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Biomedical subjects

Ryuji Tominaga

Publications and source records attributed to Ryuji Tominaga.

At least 19 recordsLinked to original sources

Efficacy and limitations of natural killer cell depletion in cyclophosphamide-induced tolerance.

PURPOSE: We previously developed a cyclophosphamide (CP)-induced tolerance protocol, consisting of an intravenous injection of 1 x 10(8) donor spleen cells (SC) given on day 0 and an intraperitoneal injection of 200 mg/kg CP given on day 2. In the present study, we modified this protocol with natural killer cell (NK) depletion in recipient mice, and evaluated the efficacy of tolerance induction. METHODS: We used B10.D2 (H-2d; IE+) and B10 (H-2b; IE-) mice as both donors and recipients. The recipient mice were treated with donor SC, CP, and donor bone marrow cells (BMCs) with or without NK depletion. RESULTS: A higher level of mixed chimerism was achieved in the NK-depleted recipients. Survival of both the skin and heart donor grafts was significantly prolonged in the NK-depleted recipients. Donor reactive Vbeta11+ T cells were found at the same level as in untreated control mice. Pretreatment with recipient NK cell depletion was effective in inducing higher levels of donor mixed chimerism; however, permanent engraftment of donor bone marrow was not achieved. CONCLUSION: Survival of donor grafts was remarkably prolonged in the NK cell-depleted group, but transplantation tolerance could not be induced. Our results suggest that NK cell depletion in CP-induced tolerance conditioning has some effect on the induction of donor-specific tolerance.

Animals↗

Stent-based local delivery of nuclear factor-kappaB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) plays a critical role in the vascular response to injury. However, the role of NF-kappaB in the mechanism of in-stent restenosis remains unclear. We therefore tested the hypothesis that blockade of NF-kappaB by stent-based delivery of a cis-element "decoy" of NF-kappaB reduces in-stent neointimal formation. METHODS AND RESULTS: Stents were coated with a polymer containing or not containing NF-kappaB decoy, which represented a fast-release formulation (<7 days). Bare, polymer-coated, and NF-kappaB decoy-eluting stents were implanted in iliac arteries of hypercholesterolemic rabbits. Increased NF-kappaB activity was noted at early stages after stenting, which was suppressed by stent-based delivery of NF-kappaB decoy. NF-kappaB decoy-eluting stents also reduced monocyte infiltration and monocyte chemoattractant protein-1 expression and suppressed CD14 activation on circulating leukocytes. Importantly, NF-kappaB decoy-eluting stents attenuated neointimal formation on day 28. There was no evidence of an incomplete healing process (persistent inflammation, hemorrhage, fibrin deposition, impaired endothelial regeneration) at the site of NF-kappaB decoy-eluting stents. Transfection of NF-kappaB decoy suppressed proliferation of human coronary artery smooth muscle cells in vitro. No systemic adverse effects of NF-kappaB decoy were detected. CONCLUSIONS: Stent-based local delivery of NF-kappaB decoy reduced in-stent neointimal formation with no evidence of incomplete healing. These data suggest that this strategy may be a practical and promising means for prevention of in-stent restenosis in humans.

Angioplasty, Balloon, Coronary↗

The logistic EuroSCORE predicts the hospital mortality of the thoracic aortic surgery in consecutive 327 Japanese patients better than the additive EuroSCORE.

