[Subclavian-aortic Bypass for Management of Aortic Coarctation in Adults:Report of a Case].

A 57-year-old man presented to the hospital with dyspnea. A diagnosis of hypertensive heart failure was made, and treatment was initiated. However, his ankle-brachial index had decreased to 0.61 on the right and 0.56 on the left side, and he had intermittent claudication with decreased renal function( serum creatinine, 1.73 mg/dl). Thoracoabdominal contrast-enhanced computed tomography showed severe stenosis with a diameter of 2.2 mm in the distal arch and marked development of collateral vessels, and a diagnosis of aortic stenosis was made. Vascular catheterization revealed a pressure gradient of 60 mmHg between the upper and lower extremities. We performed a left-sided open thoracotomy and left subclavian-descending aortic bypass( 16 mm J Graft, Shield). The patient recovered without postoperative complications, and the pressure gradient between the upper and lower extremities eventually decreased to 6 mmHg.

Renal redox dysregulation in AKI: application for oxidative stress marker of AKI.

Oxidative stress is a major determinant of acute kidney injury (AKI); however, the effects of an AKI on renal redox system are unclear, and few existing AKI markers are suitable for evaluating oxidative stress. We measured urinary levels of the redox-regulatory protein thioredoxin 1 (TRX1) in patients with various kinds of kidney disease and in mice with renal ischemia-reperfusion injury. Urinary TRX1 levels were markedly higher in patients with AKI than in those with chronic kidney disease or in healthy subjects. In a receiver operating characteristic curve analysis to differentiate between AKI and other renal diseases, the area under the curve for urinary TRX1 was 0.94 (95% confidence interval, 0.90-0.98), and the sensitivity and specificity were 0.88 and 0.88, respectively, at the optimal cutoff value of 43.0 µg/g creatinine. Immunostaining revealed TRX1 to be diffusely distributed in the tubules of normal kidneys, but to be shifted to the brush borders or urinary lumen in injured tubules in both mice and humans with AKI. Urinary TRX1 in AKI was predominantly in the oxidized form. In cultured human proximal tubular epithelial cells, hydrogen peroxide specifically and dose dependently increased TRX1 levels in the culture supernatant, while reducing intracellular levels. These findings suggest that urinary TRX1 is an oxidative stress-specific biomarker useful for distinguishing AKI from chronic kidney disease and healthy kidneys.

Treatment of anomalous arterial supply to the basal segment of left lung with aortic stent graft.

The patient was a 53-year-old man with a history of recurrent sputum. An anomalous systemic arterial supply to the basal segment of the left lung with an aneurysm of the aberrant artery detected on three-dimensional computed tomography angiography. Before left lower pulmonary lobectomy and aberrant artery resection, thoracic endovascular aortic repair was performed to block the blood flow to the aberrant artery aneurysm. Prior blockade of the blood flow to the aneurysm minimized the risk of aneurysm rupture and bleeding during lobectomy, yielding a good postoperative outcome.

Pulmonary valve myxoma requiring pulmonary valve replacement: a case report.

BACKGROUND: Most cardiac myxomas occur in the atria. Myxomas arising from the heart valves are rare, and there are only a few reports of myxomas arising from the pulmonary valve. Complete resection and prevention of embolization at the time of the first surgery are important to prevent the recurrence of myxomas. CASE PRESENTATION: An 82-year-old female was scheduled to undergo surgery for a fracture of the right femoral neck. The preoperative echocardiography showed a mass in the right ventricular outflow tract. The mass was 36 × 30 mm in size and entered into the pulmonary artery during systole. Cardiac synchronous computed tomography showed a stalked bifurcated mass near the pulmonary valve, which was suspected to be a myxoma. Surgical findings showed a lumen-occupying tumor when the main pulmonary artery was incised. Since the tumor was a single mass with a stalk on the pulmonary valve (right and left pulmonary valve cusps), tumor resection and pulmonary valve replacement (bioprosthetic valve) were performed. A right prosthetic femoral head insertion was performed on postoperative day 36, and the patient was transferred to the hospital on postoperative day 44. However, 1 year later, the patient developed a large myxoma (recurrence) that completely occluded the right pulmonary artery and died of right heart failure. CONCLUSIONS: We report the case of a patient with a very rare myxoma arising from the pulmonary valve, which was treated with tumor resection and pulmonary valve replacement surgery; however, the patient developed another myxoma 12 months later and this tumor was larger than the primary tumor. The surgical margins were indistinct, and there was a high possibility of residual tumor in the pulmonary artery wall; hence, an extended resection should have been considered. The recurrence of myxoma, in this case, suggests that it is important to completely resect the primary tumor during the first surgery and to prevent intraoperative embolization.

