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Objective: To clarify the current status of surgical treatment of acute aortic dissection (AAD) in Japan through the Japan Cardiovascular Database analysis., Methods: In total, 7194 patients who underwent surgical treatment for AAD in 2021, including type A (TAAAD) (n = 6416) and type B (TBAAD) (n = 778), were investigated., Results: The median age was 70 years, with patients older than age 80 years constituting 21.7% and 23.4% of TAAAD and TBAAD cases. Emergency admission was 88.5% and 78.5%. Shock was found in 11.8% and 6.0%. Rupture/impending rupture occurred in 10.7%/6.0% and 24.0%/11.1%, respectively. Branch malperfusion was complicated in 10.4% and 25.2%. Open repairs were performed in 97.7% and 20.3%, whereas endovascular repairs were performed in 2.3% and 79.7%, respectively. In the increased prevalence of endografting procedures, neurological complications and renal failure occurred frequently after open repair with frozen elephant trunk for 29.9% and 50.3%. The operative mortality rate was 9.8% and 11.5% for open repair and 8.1% and 10.0% for endovascular repair. In patients with TAAAD, age older than 80 years, preoperative critical comorbidities, classical dissection, and coexisting chronic vital organ diseases were independent risk factors for mortality. In frozen elephant trunk procedures, neurologic complications and renal failure were frequent. The operative mortality was higher during the superacute phase within 1 or 2 hours from onset to arrival and between arrival and surgery., Conclusions: The current status of surgical treatments for AAD including the increased prevalence of endografting of thoracic endovascular aortic repair and frozen elephant trunk were demonstrated with favorable outcomes in the Japan Cardiovascular Database analyses., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: We performed a multicenter prospective comparative study to determine the impact of a Japanese frozen elephant trunk device on total arch replacement compared with conventional repair without it., Methods: Between 2016 and 2019, a total of 684 patients (frozen elephant trunk procedure; n = 369; conventional repair, n = 315) from 41 institutions were enrolled. The 2 procedures were selected according to each center's strategy., Results: The frozen elephant trunk procedure was applied more for aortic dissection, whereas the conventional repairs were predominantly performed for aneurysms. In the former, only hypothermic circulatory arrest time was reduced among the intraoperative parameters. Although there were no differences in the 30-day and in-hospital mortality rates (0.8% and 1.6%, respectively, for the frozen elephant trunk procedure vs 0.3% and 0.6%, respectively, for conventional repair), the neurologic complication rates were significantly higher in stroke (5.7% vs 2.2%; P = .022) and paraplegia (1.6% vs 0%; P = .023). In the propensity score matching analyses using 11 variables, statistical significance disappeared in the differences for mortality and neurologic morbidity (stroke and paraplegia/paraparesis) rates of 194 patients of each group, although they were still higher for the frozen elephant trunk procedure., Conclusions: The early outcomes of total arch replacement with the frozen elephant trunk procedure were acceptable despite its higher prevalence of emergency or redo surgery, which was comparable to that of the conventional repair. This procedure had higher rates of spinal cord injury than the conventional repair, which is a disadvantage of this approach., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The study objective was to report the clinical outcomes of open surgery for acute aortic dissection by using the Japan Cardiovascular Database., Methods: Between 2013 and 2018, a total of 29,486 patients with acute aortic dissection who underwent open surgery were registered in the Japan Cardiovascular Database. Some 50% of patients were male. Age of patients at surgery was 59.8 ± 14.2 years; 61% of patients were aged less than 65 years, and 21% of patients were aged more than 75 years. Connective tissue disease was found in 1.2% of patients. Some 13% of patients had disturbed consciousness, and 12% of patients had cardiogenic shock. Some 11% of patients had moderate or severe aortic valve regurgitation, and 2.3% of patients had acute myocardial infarction. Some 94% of patients underwent surgery within 24 hours after diagnosis. Antegrade cerebral perfusion was used in 74% of patients, hypothermic circulatory arrest with retrograde cerebral perfusion was used in 17.1% of patients, and deep hypothermic circulatory arrest was used in 9.4% of patients. Cardiopulmonary bypass time was 216 ± 90 minutes, and cardiac ischemic time was 132 ± 60 minutes. Lowest body temperature was 24.6°C ± 3.2°C. Replacement of the ascending aorta (zone I) was performed in 69% of patients, and total arch replacement (zone 0 to zone II, III-) was performed in 29% of patients. The aortic valve was replaced in 7.9% of patients and repaired in 4.4% of patients., Results: The 30-day mortality was 9.2%, and in-hospital mortality was 11%. The number of operations has increased through the study periods. The in-hospital mortality has been stable or in a decreasing trend. Major complications consisted of stroke in 12% of patients, new hemodialysis in 7.3% of patients, spinal cord ischemia in 3.9% of patients, and prolonged ventilation in 15% of patients., Conclusions: Approximately 30,000 patients with acute aortic dissection in the recent 6 years (2013 - 2018) underwent open surgery according to the nationwide Japanese database. The number of operations has increased, and in-hospital mortality has been stable or in a decreasing trend. Although the early outcomes are acceptable, there is still room for improvement in patients with preoperative comorbidities., (Copyright © 2020. Published by Elsevier Inc.)

Background: The aim of this study was to evaluate the fate of the preserved aortic root after supracoronary aortic replacement for acute type A aortic dissection., Methods: Between October 1999 and March 2018, 339 patients underwent supracoronary aortic replacement for acute type A aortic dissection at our institution. Late outcomes were evaluated, including overall survival, aortic-related death, and aortic root-related reoperation. The median follow-up was 3.7 years (1.4-8.4 years)., Results: Operative mortality was 46 patients (13.6%). The cumulative incidences at 5 years for aortic root-related reoperation, aortic-related death, and non-aortic related death were 2.5%, 14.5% and 12.4%, respectively. Multivariable Cox hazard regression analysis demonstrated greater sinus of Valsalva diameter and number of commissural detachments to be significant risk factors for a composite outcome consisting of aortic-related death or aortic root-related reoperation. Mixed-effects regression demonstrated that sinus of Valsalva diameter significantly increased with time (P < .001), and aortic regurgitation significantly worsened (P < .001)., Conclusions: Sinus of Valsalva diameter and commissural detachment were independent predictors of unfavorable outcomes after supracoronary aortic replacement. Close follow-up is particularly necessary for these patients, and aortic root replacement at the time of initial operation may lead to more favorable late outcomes., (Copyright © 2019. Published by Elsevier Inc.)