OBJECTIVE: Risk stratification in thoracic aortic surgery is a topic of major interest. Recent studies have shown the European System for Cardiac Operative Risk Evaluation (EuroSCORE) to be an extremely useful and reliable risk stratification score and also a good indicator of quality of care in cardiac surgery. The purpose of this study was to evaluate the significance of the additive and logistic EuroSCOREs in patients undergoing surgery on the thoracic aorta in Japan. METHODS: We calculated the predicted mortality according to the additive and logistic EuroSCORE algorithms in 327 consecutive patients who underwent surgery of the thoracic aorta during a 30-year period (between 1976 and 2005). We compared the score validity between the two algorithms and also evaluated the score validity for the patients who underwent thoracic aortic surgery. The score validity was assessed by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: The overall in-hospital mortality was 13%. The area under the ROC curve was satisfactorily high for the additive (0.68, 0.73, 0.73) as well as the logistic EuroSCORE (0.69, 0.74, 0.75) in the patients who underwent thoracic aortic surgery during 30-, 20-, and 10-year periods, respectively. The actual mortality was 7% (Group 1; an additive EuroSCORE of 3-6), 16% (Group 2; 7-11), and 37% (Group 3; >12). The mortality expected by the additive and logistic EuroSCORE in the three different risk groups were (5%, 9%, 19%) and (5%, 14%, 43%), respectively. Namely, the mortality expected by the logistic EuroSCORE perfectly matched with the actual mortality in any of the three risk groups. In contrast, the mortality expected by the additive EuroSCORE tended to dissociate when the number of risks increased. Significant difference was observed between the observed mortality and the mortality expected by the additive EuroSCORE algorithm in the high-risk group (p=0.0473). CONCLUSIONS: Although both the additive and the logistic EuroSCORE reliably predicted the overall operative mortality for thoracic aortic surgery in 327 Japanese patients, the logistic EuroSCORE better matched with the actual mortality in the operative risk especially in the high-risk group.

Aged↗

Modified Damus-Kaye-Stansel procedure using aortic flap technique for systemic ventricular outflow tract obstruction in functionally univentricular heart.

Damus-Kaye-Stansel procedure is a useful method to relieve the systemic ventricular outflow tract obstruction in functionally univentricular heart. Regurgitation of pulmonary valve and recurrence of systemic ventricular outflow obstruction are the major concerns at the late phase of this procedure. Modification of original Damus-Kaye-Stansel procedure that can prevent the use of prosthetic materials is evaluated. The modified Damus-Kaye-Stansel procedure using aortic flap technique was performed in eight patients with functionally univentricular heart. Patients' ages ranged from 3 to 28 months (mean 14 months). Follow-up period was 37 months as a mean (9-71 months), and the follow-up was complete. There was no operative mortality and no late death. In addition, there was no recurrence of systemic ventricular outflow tract obstruction throughout the follow-up period. Regurgitation of the pulmonary valve estimated by echocardiography at the latest follow-up was none to trivial in seven patients and mild in one. The modified Damus-Kaye-Stansel procedure using aortic flap technique is a safe, useful and reproducible technique to solve systemic ventricular outflow tract obstruction in functionally univentricular heart, and it can be an alternative for original technique or the so-called double-barrel modification.

Anastomosis, Surgical↗

The UW solution has greater potential for longer preservation periods than the Celsior solution: comparative study for ventricular and coronary endothelial function after 24-h heart preservation.

OBJECTIVE: Improvement of long-term heart preservation methods would potentially increase the donor pool and improve survival. We compared the efficacies of the University of Wisconsin (UW) and Celsior solutions on ventricular and endothelial functions after 24-h preservation. METHODS: We used an isolated heart preparation perfused with blood. The heart was excised from a rabbit, stored for 24 h in the UW or Celsior solution, and then perfused with blood from a support-rabbit. We evaluated cardiac output and coronary endothelial function. RESULTS: The Frank-Starling curve showed a significant left and upward shift in the UW group compared with that in the Celsior group (p<0.01). There were no significant differences between the groups for the coronary blood flow in response to sodium nitroprusside or acetylcholine. The serum creatine kinase MB level after reperfusion was significantly lower in the UW group than in the Celsior group (10.7+/-1.4 ng/mL vs 30.4+/-5.4 ng/mL, p<0.01), whereas lipid peroxide levels did not differ significantly between the two groups. CONCLUSIONS: The UW group showed better left ventricular function than the Celsior group, indicating that the UW solution has greater potential for long-term preservation than Celsior solution.

Adenosine↗

Successful mitral valve repair for active infective endocarditis accompanied by anorexia nervosa.

Infective endocarditis of the mitral area accompanied by anorexia nervosa is extremely rare. A 34-year-old Japanese woman presented with high fever and a heart murmur that had developed over the previous 2-month period. Echocardiography revealed mitral regurgitation and vegetation attached to the anterior mitral leaflet, which had markedly prolapsed to the left atrium. We removed the vegetation with a small part of the anterior mitral leaflet and successfully repaired the mitral valve. The patient showed good recovery, and the mitral regurgitation and left ventricular chamber size had satisfactorily decreased at 2 months after the operation.

Adult↗

Sequential analysis of anti-alpha Gal natural antibody-producing B cells in GalT knockout mice in cyclophosphamide-induced tolerance.

