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Biomedical subjects

Michiko Ishida

Publications and source records attributed to Michiko Ishida.

18 recordsLinked to original sources

The SYT-SSX fusion protein down-regulates the cell proliferation regulator COM1 in t(x;18) synovial sarcoma.

Chromosomal translocations are frequently associated with soft-tissue sarcomas. Fusion proteins generated by such translocations often play critical roles in tumorigenesis. Therefore, it is important to understand the function of the fusion protein to develop therapeutic interventions. The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in a fusion between the SYT gene on chromosome 18 and an SSX gene on the X chromosome. Although SYT-SSX fusion proteins appear to trigger synovial sarcoma development, little is known about the downstream targets of SYT-SSX. We found that the SYT-SSX fusion protein produces a dominant-negative function for SYT, which is a transcriptional coactivator. We then analyzed the gene expression profiles of SYT-SSX1-expressing HeLa cells using oligonucleotide microarrays and found that the SYT-SSX1 fusion protein directly down-regulated the expression of COM1, a regulator of cell proliferation. COM1 was found to be expressed at relatively low levels in synovial sarcoma tissues and cell lines. We then investigated the impact of conditional COM1 expression in the synovial sarcoma cell line. Increased COM1 expression resulted in induced apoptosis and in reduced cell growth and colony formation activity. Our results suggested that restoration of COM1 expression may be of therapeutic benefit in synovial sarcoma.

Apoptosis↗

DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation.

Understanding how p53 activity is regulated is crucial in elucidating mechanisms of cellular defense against cancer. Genetic data indicate that Mdmx as well as Mdm2 plays a major role in maintaining p53 activity at low levels in nonstressed cells. However, biochemical mechanisms of how Mdmx regulates p53 activity are not well understood. Through identification of Mdmx-binding proteins, we found that 14-3-3 proteins are associated with Mdmx. Mdmx harbors a consensus sequence for binding of 14-3-3. Serine 367 (S367) is located within the putative binding sequence for 14-3-3, and its substitution with alanine (S367A) abolishes binding of Mdmx to 14-3-3. Transfection assays indicated that the S367A mutation, in cooperation with Mdm2, enhances the ability of Mdmx to repress the transcriptional activity of p53. The S367A mutant is more resistant to Mdm2-dependent ubiquitination and degradation than wild-type Mdmx, and Mdmx phosphorylated at S367 is preferentially degraded by Mdm2. Several types of DNA damage markedly enhance S367 phosphorylation, coinciding with increased binding of Mdmx to 14-3-3 and accelerated Mdmx degradation. Furthermore, promotion of growth of normal human fibroblasts after introduction of Mdmx is enhanced by the S367 mutation. We propose that Mdmx phosphorylation at S367 plays an important role in p53 activation after DNA damage by triggering Mdm2-dependent degradation of Mdmx.

14-3-3 Proteins↗

Bone marrow cell-seeded biodegradable polymeric scaffold enhances angiogenesis and improves function of the infarcted heart.

BACKGROUND: The present study examined whether a bioengineered polyglycolic acid cloth (PGAC) impregnated with bone marrow cells (BMC) improved the function and angiogenesis of the infarcted heart. METHODS AND RESULTS: The coronary artery was ligated in Lewis rats and the infarcted area was covered with a PGAC in group 1 (n=8), with a PGAC containing basic-fibroblast growth factor (b-FGF) in group 2 (n=11) and a PGAC containing b-FGF and freshly isolated BMC in group 3 (n=10). In addition, BMC derived from transgenic mice expressing green fluorescent protein (GFP)-BMC were seeded into a PGAC, which was sutured over the infarcted area of C57BL/6 mice (n=5). In the rat study, developed and systolic pressures, dp/dt max and dp/dt min) were the highest in group 3, as were the capillary density in the PGAC and infarcted area. In the mouse study, there were few GFP-BMC in the PGAC, but none in the infarcted area. CONCLUSIONS: A PGAC with BMC improved cardiac function by inducing angiogenesis without migration of BMC. Freshly isolated BMC work as angiogenic inducers and a PGAC is useful as a "drug delivery system".