Background: The aim of this study was to evaluate the impact of diffuse aortic atherosclerosis-related thrombosis, or "shaggy aorta" on the outcomes of open thoracoabdominal aortic aneurysm repair (TAAA)., Methods: From October 1999 to March 2018, 251 patients underwent open TAAA repair using segmental-staged aortic clamping. Twenty-eight patients (11.2%) received emergent or urgent operations. Patients were classified into 3 groups: dissection aneurysm (139 patients, 55.4%), degenerative aneurysm without shaggy aorta (76 patients, 30.3%), and degenerative aneurysm with shaggy aorta (36 patients, 14.3%). Shaggy aorta was assessed using enhanced computed tomography and defined as patients with atheroma thickness ≥5 mm with irregular atheroma surface. Mean follow-up was 4.3 ± 4.1 years., Results: Operative mortality was 8% (20 patients) and spinal cord injury occurred in 25 patients (10.0%), 16 of whom (6.4%) had permanent neurologic dysfunction. Operative mortality was significantly worse in patients with shaggy aorta (dissection: 2.2%, non-shaggy: 6.6%, and shaggy: 33.3%, P < .001) and shaggy aorta was a significant risk factor for spinal cord injury (dissection: 7.2%, non-shaggy: 6.6%, and shaggy: 27.8%, P < .003). Multivariable analysis demonstrated that shaggy aorta was a significant risk factor for composite outcome consisted of operative mortality, spinal cord injury, and acute renal failure (odds ratio, 4.78; 95% confidence interval, 1.91-12.3, P < .001)., Conclusions: Preoperative enhanced computed tomography assessment of shaggy aorta could predict high-risk patients for open TAAA repair., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluates our 18-year experience of total arch replacement in the octogenarian and nonagenarian population., Methods: Between October 1999 and March 2018, a total of 740 patients underwent total arch replacement at our institution. A total of 139 patients were aged 80 years or more (83.1 ± 2.8 years), and 601 patients were aged less than 80 years (66.9 ± 11.3 years). Early and late outcomes were compared between the groups., Results: In the group aged 80 years or more, operative mortality occurred in 12 patients (8.6%) and significantly improved over time (P = .010). Operative mortality was significantly higher in the group aged 80 years or more (P = .033) when compared with the group aged less than 80 years (4.0%). Regarding postoperative complications, deep sternal wound infection, pneumonia, and tracheostomy occurred in significantly more patients in the group aged 80 years or more. In the group aged 80 years or more, there were 52 late deaths, with 4 aortic-related deaths. Overall survival was 55.4% ± 5.0% at 5 years and 32.2% ± 6.1% at 8 years. Multivariable Cox-hazard regression analysis demonstrated that chronic kidney disease, nonelective surgery, and concurrent procedures were significant risk factors for overall survival in the group aged 80 years or more. Cumulative incidence for reoperation was significantly lower in the group aged 80 years or more (8.7% at 5 years) compared with the group aged less than 80 years (14.2% at 5 years)., Conclusions: Total arch replacement was performed with an acceptable overall survival in octogenarians and nonagenarians, although operative mortality was higher than in younger patients. However, older patients had a lesser burden of reoperation compared with younger patients., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the long-term outcomes of heart valve replacement with mechanical prosthesis (MP) versus bioprosthesis (BP) in patients on dialysis., Methods: A retrospective review was performed at 7 hospitals. Patients on dialysis who underwent valve replacement were included. Survival, reoperation, bleeding, and embolic events were compared across the MP and BP groups., Results: Between April 2000 and April 2016, 312 patients on dialysis were enrolled in our study (MP: 94 patients [30.1%], BP: 218 patients [69.9%]). Mean follow-up was 3.4 ± 3.6 years. Five-year and 10-year survival rates were similar in both groups (MP: 57.4 ± 5.5% at 5 years and 46.3 ± 6.4% at 10 years, BP: 50.2 ± 4.1% at 5 years and 38.8 ± 4.5% at 10 years, P = .305). Multivariate Cox hazard analysis demonstrated that diabetic nephropathy (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.31-2.73, P < .001), New York Heart Association functional classification ≥III (HR, 2.16; 95% CI, 1.37-3.35, P = .001), and mitral valve replacement (HR, 2.36; 95% CI, 1.58-3.49, P < .001) were significant risk factors for late death. Valve selection was not a significant risk factor. Freedom from valve-related embolic event at 5 years was significantly lower in the MP group (MP: 88.3 ± 4.3% at 5 years, BP: 97.2 ± 1.6% at 5 years, P = .007). Freedom from valve-related reoperation or hemorrhagic events was similar across both groups., Conclusions: Valve selection was not associated with late survival outcomes in patients on dialysis. However, BP may have an advantage in preventing embolic events without increasing the incidence of valve-related reoperation when compared with MP., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: We present our open surgical strategies for staged replacement of the thoracic and thoracoabdominal aorta in patients with Marfan syndrome., Methods: Between October 1999 and December 2017, 82 patients with Marfan syndrome underwent 118 aortic repairs. We divided the aorta into 4 segments for categorization: (1) the aortic root, (2) aortic arch, (3) descending thoracic, and (4) abdominal aorta. Procedures were categorized according to the types of surgery. Staged repair was defined as a subsequent operation on a different segment of the aorta after initial repair (n = 111, 94.1%), and reoperation was defined as an operation on the same segment (n = 7, 5.9%)., Results: The mean age at initial operation was 41.7 ± 14.9 years. Staged repairs included aortic root replacement (n = 42, 36%), total arch replacement (n = 11, 9.3%), combined aortic root and total arch replacement (n = 13, 11%), descending aorta replacement (n = 4, 3.4%), thoracoabdominal aortic repair (n = 36, 31%), and extensive arch-descending or thoracoabdominal repair (n = 5, 4.2%). Four patients received 3 staged repairs. Operative mortality was 0.8% (1/118). Stroke occurred in 1.7% (2/118), and spinal cord injury occurred in 1.7% (2/117). Overall survival was 95.8 ± 2.4% at 10-years. Twenty-four patients underwent replacement of the whole aorta after 2.5 ± 3.8 years following initial repair., Conclusions: Our strategies for staged replacement of the thoracic and thoracoabdominal aorta in patients with Marfan syndrome resulted in excellent early- and long-term outcomes., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of white matter changes on neurologic outcomes after total arch replacement using antegrade cerebral perfusion., Methods: White matter changes were assessed using a visual Fazekas scale on preoperative magnetic resonance images. From October 1999 to December 2016, 359 patients who had demonstrated changes on preoperative magnetic resonance imaging underwent elective total arch replacement using antegrade cerebral perfusion. Patients were classified into 3 severity groups: mild (100 patients), moderate (158 patients), and severe (101 patients). Mean follow-up time was 4.8 ± 3.6 years. Multivariate logistic regression methods were used to evaluate for an independent association between white matter changes and postoperative neurological outcomes., Results: Hospital mortality was 2.8% (10/359), and no significant differences were found across the 3 groups (P = .604). Multivariate analysis demonstrated that the severity of white matter change was significantly associated with both postoperative permanent neurologic deficit (odds ratio, 5.77; 95% confidence interval, 1.58-38.4, P = .005) and transient neurologic deficit (odds ratio, 2.46; 95% confidence interval, 1.45-4.37, P < .001)., Conclusions: White matter changes, defined using the visual Fazekas scale on preoperative magnetic resonance imaging, were significantly associated with significant postoperative adverse neurologic outcomes after total arch replacement using antegrade cerebral perfusion., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Our study evaluated the long-term outcomes of total arch replacement using a 4-branched graft., Methods: From October 1999 to December 2016, 655 patients underwent total arch replacement using a 4-branched graft (pathology in the 655 patients was distributed as 399 no dissection, 149 acute dissection, and 107 chronic dissection). Two hundred nine patients (31.9%) underwent nonelective surgery. Mean follow-up term was 5.0 ± 4.1 years and follow-up rate was 97.1%., Results: Of 655 patients who underwent total arch replacement using a 4-branched graft, operative mortality occurred in 34 patients (5.2%) and permanent neurologic deficit occurred in 24 patients (3.7%). One hundred ninety late deaths occurred, with 20 aortic event-related deaths. Overall survival was 73.1% ± 1.9% at 5 years and 54.8% ± 2.7% at 10 years. Multivariate Cox-hazard regression analysis demonstrated that older age, lower estimated glomerular filtration rate, concurrent procedures, permanent neurologic deficit, tracheostomy, and renal failure were significant risk factors for late death. Freedom from repeat operation on the aorta was 98.0% ± 0.7% at 5 years and 93.9% ± 1.8% at 10 years and freedom from additional aortic operation was 87.2% ± 1.5% at 5 years and 77.3% ± 2.7% at 10 years. The incidence of pseudoaneursym was 2.2%., Conclusions: The long-term outcomes for patients undergoing total arch replacement using 4-branched graft are favorable. However, even in the late phase, periodic follow-up is necessary to address subsequent aorta-related events., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: We present our experience with one-stage replacement of thoracic aneurysm from the ascending aorta to the thoracoabdominal aorta., Patients and Methods: Fourteen patients (10 male and 4 female; mean age 53.6 ± 12.4 years) with extended thoracic aortic aneurysms underwent graft replacement. The pathology of the diseased aorta was chronic aortic dissection in 13 patients and intraoperative retrograde aortic dissection in 1 patient. Five patients had Marfan syndrome. In a previous operation, 1 patient had undergone the Bentall procedure, 4 had hemiarch replacement for acute type A dissection, and 1 had a Y-graft for abdominal aortic aneurysm. The approach to the aneurysm was posterolateral thoracotomy with rib-cross incision extended to the retroperitoneal abdominal aorta. Arterial inflow for cardiopulmonary bypass consisted of the femoral artery in 13 patients and abdominal aortic aneurysm graft in 2. Venous drainage site was the femoral vein in 7, femoral vein and pulmonary artery in 3, and pulmonary artery in 1. All patients had antegrade cerebral perfusion and visceral perfusion., Results: Hospital mortality occurred in 1 patient due to acute myocardial infarction. Actuarial survival at 5 years after the operations was 96.5 ± 9.8%. Freedom from the subsequent aortic events was 91.0 ± 2.9% at 5 years., Conclusions: Our treatment method for extensive thoracic aneurysm, from the ascending aorta to the thoracoabdominal aorta, achieved satisfactory results via the use of specific strategies and appropriate organ protection according to the aneurysm extension in the selected patients., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To present a surgical strategy for aortoesophageal fistula (AEF)., Methods: From October 1999 to May 2017, 27 patients with AEF were