Previously, we have shown that cyclophosphamide (CP)-induced tolerance, marked by permanent acceptance of donor skin graft and establishment of donor mixed chimerism, was readily induced with treatment with donor spleen cells (SC), CP, busulfan (BU) and donor bone marrow cells (BMC). Here, we investigated the mechanism of anti-donor natural antibody (nAb) producing B-cell tolerance in our CP-induced tolerance systems in alpha1,3-galactosyltransferase-deficient knockout mice (GalT KO; GalT-/-, H-2(b/d)). After induction of tolerance using donor AKR SC and BMC, survival of donor heart and skin grafts and production of anti-Galalpha1-3Galbeta1-4GlcNAc (anti-alphaGal) Ab in recipient GalT KO mice were analyzed. In addition, the production of anti-alphaGal Ab and the presence of Gal-BSA binding B cells in GalT KO mice were analyzed by flow cytometry (FCM) after treatments with rabbit red blood cells (RRBC) and CP. Permanent acceptance of donor skin and heart grafts and abrogation of anti-alphaGal Ab were achieved in GalT KO mice treated with donor SC + CP/BU + BMC. However, in the GalT KO mice treated with donor SC and CP, donor skin grafts were acutely rejected, even though anti-alphaGal Ab was undetectable. Similarly, anti-alphaGal Ab was undetectable in GalT KO mice treated with RRBC and CP. Our data strongly indicated the following mechanisms: the clonal destruction in the early stage and the clonal anergy or ignorance in the late stage after conventional conditioning with RRBC and CP. In conclusion, our drug-induced tolerance protocols are effective to induce tolerance in recipients that produce anti-donor nAb.

Animals↗

Bilateral axillary arterial perfusion in surgery on thoracic aorta.

Bilateral axillary arterial cannulation for selective cerebral perfusion might minimize cerebral embolic complications during surgery on the ascending aorta and aortic arch. From March 2002 through February 2004, bilateral axillary arterial perfusion was applied in 12 consecutive patients (mean age, 61.3 years). Operative procedures were total arch replacement in 8 patients, hemiarch replacement in 1, and ascending aorta replacement in 3. Antegrade selective cerebral perfusion was established through vascular grafts anastomosed to the bilateral axillary arteries and a perfusion catheter placed directly into the left carotid artery. Bilateral axillary arterial perfusion through the grafts was successful in all patients. There were no early or late deaths and no incidence of neurologic deficit. There were no complications related to cannulation of the axillary arteries. Bleeding, temporary renal failure, acute respiratory distress syndrome, and graft infection occurred in one patient each; all recovered from these complications. Bilateral axillary arterial perfusion is feasible and effective for brain protection during surgery on the ascending aorta and aortic arch.

Adult↗

Impact of atrial septal defect closure on right ventricular performance.

BACKGROUND: Atrial septal defect (ASD) closure is one of the most representative cardiac operations, but there have been few assessments of right ventricular (RV) performance during the perioperative period. METHODS AND RESULTS: Using transesophageal echocardiography with automated border detection system, the RV pressure - area (P-A) loops were measured in 6 patients immediately before and after an ASD closure. Multiple RV P-A loops obtained by the inferior vena cava occlusion technique were used to evaluate end-systolic maximal elastance (Ees), preload recruitable stroke work (MEW), external work (EW) and the systolic P-A area (PAA). Ees and MEW are indices of contractility, and PAA represents the total mechanical energy. RV Ees and MEW did not change after the operation (from 3.36 +/- 2.20 to 3.70 +/- 2.04 mmHg/cm2, p = 0.4; and from 10.3 +/- 5.0 to 10.5 +/- 4.5 mmHg, p = 0.8, respectively), whereas EW and PAA were significantly reduced (from 121.4 +/- 77.4 to 48.7 +/- 26.6 mmHg/cm2, p < 0.05; and from 274.8 +/- 212.8 to 92.7 +/- 52.8 mmHg/cm2, p < 0.05, respectively). ASD closure reduced the EW and total mechanical energy of the right ventricle without influencing contractility. CONCLUSIONS: These results indicate that ASD closure preserved RV function and reduced RV myocardial oxygen consumption. Assessment of the RV P-A relationship in the operating room demonstrates the beneficial effects of ASD closure on RV performance.