Absorbable Implants↗

A novel application of myocardial contrast echocardiography to evaluate angiogenesis by autologous bone marrow cell transplantation in chronic ischemic pig model.

OBJECTIVES: We investigated the feasibility of myocardial contrast echocardiography (MCE) to evaluate regional perfusion after bone marrow cell transplantation. BACKGROUND: The myocardial microvessels improved by cell transplantation are too small to visualize with conventional angiography. METHODS: Fourteen mini-pigs from the Nippon Institute for Biological Science were used. The proximal left anterior descending coronary artery was ligated. One month later, nine pigs survived. Six pigs received autologous cell transplantation into the left ventricular anterior wall: bone marrow mononuclear cells (BMMNCs) (n = 3) and bone marrow stromal cells (BMSCs) (n = 3). The other three pigs received saline (control group, n = 3). The pigs were sacrificed one month later. Myocardial contrast intensity (MCI) with a contrast agent was measured using the SONOS 5500 system (Philips). Capillary density (CD) and MCI were measured at four areas: anteroseptum (nontransplanted infarct area), anterior wall (transplanted infarct area), septum (border zone), and lateral wall (normal). We compared the anteroseptum with the anterior wall by MCI and CD. RESULTS: In the BMMNC and BMSC subsets, the CD of the anterior wall was higher than that of the anteroseptum (p < 0.001). There was a linear relation between MCI and CD (acoustic unit [AU2] = 0.234 CD + 0.010, r = 0.92, p < 0.001). At one month after cell transplantation, MCI of the anterior wall increased in the BMMNC and BMSC subsets (p < 0.05), although it did not change in the control group. The ratio of wall thickness (systole/diastole) in the transplanted infarct area was larger than that in the nontransplanted infarct area (p < 0.01). CONCLUSIONS: Myocardial contrast echocardiography is useful to evaluate regional perfusion, which was enhanced by bone marrow cell transplantation.

Animals↗

Rationale of off-pump coronary artery bypass grafting for left main trunk disease.

OBJECTIVE: Off-pump coronary artery bypass grafting (OPCAB) remains controversial in patients with left main trunk (LMT) disease because of a concern about the ability to tolerate hemodynamic instability. This study examined the safety of OPCAB for LMT disease compared with conventional coronary artery bypass grafting (CABG). METHODS: Between April 1997 and December 2002, 257 consecutive patients with LMT stenosis who underwent CABG were enrolled. There were 98 patients who received CABG with the aid of cardiopulmonary bypass (CCAB group), and 159 patients who received OPCAB (OPCAB group). RESULTS: There was no patient who converted to on-pump intraoperatively due to hemodynamic instability. Both intraoperative blood loss and blood transfusion incidence were lower in the OPCAB group. Postoperative course was similar, however, pulmonary complications were less observed postoperatively in the OPCAB group. No hypoperfusion syndrome was seen postoperatively in both groups. The average number of anastomosis was 3.2+/-1.1 in the CCAB group and 3.2+/-1.0 in the OPCAB group (p=0.645). Total arterial OPCAB with an aorta no-touch technique was achieved in 142 patients (89.3%) in OPCAB group. Postoperative angiography was performed in 95 patients in CCAB (96.9%), and in 141 patients in OPCAB (89.8%). Although graft patency of arterial grafts was good in both groups (100% in CCAB and 98.3% in OPCAB), saphenous vein graft patency was slightly lower in both groups (93.4% in CCAB and 76.5% in OPCAB) compared with arterial grafts. CONCLUSION: OPCAB allows a safe and effective treatment of LMT disease.

Aged↗

Comparison of off-pump and on-pump coronary artery bypass grafting in midterm results.

