木村 直行

BACKGROUND: IL-16 promotes the recruitment of various cells expressing CD4; a receptor for IL-16. The precise role of IL-16 in transplant rejection remains unknown; therefore, the present study investigated the contribution of IL-16 to the development of chronic rejection in heart transplants. METHODS: C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into (1) IL-16-deficient (IL-16(-/-)) C57BL/6J or (b) wild type (WT) control recipients (MHC class II mismatch). Grafts were harvested at 52 days, parenchymal rejection was assessed by the ISHLT grading system, and CAV was examined morphometrically. Graft infiltrating cells were detected 10 and 52 days after transplantation. Intragraft cytokine and chemokine profiles were assessed. To confirm the role of IL-16 in CAV development, C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into C57BL/6J WT recipients treated with (1) anti-IL-16-neutralization monoclonal antibody or (b) control immunoglobulin G. Grafts were harvested at 52 days, and CAV was quantified morphometrically. Graft-infiltrating cells were examined histologically. RESULTS: Parenchymal rejection and CAV was significantly attenuated in donor hearts transplanted into IL-16(-/-) recipient mice compared with WT controls. Donor hearts transplanted into IL-16(-/-) recipients had a significant reduction in coronary artery luminal occlusion, intima-to-media ratio, and percentage of diseased vessels. CAV was associated with decreased donor organ inflammation, as well as donor organ cytolcine (IL-1 beta and IL-6) and chemokine (MCP-1 and KC) protein expression. Intimal proliferation and inflammatory cell infiltration were significantly reduced in hearts transplanted into recipients treated with an IL-16-neutralization antibody. CONCLUSIONS: IL-16-deficiency reduced graft inflammatory cell recruitment, and allograft inflammatory cytokine and chemokine production. Therefore, IL-16 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection. J Heart Lung Transplant 2011;30:1409-17 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.

Background: Acute type A aortic dissection (AAAD) is rare in young people. The early- and long-term outcomes after surgery for AAAD in patients aged <= 45 years was investigated. Methods and Results: Subjects were 355 patients who had undergone emergency surgery for AAAD. The patients were grouped as those aged <= 45 years (n=30; mean age, 38.3 years; younger group) and those aged >45 years (n=325; mean age, 65.3 years; older group). Clinical and prognostic variables were compared between the groups. Male sex, Marfan syndrome, and severe aortic regurgitation were more prevalent in the younger group. In-hospital mortality (16.7% vs. 8.6%, P=0.15) and postoperative patency of the distal aorta (90.8% vs. 59.1%, P<0.01) were more frequent in the younger group. The leading causes of late death were aortic rupture in the younger group (75.0%) and malignancy in the older group (27.5%). Although actuarial survival at 10 years was similar (64.5% vs. 62.5%), freedom from aortic reoperation at 10 years was decreased in the younger group (49.4% vs. 85.0%, P=0.012). A distal aorta >45 mm (P<0.001), Marfan syndrome (P<0.01), and age <= 45 years (P=0.045) were shown to be independent risk factors for reoperation. Conclusions: Early- and long-term surgical outcomes are not better for patients <= 45 years, and the risk for reoperation is high in this group. Careful follow up is important in young patients with AAAD. (Circ J 2011; 75: 2135-2143)

Background-Interleukin-17 (IL-17), which is predominantly produced by T helper 17 cells distinct from T helper 1 or T helper 2 cells, participates in the pathogenesis of infectious, autoimmune, and allergic disorders. However, the precise role in allograft rejection remains uncertain. In the present study, we investigated the role of IL-17 in acute allograft rejection using IL-17-deficient mice. Methods and Results-Donor hearts from FVB mice were heterotopically transplanted into either C57BL/6J-IL-17-deficient (IL-17(-/-)) or -wild-type mice. Allograft survival was significantly prolonged in IL-17(-/-) recipient mice due to reduced local inflammation accompanied by decreased inflammatory cell recruitment and cytokine/chemokine expression. IL-17(-/-) recipient mice exhibited decreased IL-6 production and reciprocally enhanced regulatory T cell expansion, suggesting a contribution of regulatory T cells to prolonged allograft survival. Indeed, allografts transplanted into anti-CD25 mAb-treated IL-17(-/-) recipient mice (regulatory T cell-depleted) developed acute rejection similar to wild-type recipient mice. Surprisingly, we found that gamma delta T cells rather than CD4(+) and CD8(+) T cells were key IL-17 producers in the allografts. In support, equivalent allograft rejection was observed in Rag-2(-/-) recipient mice engrafted with either wild-type or IL-17(-/-) CD4(+) and CD8(+) T cells. Finally, hearts transplanted into gamma delta T cell-deficient mice resulted in decreased allograft rejection compared with wild-type controls. Conclusions-During heart transplantation, (1) IL-17 is crucial for acceleration of acute rejection; (2) IL-17-deficiency enhances regulatory T cell expansion; and (3) gamma delta T cells rather than CD4(+) and CD8(+) T cells are a potential source of IL-17. IL-17 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection. (Circulation. 2011;124[suppl 1]:S187-S196.)