treated at Kobe University Hospital. After 9 patients with malignancies or fish bone penetration were excluded, 18 patients who had AEF secondary to aortic lesions were investigated. The mean age was 67.2 ± 10.4 years, and the male/female ratio was 16:2. Twelve patients had a nondissection thoracic aneurysm, and 6 patients had a chronic aortic dissection. Six patients were in shock. Seven patients had a previous thoracic endovascular aortic repair (TEVAR) in the descending aorta, 2 patients had descending aorta replacement, 1 had hemiarch replacement, and 2 had total arch replacement. As the first treatment for AEF, 3 patients underwent TEVAR as destination therapy, 3 patients had a bridge TEVAR to open surgery, 1 patient had an extra-anatomical bypass from the ascending aorta to the abdominal aorta, and 11 patients had an in situ reconstruction of the descending aorta. The esophagus was resected in 16 patients, and an omental flap was installed in 16 patients. Additional procedures were extra-anatomical bypass in 2 patients and in situ reconstruction of the aorta in 3 patients., Results: Hospital mortality was noted in 4 patients (22.2% persistent sepsis, n = 3: pneumonia, n = 1). However, since 2007, only 1 of 13 patients has died (pneumonia). Late death occurred in 5 patients, due to pneumonia, cerebral bleeding, diarrhea, sudden death, and persistent infection. Actuarial survival was 42.4 ± 12.8% at 5 years and freedom from aorta-related death was 59.4 ± 13.5% at 5 years. Nine patients achieved completed reconstruction of the esophagus 172 ± 57 days after initial surgery., Conclusions: Although a comparative study was not performed, 1-stage surgery consisting of resection of an aneurysm and esophagus, in situ reconstruction of the descending aorta, and omental flap installation provided a better outcome in the treatment for AEF. Bridging TEVAR to the open surgery is a useful adjunct in patients with AEF with hemorrhagic shock. Later reconstruction of the esophagus can be performed in the survivors., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: We describe a simple method to assess the aortic valve using a videoscope inserted in the left ventricle (LV-VS) during valve-sparing root replacement. The aim of this study was to evaluate the feasibility of this technique by comparing it with the findings of postoperative transesophageal echocardiography (TEE)., Methods: Thirty-six patients (29 male, mean age 45.4 ± 20.1 years) undergoing aortic root reimplantation were assessed intraoperatively with LV-VS. The LV-VS was inserted from the right upper pulmonary vein into the left ventricle and set toward the aortic valve. After completion of graft implantation, inspection was performed with LV-VS by pressurizing the neo-sinus before attachment of coronary arteries. Valve competency evaluated by LV-VS was compared with postoperative TEE findings, according to the group of cusp morphologies. Group 1 included 26 patients with tricuspid aortic valve, and group 2 included 9 patients with bicuspid aortic valve and 1 quadricuspid aortic valve., Results: The grade of aortic regurgitation (AR) improved from 2.9 ± 1.6 preoperatively to 0.33 ± 0.6 postoperatively (P < .001 vs preoperatively). In 4 patients, LV-VS was used only before repair. In group 1, intraoperative LV-VS showed a competent valve in 20 and an incompetent valve in 3 patients, and postoperative TEE showed non/trivial AR in 15, mild AR in 5, and mild-to-moderate AR in 3 patients. In group 2, 9 patients achieved a competent valve on intraoperative LV-VS and non/trivial AR on postoperative TEE., Conclusions: Intraoperative direct inspection with LV-VS is a feasible method for confirming the completion of cusp repair., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The present study aimed to determine the impact of the extent of graft replacement on early and late outcomes in acute DeBakey type I aortic dissection., Methods: Between October 1999 and July 2014, 197 consecutive patients were surgically treated for acute DeBakey type I aortic dissection. The extent of graft replacement (hemiarch, partial, or total arch replacement) was mainly determined by the location of the primary entry. Early and late results were compared in patients after total arch replacement (n = 88) and combined hemiarch and partial arch replacement: non-total arch replacement (n = 109)., Results: The in-hospital mortality rates of the total arch replacement and non-total arch replacement groups were 10.2% and 14.7%, respectively (P = .47). Multivariate analysis revealed preoperative cardiopulmonary resuscitation and visceral organ malperfusion as significant risk factors for in-hospital mortality, but not total arch replacement. During a mean follow-up period of 60 ± 48 months, the 5-year survivals in the total arch replacement and non-total arch replacement groups were 88.6% ± 4.2% and 83.8% ± 4.4%, respectively (P = .54). Rates of distal aortic events (defined as freedom from surgery for distal aorta dilation or distal arch diameter expanding to 50 mm) at 5 years were significantly better in the total arch replacement group than in the non-total arch replacement group (94.9% ± 3.5% vs 83.6% ± 4.9%, P = .01)., Conclusions: The operative mortality of patients with acute DeBakey type I aortic dissection treated by total arch replacement was acceptable with good long-term survival after both total arch replacement and non-total arch replacement. The frequency of distal aortic events might be reduced in patients after total arch replacement compared with non-total arch replacement., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the impact of preoperative identification of the Adamkiewicz artery (AKA) on prevention of spinal cord injury (SCI) through the multicenter Japanese Study of Spinal Cord Protection