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Biomedical subjects

Junya Ako

Publications and source records attributed to Junya Ako.

At least 19 recordsLinked to original sources

Transient left ventricular dysfunction under severe stress: brain-heart relationship revisited.

PURPOSE: Transient left ventricular dysfunction in patients under emotional or physical stress, also known as tako-tsubo-like left ventricular dysfunction, has been recently been recognized as a distinct clinical entity. The aims of this review are to define this phenomenon and to explore its similarities to the left ventricular dysfunction seen in patients with acute brain injury. METHODS: MEDLINE database, bibliographies of each citation for relevant articles, and consultation with clinical experts were used to examine the clinical picture of tako-tsubo-like left ventricular dysfunction. RESULTS: We identified case series and a systematic review that report on patients with this syndrome. This phenomenon occurs predominantly in female patients, presenting with a variety of ST-T segment changes and mildly elevated cardiac enzymes that mimic an acute coronary syndrome. The left ventricular dysfunction, typically showing a hyperkinetic basal region and an akinetic apical half of the ventricle, occurs in the absence of obstructed epicardial coronary arteries. The ventricular dysfunction usually resolves within weeks with a generally favorable prognosis. This phenomenon has similarities to that seen in patients with acute brain injury with regard to clinical presentation, pathology, and its reversible nature. CONCLUSIONS: Transient left ventricular dysfunction occurs in the absence of obstructive epicardial coronary artery disease. In its broadest sense, this phenomenon may encompass a range of disorders including left ventricular dysfunction after central nervous system injury.

Electrocardiography↗

Impact of angiotensin II receptor blockers on the progression and regression of coronary atherosclerosis: an intravascular ultrasound study.

BACKGROUND: Although angiotensin II receptor blockers (ARB) have been found to reduce the coronary atherosclerotic plaque burden in animal models, it is unknown whether ARB have a similar effect on human coronary arteries. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) studies of the left main (LM) coronary artery were performed in 64 patients at baseline and after 7-month follow-up. All patients were divided into 2 groups (ARB group: 23 patients; non-ARB group: 41 patients). Three-dimensional volumetric analysis was done throughout the LM coronary artery, and the volume index (VI; volume/length) was calculated for the vessel (VVI), lumen (LVI), and plaque (PVI). No significant difference was found between the 2 groups in baseline clinical characteristics, including age, gender, blood pressure levels, serum cholesterol levels, the presence of diabetes and smoking status. At baseline VVI, LVI and PVI were similar between the groups. In the non-ARB group, VVI, LVI, and PVI did not change between baseline and follow-up. In the ARB group, PVI significantly decreased during follow-up (9.9 +/-3.1 mm2 vs 9.1+/-2.7 mm2, p<0.01), whereas VVI and LVI were unaffected. CONCLUSIONS: This preliminary IVUS study suggests that ARB could cause regression of coronary atherosclerosis in humans.

Aged↗

Heterogeneity of neointimal distribution of in-stent restenosis in patients with diabetes mellitus.

Diabetes mellitus is an independent predictor of restenosis after percutaneous coronary intervention. The pattern of restenosis after bare metal stent implantation in diabetic patients was examined with 3-dimensional intravascular ultrasound analysis. Lumen and stent were manually traced at every 0.5-mm interval in stented segments. Using Simpson's method, stent, luminal, and neointimal (stent minus lumen) volumes were calculated and average area was calculated as volume data divided by length. To measure the cross-sectional and longitudinal severities of luminal encroachment by the neointima, percent neointimal area (neointimal area divided by stent area) and neointimal hyperplasia 50 (IH50) (defined as percent stent length with percent neointimal area >50%) were calculated. In 278 patients (68 with diabetes and 210 without diabetes), there was a significantly higher percentage of maximal percent neointimal area with significantly longer percent stent length that was severely encroached by the neointima in diabetic patients. Diabetic patients showed a more heterogenous pattern of the neointima after bare metal stenting, resulting in longer high-grade obstruction segments. This may have important implications for stent design and pharmacokinetic properties of next-generation drug-eluting technology for this complex patient subset.

Aged↗

Impact of asymmetric stent expansion on neointimal hyperplasia following sirolimus-eluting stent implantation.