Intratumoral gene expression of dihydrofolate reductase and folylpoly-c-glutamate synthetase affects the sensitivity to 5-fluorouracil in non-small cell lung cancer.

BACKGROUND: Various factors related to the sensitivity of non-small cell lung carcinoma (NSCLC) to 5-fluorouracil (5-FU) have been reported, and some of them have been clinically applied. In this single-institutional prospective analysis, the mRNA expression level of five folic acid-associated enzymes was evaluated in surgical specimens of NSCLC. We investigated the correlation between the antitumor effect of 5-FU in NSCLC using an anticancer drug sensitivity test and the gene expression levels of five enzymes. MATERIALS AND METHODS: Forty patients who underwent surgery for NSCLC were enrolled, and the antitumor effect was measured using an in vitro anticancer drug sensitivity test (histoculture drug response assay) using freshly resected specimens. In the same sample, the mRNA expression levels of five enzymes involved in the sensitivity to 5-FU were measured in the tumor using real-time PCR. The expression levels and the result of the sensitivity test were compared. RESULTS: No correlation was found between dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), or DPD/OPRT expression and the antitumor effects of 5-FU. On the other hand, a correlation was found between thymidylate synthase (TS), folylpoly-c-glutamate synthetase (FPGS), and dihydrofolate reductase (DHFR) expression and 5-FU sensitivity. CONCLUSION: Expression of FPGS and DHFR may be useful for predicting the efficacy of 5-FU-based chemotherapy for NSCLC.

Thrombosed abdominal aortic aneurysm associated with an extensively "shaggy" aorta repaired anatomically via a thoracoabdominal approach with supraceliac aortic clamping: report of a case.

A 76-year-old man with a history of multiple laparotomies and severe coronary artery disease was referred to our hospital after the sudden development of pain and numbness in the lower extremities. Computed tomography showed a thrombosed abdominal aortic aneurysm and diffuse aortic atherosclerosis; compatible with a "shaggy aorta." A good response to thrombolytic therapy permitted elective scheduling of abdominal aortic surgery after coronary artery bypass grafting. We operated via an extended left retroperitoneal approach through a thoracoabdominal incision. Epiaortic ultrasonography revealed that only the supraceliac aorta was free of mobile thrombi and had minimal plaque; we therefore placed a proximal aortic cross-clamp there. Anatomic aortic reconstruction was then performed successfully using an aorto-biiliac graft to restore adequate distal blood flow. There were no vital-organ ischemic complications, and the postoperative course was satisfactory.

[A case of bacterial aneurysm complicated by severe infectious endocarditis].

We report a case of bacterial aneurysm complicated by severe infectious endocarditis. A 34-year-old man developed idiopathic fever and general fatigue persisting for a month. He was admitted to our institution, and examinations revealed severe bacterial endocarditis with vegetation at the mitral valve and mitral incompetence. Right after admission, he suddenly developed acute cardiac infarction and cardiac arrest due to occlusion of the coronary artery by emboli from vegetation of the mitral valve. After achieving a good recovery, magnetic resonance (MR) imaging demonstrated an unruptured bacterial aneurysm at the distal branch of the left middle cerebral artery (MCA) supplying the left parietal lobe 5 days after admission, and T2* weighted images demonstrated multiple signal loss lesions, which were suspected of being thrombosed bacterial micro-aneurysms or micro-vasculitis. Although there was a risk of aneurysm rupture, we decided to proceed with mitral valve replacement by an artificial heart valve made of carbon, and repeatedly observed an unruptured bacterial aneurysm by serial MR imaging and angiography. Due to the preceding cardiac surgery, we were able to completely cure the severe infection and prevent new embolic showers. Under administration of antibiotics, the bacterial cerebral aneurysm did not increase over a period of 4 weeks, and finally the aneurysm disappeared about 6 weeks after admission. Although the timing of treatment of an unruptured bacterial aneurysm and cardiac surgery for infectious endocarditis associated with a bacterial cerebral aneurysm are controversial, we think that proceeding with cardiac surgery and observing the unruptured bacterial aneurysm by repeated MR imaging and angiography under administration of antibiotics was an appropriate strategy in this case.