in Descending and Thoracoabdominal Aortic Repair (JASPAR) registry., Methods: Between January 2000 and October 2011, 2435 descending/thoracoabdominal aortic repairs were performed, including 1998 elective repairs and 437 urgent repairs, in 14 major centers in Japan. The mean patient age was 67 ± 13 years, and 74.2% were males. There were 1471 open repairs (ORs), including 748 descending and 137 thoracoabdominal extent [Ex] I, 136 Ex II, 194 Ex III, 115 Ex IV, and 138 Ex V, and 964 endovascular repairs (EVRs). Of the 2435 patients, 1252 (51%) underwent preoperative magnetic resonance or computed tomography angiography to identify the AKA., Results: The AKA was identified in 1096 of the 1252 patients who underwent preoperative imaging (87.6%). Hospital mortality was 9.2% (n = 136) in those who underwent OR and 6.4% (n = 62) in those who underwent EVR. The incidence of SCI was 7.3% in the OR group (descending, 4.2%; Ex I, 9.4%; Ex II, 14.0%; Ex III, 14.4%; Ex IV, 4.2 %; Ex V, 7.2%) and 2.9% in the EVR group. The risk factors for SCI in ORs were advanced age, extended repair, emergency, and occluded bilateral hypogastric arteries. In ORs of the aortic segment involving the AKA, having no AKA reconstruction was a significant risk factor for SCI (odds ratio, 2.79, 95% confidence interval, 1.14-6.79; P = .024)., Conclusions: In descending/thoracoabdominal aortic repairs, preoperative AKA identification with its adequate reconstruction or preservation, especially, in ORs of aortic pathologies involving the AKA, would be a useful adjunct for more secure spinal cord protection., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Antegrade cerebral perfusion and hypothermic circulatory arrest, with or without retrograde cerebral perfusion, are 2 major types of brain protection that are used during aortic arch surgery. We conducted a comparative study of these methods in patients undergoing total arch replacement to evaluate the clinical outcomes in Japan, based on the Japan Adult Cardiovascular Surgery Database., Methods: A total of 16,218 patients underwent total arch replacement between 2009 and 2012. Patients with acute aortic dissection or ruptured aneurysm, or who underwent emergency surgery were excluded, leaving 8169 patients for analysis. For the brain protection method, 7038 patients had antegrade cerebral perfusion and 1141 patients had hypothermic circulatory arrest/retrograde cerebral perfusion. A nonmatched comparison was made between the 2 groups, and propensity score analysis was performed among 1141 patients., Results: The matched paired analysis showed that the minimum rectal temperature was lower in the hypothermic circulatory arrest/retrograde cerebral perfusion group (21.2°C ± 3.7°C vs 24.2°C ± 3.2°C) and that the duration of cardiopulmonary bypass and cardiac ischemia was longer in the antegrade cerebral perfusion group. There were no significant differences between the antegrade cerebral perfusion and hypothermic circulatory arrest/retrograde cerebral perfusion groups with regard to 30-day mortality (3.2% vs 4.0%), hospital mortality (6.0% vs 7.1%), incidence of stroke (6.7% vs 8.6%), or transient neurologic disorder (4.1% vs 4.4%). There was no difference in a composite outcome of hospital death, bleeding, prolonged ventilation, need for dialysis, stroke, and infection (antegrade cerebral perfusion 28.4% vs hypothermic circulatory arrest 30.1%). However, hypothermic circulatory arrest/retrograde cerebral perfusion resulted in a significantly higher rate of prolonged stay in the intensive care unit (>8 days: 24.2% vs 15.6%)., Conclusions: Hypothermic circulatory arrest/retrograde cerebral perfusion and antegrade cerebral perfusion provide comparable clinical outcomes with regard to mortality and stroke rates, but hypothermic circulatory arrest/retrograde cerebral perfusion resulted in a higher incidence of prolonged intensive care unit stay. Antegrade cerebral perfusion might be preferred as the brain protection method for complicated aortic arch procedures., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: We present a series of patients who underwent in situ total aortic arch replacement for infected distal aortic arch aneurysms., Methods: Between 2002 and 2013, 9 patients with infected distal aortic arch aneurysms underwent total aortic arch replacement using antegrade selective cerebral perfusion. There were 4 male and 5 female patients with a mean age of 72.7±9.0 years. All patients had penetrating atherosclerotic ulcer in the distal aortic arch, which formed saccular aneurysms. Four patients had preoperative hoarseness. Maximum preoperative white blood cell count was 10,211±4375/μL, and mean serum C-reactive protein concentration was 12.7±7.2 mg/dL. Causative microorganisms were identified by blood culture or aortic wall culture and were as follows: Candida albicans, Pseudomonas aeruginosa, Edwardsiella tarda, Streptococcus dysgalactiae, Listeria monocytogenes, Staphylococcus aureus (2 cases), and unknown (2 cases). Radical debridement with in situ total aortic arch replacement was performed in all patients, followed by the omental flap grafting in 7 patients. All surgery was performed on an urgent or emergency basis., Results: Average cardiopulmonary bypass time and lower body circulatory arrest time were 199.7±50.7 minutes and 66.6±13.8 minutes, respectively. There was no in-hospital mortality, but 1 patient died of asphyxia 5 months after hospital discharge. Freedom from recurrence of infection was 100%., Conclusions: Surgical treatment with the combination of radical debridement with in situ total aortic arch replacement using antegrade selective cerebral perfusion and omental flap grafting was a reliable procedure for the treatment of infected distal aortic arch aneurysms., (Copyright © 2014. Published by Elsevier Inc.)