Adult↗

Constrictive pericarditis with atrial septal defect.

We report on a case of constrictive pericarditis (CP) with atrial septal defect (ASD) in a 50-year-old man. The combination of CP with ASD is rare and occasionally difficult to diagnose. Transthoracic echocardiography demonstrated ASD, but the finding of a thickened pericardium was poor. Diagnosis was confirmed by cardiac catheterization. Pericardiectomy and direct closure of ASD was performed during cardioplegic arrest under the support of cardiopulmonary bypass. The postoperative course was uneventful with marked improvement in symptoms.

Cardiac Catheterization↗

A 10-year experience with the Carbomedics cardiac prosthesis.

BACKGROUND: There are few reports on the long-term results of Carbomedics prosthetic heart valves. METHODS: Five hundred five patients who underwent valve replacement with this prosthesis in the aortic or mitral position were chosen for this study. Patients' mean age was 57 years. There were 173 aortic (AVR), 253 mitral (MVR), and 79 double (DVR) valve implants. The mean follow-up was 5.1 years, and cumulative follow-up was 2,590 patient-years with an overall follow-up rate of 99.2%. RESULTS: The early mortality rate for the total population was 2.8% (AVR 1.2%, MVR 3.6%, DVR 3.8%). Actuarial freedom from thromboembolism at 10 years was 81.8% +/- 5.1%, 85.7% +/- 3.2%, and 88.8% +/- 6.8% for AVR, MVR, and DVR, respectively. At 10 years, 92.7% of AVR, 85.4% of MVR, and 94.7% of DVR patients were free of valve-related death. Overall survival rate at 10 years was 77.6% +/- 4.6%, 71.8% +/- 4.2%, and 81.3% +/- 5.8% for AVR, MVR, and DVR, respectively. The linearized rate of thromboembolism was 1.45%/patient-year, 1.78%/patient-year, 0.67%/patient-year; of major bleeding events, 0.52%/patient-year, 0.85%/patient-year, 0.45%/patient-year; of valve thrombosis, 0%/patient-year, 0.25%/patient-year, 0%/patient-year; of prosthetic valve endocarditis, 0.1%/patient-year, 0.25%/patient-year, 0.22%/patient-year; and of all reoperations, 0.31%/patient-year, 0.93%/patient-year, 1.1%/patient-year for AVR, MVR, and DVR, respectively. CONCLUSIONS: The Carbomedics prosthetic heart valves showed comparable or even better results than those of other mechanical valves with respect to morbidity and mortality. These results may justify the use of Carbomedics valves as one of the mechanical heart valves.

Adult↗

Extended total arch replacement for type B aortic dissection with ascending aneurysm following healed aortic dissection.

We describe a case of type B aortic dissection with large ascending aortic aneurysm occurring 12.8 years after aortic root replacement (Cabrol procedure) in a non-Marfan patient with cystic medial necrosis of the aorta. We have successfully performed an extended total aortic arch replacement using a four-branched graft through the "L-incision" approach (a combination of a left anterior thoracotomy and upper half median sternotomy). Of note, a histological specimen from the aneurysmal ascending aortic wall revealed "healed aortic dissection" with fibrous tissue replacing the media and intima in addition to multiple foci of cystic medial necrosis.

Aged↗

Coronary artery bypass grafting with absent right superior vena cava in visceroatrial situs solitus.

We report on a 63-year-old man with an absence of right superior vena cava in visceroatrial situs solitus who underwent coronary artery bypass grafting. Preoperative echocardiography showed a dilated coronary sinus, and venography confirmed an absent right and a persistent left superior vena cava. Perioperatively, placement of a pulmonary artery catheter, site of venous cannulation, and management of associated rhythm abnormalities were of great concern. The assessment of the right superior vena cava is advisable in carrying out the surgical procedure without any difficulties related to this anomaly when the persistent left superior vena cava is suspected.

Abnormalities, Multiple↗

Coronary artery bypass grafting and aortic valve replacement in a patient with a tracheostoma.

We report a 67-year-old man with a tracheostoma who successfully underwent coronary artery bypass grafting and aortic valve replacement. He had received both a tracheostoma just above the sternal notch after total laryngectomy. As the standard full sternotomy might cause mediastinitis, we performed the operation through a lower half sternotomy with a limited skin incision. Postoperatively the wound was covered with a sterile plastic drape to prevent infection from the tracheostoma. The postoperative course was uneventful.