Long-term effect of gene therapy for chronic ischemic myocardium using platelet-derived endothelial cell growth factor in dogs.

BACKGROUND: We previously reported the 2-week benefits of platelet-derived endothelial cell growth factor (PD-ECGF) gene therapy in chronically ischemic myocardium. However, the long-term effects and safety using this gene have not been reported. METHODS: Chronic myocardial ischemia was created in 24 dogs by stenosing the origin of the left anterior descending coronary artery (LAD) using an ameroid constrictor. Two weeks later, the PD-ECGF gene, the LacZ gene, or saline was infused directly into the myocardium in the LAD area. The myocardial blood volume and myocardial function were examined prior to ischemia, immediately before gene injection, and for 6 months following injection, and then the organs were harvested for histological and molecular examination. RESULTS: PD-ECGF gene treatment significantly attenuated endocardial infarction at 6 months. Myocardial blood volume and myocardial function decreased in all three groups after ameroid implantation, but recovered after 2 weeks in the PD-ECGF-treated group, and maintained a higher level of function during the examination period. Histological analysis demonstrated that angiogenesis and arteriogenesis occurred after PD-ECGF gene treatment. There was a decreased expression of the pro-apoptotic proteins, active caspase-3 and Bax, and the number of apoptotic myocardial cells was lower in the PD-ECGF-treated group. Histological examination demonstrated that no abnormal histological changes or neoplasms were found in any organs. CONCLUSIONS: We conclude that gene targeting of ischemic myocardium using PD-ECGF generated long-term improvement in cardiac function by causing angiogenesis, arteriogenesis and inhibiting apoptosis, but did not induce neoplasms in the remote organs, and may be a promising therapy.

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft.

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP) reportedly inhibits vascular smooth muscle cells (VSMCs) migration and proliferation. We hypothesized that adventitial administration of the PD-ECGF/TP gene will suppress intimal hyperplasia and prevent vein graft failure. METHODS: The study used 68 female rabbits. Rabbit jugular vein was autogenously transplanted into carotid artery with a cuff anastomotic technique. To define vascular wall gene transfer efficiency, poloxamer hydrogel (20%) containing plasmid vector encoding the LacZ gene and different concentrations of trypsin (0%, 0.1%, 0.25%, and 0.5%, n = 5 for each group) was applied to the adventitia of the vein graft. Gene transfer efficiency was evaluated 7 days later by X-gal staining. An additional 48 rabbits received poloxamer hydrogel (20%) containing 0.25% trypsin and the human PD-ECGF/TP gene, LacZ gene, or saline. Intima thickness was evaluated at 2 and 8 weeks after grafting (n = 8 for each group at each time point). Transgene expression was examined by reverse transcriptase-polymerase chain reaction, immunoblotting assay, and immunohistochemical staining. Immunohistochemical staining was also used to determine VSMC proliferation, heme oxygenase-1 expression, and macrophage infiltration. RESULTS: Incorporation of trypsin into the poloxamer hydrogel significantly increased vessel wall gene transfer. Trypsin at 0.25% and 0.5% resulted in higher gene transfer at the same level without effecting intimal hyperplasia and inflammation; thus, trypsin at 0.25% concentration was used for subsequent experiments. Compared with the LacZ and saline groups, grafts receiving the PD-ECGF/TP gene significantly reduced intimal thickness at 2 and 8 weeks after treatment. The ratio of proliferative VSMC was lower in PD-ECGF/TP treated grafts. Histologic examination of the PD-ECGF/TP transgene grafts demonstrated high expression of heme oxygenase-1, which has been reported to inhibit VSMC proliferation, suggesting that heme oxygenase-1 may be important in the inhibition effect of PD-ECGF/TP on VSMC. No neoplastic or morphologic changes were found in the remote organs. CONCLUSIONS: A safe and highly efficient gene transfer method was developed by using poloxamer hydrogel and a low concentration of trypsin. Neointimal hyperplasia was significantly reduced by adventitial application of the PD-ECGF/TP gene to the vein graft. Our data suggest that adventitial delivery of the PD-ECGF/TP gene after grafting may be promising method for preventing vein graft failure.

