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Background— Noncardiac surgery after percutaneous coronary intervention (PCI) has been reported to be carrying high risk for both ischemic and bleeding complications. However, there has been no report comparing the incidence and outcomes of surgical procedures after coronary artery bypass grafting (CABG) with those after PCI. Methods and Results— Among 14 383 patients undergoing first coronary revascularization (PCI, n=12 207; CABG, n=2176) enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/CABG Registry Cohort-2, surgical procedures were performed more frequently after CABG (n=560) than after PCI (n=2398; cumulative 3-year incidence: 27% versus 22%; unadjusted P P =0.9; adjusted hazard ratio, 0.97; 95% confidence interval, 0.47–1.89; P =0.9). The risk for the primary bleeding outcome measure (moderate or severe bleeding by Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries classification) was lower in the CABG groups than in the PCI group (cumulative incidence: 1.3% versus 2.6%; unadjusted P =0.07; adjusted hazard ratio, 0.36; 95% confidence interval, 0.12–0.87; P =0.02). There were no interactions between the timing of surgery and the types of coronary revascularization (CABG/PCI) for both ischemic and bleeding outcomes. Conclusions— Surgical procedures were performed significantly more frequently after CABG than after PCI, particularly

Treatment of coronary artery disease has significantly changed over the past decade including an introduction of drug-eluting stents and a more stringent adherence to evidence-based medications. However, the impact of these advanced treatment methods on the practice patterns and long-term outcomes in patients undergoing coronary revascularization in the real world has not been yet fully evaluated. The present study population consisted of the 2 groups of patients who underwent their first coronary revascularization in the Coronary REvascularization Demonstrating Outcome Study in Kyoto Registry Cohort-1 (bare-metal stent era: January 2000 to December 2002, n = 8,986) and Cohort-2 (drug-eluting stent era: January 2005 to December 2007, n = 10,339). Compared with Cohort-1, the proportion of patients treated with percutaneous coronary intervention significantly increased in Cohort-2 (73% vs 81%, p0.001), particularly for 3-vessel disease (50% vs 61%, p0.001) and left main disease (18% vs 36%, p0.001). Evidence-based medications were more frequently used in Cohort-2. The cumulative 2-year incidence of and the adjusted risk for all-cause death were not significantly different between Cohort-1 and Cohort-2 (6.2% vs 6.4%, p = 0.69, and hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.81 to 1.03, p = 0.15). Adjusted risks for both myocardial infarction and repeated coronary revascularization were significantly reduced in Cohort-2 compared with Cohort-1 (HR 0.80, 95% CI 0.67 to 0.96, p = 0.02, and HR 0.73, 95% CI 0.69 to 0.77, p0.001, respectively). In conclusion, despite changes in treatment methods over time, the long-term mortality of patients undergoing coronary revascularization in the real-world clinical practice has not been changed, although there was a significant reduction of myocardial infarction and repeated coronary revascularization.

A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg−1∙day−1), a medium dose of curcumin (5 mg∙kg−1∙day−1), or a high dose of curcumin (50 mg∙kg−1∙day−1). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg−1∙day−1 and disappear at 0.5 mg∙kg−1∙day−1. To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required. Keywords:: curcumin, heart failure, hypertrophy, dose-dependency, p300

Background According to the Japanese Circulation Society guidelines, a bioprosthesis is recommended for aortic valve replacement (AVR) in patients aged ≥65 years who have no risk factors for thromboembolism. There are few data, however, regarding the actual durability of bioprosthetic valves in Japanese patients. The purpose of this study was to assess the long-term durability of Carpentier-Edwards pericardial (CEP) valves in Japanese AVR patients, and to assess the risk factors for reoperation due to structural valve deterioration (SVD). Methods and results From 1986 to 2001, a total of 591 patients underwent AVR with CEP valves in 9 hospitals. Of these, 574 patients (mean age, 71.9±8.5 years) were analyzed in this study. There were 26 in-hospital deaths (4.5%). The 10-year follow-up rate was 82.6% and the median follow-up time was 9.2 years. Freedom from reoperation due to SVD was 99.5%, 96.7%, and 87.5% at 5, 10, and 15 years, respectively. Factors that raised the risk of reoperation due to SVD included younger age at operation and history of prior operation. In patients aged ≥65 years, freedom from reoperation due to SVD was 94.4% at 15 years. Conclusions The durability of CEP valves in patients with AVR was excellent, especially in elderly patients. Thus, it seems appropriate to follow the current Japanese Circulation Society recommendations for the use of bioprosthetic valves.

Objectives: The postoperative left ventricular end-systolic volume index and ejection fraction are benchmarks of surgical ventricular reconstruction but remain unpredictable. This study aimed to identify who could be associated with a higher long-term survival by adding surgical ventricular reconstruction to coronary artery bypass grafting than coronary artery bypass grafting alone (responders to surgical ventricular reconstruction). Methods: The subjects were 293 patients (median age, 63 years; 255 men) who underwent coronary artery bypass grafting for ischemic heart disease with left ventricular dysfunction in 16 cardiovascular centers in Japan. The relationships among surgical ventricular reconstruction, postoperative end-systolic volume index, ejection fraction, and survival were analyzed to identify responders to surgical ventricular reconstruction. Results: Surgical ventricular reconstruction was performed in 165 patients (56%). The end-systolic volume index and ejection fraction significantly improved (end-systolic volume index, 91 to 64 mL/m2; ejection fraction, 28% to 35%) for all patients. The postoperative end-systolic volume index and ejection fraction were estimated, and surgical ventricular reconstruction was found to be significantly associated with both end-systolic volume index (14.5 mL/m2 reduction, P < .001) and ejection fraction (3.1% increase, P = .003). During the median follow-up of 6.8 years, 69 patients (24%) died. Only the postoperative ejection fraction was significantly associated with survival (hazard ratio, 0.925; 95% confidence interval, 0.885-0.968), although this effect was limited to those with postoperative end-systolic volume index of 40 to 80 mL/m2 in the subgroup analysis (hazard ratio, 0.932; 95% confidence interval, 0.894-0.973). Conclusions: Adding surgical ventricular reconstruction to coronary artery bypass grafting could reduce the mortality risk by increasing ejection fraction for those with a postoperative end-systolic volume index within a specific range. The postoperative end-systolic volume index could demarcate responders to surgical ventricular reconstruction, and its estimation can help in surgical decision making.

