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Biomedical subjects

Shinichi Takamoto

Publications and source records attributed to Shinichi Takamoto.

At least 19 recordsLinked to original sources

Cryopreservation does not alter the allogenicity and development of vasculopathy in post-transplant rat aortas.

BACKGROUND: Cryopreservation is a valuable technique for storing heart valve and vascular allografts. However, the biological ramifications of cryopreservation are still unclear; therefore, using animal experiments we assessed how 'cryopreservation' influences graft allogenicity and cell viability. METHODS: Thoracic aortas of Lewis rats were prepared as fresh (F) or cryopreserved (CP) grafts, and implanted into the infrarenal aorta of Lewis or Brown Norway rats (BNs). The grafts and spleens were harvested at post-operative day 7 and 28 (POD7, POD28) for analyses. RESULTS: First, the systemic immune response to transplantation was estimated by mixed lymphocyte reaction analyses using spleen cells from naïve or recipient BNs. The alloreactivity of the recipients increased to 1.5 times that of the naïve BNs at POD7 and POD28, when stimulated by mitomycin C-treated Lewis spleen cells. Second, local immune response was estimated by TNFalpha, IFNgamma, and iNOS mRNA expression in the grafts by quantitative PCR, which revealed 20- to 40-fold increases at POD28 after allotransplantation. Third, endothelial cell viability was estimated by endothelial NOS mRNA expression level: it was similar and highest in F and CP grafts before transplantation then significantly decreased after both syngeneic and allogeneic transplantation. Finally, intimal hyperplasia, expressed by I/M ratio, developed over time after allotransplantation, reaching 2.5 times the thickness of F grafts before transplantation. The results of these experiments revealed no difference between F and CP grafts before and after transplantation. CONCLUSION: Cryopreservation did not modify the allogenicity of vascular allografts and had minimal adverse impacts on graft cell viability.

Animals↗

Prevention of postoperative pericardial adhesions with a novel regenerative collagen sheet.

BACKGROUND: Postoperative pericardial adhesions make a repeat sternotomy time-consuming and dangerous. The purpose of this study was to evaluate the efficacy of a new collagen pericardial substitute for preventing postoperative pericardial adhesions. METHODS: Our absorbable substitute consists of three layers: a middle layer of aterocollagen between two layers of sodium hyaluronic acid and aterocollagen. In experiment 1 in this study, the patch, made of 9,000 filaments of aterocollagen fibers, (group 1; n = 5) was compared with a patch made of 6,000 filaments (group 2; n = 7), an expanded polytetrafluoroethylene sheet (group 3; n = 6), and a control group (group 4; n = 4). Subsequently, in experiment 2, the patch was examined at 4 weeks (n = 5), 12 weeks (n = 5), and 24 weeks (n = 4) after the operation by light microscopy and scanning electron microscopy. RESULTS: The area of adhesion in group 1 was significantly less as compared with that in the other three groups, and the coronary vessels were clearly identifiable; on the other hand, all the animals in the control group showed moderate to severe adhesions, and the coronary vessels were completely obscured. In experiment 2, formation of a membranous tissue resembling the native pericardial membrane was observed in all animals, and the thickness of this membrane showed a marked increase by 24 weeks after the operation. Light microscopy and scanning electron microscopy also showed the formation of a mesothelium-like lining. CONCLUSIONS: The new absorbable and regenerative collagen patch seemed to be biocompatible, and its use was associated with minimal adhesion formation and preserved coronary anatomy.

Animals↗

Impact of diabetic retinopathy on cardiac outcome after coronary artery bypass graft surgery: prospective observational study.

BACKGROUND: Diabetic retinopathy is a manifestation of more severe diabetes. We sought to assess the impact of diabetic retinopathy on cardiac outcome of coronary artery bypass graft surgery (CABG). METHODS: We prospectively assessed the status of the retina of 74 consecutive diabetics who were referred for first-time CABG, and compared cardiac outcome of CABG in diabetics with retinopathy with that in those without retinopathy. Cardiac events included recurrent angina or congestive heart failure that needed admission to hospital, myocardial infarction, repeat revascularization, and cardiac death. RESULTS: Twenty-six diabetics had retinopathy and 48 diabetics did not have retinopathy. Diabetics with retinopathy were likely to have higher hemoglobin A1c level (p = 0.048), and receive insulin treatment (p = 0.0065). In the 12 months of follow-up, 13 cardiac events occurred in diabetics with retinopathy and 7 in those without retinopathy (p = 0.0021). Among diabetics with retinopathy, heart failure or death due to heart failure accounted for 54% (7 of 13) of these cardiac events. Kaplan-Meier analysis showed significant difference in cardiac event-free survival between the two groups (p < 0.001). After adjustment for differences in patients' characteristics, diabetic retinopathy remained a predictor of cardiac event (adjusted relative risk = 4.2, 95% confidence interval, 1.5% to 11.9%; p = 0.0067). CONCLUSIONS: After CABG, diabetics with retinopathy have a substantially increased risk of cardiac events, especially of congestive heart failure.

