Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Combined surgery for left Subclavian artery revascularization and CABG was performed in a 74-year-old man with diabetes mellitus. The preoperative coronary angiogram showed critical stenoses in all three major branches, and arteriography revealed obstruction at the left proximal subclavian artery. Severe atherosclerotic calcification was acknowledged circumferentially in the ascending aorta and in the aortic arch. For this patient axillo-axillary crossover bypass grafting was performed first using and expanded PTFE graft, followed subsequently by off-pump CABG using all in situ grafts (right internal thoracic artery-left anterior descending artery (RITA-LAD), left internal thoracic artery-diagonal branch (LITA-diagonal branch), gastroepiploic artery-right coronary artery (GEA-RCA)). Postoperative recovery was smooth, with disappearance of significant pressure difference between both arms (preoperatively, 46mmHg). An angiogram on the 7th postoperative day showed a widely patent axillo-axillary bypass graft along with good flow of all three coronary grafts, in which LITA was visualized well through the axillo-axillary bypass graft. For complex atherosclerotic disease of the proximal aorta and incipient portion of neck vessels associated with severe coronary sclerosis, this technique is a suitable option.

The use of the radial artery (RA) for coronary artery bypass grafting (CABG) is increasing. This study describes mid-term results of the use of RA for CABG. Between March 1996 and March 1999, we performed 134 CABGs using RA or saphenous vein graft (SVG) for the left circumflex branch area or diagonal branch area. The mean age was 62.6±9.6 years in the RA group and 65.0±7.8 years in the SVG group. The average number of anastomoses was 2.7per patient. RA was anastomosed with the postero-lateral branch (PL) in 69 cases, with the obtuse marginal branch (OM) in 29 cases and with the diagonal branch (DB) in 10 cases. SVG was anastomosed with PL in 26 cases, with OM in 14 cases and with DB in 2 cases. The proximal anastomosis was made with the ascending aorta in all cases. No sequential bypass anastomosis was used in any case. The early patency rate of the grafts was 97.9% (93/95) in RA and 91.7% (33/36) in SVG. The clinically negative rate in the treadmill test (TMT) performed later was 99.0% (102/103) in RA and 90.9% (30/33) in SVG. The late patency rate of the grafts was 92.9% (13/14) in RA and 50.0% (3/6) in SVG. Perioperative death occurred in 5 cases. Late cardiac death occurred in 2 cases (0.02%) of the RA group and 1 case (0.03%) of the SVG group. The 3 year-survival rate free of cardiac events was 92.8% in the RA group and 80.9% in the SVG group. The use of RA for CABGs is not only effective for myocardial revascularization, but also can be expected to bring about good patency as a late result.

Although sequential bypass with in situ arterial conduits (the left and right internal thoracic arteries; LITA and RITA, the right gastroepiploic artery; GEA) in coronary artery bypass grafting (CABG) is technically demanding, it is one of the most important procedures using a limited number of in situ arterial conduits to revascularize a wide area. In this report, we retrospectively investigated the clinical outcome of CABG with 4 or more distal anastomoses using only in situ arterial conduits. From December 1990 to May 1999, 62 patients underwent CABG with in situ arterial conduits, with at least one sequential bypass. There were 59 men and 3 women patients with mean age of 59.6 years (41 to 82 years). Mean postoperative follow-up period was 32 months (1 to 101 months). The total number of distal anastomoses was 4 (1 sequential bypass) in 54 patients, 4 (2 sequential bypasses) in 6 patients, 5 (1 sequential bypass) in 1 patient and 6 (3 sequential bypasses) in 1 patient. There were 5 emergency operations (8%), 37 patients (60%) had a history of myocardial infarction, 30 patients (48%) had diabetes mellitus and 6 patients (10%) had chronic renal failure and were on hemodialysis. Left ventricular ejection fraction was 40% or less in 15 patients (24%). There were no early deaths. Angiographic patency was satisfactory for each graft (sequential: individual, LITA 96.7%: 100%, RITA 100%: 100%, GEA 89.5%: 97.4%). Patency of a distal anastomoses of GEA was rather poorer than that of proximal (p=0.03). Three patients died during the follow-up period (all of them due to malignancy). The 5-year actuarial survival and cardiac event-free rate was 94.6% and 87.2%, respectively. In conclusion, although an indication of GEA sequential grafting needs further study, in situ arterial grafting with at least one sequential arterial conduit was associated with excellent results and achieved more complete revascularization with exclusive use of in situ arterial conduits in patients with diffuse coronary artery disease.

We evaluated the surgical strategy for thoracic aortic aneurysm associated with abdominal aortic aneurysm. From January 1982 to March 1999, 24 consecutive patients underwent surgical treatment for thoracic aortic aneurysm with abdominal aortic aneurysm. Staged operation was performed if one was only slightly dilated, but extensive operation was needed if the size of both aneurysms was greater than 6cm. In cases of thoracic aortic aneurysm with abdominal aortic aneurysm up to 4cm in size, surgical treatment was performed only for the thoracic aortic aneurysm. Circulatory support during operation was established from the ascending aorta, and circulatory arrest with deep hypothermia and retrograde cerebral perfusion were used for brain protection during surgery for thoracic aortic arch aneurysm. Hospital mortality was 12.5% (3/24 cases). The causes of death were cerebral infarction and respiratory failure. Antegrade systemic perfusion and aortic no-touch technique were an effective method of surgery for thoracic aortic aneurysm with abdominal aortic aneurysm to avoid perioperative embolism and major complications. We successfully performed staged operation, but regular radiographic follow-up was needed.