An 80-year-old male underwent a transcatheter aortic valve implantation (TAVI) for severe senile aortic stenosis. Six weeks after the surgery, he was readmitted to our institution because of a high-grade fever. Transesophageal echocardiography revealed thickening of all three leaflets of the aortic prosthesis and mobile mass on the leaflet, and Streptococcus sanguis was identified from his blood culture. Therefore, he was diagnosed with prosthetic valve endocarditis (PVE) and received intensive intravenous antibiotic therapy. Because he did not respond to the pharmacological therapy, surgical aortic valve replacement (AVR) was indicated although it was considered a relatively high-risk procedure. Herein, we report on the successful surgical AVR in this patient using a pericardial valve after removal of the infected prosthetic valve, and discuss some issues related to this rare complication after TAVI.

We present two cases of aortic valve replacement (AVR) in patients with protruding coronary artery stents from the coronary ostia. In the first case, an 87-year-old female was referred for AVR due to severe aortic stenosis (AS). During the operation, we found stents protruding from the left and the right coronary ostia into the aortic root. We performed AVR with a mechanical valve and coronary artery bypass grafting with the saphenous vein to the left anterior descending artery. In the second case, a 77-year-old female was referred for AVR due to severe AS with a history of healed infective endocarditis. During surgery on the second patient, we found a stent protruding 7mm from the left coronary ostium into the aortic root. The edge of the stent was trimmed, and AVR with a mechanical valve was performed. In both patients, we decided to use a mechanical prosthesis instead of a bioprosthesis because of the risk of leaflet injury. Herein, we discuss some issues regarding patients with AS requiring AVR with prior history of coronary stenting in the coronary ostia. Learning objective: To explore the problem of coronary stents protruding into the ostia in cases of percutaneous coronary intervention of left main or right proximal lesions, which can compromise subsequent aortic valve procedures including surgical aortic valve replacement or even transcatheter aortic valve replacement thereafter.>

BackgroundPostoperative retrosternal adhesion increases the risk of cardiac injury during cardiac reoperation. We created a novel biodegradable glue called “Lydex” that is derived from food additives. The purpose of this study is to evaluate this new biomaterial's biocompatibility and its preventive effect on retrosternal adhesion.MethodsWe performed a median sternotomy and anterior pericardiectomy on Japanese white rabbits, and then closed the chest (control, group 1; n = 12), implanted an expanded polytetrafluoroethylene membrane (group 2; n = 12), or applied Lydex (group 3; n = 12) before closure. After 4 weeks, we evaluated macroscopic adhesion (each group; n = 6) and microscopic findings for fibrosis and macrophage infiltration (each group; n = 6).ResultsIn group 3, the retrosternal adhesion score was significantly lower than in group 1 (P = .0022). There was no significant difference between groups 2 and 3. The fibrotic area ratio was significantly lower in group 3 than in groups 1 and 2 (P

AIMS We sought to investigate medium-term outcome of percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) in patients with triple-vessel coronary artery disease (TVD). METHODS AND RESULTS We identified 2,981 patients with TVD (PCI: N=1,825, CABG: N=1,156) among 15,939 patients with first coronary revascularisation enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2. Excess adjusted three-year risk of the PCI group relative to the CABG group for death/myocardial infarction (MI)/stroke was significant (HR 1.47 [95% CI: 1.13-1.92, p=0.004]). Adjusted risk for all-cause death was also significantly higher with PCI as compared with CABG (HR 1.62 [95% CI: 1.16-2.27, p=0.005]), while risk for cardiac death was neutral between the two groups (HR 1.3 [95% CI: 0.81-2.07, p=0.28]). PCI was also associated with a markedly higher risk for any coronary revascularisation. Regarding the analysis stratified by the SYNTAX score, the adjusted HR of PCI relative to CABG for death/MI/stroke was 1.66 (95% CI: 1.04-2.65, p=0.03) in the low-score (

[Objective]Patients with coronary artery disease (CAD) often have prior stroke or concomitant extra-cardiac vascular disease (EVD) such as cerebral, aortic, or peripheral vascular disease. However, clinical outcomes after coronary revascularization in patients with polyvascular disease have not been fully elucidated. [Methods]Among 15, 263 patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto registry Cohort-2 from January 2005 to December 2007, there were 1443 patients with prior stroke (stroke + CAD group), 974 patients with EVD (EVD + CAD group), 253 patients with both prior stroke and EVD (stroke/EVD/CAD group) and 12, 593 patients with neither prior stroke nor EVD (CAD alone group [reference]). [Results]The cumulative incidence of major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction and stroke) through 3 years was significantly higher in patients with polyvascular disease compared with reference patients (19.9% in the stroke + CAD group, 18.5% in the EVD + CAD group, 20.1% in the stroke/EVD/CAD group, and 11.2% in the CAD alone group, P < 0.0001). After adjusting confounders, the presence of EVD and/or stroke was independently associated with higher risk for MACE compared with the reference group (adjusted HR [95%CI]: 1.34 [1.17–1.54], P < 0.0001 in the stroke + CAD group, 1.56 [1.32–1.84], P < 0.0001 in the EVD + CAD group, and 1.66 [1.24–2.23], P = 0.0007 in the stroke/EVD/CAD group). However, the presence of EVD and/or stroke was not associated with higher risk for myocardial infarction. [Conclusions]Clinical outcome after coronary revascularization was worse in patients with prior stroke and/or EVD, which was mainly driven by the increased risk for non-coronary cardiovascular events.

It is well recognized that poor perioperative blood glucose (BG) control can increase the risk of infection, cardiovascular accidents, and even death in patients undergoing cardiac surgery. Since it has been reported that tight BG control (80-110 mg/dL) yields better outcomes in critically ill patients, it became a standard of care to control BG using intravenous insulin infusion in ICU. However, it has been debated in terms of the optimal target range whether a strict control with intensive insulin therapy is better than liberal control. Because strict BG control can often cause hypoglycemia, which in turn increases the hospital mortality. In fact, a meta-analysis of randomized clinical trials concluded that tight BG control was not associated with significantly reduced hospital mortality but was associated with an increased risk of hypoglycemia. According to the current published guidelines, it seems to be optimal to control BG level of 140-180 mg/dL in ICU. In terms of more strict BG control (110-140 mg/dL), it may be appropriate in selected patients as long as this can be achieved without significant hypoglycemia.