OBJECTIVE: Off-pump coronary artery bypass grafting (OPCAB) has become a procedure of choice for surgical treatment of coronary artery disease. Although early advantages of OPCAB were confirmed in comparison with conventional on-pump coronary artery bypass grafting (CABG), late cardiac complications are still controversial. We examined midterm results of OPCAB compared with standard CABG. METHODS: Between July 1997 and April 2002, 736 consecutive patients who underwent isolated CABG were retrospectively reviewed. The OPCAB group (Group I) comprised 357 patients (49%), and the on-pump CABG group (Group II) 379 patients (51%). Their preoperative, intraoperative, and follow-up data were analyzed. RESULTS: The mean number of distal anastomoses and the early graft patency were not greatly different between the two groups. The actuarial survival rate at 3 years was not significantly different between Group I (98.3%) and Group II (98.2%) (p = 0.71). The frequency of cardiac events was 4.2%/patient-year in Group I and 2.6%/patient-year in Group II (p = 0.12). The actuarial event free rates were not different between the two groups (p = 0.61). The cardiac event free rates at 3 years were significantly (p = 0.011) higher in patients with complete revascularization (96.7%) than without complete revascularization in Group I (69.2%) and in Group II (92.7% versus 85.9%, p = 0.026). CONCLUSIONS: Midterm clinical outcome in OPCAB is as good as conventional on-pump CABG. Incomplete revascularization caused cardiac events more frequently than complete revascularization both in OPCAB and on-pump CABG in the intermediate follow-up.

Cardiopulmonary Bypass↗

Bone marrow is a source of regenerated cardiomyocytes in doxorubicin-induced cardiomyopathy and granulocyte colony-stimulating factor enhances migration of bone marrow cells and attenuates cardiotoxicity of doxorubicin under electron microscopy.

BACKGROUND: It has been reported previously that granulocyte colony-stimulating factor (GCSF) injection improves infarcted heart function, but the mechanism remains unclear. In this study we sought to determine whether GCSF-mobilized bone marrow cells could regenerate neo-myocardium and repair doxorubicin-induced cardiomyopathy. METHODS: C57BL/6 mice were irradiated and bone marrow cells (BMC; 1 x 10(6)) from green fluorescent protein (GFP) mice (GFP-BMC) were transplanted intravenously, followed by splenectomy. Doxorubicin (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally 2 weeks later. GCSF (50 microg/kg/day for 8 days) was administered sub-cutaneously after doxorubicin injection (Group I, n = 11) and 3 weeks later (Group II, n = 8), and saline was injected in Group III animals (n = 8). Eight weeks after doxorubicin injection, the excised hearts were studied immunologically and electron microscopically. RESULTS: Survival rates were 81.8% in Group I, 50.0% in Group II and 62.5% in Group III. The number of GFP-BMC in Group I (15.4 +/- 7.4 per high-power field) was highest (p < 0.05). In all groups, cardiac troponin I-positive cells derived from GFP-BMC were observed in the hearts. GFP-BMC in hearts stained positively against cardiac troponin I (4.3 +/- 2.5%), myosin heavy chain (5.0 +/- 4.3%), atrial natriuretic peptide (ANP; 3.9 +/- 2.4%) and connexin 43 (11.9 +/- 7.3%) in Group I. Myofibrils, mitochondria and fundamental architecture were almost all preserved in Group I, whereas hearts were severely damaged in Groups II and III. CONCLUSIONS: Bone marrow was shown to be one of the sources of regenerated cardiomyocytes in the doxorubicin-induced cardiomyopathic heart. Early administration of GCSF enhanced the migration of bone marrow cells into the heart, and attenuated the cardiotoxicity of doxorubicin.

Animals↗

Acute effects of direct cell implantation into the heart: a pressure-volume study to analyze cardiac function.