A 50-year-old man was referred to our hospital with a tumor in the left ventricle. He had suffered from rheumatic fever when 14 years old. He had shown signs of chronic heart failure due to atrial fibrillation and rheumatic valves (ASr, MSr) for 10 years. There was a history of unaccountable fever and rash, so infective endocarditis was suspected and echocardiography was performed. It showed a homogeneous mass with a diameter of approximately 10mm, fixed directly to the left ventricular septum 20mm below the aortic valvular ring. At operation, the tumor was excised together with endocardium and a part of the muscular coat. The rheumatic aortic and mitral valves were replaced with a 21mm SJM AHP and a 27mm SJM MTK mitral valve, respectively. Tricuspid annuloplasty (TAP) (De Vega 29mm) was also performed. Histopathological examination of the tumor revealed benign papillary fibroelastoma. It suggested that the tumors were secondary to mechanical wear and tear, and represent a degenerative process due to rheumatic valve disease.

We encountered two cases of infected aortic abdominal aneurysm with spondylodiskitis. Both cases were diagnosed on the basis of fever, back pain and pulsatile abdominal mass. A 69-year-old man, case 1, underwent in situ reconstruction 1 year from the onset, because the infection was controllable by antibiotics and he had diabetes mellitus. A 68-year-old man, case 2, underwent operation while his infection was still active, because of paralysis of the bilateral lower extremities, aggravated by invasion of the vertebrae by the abscess. To prevent artificial graft infection, he underwent axillo-femoral bypass, which was extra-anatomical reconstruction, after the infected aneurysm and vertebrae were removed during aortic clamping above the aneurysm and bilateral common iliac arteries. Each stump was sutured and anterior fixation of the vertebrae was performed using an iliac bone graft. The postoperative course of both patients was successful. These cases suggest that the timing and procedure of the operation for infected aortic abdominal aneurysm with spondylodiskitis should be decided depending on the activity of infection, complications, age and activity of daily life of patients.

Forty-four cases of ruptured abdominal aortic aneurysm were treated between January 1980 and December 1995. We classified the cases into three groups: Group I, 1980-1984; Group II, 1985-1989; and Group III, 1990-1995 and evaluated the surgical results, the preoperative states, the bleeding and blood transfusion volume and so on. The surgical results have improved every year and there were no surgical deaths during the past seven years. Most of the causes of previous surgical deaths were DIC (4 cases) and renal failure (3 cases). The volume of intraoperative bleeding was 7227.3±3293.4ml in Group I, 4176.0±2577.9ml in Group II and 1781.9±1877.0ml in Group III. The volume of intraoperative blood transfusion was 6975.5±2711.6ml in Group I, 4826.7±2596.6ml in Group II and 3542.4±1561.5ml in Group III. We decreased the volume of intraoperative blood transfusion significantly in Group III by using a Cell Saver. The surgical results have improved significantly due to the decrease of bleeding and blood transfusion under the rapid control of bleeding and the autotransfusion of shed blood using the Cell Saver. The technique of postoperative care also contributed to the more satisfactory results.

A 29-year-old man, who had undergone valvotomy for pure pulmonary stenosis at 6 months of age, was admitted to our institution for surgical treatment of a giant ascending aortic aneurysm and annuloaortic ectasia. Chest MRI revealed a 14-cm ascending aneurysm in contact with the sternum. After establishing femoro-femoral bypass for hypothermia, a left lateral thoracotomy was perfomed at the 4th intercostal space. Pulmonary artery cannulation was performed for left heart venting, and the proximal aortic arch was dissected for aortic cross-clamping. Median sternotomy was performed under circulatory arrest at 18°C and the aortic arch was opened. Under retrograde cerebral perfusion, the proximal arch was replaced by an artificial graft, and then aortic root replacement was completed using a composite graft under CPB. The postoperative course was uneventful, and the patient was discharged on the 37th postoperative day. He has been well without any complications. This case suggests that our method of approach to the giant aortic aneurysm with sternal adhesion and aortic regurgitation, and the use of extracorporeal circulation in view of the annuloaortic ectasia is effective and safe in case of reoperation.

The surgical results of 9 patients (group II) who were treated for thoracoabdominal aneurysm using left heart bypass combined with oxygenation were compared to those of 16 patients (group I) using left heart bypass without oxygenation. The left heart bypass time in group II was longer than that in group I, and the operations performed in group II were more extensive with more intercostal and lumbar arteries being reconstructed than those in group I. Nevertheless, bleeding associated with transfusion was less in group II than in group I. Intraoperatively, hypothermia and hypoxemia developed in 44% and 31%, respectively of group I, whereas neither of these conditions occurred in group II. There were three operative deaths in group I, compared with one in group II. Paraplegia was encountered in one patient of group I, but in none of the patients in group II. There were a few patients with respiratory failure or other organ failures in both groups. Our results showed that left heart bypass combined with oxygenation offered more stable and effective respiratory as well as circulatory support for a long duration compared to conventional left heart bypass without oxygenation in the surgical treatment of thoracoabdominal aortic aneurysm.