The stroke rate after coronary artery bypass grafting (CABG) compared to percutaneous coronary intervention (PCI) is generally considered high because cardiopulmonary bypass and aortic manipulations are often associated with cerebrovascular complications. However, an increasing number of CABGs performed without cardiopulmonary bypass (OPCAB) may improve those outcomes. Of 6,323 patients with multivessel and/or left main coronary artery disease, 3,877 patients underwent PCI, 1,381 conventional on-pump CABG, and 1,065 OPCAB. Median follow-up was 3.4 years. Stroke types were classified as early (onset of stroke within 24 hours after revascularization), delayed (within 30 days), and late (after 30 days). Propensity score analysis showed that the incidences of early, delayed, and late stroke did not differ between PCI and OPCAB (0.65, 95% confidence interval 0.08 to 5.45, p = 1.00; 0.36, 0.10 to 1.29, p = 0.23; 0.81, 0.52 to 1.27, p = 0.72, respectively). In contrast, incidence of early stroke after on-pump CABG was higher than after OPCAB (7.22, 1.67 to 31.3, p = 0.01), but incidences of delayed and late stroke were not different (1.66, 0.70 to 3.91, p = 0.50; 1.18, 0.83 to 1.69, p = 0.73). In conclusion, occurrence of stroke was not found to differ in patients after PCI versus OPCAB regardless of onset of stroke. Occurrence of early stroke after OPCAB was lower than that after on-pump CABG, yet occurrences of delayed and late strokes were similar for the 3 revascularization strategies.

A large number of clinical trials of therapeutic angiogenesis in patients with critical limb ischemia have been conducted in recent years. However, limb amputation, which is used as a primary endpoint in such studies, is not often required in Japan, which can make it difficult to carry out related clinical trials. Transcutaneous oxygen pressure (TcPO2) is widely used to evaluate the severity of limb ischemia, to decide the level of amputation, and to predict wound healing after limb amputation. The aim of the present study was to elucidate whether TcPO2 can be a surrogate index of limb ischemia, and to define an appropriate cutoff value for wound healing after limb amputation using meta-analysis.A computer search was performed to identify studies describing the association between TcPO2 and limb ischemic events. From these, studies focused on wound healing after limb amputation were combined and analyzed.Eleven studies were identified for inclusion in this analysis. The analysis demonstrated that TcPO2 20 mmHg was a valid cutoff value for limb amputation and TcPO2 30 mmHg would be an appropriate value for wound healing after limb amputation.TcPO2 of 20 and 30 mmHg were considered appropriate cutoff values for limb amputation and wound healing after amputation, respectively.

Background— Many of the previous randomized trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary artery disease reported equivalent or better survival with CABG as compared with PCI at 5-year follow-up. However, 5-year follow-up might be too short to evaluate the true differences in long-term clinical outcomes between PCI and CABG. Methods and Results— Among 8934 patients enrolled in the extended 10- to 14-year follow-up study of the CREDO-Kyoto registry cohort-1 (Coronary Revascularization Demonstrating Outcome study in Kyoto) conducted in the bare-metal stent era, 5152 (PCI: n=3490 and CABG: n=1662) patients had multivessel coronary artery disease without left main disease. Median follow-up duration was 11.2 (interquartile range: 10.2–12.2) years. The cumulative 10-year incidence of all-cause death was not significantly different between PCI and CABG (32.2% versus 31.7%; log-rank P =0.93). After adjusting for confounders, however, the mortality risk of PCI was significantly higher than that of CABG (hazard ratio, 1.19 [95% confidence interval, 1.02–1.39]; P =0.03). Within 5 years after the index procedure, the risk for all-cause death was significantly higher after PCI than after CABG (hazard ratio, 1.41; 95% CI, 1.12–1.79; P =0.004). By a landmark analysis at 5 years, however, the cumulative 10-year incidence of and adjusted risk for all-cause death beyond 5 years were not significantly different between PCI and CABG (19.3% versus 20.0%; log-rank P =0.22 and hazard ratio, 1.02, 95% confidence interval, 0.83–1.26; P =0.82). Conclusions— CABG as compared with PCI was associated with better 10-year survival in patients with multivessel coronary artery disease. However, the benefit of CABG compared with PCI on late mortality beyond 5 years was not observed in this study.

Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation.

A 12-month-old microminipig, weighing 12.6 kg, showed 3 repeated episodes of transient ST-segment elevation in 24 hr Holter electrocardiogram after placing an ameroid constrictor around the left anterior descending coronary artery. Ventricular fibrillation was noticed just after the cessation of the 24 hr Holter-electrocardiogram recording. Direct current defibrillations and cardiopulmonary resuscitation were performed; however, they were unsuccessful, leading to the animal’s death. Its heart was excised for macroscopic analysis, which indicated that lumen of the ameroid constrictor was not narrowed and that there was no dissection, embolus or thrombus in the coronary arteries, indirectly suggesting that coronary artery vasospasm may have caused the ischemic attacks. Thus, microminipig may possess some potential to have coronary vasospasm.

Inflammation-mediated elastin destruction in the aortic medial layer is related to progression of abdominal aortic aneurysm (AAA). Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols, reportedly increases elastin synthesis in vitro and may possess anti-inflammatory effects. We used a rat model to investigate whether EGCG could prevent AAA progression.AAA was induced with administration of intraluminal elastase and extraluminal CaClThe abdominal aortic diameter was significantly smaller in the EGCG group than in the control group on day 28 (2.9 ± 0.2 vs 2.3 ± 0.1 mm; P .0001). The medial layer wall thickness and elastin content were significantly greater in the EGCG group than in the control group on day 28 (68.4 ± 13.6 vs 46.7 ± 13.4 μm [P .001] and 20.3 ± 4.6 vs 9.5 ± 3.6% [P .0001], respectively). Gene expression levels of tropoelastin and lysyl oxidase were significantly higher in the EGCG group immediately before AAA induction, indicating promoted elastoregeneration by EGCG administration (tropoelastin: 0.59 ± 0.36 control vs 1.24 ± 0.36 EGCG [P .05], lysyl oxidase: 0.77 ± 0.45 control vs 1.34 ± 0.4 EGCG [P .05]) (fold increase). Gene expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were significantly downregulated in the EGCG group (1.82 ± 0.71 vs 0.97 ± 0.59 [P .05] and 3.91 ± 3.24 vs 0.89 ± 0.59 [P .05], respectively). On day 7, gene expression levels and gelatinolytic activity of matrix metalloproteinase 9 were significantly lower in the EGCG group (1.41 ± 0.86 vs 0.51 ± 0.42 [P .05] and 1.00 ± 0.17 vs 0.29 ± 0.12 [P .0001], respectively), whereas gene expression levels of tissue inhibitors of metalloproteinase-1 were significantly higher in the EGCG group (0.96 ± 0.11 vs 1.14 ± 0.09; P .05).EGCG attenuated AAA progression in a rat model by preserving the aortic thickness and elastin content of the medial layer through regeneration of elastin, as mediated by anti-inflammatory effects, and subsequent reduction of matrix metalloproteinase activity.