Aged↗

Successful aortic valve replacement in severe pancytopenia related to myelodysplastic syndrome.

We report a 60-year-old man with myelodysplastic syndrome (MDS) whose aortic valve was replaced successfully. He suffered from dyspnea on exertion and was confirmed by echocardiography and cardiac catheterization to have severe aortic stenosis. A peripheral blood examination showed pancytopenia and a bone marrow examination showed MDS with a subtype of refractory anemia with excess blasts. His preoperative neutrophil count was 468/mm3, hemoglobin 9.8 g/dl, and platelet count 27,000/mm3. We conducted aortic valve replacement (AVR) using a bioprosthesis in July 2001. Pre- and postoperatively, we injected granulocyte colony-stimulating factor to keep the neutrophil count at 2,000/mm3 or more. We also transfused platelet concentrate and infused tranexamic acid. Despite potential risks of infection and bleeding, the AVR involved no significant complications. Careful preoperative planning thus plays an important role in managing such cases.

Aortic Valve↗

Total aortic arch replacement through the L-incision approach.

BACKGROUND: Even though the median sternotomy is the standard approach for surgery involving the aortic arch, access to the site of distal anastomosis is problematic when the aortic pathology involves the distal arch. We recently developed an "L-incision" approach (a combination of a left anterior thoracotomy and upper half median sternotomy) for total arch replacement. METHODS: We reviewed our surgical technique and operative results for 11 patients who underwent total aortic arch replacement through the L-incision between July 1999 and July 2000. With a patient in a left anterolateral position, a left anterior thoracotomy was performed through the fourth to sixth intercostal space. An upper half median sternotomy followed. Operative exposure was enhanced with spring retractors. The proximal anastomosis (between the four branched graft and ascending aorta) was accomplished first. Upon completion of the proximal anastomosis, the heart was reperfused from one branch of the graft. The three arch vessels were subsequently reconstructed under deep hypothermia and retrograde cerebral perfusion. Antegrade cerebral perfusion was accomplished through the graft as the distal anastomosis (between the graft and descending thoracic aorta) was performed. RESULTS: No early operative deaths were observed. One patient sustained a permanent neurologic deficit. A transient recurrent laryngeal nerve palsy lasting 1 month occurred in 1 patient. No patient required reoperations for bleeding, nor did any patient develop a postoperative phrenic nerve palsy, aspiration pneumonia, or renal dysfunction. CONCLUSIONS: The L-incision allows extensive replacement of the aortic arch and is associated with a low incidence of postoperative bleeding and respiratory insufficiency.

Aged↗

A modified valve-on-valve approach for aortic root replacement.

We describe an alternative surgical technique for aortic root replacement in a patient whose aortic valve was previously replaced with a bioprosthesis. It consists of resecting the leaflets of the original bioprosthesis in situ, amputating the struts, and suturing the skirt of a composite graft on the preserved annulus of the original bioprosthesis. Coronary circulation is reconstructed according to the Cabrol modification. This approach simplifies and shortens the procedure of aortic root replacement, minimizing the potential hazard of hemorrhage from the proximal suture line in these cases.

Aged↗

[Recent advances in cardiac protection].

In order to protect the heart from unfavorable conditions such as myocardial ischemia or heart failure, it seems necessarily to investigate what components are related to such conditions or what drugs affect them. For this purpose, at symposium No. 40 "Recent Advances in Cardiac Protection" at the 75th Annual Meeting of The Japanese Pharmacological Society held in Kumamoto City, the following 6 studies were presented: (1) The Role of Sarcoglycan Complex in Chronic Heart Failure (H. Yoshida et al.); (2) Heart Failure and Proinflammatory Cytokines (T. Kubota et al.); (3) Fundamental Strategies and Current Topics for Cardiac Protection During Open-Heart Surgery (R. Tominaga et al.); (4) Role of Tetrahydrobiopterin in Myocardial Ischemia/ Reperfusion Injury (K. Noguchi et al.); (5) Cardiac Protection by Nitric Oxide (T. Obata); (6) Reconsideration of Anti-oxidants as Protective Drugs on Ischemic Myocardium (K. Ichihara et al.). This review gathers the reports of studies presented at this symposium.

Animals↗