To assess whether asymmetric stent expansion affects suppression of neointimal hyperplasia after sirolimus-eluting stent implantation, 64 patients in the SIRolImUS-coated Bx Velocity stent trial who underwent single 18-mm stent implantation and 3-dimensional intravascular ultrasonography at 8-month follow-up were enrolled. To assess the longitudinal stent asymmetric expansion, 2 cross sections with a maximal/minimal stent area were chosen in each patient. To assess for tomographic stent asymmetric expansion, stent eccentricity was determined by dividing the minimum stent diameter by the maximum stent diameter. At the 2 cross sections with a maximal/minimal stent area, a sirolimus-eluting stent reduced neointimal hyperplasia significantly with no interaction between the treatment and stent areas. A sirolimus-eluting stent also significantly reduced neointimal hyperplasia in the concentric and eccentric stent groups.

Angioplasty, Balloon, Coronary↗

Late incomplete stent apposition after sirolimus-eluting stent implantation: a serial intravascular ultrasound analysis.

OBJECTIVES: We sought to identify the frequency of incomplete stent apposition (ISA) in sirolimus-eluting stents (SES) and clarify its findings and clinical sequelae. BACKGROUND: Late-acquired ISA has been reported in bare-metal stents (BMS) and brachytherapy and recently in drug-eluting stents. However, the characteristics of late ISA in SES have not been clarified. METHODS: From the SIRIUS trial, a randomized, multicenter study comparing SES and BMS, serial qualitative intravascular ultrasound (IVUS; at stent implantation and eight-month follow-up) was available in 141 patients (BMS: n = 61; SES: n = 80). The IVUS images were reviewed for the presence of ISA. RESULTS: Incomplete stent apposition at follow-up was observed in 19 patients (BMS: n = 6 [9.8%]; SES: n = 13 [16.3%]; p = NS). Among these, 12 had ISA after intervention and at follow-up (persistent ISA). Late-acquired ISA was seen in the remaining seven cases, all from the SES group (BMS: n = 0; SES: n = 7 [8.7%]; p < 0.05). In late-acquired ISA, there was an increase in external elastic membrane area (after intervention: 16.2 +/- 2.7 m2; follow-up: 18.9 +/- 3.6 mm2; p < 0.05). The location of stent-vessel wall separation was primarily at the stent edges in persistent ISA cases, whereas late-acquired ISA in SES occurred mostly in the mid portion of the stent. There were no negative clinical events reported for any ISA cases at 12-month clinical follow-up. CONCLUSIONS: Late ISA was observed in 8.7% of patients after SES implantation. There were no negative clinical events associated with this IVUS finding at 12-month clinical follow-up; however, careful long-term follow-up will be necessary.

Combined Modality Therapy↗

Predictors of edge stenosis following sirolimus-eluting stent deployment (a quantitative intravascular ultrasound analysis from the SIRIUS trial).

To study the interaction of the sirolimus-eluting stent and vessel margins, we analyzed the intravascular ultrasound parameters in 317 edges of 167 stents having 18 edge stenoses at 8 months of follow-up from the SIRIUS trial. Of the baseline parameters, a larger reference percentage of plaque area and a larger edge stent area/reference minimum lumen area were associated with edge stenosis in the sirolimus-eluting stent cohort compared with the incidence of edge stenosis in the bare metal stent cohort. Thus, full lesion coverage and matching the stented segment properly to the adjacent segment using intravascular ultrasound guidance may improve sirolimus-eluting stent implantation efficacy further.

Blood Vessel Prosthesis Implantation↗

Impact of intravascular ultrasound lesion characteristics on neointimal hyperplasia following sirolimus-eluting stent implantation.

The effect of lesion characteristics on neointimal hyperplasia after sirolimus-eluting stent implantation was examined in 45 patients who underwent successful preinterventional intravascular ultrasound. There were no differences in neointimal hyperplasia between the moderate/severe calcified lesion group (calcium arc >120 degrees ) and the non/mild calcified lesion group or between the positive vessel remodeling group (external elastic membrane area at the minimal lumen area site larger than that at the proximal reference site) and negative vessel remodeling group. No correlation between preinterventional plaque burden and neointimal hyperplasia was found. In patients who have coronary artery disease, sirolimus-eluting stents continue to demonstrate striking suppression of neointimal proliferation, irrespective of lesion characteristics previously associated with greater restenotic risk.

Blood Vessel Prosthesis Implantation↗

Effect of lumen narrowing within coronary stents on proximal and distal vessel segments following bare metal stent implantation.

Adjacent reference vessel response to smaller lumens at stented segments was examined with 3-dimensional intravascular ultrasound analysis. In 128 patients after bare metal stent implantation, minimal lumen area (MLA) within the stent and average lumen area at distal/proximal adjacent reference segments (5 mm) were obtained at baseline and follow-up. In the smaller in-stent MLA group (MLA <3 mm2), lumen area decreased significantly at the distal edge compared with the larger in-stent MLA group (MLA > or =3 mm2), although no significant difference was seen at the proximal edge. In-stent lumen patency may influence vascular responses at adjacent reference segments after bare metal stent implantation.