BACKGROUND: In this study we systematically dissect the prenylation pathway to better define the mechanism behind statin inhibition in chronic allograft rejection in heart transplants, or transplant' coronary artery disease (TCAD). METHODS: Utilizing a murine heterotopic heart transplant model, animals received daily treatments of either statin or selective isoprenoid blockade inhibitors to block the four major downstream branches of the mevalonate pathway. TCAD was assessed by morphometric analysis at Day 52. Graft-infiltrating cells, cytokine production, smooth muscle cell proliferation and migration and endothelial cell MHC II expression were detected on Day 7. RESULTS: Atorvastatin and two prenylation inhibitors, NE-10790 and manumycin A, significantly reduced TCAD lesions compared with untreated animals. Perillyl alcohol treatment resulted in a trend toward decreased luminal narrowing. Finally, zaragozic acid (cholesterol blockade only) did not alter TCAD severity. Statins and prenylation inhibitors reduced inflammatory cell allograft recruitment, but did not always correlate with TCAD reduction. Cytokine production was decreased in recipient spleens in all treatment groups. Both in vitro and in vivo IFN-gamma-stimulated MHC II expression was decreased in a dose-dependent manner in the atorvastatin, perillyl alcohol and NE-10790 groups. In vitro smooth muscle cell proliferation was decreased in all treatment groups. Finally, in vitro smooth muscle cell migration was decreased in the atorvastatin, NE-10790 and manumycin A groups only. CONCLUSIONS: FPT and GGPT-2 (inhibition) are the key enzymes in the HGM-CoA reductase pathway and most influential in TCAD prevention. TCAD reduction is most closely related to smooth muscle cell migration, but not its anti-inflammatory properties. J Heart Lung Transplant 2011;30:761-9 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.

Intravenous leiomyomatosis with cardiac extension is rare and may result in a fatal outcome. A 58-year-old woman with a surgical history of myoma uteri was admitted to our hospital for treatment of intravenous leiomyomatosis extending into the right atrium through the inferior vena cava. We partially resected the tumor inside the right atrium and the inferior vena cava via the right atrium using cardiopulmonary bypass. There is no progression of the residual tumor after 25 months of follow-up. © 2011 The Japanese Association for Thoracic Surgery.

Although interleukin-17 (IL-17) has been reported to participate in the pathogenesis of infectious, autoimmune and allergic disorders, the precise role in allograft rejection remains uncertain. This study illustrates that IL-17 contributes to the pathogenesis of chronic allograft rejection. Utilizing a murine heterotopic heart transplant model system, IL-17-deficient recipient mice had decreased allograft inflammatory cell recruitment, decreased IL-6, MCP-1, and KC production, and reduced graft coronary artery disease (GCAD). Intragraft gamma delta (gamma delta) T cells appear to be the predominant source of IL-17 production. Therefore, IL-17 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.