Regenerative medicine is emerging as a new approach to the treatment of severe cardiovascular diseases that are resistant to conventional therapies. Although the type of cell transplanted (e.g., pluripotent stem cells, bone marrow-derived stem cells, skeletal myoblasts, or cardiac stem cells) influences the outcome of stem cell transplantation, the method of transplantation is also important, as the efficiency of engraftment after simple needle injection is poor. Scaffold-free cell sheet transplantation technology is one of the most promising methods in this regard. Although the results of clinical trials of stem cell therapy have been marginal to date, further elucidation of the actual mechanisms of cardiac repair following cell therapy would enhance the potential for full-scale implementation of stem cell therapy. In addition to stem cell therapy, the field of cardiovascular regenerative medicine includes interspecific chimera technology, drug delivery systems using biodegradable materials, and gene therapy. Integration of these new modalities with conventional therapies will be important to realize the goal of cardiovascular regenerative medicine tailored to the condition of each individual patient. Cardiovascular surgery would be an excellent means of carrying out this strategy and could potentially resolve the health problems of the increasing number of advanced cardiovascular patients. Herein, we review the recent basic and clinical research associated with the realization of regenerative medicine in the field of cardiovascular surgery.

Although stem cell therapy is a promising strategy for cardiac restoration, the heterogeneity of transplanted cells has been hampering the precise understanding of the cellular and molecular mechanisms. Previously, we established a cardiovascular cell differentiation system from mouse pluripotent stem cells, in which cardiomyocytes (CMs), endothelial cells (ECs), and mural cells (MCs) can be systematically induced and purified. Combining this with cell sheet technology, we generated cardiac tissue sheets reassembled with defined cardiovascular populations. Here, we show the potentials and mechanisms of cardiac tissue sheet transplantation in cardiac function after myocardial infarction (MI). Transplantation of the cardiac tissue sheet to a rat MI model showed significant and sustained improvement of systolic function accompanied by neovascularization. Reduction of the infarct wall thinning and fibrotic length indicated the attenuation of left ventricular remodeling. Cell tracing with species-specific fluorescent in situ hybridization after transplantation revealed a relatively early loss of transplanted cells and an increase in endogenous neovascularization in the proximity of the graft, suggesting an indirect angiogenic effect of cardiac tissue sheets rather than direct CM contributions. We prospectively dissected the functional mechanisms with cell type-controlled sheet analyses. Sheet CMs were the main source of vascular endothelial growth factor. Transplantation of sheets lacking CMs resulted in the disappearance of neovascularization and subsequent functional improvement, indicating that the beneficial effects of the sheet were achieved by sheet CMs. ECs and MCs enhanced the sheet functions and structural integration. Supplying CMs to ischemic regions with cellular interaction could be a strategic key in future cardiac cell therapy. Disclosure of potential conflicts of interest is found at the end of this article.

SummaryBackground and purposeThere have been no large-scale studies on the impact of diabetes mellitus (DM) on outcomes in Japanese patients undergoing coronary artery bypass grafting (CABG).Methods and subjectsA multi-institutional retrospective cohort study was conducted in 14 Japanese centers. All adult patients who underwent isolated CABG from 2007 to 2008 were included (n=1522, mean age: 68.5years). The definitions of DM were all patients admitted with diagnosis of DM and preoperative glycated hemoglobin (Hb) A1c≥6.5%. Univariate and multivariate analyses were performed to identify the risk of morbidity and mortality.ResultsThere were 849 DM and 572 non-DM patients. Preoperative mean HbA1c were 7.1% in the DM group and 5.7% in the non-DM group (p

We report the case of a 68-year-old man with progressive heart failure due to effusive-constrictive pericarditis. During approximately 1 month, echocardiography revealed rapid progression from pericarditis with effusion without tamponade to pericardial thickening and diastolic dysfunction. Cardiac catheterization revealed that the pressure in the right heart chambers remained high after pericardiocentesis. The patient was rescued by aggressive pericardiectomy and sharp dissection of the epicardium into small fragments. This on-pump beating-heart surgery is known as the waffle procedure.

OBJECTIVE Approximately 25% of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have diabetes, and the diagnosis of diabetes roughly doubles the mortality risk associated with coronary artery disease. However, the impact of diabetes may differ according to ethnicity. Our objective was to examine the impact of diabetes on long-term survival among U.S. and Japanese patients who underwent PCI or CABG. RESEARCH DESIGN AND METHODS For the current analysis, we included 8,871 patients from a Japanese multicenter registry (Coronary Revascularization Demonstrating Outcome database in Kyoto; median follow-up 3.5 years; interquartile range [IQR] 2.6–4.3) and 7,229 patients from a U.S. multipractice registry (Texas Heart Institute Research Database; median follow-up 5.2 years; IQR 3.8–6.5). RESULTS Diabetes was more prevalent among Japanese than U.S. patients (39.2 vs. 31.0%; P < 0.001). However, after revascularization, long-term all-cause mortality was lower in diabetic Japanese patients than in diabetic U.S. patients (85.4 vs. 82.2%; log-rank test P = 0.009), whereas it was similar in nondiabetic Japanese and U.S. patients (89.1 vs. 89.5%; P = 0.50). The national difference in crude mortality was also significant among insulin-using patients with diabetes (80.8 vs. 74.9%; P = 0.023). When long-term mortality was adjusted for known predictors, U.S. location was associated with greater long-term mortality risk than Japanese location among nondiabetic patients (hazard ratio 1.58 [95% CI 1.32–1.88]; P < 0.001) and, especially, diabetic patients (1.88 [1.54–2.30]; P < 0.001). CONCLUSIONS Although diabetes was less prevalent in U.S. patients than in Japanese patients, U.S. patients had higher overall long-term mortality risk. This difference was more pronounced in diabetic patients.

