Masahiro Yamawaki

Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit cardiomyocytes.

We examined whether edaravone (Eda), a clinically available radical scavenger, directly protects cardiomyocytes from ischemia/reperfusion (I/R) injury, and whether the timing of its application is critical for protection. Cardioprotective effects of edaravone were tested in the modified cell‐pelleting model of ischemia and under exogenous oxidative stress (hydrogen peroxide: H2O2) in isolated adult rabbit ventricular cells. Cell death and reactive oxygen species (ROS) generation were detected using propidium iodide (PI) and DCFH‐DA, respectively. These parameters were evaluated objectively using flow cytometory. Hypoxia and reoxygenation aggravated the proportion of dead cells from 32.2±1.8% (Baseline) to 51.3±2.7% (Control). When 15 μM edaravone was applied either throughout the entire experiment (Through) or only at reoxygenation (Reox), cell death was significantly reduced to 39.9±1.8% (P<0.01 vs Control) and 43.3±2.5% (P<0.05 vs Control), respectively. In contrast, when edaravone was applied 10 min after reoxygenation, its protective effect disappeared. Cardioprotection by edaravone was more remarkable than that afforded by other free radical scavengers, such as ascorbate and superoxide dismutase (SOD). There is a positive correlation between the cardioprotective effect of edaravone and the extent of ROS reduction. Edaravone blunted the H2O2‐induced changes in electrical properties, and significantly prolonged the time to contracture induced by H2O2 in single ventricular myocytes. Taken together, edaravone directly protects cardiomyocytes from I/R injury by attenuating ROS production, even when applied at the time of reoxygenation, suggesting that edaravone could be a potent cardioprotective therapeutic agent against hypoxia–reoxygenation injury.

Loss of the Tumor Suppressor p53 Gene at the Liver Cirrhosis Stage in Japanese Patients with Hepatocellular Carcinoma

The incidence of p53 gene aberrations is reported to be about 20-50% in hepatocellular carcinomas (HCCs). In most cases, HCC is clinically preceded by liver cirrhosis, but the genetic changes in cirrhosis are not known well. Therefore, we studied the loss of heterozygosity (LOH) of the p53 gene in cirrhotic and neoplastic foci in the livers of patients with HCC. To assess the relationship between the LOH status of the p53 gene in the liver cirrhosis stage and that in HCC, we analyzed the samples microdissected from paraffin-embedded tissues using the polymerase-chain-reaction-based assay. We studied 18 patients with HCC. Fourteen of the 18 cases showed constitutional heterozygosity for the microsatellite markers. In 8 (57%) of the 14 informative cases, LOH was detected in primary HCCs. Among these 8 doubly informative (informative and LOH positive in primary HCC) cases, 5 cases (63%) showed LOH in liver cirrhosis lesions. The pattern of p53 allelic loss in the cirrhotic foci was identical with that in the corresponding tumor. The remaining 6 cases without LOH of the p53 gene in HCC showed on p53 loss in any cirrhotic foci. LOH of the p53 gene may occur before the development of HCC.

Prognosis of critical limb ischemia patients with tissue loss after achievement of complete wound healing by endovascular therapy

OBJECTIVE Critical limb ischemia (CLI) patients with tissue loss have been recognized to have a poor survival rate. In this study, we aimed to determine whether the prognosis of CLI patients with tissue loss improves after complete wound healing is achieved by endovascular therapy. METHODS We treated 187 CLI patients with tissue loss by endovascular therapy from April 2007 to December 2012. Among these patients, 113 patients who achieved complete wound healing were enrolled. The primary end point was survival rate at 3 years. The secondary end points were limb salvage rate and recurrence rate of CLI at 3 years. RESULTS The mean follow-up period after achievement of complete wound healing was 32 ± 18 months. At 1 year, 2 years, and 3 years, the survival rates were 86%, 79%, and 74%; the limb salvage rates were 100%, 100%, and 100%; the recurrence rates of CLI were 2%, 6%, and 9%, respectively. On multivariate Cox proportional hazard analysis, age >75 years (hazard ratio, 3.18; 95% confidence interval, 1.23-8.24; P = .017) and nonambulatory status (hazard ratio, 2.46; 95% confidence interval, 1.08-5.65; P = .035) were identified as independent predictors of death for CLI patients with tissue loss even after complete wound healing was achieved. The Kaplan-Meier curve for the overall survival rate at 3 years showed that CLI patients of older age (>75 years) had a significantly decreased survival rate compared with CLI patients of younger age (≤75 years) (58% vs 87%; log-rank test, P < .001). In addition, nonambulatory CLI patients had a significantly poor survival rate relative to ambulatory CLI patients (40% vs 93%; log-rank test, P < .001). CONCLUSIONS The overall survival rate of CLI patients was acceptable and the recurrence rate of CLI was extremely low once complete wound healing was achieved. Nonambulatory status and age >75 years can serve as predictors of death even after complete wound healing is achieved.

Deployment of self‐expandable stents for complex proximal superficial femoral artery lesions involving the femoral bifurcation with or without jailed deep femoral artery

To (1) compare the outcome of self‐expandable stents with versus without jailed deep femoral artery (DFA) for proximal superficial femoral artery (SFA) lesions, and to (2) ascertain the fate of jailed DFA.