Thymidine phosphorylase gene transfer inhibits vascular smooth muscle cell proliferation by upregulating heme oxygenase-1 and p27KIP1.

OBJECTIVE: Thymidine phosphorylase (TP) reportedly promotes endothelial cell migration and induces heme oxygenase (HO)-1 expression. However, its effect on vascular smooth muscle cells (VSMCs) is poorly understood. In this study, we examined the effect of TP on VSMCs in vitro and in vivo. METHODS AND RESULTS: Phagemid vector encoding human TP gene was transfected into rat VSMCs, and a clone overexpressing TP was selected (C2). C2 showed a slower migration and proliferation than VSMCs cloned with empty vector (pC) under basal, serum-stimulated, and hypoxic conditions. This decrease in proliferation correlated with TP-induced HO-1 expression and was reversed by inhibitors of either TP or HO activity. Furthermore, in C2, the cyclin-dependent kinase inhibitor (p27KIP1) was much more abundant than in pC, and the cell cycle was arrested at the G1 phase. TP or HO activity inhibitors decreased p27(KIP1) expression in C2 to the level seen in pC. Adventitial TP gene delivery significantly reduced neointimal VSMC migration and neointima formation in balloon-injured rat carotid arteries. CONCLUSIONS: TP overexpression upregulated HO-1 expression and consequently increased p27(KIP1) in cultured VSMCs, and inhibited VSMC migration and proliferation in vitro and in vivo. TP represents a promising target for treating vascular obstructive disease.

Adventitial inversion technique without the aid of biologic glue or Teflon buttress for acute type A aortic dissection.

OBJECTIVE: This study was performed to evaluate the clinical usefulness of the adventitial inversion technique in acute type A aortic dissection, with special attention to the impact of this procedure on the postoperative status of false lumen evaluated by computed tomographic scan. METHODS: From March 2001 to November 2004, 18 consecutive patients underwent emergent surgery for acute type A aortic dissection. Supracoronary graft replacement was performed in all the patients (ascending aorta/hemiarch replacement: 13/18=72%, total arch replacement: 5/18=28%). The adventitial inversion technique was used for both the proximal and the distal stump constructions of the dissected aortic wall without the aid of Teflon felt or biologic glue. Aortic regurgitation was treated with resuspension of the aortic commissures. RESULTS: There were two hospital deaths and the overall hospital mortality rate was 11.1%. The mean postoperative blood loss was 635+/-214 ml and no reexploration was required in any of the patients. Postoperative computed tomography showed closure of the false lumen in aortic root, aortic arch, and proximal descending thoracic aorta in all of the surviving patients. Postoperative echocardiography demonstrated no aortic regurgitation in any of the patients. Two patients died late postoperatively from unrelated causes to aortic dissection. The remaining 14 patients are doing well without a second-stage operation for aortic root or distal aortic lesions during the follow-up period of 7-51 months (mean: 28+/-14 months). CONCLUSIONS: The adventitial inversion technique provides an excellent immediate hemostasis and facilitates thrombotic closure of the proximal and the distal false lumen in the treatment for acute type A aortic dissection.

Controlling air leaks using free pericardial fat pads as surgical sealant in pulmonary resection.