Purpose: We investigated whether mitral annuloplasty (MAP) should be performed for mild ischemic mitral regurgitation (IMR).Methods: We selected 57 patients with preoperatively mild IMR. Twenty-eight patients who previously had moderate MR or more, underwent MAP (group 1) while 29 patients with persistent mild MR, did not (group 2). We reviewed MR changes and outcomes of these patients. We also investigated other IMR patients with preoperatively moderate or more MR as reference data (group 3).Results: In group 1, MR was none or trace in 25 patients immediately after operation, however, eleven out of these patients (44%) showed postoperative MR up-grade. The trends of MR changes in group 1 were similar to those of patients in group 3. In group 2, MR was graded mild in 79% of patients in mid-term postoperative stage although 28% of patients were up-graded or down-graded during postoperative follow-up.Conclusion: MAP is not necessary for patients with persistently mild IMR. Patients with preoperatively mild IMR with episodes of MR exacerbation had better be treated similarly as those with moderate or more IMR and undergo MAP.

Background: We explored the determinants of mortality in order to develop and validate the Kyoto model, which predicts outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Methods and Results: A total of 9,393 patients who underwent their first coronary revascularization without concomitant valvular, left ventricular, or major vascular surgery were followed over a median follow-up of 3.5 years in the CREDO-Kyoto Registry. We fitted separate Cox regression to mortality after PCI and CABG. The best-fitting model was internally validated by 10-fold cross-validation. The Cox regression identified the following predictors: age, sex, body mass index, ejection fraction, atrial fibrillation, diabetes mellitus, hyperlipidemia, current smoker, stroke, peripheral vascular disease, chronic obstructive pulmonary disease, malignancy, kidney disease, anemia, liver cirrhosis, diseased vessel, left main disease, proximal left anterior descending artery disease, and total occlusion. This model simulated that the 3-year mortality for a hypothetical 70-year-old man with 2-vessel disease is 2.0% after PCI and 2.6% after CABG, or 4.2% and 5.1% if he has diabetes and chronic kidney disease. The Hosmer-Lemeshow test showed no significant deviations between the observed and predicted events. The C statistics were greater than 0.78. Conclusions: The Kyoto model can assist clinicians and patients in adherence to medication and lifestyle changes after revascularization and in individualized decision making. A web application is available at http://www.biostatistics.jp/prediction/kyoto-model. (Circ J 2012; 76: 328-334)

Traumatic tricuspid valve regurgitation (TR) is a fairly rare complication of blunt chest trauma, and is usually caused by chordal and/or papillary muscle rupture. A 45-year-old woman, with a history of blunt chest trauma 16 years previously, was referred for surgery due to severe TR. During surgery, we found a large perforation on the right atrial wall located just anteriorly to the anterior leaflet, which was caused by annular detachment, in addition to anterior leaflet prolapse due to rupture of anterior chordae. The tricuspid valve was successfully repaired by direct closure of the perforation and chordal replacement with suture annuloplasty. Herein, we report a successful surgical repair of TR with annular detachment with right atrial dissection caused by blunt chest trauma. Learning objective: Traumatic tricuspid valve regurgitation is rare, but one may encounter it from time to time. In this report, we describe the first case report of tricuspid annular detachment with fistula between the right atrium and the right ventricle caused by right atrial dissection, in which successful surgical repair was performed.>

Background— Age and sex are important considerations in the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in daily clinical practice. Methods and Results— Of 25 816 patients enrolled in the multicenter Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto; Cohort-1, n=9877; Cohort-2, n=15 939), the present study population consisted of 5651 patients (men, n=3998; women, n=1653) with triple-vessel coronary artery disease who were considered to be pertinent in comparisons of PCI with CABG (PCI, n=3165; CABG, n=2486). Patients were divided into 3 groups according to the tertiles of age: ≤65 years (n=1972), 66 to 73 years (n=1820), and ≥74 years (n=1859). The excess adjusted mortality risk of PCI relative to CABG was significant in patients ≥74 years of age (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.10–1.79; P =0.006), whereas the risks were neutral in patients ≤65 years of age (HR, 1.05; 95% CI, 0.73–1.53; P =0.78) and in patients 66 to 73 years of age (HR, 1.03; 95% CI, 0.78–1.36; P =0.85; interaction P =0.003). The excess mortality risk of PCI relative to CABG was significant in men (HR, 1.24; 95% CI, 1.03–1.50; P =0.02) and trended to be significant in women (HR, 1.34; 95% CI, 0.98–1.84; P =0.07) without significant interaction between sex and the mortality risk of PCI relative to CABG (interaction P =0.40). Conclusions— There was a significant association between age and the mortality risk of PCI relative to CABG with excess risk in patients ≥74 years of age and neutral risk in younger patients. There was no significant sex-related difference in the mortality risk of PCI relative to CABG.

Poly(ADP-ribose) polymerase (PARP)-1 inhibitor has been suggested to attenuate the ischemia-reperfusion injury. We investigated the protective effect of the cardioplegia with a PARP-1 inhibitor, 4-hydoxyquinazoline (4-HQ), against myocardial ischemia-reperfusion injury. Isolated rat hearts were perfused on a Langendorff apparatus and cardioplegically arrested for 90 min by perfusion with St. Thomas' Hospital solution (ST-solution). In the Group ST (n = 8), the hearts were arrested with the ST-solution alone. The Group HQ (n = 8) were treated with the ST-solution containing 4-HQ (10 µM) for cardioplegia. During reperfusion, the Group HQ showed significantly greater functional recovery of +dp/dt(max) (p = 0.005) and lower enzymatic leakage (p 0.01). NAD(+) levels were also preserved higher in the Group HQ (p 0.01). Immunohistochemical study revealed lesser extents of oxidative stress and apoptosis, in the Group HQ. Thus, addition of 4-HQ in the cardioplegia may provide a new intervention for myocardial protection against ischemia-reperfusion injury by decreasing NAD(+) consumption and suppressing oxidative stress.