Recent Perspective on Coronary Bifurcation Intervention: Statement of the “Bifurcation Club in KOKURA”

The treatment of coronary bifurcation lesion remains a challenging issue even in the drug-eluting stent era. Frequent restenosis and stent thrombosis have been recently shown to be related not only to geometrical gap or stent structural deformation but also to rheological disturbance. Low wall shear stress at the lateral side of the bifurcation is likely to cause atherosclerotic changes due to easy access of the macrophages that induce chemical mediators. The turbulent flow over stent metal may facilitate accumulation of platelets, which results in thrombosis. The jailed strut and excess metal overlap may increase these risks. Since dramatic changes of the coronary flow pattern at the bifurcation are closely related to the genesis of atherosclerosis, future bifurcation intervention technique should be considered to restore the original physiological state as well as the anatomical structure. This article summarizes the global consensus of the members of the Asian Bifurcation Club and European Bifurcation Club at the KOKURA meeting. It also provides a perspective of basic sciences relating to bifurcation anatomy, physiology, and pathology, in the search for a best strategy for bifurcation intervention.

Predictors of non-healing in patients with critical limb ischemia and tissue loss following successful endovascular therapy

To evaluate the predictors of non‐healing in patients with critical limb ischemia (CLI) after successful endovascular therapy (EVT).

Natural history of side branches jailed by drug-eluting stents.

BACKGROUND  Stent deployment across side branch (SB) ostium is common in daily practice. The present study investigated the natural history of SBs jailed by drug-eluting stents (DES). METHODS  The thrombolysis in myocardial infarction (TIMI) flow grades of 271 consecutive SBs jailed by DES in 196 patients was assessed immediately after the procedure and at 9 months of follow-up. Patients receiving any SB intervention were excluded. RESULTS Of 271 jailed SBs, occlusion occurred in 6.27% and deterioration of flow occurred in 6.27% immediately after stenting. In patients with these SB changes, periprocedural myocardial infarction was more likely than in those without (10.0% vs. 1.8%, P = 0.017), while there was no increase of cardiac death or life-threatening complications such as stent thrombosis and Q-wave myocardial infarction (Q MI) during follow-up. At 9 months, angiography showed that one-third of the initially obstructed SBs were still occluded. In contrast, flow was maintained in almost all (98.6%) SBs with early TIMI flow grade 3 and there was no delayed occlusion of these branches. Multiple regression analysis showed that lesion complexity (Medina bifurcation class, calcification, and preprocedural TIMI grade 2 flow in the SB) and technical factors (jailing by overlapping stents) were related to SB occlusion or flow deterioration. CONCLUSIONS  Jailed SBs showing good flow after stenting had a favorable angiographic and clinical outcome after 9 months of follow-up. However, preprocedural lesion complexity and technical factors should be considered to avoid SB occlusion/flow deterioration associated with periprocedural myocardial infarction.

Predictive Factors of Re-restenosis after Repeated Sirolimus-Eluting Stent Implantation for SES Restenosis and Clinical Outcomes after Percutaneous Coronary Intervention for SES Restenosis

Sirolimus-eluting stent (SES) is established to be effective in reducing restenosis. Repeat revascularization, however, is still required in up to 5-8% of patients. In this study, we analyzed clinical and angiographic variables that might be related with SES re-restenosis and variables related with re-restenosis after repeat SES implantation for SES restenosis. We also assessed clinical outcomes at 2-year follow-up after percutaneous coronary intervention (PCI) for SES restenosis. Repeat revascularization for SES restenosis was performed in 113 patients with 140 lesions. Of the 140 lesions, follow-up coronary angiography (CAG) was performed on 117 lesions (101 patients) and revealed 46 SES re-restenotic and 71 non-re-restenotic lesions. In multivariate analysis, SES-in-SES-strategy and reference diameter before the second PCI were independent predictors of re-restenosis after PCI for SES restenosis. However, the reference diameter was the only independent predictor of re-restenosis after SES-in-SES. Major adverse cardiac events (MACE) at 2 years were found in 44 patients (43.5%), and target lesion revascularization (TLR) was performed in 33.7% of patients after SES restenosis. In conclusion, the incidence of MACE and TLR was relatively high in patients with SES restenosis, but the placement of another SES on larger-diameter vessels may be an effective strategy for the second PCI.

Impact of ultra-long second-generation drug-eluting stent implantation.

This study investigated the safety and prognosis of ultra‐long second DES (UL‐2nd DES) implantation in real‐world practice.

A case of coronary artery perforation with successful hemostasis using over-the-wire balloon and autologous blood perfusion

Advances in coronary intervention have increased the opportunity to intervene on complex lesions, resulting in an increase in PCI-related complication, including coronary artery perforation. However, treatment options for coronary perforation are limited, with delivery of devices to complex lesions being problematic. Balloon hemostasis is the usual bailout method, despite the risk of myocardial ischemia. In this report, we describe an over-the-wire balloon method to treat a patient with coronary perforation. Ischemia was avoided by injecting autologous blood through the catheter, while hemostasis was achieved by prolonged balloon inflation. This new technique is applicable when a perfusion balloon is not indicated.