Angina Pectoris↗

A surgical case of symptomatic coronary artery-pulmonary artery fistula.

We describe a 55-year-old female patient with multiple plexiform coronary artery-pulmonary artery fistulas, who presented with ischemic episodes accompanying an inversion of T wave on an electrocardiogram even though it was a small shunt size. The surgical procedure involved closure of the openings of the fistulas from inside the pulmonary trunk using cardiopulmonary bypass with additional ligations. Postoperative coronary angiogram revealed complete interruption of the coronary artery-pulmonary trunk fistulas resulting in complete resolution of the patient's chest symptoms.

Angina Pectoris↗

The angiotensin II type 1 receptor blocker candesartan attenuates graft vasculopathy.

OBJECTIVE: Transplant arteriosclerosis remains the major cause of graft failure after cardiac transplantation, although recent progress in immunosuppressive therapy has dramatically improved short-term survival of recipient. We investigated the effects of the angiotensin II type 1 receptor (AT(1)R) blocker candesartan on the development of transplant arteriosclerosis in a murine model of cardiac transplantation. MATERIALS AND METHODS: Hearts from DBA/2 (H-2(d)) mice were heterotopically transplanted into B10.D2 (H-2(d)) mice. Recipients were treated with oral administration of candesartan (1 mg/kg per day) or vehicle. Allografts were analyzed at 14 or 30 days after transplantation. RESULTS: Candesartan significantly reduced the development of coronary arteriosclerosis (intima/media ratio: 0.86 +/- 0.09 versus 0.57 +/- 0.10, P < 0.05), without affecting the degree of parenchymal rejection at 30 days. There was no significant difference in the expression of adhesion molecules and cytokines at 14 days. Candesartan significantly reduced the number of peripheral mononuclear cells that differentiated into smooth muscle-like cells in the presence of basic fibroblast growth factor and platelet-derived growth factor BB (27.1 +/- 3.1 versus 17.3 +/- 1.8 cells/HPF, P < 0.05). CONCLUSIONS: Angiotensin II may play a role in the pathogenesis of transplant arteriosclerosis. Blockade of AT(1)R might be effective as a prophylactic therapy for transplant arteriosclerosis along with conventional immunosuppressive drugs.

Angiotensin II Type 1 Receptor Blockers↗

Age-associated aortic stenosis in apolipoprotein E-deficient mice.

OBJECTIVES: The present study was designed to assess aortic valve morphology and function in mice of advanced age. We also evaluated the potential contribution of bone-marrow-derived cells to the pathogenesis of aortic stenosis. BACKGROUND: Age-associated valvular degeneration is characterized by lipid accumulation, collagen deposition, and calcification containing smooth muscle-like cells and osteoblast-like cells. Cellular and molecular factors that mediate these changes remain unknown. METHODS: We extensively examined the aortic valves of senile wild-type and apolipoprotein E (ApoE)-/- mice with echocardiography. The aortic valves were analyzed by immunohistochemistry and electron microscopy. The bone marrow of wild-type and ApoE-/- mice was reconstituted with that of green fluorescent protein (GFP) or beta-galactosidase (LacZ) mice, which expressed GFP or LacZ ubiquitously. RESULTS: Transaortic flow velocity was correlated with age in wild-type and ApoE-/- mice. The aortic valves of old ApoE-/- mice showed sclerosis that resembled the pathology of human aortic stenosis. A significant number of GFP-positive cells (10.7 +/- 4.1%) in the sclerotic valves of ApoE-/- mice expressed alpha-smooth muscle actin, whereas most of the GFP-positive cells were identified as endothelial cells or macrophages in wild-type mice. There were bone-marrow-derived cells that were positive for osteoblast-related proteins near the sites of ectopic calcification. The sclerotic valves displayed frequent apoptotic cell death and chemokine expression. CONCLUSIONS: Senile ApoE-deficient mice display aortic valve sclerosis that is similar to that observed in humans. The sclerotic valves displayed frequent apoptotic cell death and chemokine expression. Smooth muscle-like cells observed in degenerative valves might derive, at least in part, from bone marrow.