SummaryBehçet's disease is a chronic, relapsing, multi-systemic inflammatory disorder characterized by recurrent orogenital aphthous ulcers, uveitis, and skin lesions. Vascular involvement affects the veins more commonly than the arteries of these patients. Arterial involvement may include aneurysm formation, occlusive disease, and stenosis, with the most common sites being the abdominal aorta and femoral and pulmonary arteries. Thus, coronary arterial involvement is very rare but can cause serious complications when it occurs. In this report, we present a 28-year-old male patient with Behçet's disease who developed a giant right coronary artery aneurysm with minimal cardiac manifestation of a recently developed slight palpitation. The patient underwent surgical repair. We present the results of cardiovascular imaging and histopathological examinations. Our case demonstrates the necessity of regular cardiovascular examination for patients with Behçet's disease, even for those without cardiac symptoms.

Liver cirrhosis is a major risk factor for cardiac surgery using cardiopulmonary bypass. However, percutaneous coronary intervention (PCI) or off-pump coronary artery bypass graft surgery (OPCABG) may be a less invasive alternative strategy.Among the 9,877 patients undergoing first PCI or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 332 patients diagnosed with liver cirrhosis were entered into the study (age 67.1±9.4 years; 246 male). Liver cirrhosis was diagnosed by liver biopsy or signs of portal hypertension with characteristic morphologic liver and spleen changes.A total of 233 patients received PCI, 58 conventional on-pump CABG (CCABG), and 41 OPCABG. Median follow-up was 3.3 years. The PCI group included less complex coronary lesions such as triple vessel and left main disease (p0.01 each). Propensity score adjusted in-hospital mortality after CCABG or OPCABG was higher than that after PCI; however, the differences were not significant (odds ratio [95% confidence interval]: 6.84 [0.52 to 90.8], p=0.14 for CCABG versus PCI; and 1.86 [0.08 to 45.8], p=0.71 for OPCABG versus PCI). Adjusted overall mortality after CCABG or CABG was lower than that after PCI, but the differences were not significant (0.66 [0.31 to 1.40], p=0.28; and 0.64 [0.28 to 1.49], p=0.31, respectively). Approximately two thirds of patients died of noncardiovascular morbidities (malignancies, including hepatocarcinoma, or hepatic decompression).Because overall noncardiovascular mortality is high among patients with liver cirrhosis, complete revascularization may not be associated with better survival outcomes. Further study is warranted to determine the impact of a coronary revascularization strategy for liver cirrhosis patients.

Amiodarone is a potent anti-atrial fibrillation (AF) agent; however, its systemic administration induces serious side effects such as interstitial pneumonia. To avoid such effects, we developed a local sustained-release system for amiodarone.A biodegradable, cross-linkable dextran disc was developed as a sustained-release carrier for amiodarone. Under general anesthesia, Japanese white rabbits underwent median sternotomy and the biodegradable disc with or without amiodarone (30 mg) was implanted onto the surface of the right atrium. Three days after implantation, we measured tissue amiodarone concentrations (n = 5), the AF threshold, and the atrial effective refractory period of the left atrium by using the Langendorff apparatus. The incidences of induced AF evoked by rapid pacing were measured and compared.The right atrial concentration of amiodarone was far higher than that in the lungs, ventricles, or other organs (p0.01). The blood concentration of amiodarone was below detectable levels. The amiodarone biodegradable disc significantly increased the AF threshold (amiodarone group, 6.9 ± 4.6 mA versus control group, 0.5 ± 0.6 mA; p0.01) and the effective refractory period (amiodarone group, 53.9 ± 8.9 milliseconds versus control group, 43.9 ± 9.5 milliseconds; p = 0.035) of the left atrium, indicating the electrophysiologic effect of the amiodarone biodegradable disc on the left atrium. Further, the amiodarone group was significantly less likely to experience AF, as compared with the control group (p0.01).This approach may be a less invasive and effective therapeutic option for preventing postoperative AF.

ObjectiveIschemia–reperfusion injury is among the most serious problems in cardiac surgery. Epigallocatechin-3-gallate, a major polyphenolic component of green tea, is thought to be cardioprotective through its antioxidant activities. We investigated cardioprotective effects of oral epigallocatechin-3-gallate pretreatment against ischemia–reperfusion injury in isolated rat hearts and considered possible underlying mechanisms.MethodsRats were given epigallocatechin-3-gallate solution orally at 0.1, 1, or 10 mmol/L (n = 12 per group) for 2 weeks; controls (n = 12) received tap water alone for 2 weeks. Subsequently, Langendorff-perfused hearts were subjected to global ischemia for 30 minutes, followed by 60 minutes of reperfusion.ResultsRecoveries at 60 minutes after reperfusion of left ventricular developed pressure and maximum positive and minimum negative first derivatives of left ventricular pressure were significantly higher in 1-mmol/L group than in 0.1-mmol/L (P

Background: Among hemodialysis (HD) patients, those who have diabetes have poorer cardiovascular outcomes than non-diabetic patients, but the impact of diabetes on cardiovascular outcomes has not been fully elucidated in HD patients undergoing coronary revascularization. Methods and Results: We identified 375 HD patients (203 diabetes, 172 non-diabetes) and 9,006 patients without HD (3,455 diabetes, 5,551 non-diabetes) in the database of the CREDO-Kyoto registry of patients undergoing their first coronary revascularization. In non-HD patients, significantly higher risks of death (10.8% vs. 7.7%, P

We describe a redo mitral valve replacement operation in a 71-year-old man with a tracheostoma and patent bypass grafts to the coronary arteries. Preoperative investigations revealed that the patent right internal thoracic artery graft ran directly under the sternum just anterior to the ascending aorta, and a saphenous vein graft was adhering to a surgical wire. To prevent injury to the patent grafts and cardiac structures, and to avoid communication with the tracheostoma, the redo procedure was performed via an anterior minithoracotomy combined with a low T-shaped partial sternotomy. The reoperation was successfully completed without any complications.

Aneurysm of the left atrial appendage is an extremely rare anomaly. We describe the case of a 68-year-old man who presented with palpitation and was found to have a very large aneurysm located near the left atrial appendage on routine echocardiography. During surgery, an additional small aneurysm of the right atrial appendage was found. Both atrial aneurysms were resected in addition to mitral annuloplasty and a maze procedure.