BACKGROUND: This study evaluated the feasibility and efficacy of a new operative method for controlling intraoperative air leaks using free pericardial fat pads as a covering sealant in pulmonary resection. METHODS: To manage air leaks that must be controlled in pulmonary resection at the first water sealing test, collected free pericardial fat was used as a covering sealant and sewn on by the suture closing the lesion. In cases of uncontrolled air leaks at the second sealing test, fibrin glue was used to fill the residual lesion between the fat and visceral pleura. Fifty-one eligible patients were enrolled in this study to evaluate the duration of postoperative air leaks and the condition of the implanted fat on chest computed tomography (CT) 6 months later. RESULTS: The mean duration of postoperative air leaks was 1.05 ± 1.84 days in the 39 cases that received the pericardial fat covering technique only and 2.66 ± 3.42 days in the 12 cases that received the pericardial fat covering technique combined with fibrin glue. Prolonged alveolar air leaks occurred in 1 case and 2 cases, respectively. No cases required conversion to conventional methods, and there were no further adverse events. On follow-up chest CT approximately 62.7% of obvious engrafted fat survived. CONCLUSIONS: Using free pericardial fat pads as a sealant to control air leaks in pulmonary resection is safe and has good feasibility and potent efficacy. This new method can be an innovative technique for preventing prolonged air leaks.

Platelet-derived endothelial cell growth factor gene therapy for limb ischemia.

OBJECTIVES: Platelet-derived endothelial cell growth factor (PD-ECGF) is identical to thymidine phosphorylase (TP), and it can induce angiogenesis, including arteriogenesis, in chronically ischemic canine myocardium. Because its effect on peripheral arterial disease has not been elucidated, we investigated whether overexpression of PD-ECGF/TP could ameliorate chronic limb ischemia in rabbits. METHODS: Left femoral arteries were resected from 24 male rabbits. After 10 days, a plasmid vector containing human PD-ECGF/TP complimentary DNA was injected into 10 sites in the adductor muscles. Control groups received either the LacZ plasmid vector or saline vehicle only (n = 8 per group). Blood pressure was measured in the calf before surgery, at the onset of ischemia, 10 days later, and 20 and 30 days after gene transfer. Collateral vessel development and limb perfusion were assessed by angiography, and resected tissues underwent molecular and histologic examination. RESULTS: In the PD-ECGF/TP group, human PD-ECGF/TP messenger RNA and protein were still detected at 30 days after treatment. Calf blood pressure decreased significantly after femoral artery resection in all three groups. It subsequently showed a greater increase in the PD-ECGF/TP group than in either control group, and the difference was significant at 20 days after treatment (PD-ECGF/TP, 97.4 +/- 7.4; LacZ, 58.6 +/- 6.9; saline, 41.3 +/- 3.6). Immunohistochemical staining demonstrated an increased ratio of capillaries and arterioles to muscle fibers in the PD-ECGF/TP group (2.14 +/- 0.13 and 1.51 +/- 0.06), but not in the LacZ group (1.39 +/- 0.04 and 0.71 +/- 0.05) or the saline group (1.34 +/- 0.05 and 0.71 +/- 0.04, P < .01). The angiographic score was higher in the PD-ECGF/TP group (0.96 +/- 0.08) than in the LacZ group (0.50 +/- 0.02) or saline group (0.51 +/- 0.03) at 30 days after gene transfer (P < .01). CONCLUSIONS: This study demonstrated that PD-ECGF/TP gene transfer induced angiogenesis and decreased ischemia in a rabbit hindlimb model by promoting arteriogenesis, suggesting that targeting this gene may be a promising therapeutic strategy for peripheral vascular disease.

Preoperative detection of pleural adhesions by chest ultrasonography.

BACKGROUND: The presence of pleural adhesions may render video-assisted thoracoscopic surgery difficult or impossible. The aim of this study was to assess the value of chest ultrasonography in the detection of pleural adhesions prior to thoracotomy. METHODS: Between October 2001 and September 2002, 42 consecutive patients undergoing thoracotomies (including video-assisted thoracic surgery) were evaluated with chest ultrasonography. These patients underwent a preoperative ultrasonic examination of the chest wall using a 7-MHz linear ultrasound probe at 7 points along the chest wall. We measured the movement of the visceral pleural slide. RESULTS: When restricted viscera sliding was defined as less than 1 cm of excursion at the upper thoracic wall during exaggerated respirations, ultrasonography demonstrated a sensitivity of 63.6%, a specificity of 79.4%, a negative predictive value of 87.7%, a positive predictive value of 50.0%, and an overall accuracy of 75.6%. When restricted viscera sliding was defined as less than 2 cm of excursion at the lower thoracic wall during exaggerated respirations, ultrasonography demonstrated a sensitivity of 81.5%, a specificity of 81.0%, a negative predictive value of 96.0%, a positive predictive value of 44.0%, and an overall accuracy of 81.0%. CONCLUSIONS: Chest ultrasonography is moderately accurate in detecting the presence and location of pleural adhesions. Use of preoperative chest sonographic findings to plan trocar placement and to determine the need for an open approach is valuable in helping prevent visceral injury and facilitating video-assisted thoracoscopic surgery.

Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs.

Platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP), has been reported to possess angiogenic activity and to inhibit apoptosis. This study was performed to determine whether PD-ECGF/TP can be used to ameliorate chronic myocardial ischemia. Myocardial ischemia was created in 40 mongrel dogs by placement of an ameroid constrictor on the proximal left anterior descending coronary artery (LAD). Plasmid vector encoding human PD-ECGF/TP cDNA (pCIhTP group; n = 12), empty vector pCI (pCI group; n = 12), or saline (Saline group; n = 12) was directly injected into the LAD territory 3 wk after ameroid constrictor implantation. Myocardial blood flow was detected using PET at baseline, 3 wk after ameroid constrictor implantation, and 2 wk after therapeutic treatment. At the end of the experiment, the hearts were isolated for biological and histological analysis. In the pCIhTP group, the transfected heart strongly expressed PD-ECGF/TP. The size of the infarct was smaller in the pCIhTP group than in the pCI or Saline group. The number of apoptotic myocardial cells was decreased in the pCIhTP group compared with the control groups based on triple immunohistochemical staining for von Willebrand factor, alpha-actin smooth muscle cells, and single-strand DNA. The level of proapoptotic protein Bax markedly decreased in the pCIhTP group compared with the other groups. Double immunohistochemical staining for von Willebrand factor and alpha-actin smooth muscle cells demonstrated that angiogenesis and arteriogenesis occurred, and paralleled the changes in myocardial blood flow and myocardial function in the pCIhTP group. We conclude that genetic approaches using PD-ECGF/TP to target the myocardium are effective for alleviating chronic myocardial ischemia.

Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs.

We examined the role of matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs), and plasminogen activator (PA) in transmyocardial laser revascularization (TMLR)-induced angiogenesis. TMLR was accomplished with a carbon dioxide laser in seven dogs whose left anterior descending coronary artery (LAD) was ligated. Seven control dogs underwent only LAD ligation, and four dogs underwent a sham operation, consisting only of a left thoracotomy. Two weeks later, transmural myocardial samples were harvested from the distributions of the LAD and the left circumflex artery for substrate zymography, immunohistochemical staining, and in situ zymography. MMP-1, MMP-2, TIMP-1, TIMP-2, and urokinase-type PA levels in the distribution of the LAD were higher in the laser group than in the control or sham group. Counts of von Willebrand factor-positive microvessels and smooth muscle alpha-actin-positive arterioles demonstrated that the angiogenesis and ateriogenesis was promoted in the laser group and correlated directly with the number of MMP-stained microvessels. We conclude that TMLR induces the expression of MMPs, TIMPs, and urokinase-type PA and that these proteinases play an important role in angiogenesis after TMLR.

Giant mediastinal bronchial artery aneurysm mimicking benign esophageal tumor: a case report and review of 26 cases from literature.

Mediastinal bronchial artery aneurysm is rare but potentially life-threatening, and requires prompt treatment to avert rupture with catastrophic results. A 78-year-old man was referred to our hospital with a benign esophageal tumor, which appeared as an extrinsic, extramucosal filling defect on an esophagogram. Chest computed tomography and selective bronchial arteriography led to a definitive diagnosis of mediastinal bronchial artery aneurysm. Aneurysmectomy and closure of the ostia of both the afferent and efferent bronchial arteries was performed via standard posterolateral thoracotomy. Postoperative course was uneventful, and the patient was discharged on the seventh postoperative day.