Masahiro Sasaki

Differential angioscopic findings of neointimal coverage among first-, second-, and next generation drug-eluting stents.

Article history: Received 21 July 2016 Accepted 7 August 2016 Available online 9 August 2016 markedly yellow plaques (45%) were observed by angioscopy (N = 24 patients; Panel 1A and B). In the second generation DES, white but thin neointimal coverage of stent struts was observed as a transparent and homogeneous layer with less thrombi (20% of patients) or yellow plaques (20%) (N = 24 patients; Panel 2A–C), an indication of better neointimal coverage than first-generation DES.

Optical frequency-domain imaging and pulmonary angioscopy in chronic thromboembolic pulmonary hypertension.

Unresolved thromboemboli in the pulmonary arteries (PAs) cause chronic thromboembolic pulmonary hypertension (CTEPH), which is usually diagnosed by mismatched perfusion defects on ventilation-perfusion lung scintigraphy and chronic thromboembolic signs on computed tomography (CT) scan and/or conventional pulmonary angiography. In our recent three cases of CTEPH (Case 1; …

FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs.

The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs.

Intrapulmonary bronchial blood flow of rats as studied by the microsphere method

SummaryThe intrapulmonary bronchial blood flow of the left lung (systemic arterial blood flow to the left lung via the bronchial artery) was determined in 45 anesthetized and artificially ventilated male Wistar rats, weighting 263±5 g (mean ± SEM). The microsphere method was employed and designed so that recirculating microspheres across the peripheral arteriovenous anastomoses were prevented from lodging in the left lung, and disturbances of the isovolemic state of the animals became minimal. Under normal conditions with a mean arteiral pressure of 115±2 mmHg (n=40), the bronchial blood flow of the left lung was found to be 0.307±0.033 ml/min on average, and amounted to 0.52±0.06% of the cardiac output. The flow (ml/min) normalized per kg body weight, 100 g wet lung, or 100 g dry lung was 1.14±0.12, 76±8, or 368±39, respectively. The total intrapulmonary bronchial blood flow of the left and right lungs could be estimated by multiplying the intrapulmonary bronchial flow of the left lung by the weight ratio (total: left) of 2.9. The variability of the flow data was small, as confirmed in a study with simultaneous injection of two differently radiolabeled microspheres. The reproducibility of duplicate measurements was excellent.

Interleukin-1β is associated with coronary endothelial dysfunction in patients with mTOR-inhibitor-eluting stent implantation

Implantation of mammalian target of rapamycin (mTOR)-inhibitor drug-eluting stents (DESs) impairs coronary endothelial function. There are no known non-invasive biomarkers of coronary endothelial dysfunction. We aimed to assess the association between serum interleukin-1beta (IL-1β) and coronary endothelial dysfunction in patients with mTOR-inhibitor DES implantation and to investigate the association between the mTOR pathway and IL-1β. We enrolled 35 patients who had implanted DESs for coronary artery disease. At a 10-month follow-up, peripheral venous blood samples were collected to measure IL-1β levels. Coronary endothelial dysfunction was evaluated by intracoronary infusion of incremental doses of acetylcholine. Serum IL-1β levels were significantly associated with the magnitude of vasoconstriction to acetylcholine at the segment distal (P < 0.05) but not proximal to the stent. Serum IL-1β levels were positively correlated with stent length (P < 0.05). To examine the direct effects of mTOR inhibition on IL-1β release, sirolimus was incubated in cultured human umbilical vein endothelial cells (HUVECs) or coronary artery smooth muscle cells (CASMCs). Sirolimus directly increased IL-1β mRNA expression (P < 0.01) and enhanced IL-1β release into the culture media (P < 0.01) in CASMCs, but not in HUVECs. Inhibition of mTOR triggers IL-1β release through transcriptional activation in CASMCs. Serum IL-1β levels are a potential biomarker for mTOR-inhibitor DES-associated coronary endothelial dysfunction.

FDG-PET reveals coronary artery inflammation proceeding to cardiac allograft vasculopathy progression

A 48-year-old man with idiopathic dilated cardiomyopathy received heart transplantation on March 2005, who has undergone coronary angiography (CAG) and intravascular ultrasound (IVUS) to examine cardiac allograft vasculopathy (CAV) every 1–3 years. Although CAG has not shown significant stenoses or angiographic changes …