Objective: The objective of this investigation was to establish the effectiveness of sustained-release platelet-rich plasma (PRP) on perfusion and neovascularization in diabetic murine hind limb ischemia. Methods: After surgery in streptozotocin-induced diabetic mice, the mice were randomly assigned to the following 4 experimental groups: control (C), 100 µl of the sustained-release form of platelet-poor plasma (PPP), 100 µl of the solution form of PRP (PRP-sol), and 100 µl of the sustained-release form of PRP (PRP-sr). Endpoint evaluations were: blood perfusion by laser Doppler perfusion imaging (LDPI), vascular density by anti-vWF, and mature vessel density by anti-smooth muscle actin antibody. Results: This study demonstrated that a sustained release of PRP increases the perfusion of ischemic tissue as measured by LDPI (57 ± 12; 56 ± 9; 72 ± 7, and 98 ± 4 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05), capillary density (151 ± 16; 158 ± 12; 189 ± 39, and 276 ± 39 for groups C, PPP, PRP-sol, and PRP-sr, respectively; p < 0.05), and mature vessel density (28 ± 2; 31 ± 3; 52 ± 10, and 85 ± 13 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05). Conclusion: A sustained release of PRP containing potent angiogenic growth factors restores blood perfusion by stimulating angiogenesis and arteriogenesis.

The infusion of a cardioplegic solution is the standard method of myocardial protection during open heart surgery. However, this method interrupts the surgical procedure and it is difficult to ensure a bloodless surgical field. To address these problems, the effect of continuous retrograde gaseous oxygen persufflation (ROP) on myocardial protection was assessed in comparison to St. Thomas' solution (STS).Eighteen adult mongrel dogs were divided into three groups of six. Group G received continuous ROP, Group C received STS every 30 min, and Group N received hypothermia alone during the 120 min hypothermic ischemia. The myocardial metabolism was assessed by measuring the coronary sinus lactate concentration, lactate extraction ratio (LER), coronary sinus lipid peroxidation (LPO) concentration, left ventricular myocardial adenosine triphosphate (ATP) concentration, and water content. Cardiac function was assessed by the percent recovery relative to the baseline.In Group G, the lactate, LPO, and water content were significantly lower (P = 0.0062, P = 0.03, and P = 0.0065, respectively), and ATP was significantly higher (P = 0.028) than in Group C. The LER was only positive in Group G. In addition, the cardiac functions in Groups G and C were not significantly different.Retrograde gaseous oxygen persufflation was not inferior to STS in regard to myocardial protection. This technique could therefore represent a potentially promising cardioplegic method.

Purpose Although most Gunther Tulip filters (GTFs) can be safely retrieved within a few months after implantation, their recommended safe retrieval period is within a few weeks. This study aims to assess the feasibility of excimer laser–assisted retrieval of GTFs incorporated into the inferior vena cava (IVC) wall in a canine model. Materials and Methods Six GTFs were implanted in six mongrel dogs and retrieved after four weeks. The retrieval system consisted of a 14-F excimer laser sheath, an 8-F guide catheter, and a 15-mm Goose Neck snare. Results All filters were tightly fixed to the IVC wall. After ablation of the adhesions by excimer laser emission, all filters were successfully retrieved. Final cavography after retrieval revealed no caval damage except for minor extravasation in three dogs. Examination of the caval specimen taken from a dog immediately after filter retrieval revealed partial absence of the intima and media. In the remaining five dogs, cavography performed 2 days after filter retrieval revealed complete hemostasis and almost indistinguishable intimal indentations. On follow-up cavography 28 days after filter retrieval, caval stenosis with 38% ± 11% diameter narrowing was noted. The caval specimen obtained from a dog at 28 days showed neointima formation at the level where the filter struts were in contact with the caval wall. The other four dogs have survived for more than 3 months without any adverse events. Conclusions Laser-assisted retrieval of a GTF incorporated into the IVC wall is feasible in dogs.

Objectives Paraplegia remains a serious complication after endovascular repair of thoracic aortic aneurysms, and it has been reported that paraplegia might be due to ischemia of the artery of Adamkiewicz. This study investigates the feasibility of an Inoue stent graft with a side branch of a small caliber for the reconstruction of the intercostal artery branching the artery of Adamkiewicz. Methods Branched Inoue stent grafts were implanted into the thoracic aorta and 11th intercostal artery of 5 mongrel dogs. The side branch measured 3 × 5 mm and contained a bare-metal coronary stent for fixing to the intercostal arterial wall. Aortography and selective angiography of the 11th intercostal artery were performed before and immediately after implantation and after 1, 4, 8, and 12 weeks. The luminal diameter of the intercostal artery before implantation was 2.4 ± 0.3 mm. Results All stent grafts were successfully deployed. The main body of the graft did not develop endoleak or migrate, and the side branch remained patent for 12 weeks. Angiography performed 1 week postoperatively revealed smooth flow with slight stenosis (4.2% ± 1.7%) along the side branches and the intercostal arteries in all dogs. Four weeks postoperatively, however, mild concentric stenosis (38% ± 16%) along the side branch was observed in 4 of the 5 dogs. The percent stenosis at 8 and 12 weeks was 38% ± 15% and 33% ± 11%, respectively; these values were not significantly different from the value at 4 postoperative weeks. Conclusions A novel Inoue stent graft with a side branch of small caliber was successfully deployed into the canine thoracic aorta and intercostal artery; the side branch remained patent for 12 weeks. This novel technique may enable endovascular reconstruction of the Adamkiewicz artery.

Cardiopulmonary bypass (CPB) may induce systemic inflammatory responses causing acute lung injury. Recombinant human soluble thrombomodulin (rTM) is reported to attenuate the secretion of inflammatory cytokines and the high-mobility group box 1 (HMGB1) protein, which is critical in controlling systemic inflammation and apoptosis. We investigated the protective effects of rTM on CPB-induced lung injury in a rat model.Eighteen male Sprague-Dawley rats were divided into 3 groups: sham, control (CPB alone), and rTM (CPB + rTM). CPB was conducted in the control group and the rTM group. A bolus of rTM (3 mg/kg) was administered to the rTM group rats before CPB establishment.The ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen only dropped markedly from before CPB in the control group (P .001). Serum tumor necrosis factor α, interleukin (IL) 6, and HMGB1 levels were significantly higher in the control group after CPB. Pathologic study revealed significantly more severe congestion, alveolar hemorrhage, neutrophil accumulation, and edema, and the number of lung cells expressing HMGB1 increased in the control group. The mRNA expression levels of tumor necrosis factor α, IL-6, IL-1β, and HMGB1 in the control group were significantly higher than those in other groups. According to Western blot analysis, nuclear factor-κB p65 in lung tissue was significantly downregulated in the rTM group. The number of apoptotic cells and the protein of cleaved Caspase-3 were reduced in the rTM group.These results suggest that rTM prevents acute lung injury through attenuating inflammation and apoptosis during and after CPB in a rat model.