Coronary Disease↗

Impact of blood pressure variability on cardiovascular events in elderly patients with hypertension.

Blood pressure variability is one of the characteristic features of hypertension in the elderly. However, its clinical significance remains to be determined. We therefore examined the impact of blood pressure variability on the development of cardiovascular events in elderly hypertensive patients. A total of 106 consecutive hypertensive patients aged more than 60 years old (mean age, 73.9 +/- 8.1 years old; male, 54%), all of whom underwent 24-h ambulatory blood pressure monitoring, were followed up (median, 34 months; range, 3-60 months). During the follow-up period, 39 cardiovascular events were observed, including 14 cases of cerebral infarction and 7 cases of acute myocardial infarction. The coefficient of variation (CV) of 24-h systolic blood pressure (SBP) values was used as an index of blood pressure variability. The patients showed a mean CV value of 10.6%, and were divided into two groups according to this mean value as a cut-off point: a high CV group (n = 46) and a low CV group (n = 60). Although baseline clinical characteristics were similar in the two groups, Kaplan-Meier plots for event-free survival revealed that the rate of cardiovascular events was significantly higher in high CV group than in low CV group (p < 0.05). Cox's proportional hazards analysis showed that increased blood pressure variability (a high CV value of 24-h SBP) was an independent predictive variable for cardiovascular events. The CV value of daytime SBP and the SD value of both 24-h SBP and daytime SBP also had positive correlations with the onset of cardiovascular events. These results suggest that increased blood pressure variability may be an independent risk factor for cardiovascular events in elderly hypertensive patients.

Aged↗

Impact of final stent dimensions on long-term results following sirolimus-eluting stent implantation: serial intravascular ultrasound analysis from the sirius trial.

OBJECTIVES: We assessed the predictive value of minimum stent area (MSA) for long-term patency of sirolimus-eluting stents (SES) implantation compared to bare metal stents (BMS). BACKGROUND: Although MSA is a consistent predictor of in-stent restenosis, its predictive value in BMS is still limited because of biologic variability in the restenosis process. METHODS: From the SIRolImUS (SIRIUS) trial, 122 cases (SES: 72; BMS: 50) with complete serial intravascular ultrasound (IVUS) (baseline and 8-month follow-up) were analyzed. Postprocedure MSA and follow-up minimum lumen area (MLA) were obtained. Based on previous physiologic studies, adequate stent patency at follow-up was defined as MLA >4 mm(2). RESULTS: In both groups, a significant positive correlation was observed between baseline MSA and follow-up MLA (SES: p < 0.0001, BMS: p < 0.0001). However, SES showed higher correlation than BMS (0.8 vs. 0.65) with a higher regression coefficient (0.92 vs. 0.59). The sensitivity and specificity curves identified different optimal thresholds of MSA to predict adequate follow-up MLA: 5 mm(2) for SES and 6.5 mm(2) for BMS. The positive predictive values with these cutoff points were 90% and 56%, respectively. CONCLUSIONS: In this SIRIUS IVUS substudy, SES reduced both biologic variability and restenosis, resulting in increased predictability of long-term stent patency with postprocedure MSA. In addition, SES had a considerably lower optimal MSA threshold compared to BMS.

Angioplasty, Balloon, Coronary↗

Correlation between electroencephalography and heart rate variability during sleep.

It is known that autonomic nervous activities change in correspondence with sleep stages. However, the characteristics of continuous fluctuations in nocturnal autonomic nerve tone have not been clarified in detail. The study aimed to determine the possible correlation between the electroencephalogram (EEG) and autonomic nervous activities, and to clarify in detail the nocturnal fluctuations in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven healthy males were obtained. These EEGs were analyzed by fast Fourier transformation algorithm to extract delta, sigma and beta power. Heart rate and heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV indices of low frequency (LF), high frequency (HF) and LF/HF ratio were calculated from the spectral analysis of R-R intervals. The sleep stages were manually scored according to Rechtschaffen and Kales' criteria. Low frequency and LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG showed inverse correlations with LF (r = - 0.44, P < 0.001) and LF/HF (r = - 0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among NREM sleep stages. Detailed analysis revealed that correlation was evident from the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power showed negative correlations with LF and LF/HF, suggesting that sympathetic nervous activities continuously fluctuate in accordance with sleep deepening and lightening.

Adult↗

Changing spectrum of infective endocarditis: review of 194 episodes over 20 years.