Age Factors↗

Superior vena cava graft for right liver and right lateral sector transplantation.

BACKGROUND: The usefulness of cryopreserved superior vena cava (SVC) grafts for venous reconstruction remains to be evaluated in right liver and right lateral sector transplantation. METHODS: Reconstruction of the hepatic vein was performed when the congested area in the liver graft was significant. A vein graft with a suitable shape and length meeting the demands for the venoplasty was selected, and SVC grafts were used in 20 recipients. Surgical techniques were classified into five types according to the necessity of middle or short hepatic vein reconstruction in the liver graft. Surgical outcomes and vein graft patency were evaluated. RESULTS: All 20 recipients survived the operation without any complications caused by congestion. Liver functions were well recovered in the early postoperative period. The 1-year primary patency rates of cryopreserved vein grafts used for reconstructed right hepatic veins, inferior right hepatic veins, and middle hepatic vein tributaries were 100%, 94%, and 42%, respectively. CONCLUSIONS: SVC grafts were feasible for outflow tract reconstruction in right liver and right lateral sector transplantation, although the long-term patency of the grafts for middle hepatic vein reconstruction remains to be evaluated.

Aspartate Aminotransferases↗

Comparison of neurocognitive results after coronary artery bypass grafting and thoracic aortic surgery using retrograde cerebral perfusion.

OBJECTIVE: Retrograde cerebral perfusion (RCP) is used as an adjunctive method to hypothermic circulatory arrest to enhance cerebral protection in patients undergoing thoracic aortic surgery. It remains unclear whether RCP provides improved neurological and neuropsychological outcome. METHODS: Forty-six patients undergoing thoracic aortic surgery using RCP, and 28 undergoing coronary artery bypass grafting (CABG; n = 28) with CPB, were enrolled in the study. Patients receiving RCP were subdivided into two groups, those with less than 60 min of RCP (S-RCP; n = 27) and with 60 min or more (L-RCP; n = 19). The patients' neurocognitive state was assessed by the revised Wechsler Adult Intelligence Scale a few days before operation, at 2-3 weeks and 4-6 months after operation. RESULTS: There were no stroke, seizure, and hospital mortality in either group. Significant decline between baseline and early scores were seen in three subtests (digit span, arithmetic, and picture completion) for S-RCP and four (digit span, arithmetic, picture completion, and picture arrangement) for L-RCP. Significant decline between baseline and late scores were seen in one subtest (arithmetic) for S-RCP, four (digit span, arithmetic, picture completion, and picture arrangement) for L-RCP, and one (object assembly) for CABG. The mean change of scores for one late test (digit symbol) was significantly lower in S-RCP than in CABG. The mean change of scores for three early tests (digit span, vocabulary, and picture arrangement) and four late tests (information, digit span, picture completion, and picture arrangement) were significantly lower in L-RCP than in CABG. Stepwise logistic regression analysis disclosed that, after considering the other variables, significant difference in test score changes were observed between CABG and L-RCP for two early tests (picture completion and digit symbol) as well as for three late tests (digit span, similarities, and picture completion). None of test score changes showed significant difference between CABG and S-RCP. CONCLUSIONS: The neurocognitive outcome in patients undergoing RCP less than 60 min were comparable with patients undergoing CABG without circulatory arrest. Prolonged RCP of 60 min or more in patients undergoing surgery of the thoracic aorta was associated with postoperative neurocognitive impairment.

Adult↗

Human umbilical cord blood cells improve cardiac function after myocardial infarction.

Human umbilical cord blood (UCB) contains an abundance of immature stem/progenitor cells and has been clinically used as an alternative to bone marrow transplantation. In addition, cord blood can be obtained non-invasively, in contrast to invasive bone marrow aspiration. We investigated the potential of human UCB CD34(+) cells to improve cardiac function following myocardial infarction. Myocardial infarction was induced in Wistar rats by ligation of the left coronary artery. Either 2x10(5) human UCB CD34(+) cells or equivalent cell-free medium was injected into the injured myocardium of the rats following induction of myocardial infarction. CD34(+) cell transplantation significantly improved ventricular function as compared to the control group. Immunofluorescence staining for human CD34, CD45, and PECAM-1 revealed surviving cells in the myocardium. Our findings suggest that transplanted human cells survived and improved cardiac function following myocardial infarction. These results may show the usefulness of UCB CD34(+) cells for myocardial infarction.

