% of such exciton migration is found to be carried out by the relaxation among two-exciton states in the present model. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 95: 472- 478, 2003

Neisseria gonorrhoeae strains with reduced susceptibility to cefixime (MICs, 0.25 to 0.5 μg/ml) were isolated from male urethritis patients in Tokyo, Japan, in 2000 and 2001. The resistance to cephems including cefixime and penicillin was transferred to a susceptible recipient, N. gonorrhoeae ATCC 19424, by transformation of the penicillin-binding protein 2 gene ( penA ) that had been amplified by PCR from a strain with reduced susceptibility to cefixime (MIC, 0.5 μg/ml). The sequences of penA in the strains with reduced susceptibilities to cefixime were different from those of other susceptible isolates and did not correspond to the reported N. gonorrhoeae penA gene sequences. Some regions in the transpeptidase-encoding domain in this penA gene were similar to those in the penA genes of Neisseria perflava ( N. sicca ), Neisseria cinerea , Neisseria flavescens , and Neisseria meningitidis . These results showed that a mosaic-like structure in the penA gene conferred reductions in the levels of susceptibility of N. gonorrhoeae to cephems and penicillin in a manner similar to that found for N. meningitidis and Streptococcus pneumoniae .