A review of admission records identified 194 episodes of infective endocarditis (IE) from January 1980 to December 1999 at a community hospital in Tokyo. The cases were divided into decades, and the clinical picture and short-term outcomes were compared and analyzed. The mean age of patients in the 1990s was older (45.5 +/-13.2 vs 55.1+/-12.6 years, p<0.001), and prosthetic valve endocarditis was significantly more frequently seen (14.4% vs 31.8%, p=0.004). None had a history of intravenous drug abuse (IVDA). Patients on chronic hemodialysis comprised 5.8% of IE cases in the 90s. Overall, dental procedure or caries still remained the main presumed source of infection. Staphylococcal IE showed a tendency to increase, and methicillin-resistant staphylococcal IE was significantly prominent in the 90s (0% vs 10.4%, p=0.0006). The overall in-hospital mortality was similar between the 2 groups (13.6% vs 18.8%, NS). Multivariate analysis found neurological abnormality, renal insufficiency and staphylococcal IE as predictors of in-hospital mortality. The characteristics of IE in Japan have changed, even among non-IVDA patients, and it appears to occur in a more high-risk patient population, which may warrant a more aggressive therapeutic approach to its management and treatment.

Adolescent↗

Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via a p21(WAF1)-dependent pathway.

OBJECTIVE: N-(3'4'-dimethoxycinnamoyl)-anthranilic acid (tranilast) is a drug that has been shown to reduce the incidence of restenosis after angioplasty in middle-scale clinical trials. Despite clinical interest in this drug, the pharmacological actions of tranilast remain relatively unexplored at a molecular level. METHODS AND RESULTS: We evaluated the effects of tranilast on vascular smooth muscle cell (VSMC) proliferation in wild-type mice and in mice lacking a cyclin-dependent kinase inhibitor, p21(WAF1) (p21). Tranilast potently inhibited the proliferation of VSMC cultures derived from wild-type mice, but VSMCs derived from p21-deficient (p21-/-) mice were unaffected by this treatment. In a mouse femoral artery model of vascular injury, tranilast administration to wild-type mice led to an upregulation of p21 expression and a decrease in the number of proliferating VSMCs, as determined by immunostaining for proliferating cell nuclear antigen. In contrast, tranilast had no effect on the number of proliferating cell nuclear antigen-positive cells in the injured arteries of p21-/- mice. Administration of tranilast significantly reduced the neointimal VSMC hyperplasia in wild-type mice at 4 weeks but had no effect on lesion formation in p21-/- mice. CONCLUSIONS: Our findings provide genetic evidence that tranilast inhibits intimal hyperplasia via a p21-dependent pathway, an activity that may contribute to its efficacy in the prophylactic treatment of postangioplasty restenosis.

Animals↗

Red wine polyphenols inhibit vascular smooth muscle cell migration through two distinct signaling pathways.

BACKGROUND: Red wine polyphenols (RWPs) have been shown to have an antiatherogenic activity mainly through antioxidative effects on LDL oxidation. Although vascular smooth muscle cell (SMC) migration is critical to atherosclerosis formation, the effect of RWPs on SMC migration has not been elucidated. In this study, we investigated whether RWPs could affect the migration of cultured SMCs stimulated by growth factors. METHODS AND RESULTS: RWP concentration dependently inhibited platelet-derived growth factor (PDGF)-BB-induced and serum-induced SMC migration in wounding assay and Boyden chamber assay. However, these inhibitory effects of RWPs were not seen in serum-stimulated vascular endothelial cell migration in either assay. Moreover, specific inhibitors of phosphatidylinositol-3' kinase (PI3K) and p38 mitogen-activated protein kinase (p38(MAPK)), but not of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), reduced PDGF-BB-induced SMC migration. To elucidate the signaling mechanism underlying the RWP effects, we investigated the effects of RWPs on the activity of PI3K and the phosphorylation of MAPK pathways in PDGF-BB-stimulated SMCs. RWPs inhibited the PI3K activity and p38(MAPK) phosphorylation, but not ERK1/2 phosphorylation, in a concentration-dependent manner. Moreover, the phosphorylation of MKK3/6, an upstream kinase of p38(MAPK), was also inhibited by RWP treatment in a concentration-dependent manner, suggesting that the inhibitory effect of RWPs on the p38(MAPK) pathway works upstream of MKK3/6. The concentration-effect relationship of RWPs necessary for the inhibition of PI3K and p38(MAPK) pathways was similar to that of cell migration assays. CONCLUSIONS: RWPs inhibit the SMC migration through the inhibition of 2 distinct signaling pathways and thus exert antiatherogenic actions.

Animals↗