Objectives: The management of acute type A aortic dissection complicated by coma remains controversial. We previously reported an excellent rate of recovery of consciousness provided aortic repair was performed within 5 hours of the onset of symptoms. This study evaluates the early and long-term outcomes using this approach., Methods: Between August 2003 and July 2013, of the 241 patients with acute type A aortic dissection brought to the Japanese Red Cross Kobe Hospital and Hyogo Emergency Medical Center, 30 (12.4%) presented with coma; Glasgow Coma Scale was less than 11 on arrival. Surgery was performed in 186 patients, including 27 (14.5%) who were comatose. Twenty-four comatose patients underwent successful aortic repair immediately (immediate group). Their mean age was 71.0 ± 11.1 years, Glasgow Coma Scale was 6.5 ± 2.4, and prevalence of carotid dissection was 79%. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative induced hypothermia was performed. Neurologic evaluations were performed using the Glasgow Coma Scale, National Institutes of Health Stroke Scale, and modified Rankin Scale., Results: In the immediate group, the time from the onset of symptoms to arrival in the operating theater was 222 ± 86 minutes. Hospital mortality was 12.5%. Full recovery of consciousness was achieved in 79% of patients in up to 30 days. Postoperative Glasgow Coma Scale and National Institutes of Health Stroke Scale improved significantly when compared with the preoperative score (P < .05), and postoperative activities of daily living independence (modified Rankin Scale <3) was achieved in 50% of patients. The mean follow-up period was 56.5 months, and the cumulative survival was 48.2% after 10 years. Cox proportional hazards regression analysis indicated that immediate repair (hazard ratio, 4.3; P = .007) was the only significant predictor of postoperative survival over a 5-year period., Conclusions: The early and long-term outcomes as a result of immediate aortic repair for acute type A aortic dissection complicated by coma were satisfactory., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: The present study analyzes the early patency of intercostal artery reconstruction, using graft interposition and aortic patch anastomosis, and determines the fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms., Methods: We selected 115 patients (mean age, 63 ± 15 years; range, 19-83 years; male, n = 83) treated by thoracoabdominal aortic aneurysm repair with 1 or more reconstructed intercostal arteries at the Kobe University Graduate School of Medicine between October 1999 and December 2012. The intercostal arteries were reconstructed using graft interposition (n = 66), aortic patch anastomosis (n = 42), or both (n = 7)., Results: The hospital mortality rate was 7.8% (n = 9). Eleven patients (9.6%) developed spinal cord ischemic injury (permanent, n = 6, transient, n = 5). The average number of reconstructed intercostal arteries per patient was 3.0 ± 1.5 (1-7), and 345 intercostal arteries were reattached. The overall patency rate was 74.2% (256/345) and that of aortic patch anastomosis was significantly better than that of graft interposition (90.8% [109/120] vs 65.3% [147/225], P < .01), but significantly worse for patients with than without spinal cord ischemic injury (51.9% [14/27] vs 76.1% [242/318], P = .01). There was no patch aneurysm in graft interposition during a mean of 49 ± 38 (range, 2-147) postoperative months, but aortic patch anastomosis including 4 intercostal arteries became dilated in 2 patients., Conclusions: Aortic patch anastomosis might offer better patency rates and prevent spinal cord ischemic injury compared with graft interposition. Although aneurysmal changes in intercostal artery reconstructions are rare, large blocks of aortic wall reconstruction should be closely monitored., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Little is known about the impact of preoperative renal function stratified by estimated glomerular filtration rate (eGFR) on outcomes of total aortic arch replacement (TAR). The current study addressed this issue and identified a cutoff value of eGFR for the requirement of postoperative renal replacement therapy., Methods: From January 2000 to May 2011, 229 consecutive patients who did not require preoperative hemodialysis were retrospectively studied after elective TAR. Patients were grouped into the following categories: those with normal renal function (eGFR >90 mL/min/1.73 m(2); n = 11) and those with mild (eGFR, 60-90 mL/min/1.73 m(2); n = 86), moderate (eGFR, 30-59 mL/min/1.73 m(2); n = 111), or severe (eGFR <30 mL/min/1.73 m(2); n = 21) renal dysfunction. Linear trend tests demonstrated that the lower categories of eGFR were associated with a higher age, hypertension, coronary artery disease, peripheral arterial disease, and a higher EuroSCORE II., Results: The overall hospital mortality was 2.2%. A lower categories of eGFR were an independent risk factor for hospital mortality (odds ratio, 0.91; P = .002) and postoperative renal replacement therapy (odds ratio, 0.94; P < .002). A cutoff value for the requirement of postoperative renal replacement therapy was 26.0 mL/min/1.73 m(2). Patients in the lower categories of eGFR had significantly higher hospital mortality (P = .03) and more morbidities, such as renal replacement therapy (P < .01), postoperative permanent neurologic deficits (P = .013), and prolonged mechanical ventilatory support (P < .01). Midterm survival and freedom from major adverse cerebrocardiovascular events were worse across the levels of the lower categories of eGFR., Conclusions: Preoperative eGFR is a strong predictor of short- and midterm outcomes in contemporary TAR., (Copyright © 2014. Published by Mosby, Inc.)

Objectives: Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM., Methods and Results: ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area., Conclusions: Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The effect of an atherothrombotic aorta on the short- and long-term outcomes of total aortic arch replacement, including postoperative neurologic deficits, remains unknown. We evaluated this relationship and also elucidated the synergistic effect of multiple other risk factors, in addition to an atherothrombotic aorta, on the neurologic outcome., Methods: A group of 179 consecutive patients undergoing total aortic arch replacement were studied. An atherothrombotic aorta was present in 34 patients (19%), more than moderate leukoaraiosis in 71 (39.7%), and significant extracranial carotid artery stenosis in 27 (15.1%). In-hospital deaths occurred in 2 patients, 1 (2.9%) of 34 patients with and 1 (0.7%) of 145 patients without an atherothrombotic aorta (P = .26). Permanent neurologic deficits occurred in 4 (2.2%) and transient neurologic deficits in 17 (9.5%) patients. Multivariate analysis demonstrated that the risk factors for transient neurologic deficits were an atherothrombotic aorta (odds ratio, 4.4), extracranial carotid artery stenosis (odds ratio, 5.5), moderate/severe leukoaraiosis (odds ratio, 3.6), and cardiopulmonary bypass time (odds ratio, 1.02). To calculate the