SummaryBackgroundA Tei index is known to reflect overall cardiac performance including systolic and diastolic function in a variety of heart disease. We investigated the relationship between preoperative Tei index and postoperative left ventricular (LV) mass regression and survival after aortic valve replacement (AVR) for aortic valve stenosis (AS).MethodsOne hundred fifty-four patients with AS were classified into a group with abnormal (Abn) LV function (n=47, 0.45≤Tei index) and a group with normal (Nor) LV function (n=107, Tei index

To investigate platelet responsiveness during cold storage of whole blood, we examined platelet aggregation, expression of CD40 ligand (CD40L) on platelets, the plasma levels of soluble form of CD40L (sCD40L) as well as platelet-leukocyte aggregates. Flow cytometry analysis was performed to investigate platelet-leukocyte aggregate formation using antibodies against CD42b and CD45 and platelet activation using antibodies against P-selectin and PAC-1. Blood samples were collected from healthy volunteers, patients with cardiovascular diseases, or both. In the healthy volunteers' blood samples stored at 4 degrees C for 6 h, platelet aggregation in response to 1 micromol/l ADP was enhanced, and released levels of soluble form of P-selectin and thromboxane B2 in response to 1 micromol/l ADP markedly increased. In the samples stored at 4 degrees C for 6 h but not stimulated by any agonists, CD40L expression on the platelets was increased, and plasma levels of sCD40L were also elevated. Under the same condition, the increase in simultaneous expression of CD45 and CD42b was observed. In patients with cardiovascular diseases, the platelet aggregability, coexpression of P-selectin and PAC-1, expression of CD40L on platelets and both CD45-bound and CD42b-bound subsets were all comparable to those of healthy volunteers' samples stored at 4 degrees C for 6 h. Plasma levels of sCD40L in patients were higher than those in healthy volunteers' control. Taken together, storage of whole blood at 4 degrees C for 6 h caused platelet activation comparable to that of patients with cardiovascular diseases, and enhanced platelet activity in such patients may be involved in increased risk for thromboembolic events.

Prevention of paraplegia remains an important issue in repair of descending thoracic and thoracoabdominal aneurysms. Therefore, we investigated the protective effect of sivelestat sodium hydrate (ONO-5046) on ischemia-induced spinal cord damage in a rabbit model. Twenty New Zealand white rabbits were divided into two equal groups; ONO-5046 (1.6 mg/kg)+isotonic NaCl (30 ml) was administered selectively to the spinal cord via the lumbar arteries for the first 3 min during 30 min of infra-renal aorta clamping in the experimental group (group E), whereas NaCl was given alone in the control group (group C). Motor function of the lower limbs was assessed two days later by Tarlov criteria. The number of intact motor neurons in the anterior segment of the cord (L5 level) was counted after hematoxylin-eosin staining and the number of apoptotic motor neurons after TUNEL staining. Motor function of the lower limbs in group E was significantly better (P=0.003) than that in group C. The number of intact motor neurons was greater and of apoptotic motor neurons was less in group E than C. Selective infusion of sivelestat sodium hydrate directly into the spinal cord via the lumbar arteries significantly attenuated functional and morphological ischemia-induced spinal cord injury.

SummaryThe basic mechanism of ischemic mitral regurgitation (MR) is believed augmented leaflet tethering due to the outward displacement of the papillary muscles by left ventricular (LV) remodeling or dilatation. Annular dilatation and LV dysfunction may not be the central mechanism, but contribute to the development of MR in the presence of augmented tethering. Papillary muscle dysfunction was initially expected to cause leaflet prolapse and MR. However, multiple studies have confirmed that papillary muscle dysfunction per se does not usually cause ischemic MR and recent studies further suggest that papillary muscle dysfunction may occasionally attenuate tethering and MR. Although surgical annuloplasty is usually effective to treat ischemic MR, occasional patients with persistent or recurrent ischemic MR after surgical ring annuloplasty even with advanced downsizing suggest the need for approaches to address tethering. Finally, leaflet tethering in patients with ischemic MR can be heterogeneous, indicating the need for individualized approaches to correct ischemic MR in affected patients.

症例は55歳の男性で, 平成13年2月心窩部痛が出現し近医を受診. 腹部超音波検査, CTで肝外側区域を中心とした多発肝腫瘤を認めた. 生検で悪性腫瘍が疑われたため, 3月当科へ紹介された. CT, MRI, 血管造影検査では肝外側区域に約10cmの淡く濃染される腫瘍を認め, 内側区域と右葉にも腫瘍が散在していた. 肝内転移を伴う胆管細胞癌を疑い肝左葉切除および右葉の転移巣に対する部分切除とラジオ波焼灼 (以下, RFA) 術を施行した. 病理組織学的には索状, リボン状に配列する腫瘍細胞からなり, SynaptophysinとNSEにびまん性に陽性でChromograninAとGrimeliusはfocalに陽性なカルチノイドと診断された. 術前後に消化管を含めた全身検索を行っているが, 肝外病変を確認できなかった. 6年経過したが, 肝外病変を認めず肝原発カルチノイドと考えられた. RFA部を含め, 現在, 無再発生存中である. 肝原発カルチノイドはまれであり, 文献的考察を加えて報告した.

ウエステルマン肺吸虫症による気胸の1例を経験したので報告する．症例は76歳，男性．気胸の診断にて前医で胸腔ドレナージ施行され一旦は治癒したが，再発したため当科紹介となった．末梢血好酸球比率の上昇，好酸球性胸水を認め肺吸虫症を疑ったが，混濁した胸水と肺瘻の持続を認めたため胸腔鏡下手術を施行した．明らかな肺瘻部は不明であったが，膿苔の付着した肺を部分切除し気胸は改善した．術後，血清学的診断にて肺吸虫症と診断し，プラジカンテルの内服治療を行った．術後約8ヵ月を経過し再発を認めていない．