We report our experience with patients who died of early aortic rupture following surgical treatment for acute type A aortic dissection in a consecutive series of 324 patients who underwent surgery for this condition between 1991 and 2007. In-hospital mortality rate was 9.9% (32/324), and seven patients (two men, mean age, 67 years) died of postoperative aortic rupture. Rupture sites were the proximal aorta in two and distal aorta in five patients. Surgical procedures included ascending aorta replacement in six and ascending aorta plus aortic arch replacement in one. The common characteristics of the two patients with proximal aortic rupture were preoperative aortic insufficiency, intraoperative bleeding from the proximal stump, and high blood pressure before the rupture. In contrast, the distal aortic ruptures occurred in patients with uncomplicated postoperative courses, with three distal aortic ruptures occurring on the inpatient ward. The only common characteristic of the distal aortic ruptures was residual patent false lumen (80%, 4/5 patients), the other patient had a large pre-existing aneurysm in the descending thoracic aorta. Careful postoperative management, including strict blood pressure control, is especially important in patients with residual patent false lumen following surgery for acute type A aortic dissection. © 2009 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

Background. When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch is of concern. Such prosthesis-patient mismatch may affect postoperative clinical status and survival. We investigated the outcomes of isolated aortic valve replacement performed with a 17-mm mechanical prosthesis in patients with aortic stenosis. Methods. Twenty-three patients with aortic stenosis (mean age, 74.6 +/- 6.3 years) underwent isolated aortic valve replacement with a 17-mm St. Jude Medical Regent prosthesis. Mean body surface area was 1.41 +/- 0.13 m(2). Preoperative echocardiography yielded a mean aortic valve area of 0.36 +/- 0.10 cm(2)/ m(2), a mean left ventricular-aortic pressure gradient of 68.4 +/- 25.3 mm Hg, and a mean left ventricular mass index of 200 +/- 69 g/m(2). Results. There was no operative mortality, and there were no valve-related events. Echocardiography at 14.0 +/- 10.0 months after aortic valve replacement showed a significant increase in the mean effective orifice area index (0.95 +/- 0.24 cm(2)/m(2)), decrease in the mean left ventricular-aortic pressure gradient (17.4 +/- 8.2 mm Hg), and decrease in the mean left ventricular mass index (124 +/- 37 cm(2)/m(2)). Prosthesis-patient mismatch (effective orifice area index < 0.85 cm(2)/m(2)) was present in 8 patients at discharge. In these patients as well as in those without prosthesis-patient mismatch, the left ventricular mass index decreased remarkably during follow-up. Conclusions. Aortic valve replacement with a 17-mm Regent prosthesis appears to provide satisfactory clinical and hemodynamic results in patients with a small aortic annulus. Remarkable left ventricular mass regression during follow-up was achieved irrespective of the effective orifice area index at discharge.

Background The aim of this study was to identify predictors of prolonged mechanical ventilation (PMV) following surgery for acute type A aortic dissection (AAAD) and to assess the influence of this complication on clinical outcomes. Methods and Results A total of 243 patients underwent emergency surgery for AAAD in the period of 1997-2006. Ten patients died within 48 h after surgery. The remaining 233 patients were divided into 2 groups according to the duration of mechanical ventilation; less than 48 h (group A: n=149) or 48 h or longer (group 13; n=84). Multivariate analysis was used to identify predictors of PMV. Short and late outcomes were compared between groups. Multivariate analysis showed that shock (systolic BP < 90 mmHg; p=0.007), postoperative renal dysfunction (creatinine > 2.0 mg/dl; p=0.016), coronary artery bypass grafting (CABG) (p=0.017), and limb ischemia (p=0.044) were independent predictors of PMV. There was no significant difference in in-hospital mortality (group A, 2.7% vs group B, 3.6%) or 5-year survival (group A, 85.9% vs group 13, 76.8%). Conclusions Shock, limb ischemia, CABG, and postoperative renal dysfunction increase the risk for PMV. Knowing the predictors of PMV should help optimize postoperative management of these patients. (Circ J 2008; 72: 1751-1757)