Animals↗

Alternatives to the double vena cava method in partial liver transplantation.

Minimizing graft congestion in partial liver transplantation is important, especially when the graft weight is marginal for the recipient metabolic demand. We prefer the double vena cava technique for reconstructing middle hepatic vein tributaries with thick, short hepatic veins because the technique can reduce the warm ischemic time of the graft and make a wide anastomosis. This technique requires a cryopreserved superior or inferior vena cava. We devised an alternative double vena cava method using iliac or femoral vein grafts and applied it to two right liver transplantation patients. There was no postoperative hepatic venous outflow block in either patient. In conclusion, application of this technique, even in the absence of a suitable vena cava, can help to minimize graft congestion.

Adult↗

Appraisal of surgical treatment for pulmonary metastasis from hepatocellular carcinoma.

The outcome of pulmonary metastasectomy of hepatocellular carcinoma (HCC) was appraised in this study. Twenty patients with pulmonary metastasis from HCCs undergoing pulmonary resection between 1990 and 2003 were included in this study. They had undergone curative treatment for the primary lesion and were candidates for a pulmonary metastasectomy for complete resection. Among the 20 patients, 13 died: 5 from hepatic failure, 5 from respiratory failure, and 2 from brain metastasis due to recurrence of the HCC. One patient died from cardiac failure without HCC recurrence. At the latest observation, three of the seven survivors were doing well without HCC recurrence, and others survived with recurrence. The overall survival rates after the initial lung surgery were 45.3% at 1 year and 23.8% at 3 years, respectively. The survival rates without recurrence were 32.4% at 1 year and 21.6% at 3 years, respectively. A Kaplan-Meier analysis showed that multiple lung surgeries and a negative histologic finding of the liver cut surface were favorable characteristics for survival without recurrence. In conclusion, the selected patients were Candidates for pulmonary metastasectomy after a curative hepatectomy for HCC and could benefit from the complete resection. Also, repeated pulmonary resections through thoracoscopy could result in the long-term survival of patients with pulmonary recurrence of HCC.

Adult↗

Management of infected grafts and aneurysms of the aorta.

Seventeen patients treated for infected grafts (11/17) or aneurysms (6/17) of the aorta between 1998 and 2003 were reviewed to evaluate our experience with aortic infection. The causative organisms were identified in 12 patients (71%), with 5 (29%) having methicillin-resistant Staphylococcus aureus. A periaortic abscess occurred in eight patients, and all of them were associated with infected grafts. Surgical treatment included cryopreserved allograft replacement in eight patients, prosthetic graft replacement in four patients, and drainage with or without omental wrapping in five patients. One patient was still hospitalized at the end of the study period. Five patients with infected grafts died after the operation during the initial hospitalization. No early mortality occurred in the aneurysm group. The early mortality rate was 31% for all patients, 50% for the graft group, and 63% for patients with a periaortie abscess. Another patient with an infected aneurysm died of arrhythmia after discharge from the initial hospitalization, Ten patients are still alive without evidence of reinfection. The early mortality rate for patients with infected aortic grafts is higher than that for those with infected aneurysms, especially when a periaortic abscess accompanies them. However, the late outcome is favorable, with no reinfection or late treatment-related deaths.

Abscess↗

Japanese multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system.

Implantable left ventricular assist device systems (LVAS) are increasingly being used to bridge patients to heart transplantation because of the limited number of available donor hearts. This prospective, multicenter trial was designed to evaluate the usefulness of the HeartMate vented electric (VE) LVAS as a bridge to transplantation in Japan. Between November 2001 and June 2003, six patients with end-stage heart failure [New York Heart Association (NYHA) class IV] were supported with the LVAS and five of the six were able to implement the evaluation (one dropped out). The five were men with an average age of 38.6 years and were supported for 2390 cumulative days (6.6 years). Average preimplant cardiac index improved from 1.93 l/min/m(2) to a 3.79 l/min/m(2) VAD flow index at the end of the clinical trial. All five patients improved to NYHA class I or II, survived more than 1 year, and one patient was discharged from the hospital. Mean LVAS support duration was 478 days (range 390-575 days) and four patients remain supported. One patient died from cardiac failure and sepsis. Device-related complications included: infections (four patients), thromboembolism (one patient), hemolysis (two patients), and repeat operation for bleeding (two patients). There was one case of inflow valve incompetence and two pump motor malfunctions. We conclude that the LVAS can effectively support patients as they await cardiac transplantation and offers improvement to the patient's quality of life.