probability of transient neurologic deficits, the following equation was derived: probability of transient neurologic deficits = {1 + exp [7.276 - 1.489 (atherothrombotic aorta) - 1.285 (leukoaraiosis) - 1.701 (extracranial carotid artery stenosis) - 0.017 (cardiopulmonary bypass time)]}(-1). An exponential increase occurred in the probability of transient neurologic deficits with presence of an atherothrombotic aorta and other risk factors in relation to the cardiopulmonary bypass time. Survival at 3 years after surgery was significantly reduced in patients with vs without an atherothrombotic aorta (75.0% ± 8.8% vs 89.2% ± 3.1%, P = .01)., Conclusions: Patients with an atherothrombotic aorta and associated preoperative comorbidities might be predisposed to adverse short- and long-term outcomes, including transient neurologic deficits., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The technical details of total arch replacement using antegrade cerebral perfusion are presented., Methods: From January 2002 to May 2012, 423 consecutive patients (mean age, 69.2 ± 13.1 years) underwent total arch replacement using antegrade selective cerebral perfusion through a median sternotomy. Acute aortic dissection was present in 81 patients (19.1%; 75 type A, 6 type B), and a shaggy aorta was present in 37 patients (8.7%). Emergency/urgent surgery was required in 135 patients (31.9%). Our current approach included meticulous selection of the arterial cannulation site and type of arterial cannula, antegrade selective cerebral perfusion, maintenance of the minimal tympanic temperature between 20 °C and 23 °C, early rewarming immediately after distal anastomosis, and maintenance of the fluid balance at less than 1000 mL during cardiopulmonary bypass. A woven Dacron 4-branch graft was used in all patients., Results: The overall hospital mortality was 4.5% (19/423): 9.6% (13/135) in urgent/emergency surgery cases and 2.1% (6/288) in elective cases. Permanent neurologic deficits occurred in 3.3% patients (14/423). Prolonged ventilation was necessary in 57 patients (13.4%). A multivariate analysis demonstrated the risk factors for hospital mortality to be age (octogenarian; odds ratio, 4.45; P = .02), brain malperfusion (odds ratio, 22.5; P = .002), and cardiopulmonary bypass time (odds ratio, 1.06; P = .04). The follow-up was completed in 97.2% of patients (mean, 29 ± 27; 1-126) and included 2.3 patients per year. Survival at 5 and 10 years after surgery was 79.6% ± 3.3% and 71.2% ± 5.0%, respectively. In the acute A dissection group, the 10-year survival was 96.6% ± 2.4%. In the elective nondissection group, the 5- and 10-year survivals were 80.3% ± 4.2% and 76.1% ± 5.7%, respectively., Conclusions: Our current approach for total aortic arch replacement is associated with low hospital mortality and morbidity, thus leading to a favorable long-term outcome., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Recent advancements in total aortic arch replacement achieved by our approach were presented., Methods: From January 2002 to December 2010, 321 consecutive patients (mean age 69.8 ± 13.3 years) underwent total arch replacement through a median sternotomy at our institute. Aortic dissection was present in 94 (28.3%) patients and shaggy aorta in 36 (11.2%), with emergency/urgent surgery required in 106 (33.0%). Our current approach included the following: (1) meticulous selection of arterial cannulation site and type of arterial cannula; (2) antegrade selective cerebral perfusion; (3) maintenance of minimal tympanic temperature between 20 °C and 23 °C; (4) early rewarming just after distal anastomosis; (5) after 2004, bolus injection of 100 mg of sivelestat sodium hydrate into the pump circuit at the initiation of cardiopulmonary bypass; (6) after 2006, maintaining fluid balance below 1000 mL during cardiopulmonary bypass., Results: Overall hospital mortality was 4.4% (14/321) and was 1.9% (4/215) in elective cases. Permanent neurologic deficit occurred in 4.4% (14/321) of patients and in 2.8% (6/215) of elective cases. Prolonged ventilation was necessary in 53 (16.5%), with a significant reduction after 2006 (22.8% vs 12.6%; P = .02). Multivariate analysis demonstrated that risk factors for hospital mortality were octogenarian (odds ratio, 4.32; P = .03), brain malperfusion (odds ratio, 21.2; P = .001) and cardiopulmonary bypass time (odds ratio, 1.01; P = .04). Survival at 3 and 5 years after surgery was 82.4% ± 2.5% and 78.5% ± 3.1%, respectively., Conclusions: Our current approach for total aortic arch replacement was associated with low hospital mortality and morbidities and with favorable long-term outcome., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Surgical treatment of acute type A aortic dissection complicated by cerebral malperfusion remains challenging. This study evaluated predictors of lack of neurologic improvement after aortic repair for acute type A dissection complicated by cerebral malperfusion and assessed relationship with survival., Methods: We retrospectively reviewed 41 consecutive patients operated on between 1999 and 2008 for acute type A dissection complicated by cerebral malperfusion. Lack of postoperative neurologic improvement was defined as a difference between baseline and postoperative National Institutes of Health Stroke Scale scores of 3 points or less., Results: Lack of neurologic improvement was seen in 15 patients (37%). Logistic regression analysis, baseline National Institutes of Health Stroke Scale score (odds ratio, 6.7; 95% confidence interval, 1.4-32.4; P = .02), and time to surgery (odds ratio, 14.6; 95% confidence interval, 2.7-8.5; P = .002) were significantly associated with lack of neurologic improvement. In receiver operating characteristic analysis, National Institutes of Health Stroke Scale score greater than 11 and time to surgery longer than 9.1 hours were best cutoffs for predicting lack of neurologic improvement. Thirty-day mortality was 14.6%. All early deaths were caused by large hemispheric infarction. Postoperative computed tomography or magnetic resonance imaging revealed cerebral infarction in 21 patients (51%). Five-year survival was significantly lower in patients without neurologic improvement (33% ± 12% vs 84% ± 7%, log-rank P <.001)., Conclusions: Time to surgery and baseline National Institutes of Health Stroke Scale score were predictors of lack of improvement, which was associated with poor survival., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: We have demonstrated that therapeutic augmentation of systemic blood pressure during spinal cord ischemia plays an important role in minimizing spinal cord injury in both experimental and clinical aortic surgery. However, there remain concerns that excessively high blood pressure during spinal cord reperfusion may aggravate the reperfusion injury. The purpose of this study is to investigate the effect of high blood pressure during spinal cord reperfusion on postoperative neurologic outcomes after aortic surgery in rabbits., Methods: Experiments were performed using a rabbit spinal cord ischemia-reperfusion model in 2 randomly divided groups: (1) In the HR group, the