Objective: The fate of the dissected distal aorta after surgery for acute type A aortic dissection has not been fully understood. We assessed the influence of a residual patent false lumen on long-term outcomes. Methods: Two hundred eighteen patients underwent emergency surgery for DeBakey type I or IIIb retrograde acute type A aortic dissection (1997-2006). Aortic arch replacement was performed in selected patients whose entry site was in or extended into the aortic arch. In-hospital mortality was 7.3% (16/218), and 193 survivors (mean age 62 years) underwent enhanced computed tomography within 1 month after the operation. These patients were divided into two groups according to the status of the false lumen, whether patent (n = 124) or thrombosed (n 69). In each group, segment-specific aortic growth rate, distal reoperation, and late survival were examined. Results: Growth rate was determined in 139 (72.0%) patients who underwent serial computed tomography. Average growth rate in the patent group was greater than that in the thrombosed group (aortic arch [1.1 vs -0.41 mm per year; P.005], proximal descending aorta [1.9 vs-0.71 mm per year; P<. 001], and distal descending aorta [1.3 vs-0.70 mm per year; P = .002]). However, growth was slow (< 1 mmper year) in about 50% of patients in the patent group. There was no significant difference in distal reoperation or late survival between the two groups. Conclusions: The patent false lumen influences postoperative aortic enlargement. However, with careful followup, a favorable prognosis is expected even for patients with a residual patent false lumen.

A previously healthy 77-year-old woman with a 4-week history of back pain and fever was admitted to our hospital for chronic type A aortic dissection. The aortic arch was enlarged to 7.5 cm in diameter, and the large dissecting aortic aneurysm involved all three branches of the aortic arch and compressed the trachea. Laboratory tests showed an increased C-reactive protein level (10.5 mg/dl). Blood cultures performed upon admission were negative. Progression of the symptoms suggested the possibility of impending aneurysm rupture. The patient underwent urgent total arch replacement, and cultures of samples obtained from the aortic wall during surgery were positive for Listeria monocytogenes. Two months after surgery, advanced rectal cancer was diagnosed. It is believed that the rectal cancer predisposed the patient to development of an arterial infection associated with L. monocytogenes. © 2008 The Japanese Association for Thoracic Surgery.

An 80-year-old woman was admitted to our hospital complaining of severe abdominal and back pain. Computed tomography (CT) showed an 8.5 x 7.0-cm infrarenal abdominal aortic aneurysm (AAA) with a large contained retroperitoneal hematoma. Known situs inversus totalis was reconfirmed by CT. Just after the CT examination, the patient collapsed and was immediately taken to the operating room. Her hemodynamics stabilized after clamping of the descending aorta via a right anterolateral thoracotomy. A resection of the abdominal aneurysm and prosthetic graft replacement were successfully performed. To our knowledge, there has been no other report of a ruptured AAA in a patient with situs inversus totalis.

A 46-year-old man underwent emergency surgery for heart rupture after acute infarction of the posterior wall. Echocardiography revealed limited myocardial thinning, so rather than sutureless repair, a covering patch was used in view of the risk of recurrent rupture. Postoperative echocardiography showed the myocardial thinning had progressed to a wide defect, and computed tomography demonstrated that the covering patch had prevented a repeat rupture.

A 59-year-old man with a long history of hypertension and diabetes was admitted to our hospital with acute type B aortic dissection 14 days after the sudden onset of back pain. The dissecting descending thoracic aorta was enlarged to 5.2cm in diameter, and laboratory tests showed an elevated white blood cell count (15530/mm3) and an increased C-reactive protein level (19.2mg/dl). Computed tomography performed 2 days after admission revealed rapid growth of the aortic dissection. Blood cultures obtained upon admission were positive for Salmonella. Impending rupture of the aortic dissection complicated by Salmonella infection was strongly suspected, and the patient underwent emergency surgery consisting of debridement and prosthetic graft placement covered by an omental flap. In this case, it is believed that insidious Salmonella aortitis caused acute type B aortic dissection. © 2007 The Japanese Association for Thoracic Surgery.

冠状動脈バイパス術(CABG)後の広範囲冠状動脈攣縮に対するnicorandilの有用性を報告した.対象は,CABG後24時間以内に循環動態が破綻し緊急冠状動脈造影(CAG)で冠状動脈攣縮と診断した7例(男性6例,女性1例・平均年齢60.4歳)で,全例に冠攣縮性狭心症の既往,術前の低左心機能例はなかった.術式はoff-pumpCABG 2例,on-pumpCABG 4例,on-pump beating 1例であった.冠状動脈攣縮の発症形態はショック5例,心停止2例,発症時期は術中2例,5例は術後平均5.2時間に発症した.治療は術中発症例は術直後に,術後発症例は補助循環確立後にカテーテル室へ搬送し緊急CAGを施行した.全例にnitroglycerin,diltiazem hydrochlorideのグラフトおよび冠状動脈注入を行ったが十分な拡張が得られず,nicorandilのグラフトと冠状動脈注入で拡張が得られ,心電図でもST変化が改善し,造影上で攣縮の軽減を確認した.転帰は心停止で発症の1例は蘇生後脳症で11日目に死亡したが,他6例は合併症を残さず回復した