Pulmonary artery dysfunction in chronic thromboembolic pulmonary hypertension

Background Unresolved thromboemboli in the pulmonary arteries (PA) is known to cause chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains unknown if vascular dysfunction in pulmonary arteries exists in patients with CTEPH. Methods and results We enrolled 7 female patients with CTEPH in this study, who have stable pulmonary hemodynamics after balloon pulmonary angioplasty (age; 73.6 ± 3.0 years old, mean right atrial pressure; 4.1 ± 0.4 mm Hg, mean pulmonary arterial pressure; 29.4 ± 2.7, mean pulmonary artery wedge pressure; 8.1 ± 1.2, pulmonary vascular resistance; 397.3 ± 51.7 dynes, cardiac index; 3.1 ± 0.2 L/min/m2). Pulmonary artery vascular function was evaluated by measuring pulmonary artery vasomotion in response to acetylcholine (Ach) at 10-month follow-up after balloon pulmonary angioplasty. All pulmonary vasoactive drugs were discontinued on the day of the procedures. The endothelium-dependent vasomotor response was evaluated by intra-pulmonary artery infusion of Ach at the dose of 10− 8 mol/l, and the vaso-spastic response was at 10− 6 mol/l. We evaluated vasomotor responses at the same segment in each patient, by measuring % changes of luminal area detected by quantitative pulmonary arterial optical frequency-domain imaging (OFDI), where OFDI catheter was fixed during the procedure. Endothelial dysfunction was observed at the dose of Ach at 10− 8 mol/l and vasoconstriction was also confirmed at the dose of Ach at 10− 6 mol/l in the diseased pulmonary arteries in CTEPH. Conclusions These results indicated that the pulmonary artery dysfunction exists in patients with CTEPH, which may be involved in the pathogenesis and progression of CTEPH.

Effects With and Without Clopidogrel Loading Treatment for Acute Ischemic Cerebrovascular Disease Patients: A Retrospective Cohort Study

OBJECTIVES We investigated the effectiveness of clopidogrel loading (CL) treatment compared with usual clopidogrel non-loading (NL) treatment for acute ischemic cerebrovascular disease. METHODS We screened consecutive 1072 patients with ischemic cerebrovascular disease within 48 hours of symptom onset admitted to our hospital. Eligible patients were divided into the CL group (300 mg on day 1, followed by 50-75 mg once daily) and NL group (50-75 mg once daily). The incidence proportion of neurologic deterioration during hospitalization was compared between the 2 groups using logistic regression analysis. RESULTS A total of 224 patients, 39 in CL group and 185 in NL group, were enrolled. The frequency of neurologic deterioration did not significantly differ between the 2 groups (risk ratio [95% confidence interval]: 1.47 [.88-2.46]). On the preset subgroup analysis according to stroke subtype, the frequency of neurologic deterioration in CL group was significantly higher in branch atheromatous disease (risk ratio: 2.44 [1.67-3.55]) and was not different statistically in transient ischemic attack (risk ratio: 0). The analysis adjusted by several confounders showed that the incidence proportion of neurologic deterioration was not significantly different in large artery atherosclerosis (adjusted odds ratio: 1.06 [.23-4.84]) as crude analysis. The incidence proportion of adverse events was not significantly different between the 2 groups. CONCLUSIONS The effect of CL therapy differed by stroke subtypes in preventing neurologic deterioration. CL therapy appeared to be ineffective in branch atheromatous disease. Therefore, the choice of CL therapy should carefully be made according to stroke subtypes.

Clinical features of patients who died within 24 h after admission to a stroke care center

Objective In Japan, stroke care is provided through medical cooperation and standardized treatment. However, various factors affect mortality in the hyperacute phase. The present study investigated factors associated with death within 24 h after admission for acute stroke. Methods Among 2335 patients admitted within 24 h after stroke onset from 1 January 2007 to 31 December 2012, a total of 139 deaths occurred. Forty-eight deaths occurred within 24 h after admission. We retrospectively examined the clinical features of these 48 patients. Results The overall mortality rate was 6.0%. When the initial 72-h period was divided into ≤24 h (Period I), >24 to 48 h (Period II), and >48 to 72 h (Period III), deaths were significantly more frequent in Period I than in the other two periods. The frequency of intracerebral haemorrhage (ICH) was also significantly higher in Period I than in the other two periods. Factors significantly associated with death from ICH were systolic blood pressure, hematoma volume, and surgery. Conclusion The mortality rate was low among patients with stroke transported to the authors’ medical center within 24 h of onset. Blood pressure management and the timing of determining indications for surgery are important factors in acute haemorrhagic stroke care.

Successful Endovascular Treatment of Aortoiliac Bifurcation Stenosis Using an Empirically Based T and Protrude-Stenting with Self- and Balloon-Expandable Stents

A 73-year-old woman with arteriosclerosis obliterans (ASO) was underwent a crossover stenting for an aortoiliac bifurcation from the right common iliac artery (CIA) with a self-expandable bare-metal stent (SE-BMS); however, a new stenosis later occurred just behind the bifurcation of the left CIA. An ex vivo experiment demonstrated that culotte-stenting by additional implantation of a balloon-expandable bare-metal stent (BE-BMS) through stent struts of the SE-BMS would be empirically infeasible. Although we had initially planned a T-stenting for the additional implantation of a BE-BMS in the left CIA, we finally deployed the stent in the CIA with the proximal end protruding into the previously-implanted SE-BMS through the stent struts to avoid incomplete coverage of the stenosis by reference to the ex vivo experiments. The patient has had no recurrence for 36 months.