Adult↗

Coccidioidomycosis of the lung contracted abroad.

Coccidioides immitis is endemic in the southwestern United States. Coccidioidomycosis is rare in Japan, but the number of coccidioidomycosis cases from overseas is expected to increase markedly in the near future. A 33-year-old Japanese man with coccidioidomycosis who had lived in Arizona presented to our hospital. We performed wedge resection of the lung by video-assisted thoracoscopic surgery (VATS), and were able to completely remove the lesion. VATS wedge resection of the lung is effective in treating localized coccidioidomycosis. Before the operation, we could not confirm the existence of satellite lesions, but microscopically the main lesion was accompanied by several daughter lesions. It is very important that the surgical margin be sufficient to achieve complete resection.

Adult↗

Beneficial effect of acute normovolemic hemodilution in cardiovascular surgery.

OBJECTIVE: The efficacy of acute normovolemic hemodilution (ANH) in avoiding homologous blood transfusion (HBT) during cardiovascular surgery remains controversial. Our objective was to evaluate the impact of ANH on blood transfusion requirements during open cardiovascular surgery using cardiopulmonary bypass (CPB). METHODS: We retrospectively reviewed 243 patients who had undergone open cardiac or thoracic aortic surgery using CPB between September 2001 and July 2003 in our department. ANH was performed when the hematocrit was over 35% and the patient was hemodynamically stable. Risk factors were selected in accordance with the Japanese Adult Cardiovascular Surgery Database and analyzed to determine their effect on perioperative HBT requirement. RESULTS: Of the 243 patients, 64 (26%) underwent preoperative autologous blood donation and 62 (26%) ANH. HBT was required in 62% of patients (150/243) overall, in 32% (20/62) of ANH patients, and in 76% (130/171) of non-ANH patients. Multivariate stepwise logistic regression analysis revealed that preoperative or pre-donation hemoglobin value (p < 0.001), duration of surgery (p = 0.001), intraoperative minimum rectal temperature (p = 0.001), age (p = 0.002), need for emergency surgery (p = 0.003), amount of ANH (p = 0.018), blood loss (p = 0.033) and amount of preoperative autologous blood donation (p = 0.042) were independent predictors of the need for perioperative HBT. CONCLUSIONS: Our data showed that open cardiovascular surgery using CPB continues to pose a high risk of HBT, but that ANH is an effective means of reducing this risk in those patients undergoing these operations.

Adult↗

Epicardial maze procedure on the beating heart with an infrared coagulator.

PURPOSE: Maze surgery is widely used to treat atrial fibrillation (AF) but requires cardiopulmonary bypass and longer aortic cross-clamping time. Percutaneous transcatheter pulmonary vein (PV) isolation is time consuming and relies on fluoroscopy and contrast media, and PV obstruction and cardiac tamponade are still major problems. To overcome these drawbacks, we developed an epicardial maze procedure with an infrared coagulator on the beating heart, and the aim of this study was to confirm electrophysiologically the efficacy of this method. DESCRIPTION: Light from a lamp in the infrared coagulator is focused into a quartz rod, and the distal exit-plane of the rod is connected to a sapphire tip that allows 10 mm of linear photocoagulation. In an experiment in 5 dogs with AF, instead of making all of the incisions usually required for maze surgery, the infrared coagulator was applied epicardially to create a continuously overlapping linear lesion that was the same as the incision line in the maze III procedure except for the intraatrial incision. After the procedure, 11 electrodes were attached to both atria, and an electrophysiologic study was performed. EVALUATION: The electrophysiologic study confirmed electrophysiologic isolation of both atrial appendages and within the PV encircling lesion. Sustained atrial fibrillation could no longer be induced. CONCLUSIONS: The epicardial maze procedure was successfully performed on a beating heart with the infrared coagulator.

Animals↗