We have applied omental transfer in cases of deep sternal wound infection (DSWI) that occurred after the right gastroepiploic artery was used as a coronary artery bypass graft. Study subjects were 7 patients (mean age was 66 years) who underwent coronary artery bypass grafting with the right gastroepiploic artery during the period January 1990-March 2004, then suffered DSWI and underwent single-stage treatment consisting of debridement and omental transfer 33 days on average (range 12-93 days) after the primary surgery. Patients were followed-up, and the following data were collected in retrospect: clinical presentation and in-hospital and long-term results. Three of the 7 patients underwent omental transfer based on the left gastroepiploic artery alone, 3 underwent omental transfer based on blood supply from a branch of the right gastroepiploic artery, and 1 underwent omental transfer based on blood supply from both branches. The hospital mortality rate was 14% (1 of 7 patients) death was caused by recurrent mediastinitis. Postoperative hospitalization was 47 days (range 21-83 days). Two patients died of cardiac failure, and 1 patient suffered abdominal wall hernia during the follow-up period. Even after harvesting of the right gastroepiploic artery, omental transfer was effective for the treatment of DSWI.

Percutaneous cardiopulmonary support (PCPS) is a powerful resuscitation tool for patients in cardiogenic shock. The femoral artery is generally used for arterial access however, vascular complications, particularly in atherosclerotic arteries, can occur. Although such complications occur infrequently, they can be fatal. We describe the case of a 75-year-old woman who required extended PCPS for cardiogenic shock secondary to coronary spasm after on-pump beating coronary artery bypass grafting. Limb ischemia occurred because of an occlusive cannula, and distal perfusion with a 20G elastic intravenous catheter inserted into the dorsalis pedis artery resolved the ischemia. The catheter was connected to the side port of an oxygenator and provided distal limb perfusion during PCPS. This technique appears to be useful in treating limb ischemia and may have application in patients with arterial occlusive disease who are dependent on mechanical support. © The Japanese Society for Artificial Organs 2005.

A 55-year-old man was admitted for acute myocardial infarction. Cardiac catheterization revealed total occlusion of the left circumflex artery. During catheterization, he suffered cardiogenic shock. Percutaneous cardiopulmonary support was established, and the patient was transferred to the operating room. A blow-out left ventricular free wall rupture (LVFWR) with an epicardial tear, 1 mm in diameter, was found, and sutureless repair with a collagen hemostat (TachoComb™) was performed. However, on postoperative day 7, echocardiography revealed an echo-free space resembling a pseudoaneurysm. A second operation was performed immediately for impending re-rupture. An epicardial tear, 2×10 mm in diameter, was found at the previous bleeding point where hemostasis had been achieved with only one sheet of TachoComb™. The defect was closed with mattress sutures buttressed with Teflon® felt. We conclude that even if the risk of re-rupture is low, sutureless repair with a collagen hemostat alone should be avoided in treating blow-out LVFWR.

A 58-year-old man was admitted for an aortoesophageal fistula (AEF) resulting from a thoracic aortic aneurysm. He underwent immediate in-situ prosthetic graft replacement, primary esophageal repair and wrapping of the aneurysm. Postoperative upper gastrointestinal endoscopy and computerized tomography (CT) findings were unremarkable. He was discharged on postoperative day (POD) 25. Three months after surgery, he was readmitted with complaints of worsening cough and hemoptysis. CT showed a thrombosed aneurysm adjacent to the left bronchus. Aortobronchial fistula due to mycotic pseudoaneurysm was suspected. The patient underwent immediate resection of the infected graft and prosthetic graft replacement positioned to avoid the infected area. The graft was wrapped with omentum. On POD 7, pleural empyema developed, and esophagography revealed a residual leak. Staged reconstruction of the esophagus was performed successfully. We conclude that even if the fistulous opening is small, simultaneous esophageal resection should be performed during the initial treatment of AEF.