mean blood pressure was maintained at a high level (121 +/- 1.3 mm Hg) during reperfusion with intravenously administered phenylephrine; and (2) in the CR group, the mean blood pressure was not medically controlled (75 +/- 9.1 mm Hg) during reperfusion. Neurologic and histologic assessments and evaluation of early reperfusion injury were performed., Results: In the HR group, slow and incomplete recovery of transcranial motor-evoked potentials (P = .02) and low neurologic scores (P < .005) were observed during spinal cord reperfusion compared with the CR group. At 48 hours of reperfusion, there were significantly fewer viable neuron cells, more apoptosis, and more perivascular edema with gray matter vacuolation in the HR group (P < .001 for each). At 3 hours, myeloperoxidase activity (P = .0021), vascular permeability (P = .0012), and superoxide generation (P < .0001) were significantly increased in the HR group., Conclusion: Excessively high blood pressure in the early phase of spinal cord reperfusion increased reperfusion injury in the spinal cord, leading to exacerbation of early-onset paraplegia. Avoidance of spinal cord reperfusion with high blood pressure may be one management strategy in thoracoabdominal aortic surgery., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Improvement of vein graft patency may be highly beneficial in coronary artery bypass grafting, but graft degeneration is considered to be one of the main pathophysiologic causes for vein graft failure. Because peroxisome proliferator-activated receptor-gamma activator pioglitazone was recently reported to possess pleiotropic protective effects on various organs and tissues, we conducted experiments to test the hypothesis that pioglitazone could prevent graft degeneration, leading to the preservation of vein graft integrity., Methods: In a rat aortic interposition model with autologous femoral vein, pioglitazone (3 mg/kg/d) or vehicle (normal saline) was given to rats by gastric gavage once per day beginning 3 days before surgery and ending 8 weeks after surgery. Vein graft degeneration and remodeling were assessed at 24 hours, 7 days, 8 weeks, and 6 months after surgery., Results: At 24 hours, pioglitazone significantly reduced endothelial desquamation, reactive oxygen species generation, myeloperoxidase activity, and lipid peroxidation in vein grafts. At 7 days, mRNA expression and gelatinolytic activity of matrix metalloproteinase-2 and 9 in vein grafts were significantly suppressed by pioglitazone treatment. Immunofluorescent staining showed that pioglitazone enhanced peroxisome proliferator-activated receptor-gamma expression in vein grafts at 8 weeks, especially in their intimal side. At 6 months, pioglitazone treatment prevented graft dilation (52.3% +/- 3.1% vs 90.7% +/- 9.9%, P = .0041) and neointimal hyperplasia (14.6% +/- 1.3% vs 29.9% +/- 2.9%, P = .0008), and increased graft flow velocity ratio (0.86 +/- 0.03 vs 0.59 +/- 0.04, P < .0001), compared with vehicle treatment., Conclusion: Pioglitazone prevents graft degeneration under arterial pressure stress and preserves the vein graft integrity in a rat aortic interposition model., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia., Methods: Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated., Results: Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group., Conclusions: Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The peroxisome proliferator-activated receptor gamma activator pioglitazone has recently been reported to possess pleiotropic cardioprotective and renoprotective actions. We hypothesized that pioglitazone would reduce a dose of the immunosuppressant cyclosporine after heart transplantation, resulting in beneficial protective effects for both cardiac allografts and recipient kidneys., Methods: Experiments were performed by using an allomismatched rat heterotopic heart transplantation model. Recipients were treated with cyclosporine with or without pioglitazone and were divided into one of 4 groups: group I, no treatment; group II, low-dose cyclosporine (2 mg x kg(-1) x d(-1)); group III, high-dose cyclosporine (5 mg x kg(-1) x d(-1)); and group IV, low-dose cyclosporine with pioglitazone (3 mg x kg(-1) x d(-1))., Results: Cyclosporine-treated rats showed significantly longer graft survival and less graft rejection but severe renal damage in a dose-dependent manner. Compared with group II, treatment with pioglitazone with low-dose cyclosporine (group IV) significantly suppressed graft infiltration of CD4/CD8 T lymphocytes and serum concentrations of interleukin 2 and interferon gamma, leading to extended graft survival up to 60 days. These immunosuppressive effects in group IV were equivalent to those in group III. In addition, recipient kidneys in group IV had few apoptotic cells, possibly through upregulation of peroxisome proliferator-activated receptor gamma and downregulation of transforming growth factor beta1, and maintained stable renal functions, as evidenced by a normalization of blood urea nitrogen, creatinine, and creatinine clearance values. In vitro experiments also confirmed the renoprotective effects of pioglitazone on cyclosporine-induced toxicity., Conclusions: Collectively, pioglitazone can reduce a dose of cyclosporine with sufficient immunosuppressive effects. Pioglitazone treatment with low-dose cyclosporine has synergistic protective effects for cardiac allografts and recipient kidneys, leading to improvement of graft survival with a minimal cyclosporine-induced nephrotoxicity.

Objectives: Sinus node dysfunction is known as a major complication after repair of partial anomalous pulmonary venous connection. We retrospectively analyzed the results of the atrial wall flap technique compared with the results of patch repair or direct suturing in the intra-atrial tunnel technique., Methods: Between 1991 and 2007, 23 patients (mean age, 6 years; range, 5 months-17 years) with partial anomalous pulmonary venous connection underwent surgical intervention. The right anomalous pulmonary veins drained to either the right atrium or superior vena cava in 8 and 15 patients, respectively. Patients were divided into 2 groups: group F (n = 14), who had repair with an atrial flap, and group N (n = 9), who had repair without an atrial flap. All patients had normal sinus rhythm preoperatively., Results: No patients had signs of superior vena cava or pulmonary venous obstruction within a mean follow-up of 4.8 years. One patient in group F required pacemaker implantation. In the early postoperative period, sinus node dysfunction developed in 93% of group F and 44% of group N patients (P < .01) and was prolonged until discharge in 57% of group F and 0% of group N patients (P < .01). At the most recent clinical visit, sinus node dysfunction was identified in 50% of group F patients, whereas all patients in group N had normal sinus rhythm (P < .02)., Conclusions: The atrial flap technique, which requires incision or suture crossing the crista terminalis, could cause sinus node dysfunction, whereas the intra-atrial rerouting method with a patch or direct suture maintains normal sinus node function postoperatively.