BACKGROUND: To safely implant cells into the myocardium, we must establish a volume that prevents compromising cardiac performance. We studied pressure-volume (PV) to investigate the adverse effects of direct cell implantation in the acute phase. METHODS: We used 21 minipigs. In the normal heart model, we studied PV by measuring various parameters (including end-systolic pressure, end-systolic elastance, dp/dtmax, end-diastolic volume, and time constant of isovolumetric left ventricular pressure fall [Tau]). We injected solutions into the left ventricular free wall (15 cm(2)). Sampling points were at baseline and after injection of saline (Group I, n = 4) or of blood (Group II, n = 4) at volumes of 1 ml and 10 ml up to 30 minutes after injection. In Group II, we injected additional blood (10 ml) 4 times. In the ischemic heart model, 1 month after ligating the left anterior descending artery, we injected 1 ml saline (Group III, n = 4), bone marrow mononuclear cells (10(8) cells/1 ml; Group IV, n = 4), or bone marrow stromal cells (10(8) cells/1 ml; Group V, n = 3). We studied PV before and after injection. RESULTS: In Group I, we found no significant changes in parameters. In Group II, end-diastolic volume after 10-ml injection (24.4 +/- 3.6 ml) was smaller than end-diastolic volume at baseline (29.5 +/- 5.8 ml, p < 0.01). Tau after 10-ml injection (39.4 +/- 5.3 msec) was greater than at baseline (35.6 +/- 4.0 msec, p < 0.01). One pig died of ventricular fibrillation after a 20-ml injection of blood. We observed no detrimental effects in Groups III, IV, and V. CONCLUSIONS: More than 10 ml cell suspension compromised diastolic function. We safely performed direct injection of bone marrow cells (1 x 10(8)/1 ml).

Animals↗

Bone marrow mononuclear cell transplantation had beneficial effects on doxorubicin-induced cardiomyopathy.

BACKGROUND: Cell transplantation is a promising therapy for treating end-stage heart failure. Bone marrow mononuclear cells (BMMNC) have been used to enhance angiogenesis in ischemic heart disease. However, the effect of BMMNC transplantation in non-ischemic dilated cardiomyopathy is unknown. In this study, we evaluated the efficacy of BMMNC transplantation in doxorubicin-induced cardiomyopathy in a rat model. METHODS: Doxorubicin (15 mg/kg, IP) was introduced into 52 Lewis rats. They were divided into 3 groups at 4 weeks after injection: transplant group (TX, BMMNC [1 x 10(6)] implantation, n = 18), control group (CN, saline injection, n = 18), and sham group (SH, thoracotomy, n = 16). At 4 weeks after surgery, we used echocardiography to measure systolic left ventricular diameter (LVDs), diastolic left ventricular diameter (LVDd), fractional shortening (FS), and left ventricular wall thickness/LVDs. We used a Langendorff apparatus to measure systolic, diastolic, and developed pressures. We used radioimmunoassay to measure circulating atrial natriuretic peptide concentration, and we performed histologic study, including electron-microscopic study. RESULTS: Left ventricular wall thickness/LVDs in the TX group was the largest of all groups (p < 0.05). Systolic and developed pressures in the TX group were the greatest (p < 0.005). Systolic left ventricular diameter, FS, and end-diastolic pressure in the TX group were smaller than in the SH group (p < 0.05). These cardiac parameters did not differ significantly between TX and CN groups, but secondary changes (decreased heart weight, developed ascites, and increased atrial natriuretic peptide concentration) caused by doxorubicin-induced heart failure were most attenuated in the TX group. In the TX group, vascular density was greatest (p < 0.05) in the left ventricular free wall and in the septum. In addition, electron microscopy showed that myocardium in the TX group was most maintained. CONCLUSION: Bone marrow mononuclear cell transplantation had beneficial effects in doxorubicin-induced cardiomyopathy.

Animals↗

Transcriptional co-activator activity of SYT is negatively regulated by BRM and Brg1.

The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the fusion of the SYT gene on chromosome 18 to the SSX gene on chromosome X. Although the SYT-SSX fusion proteins may trigger synovial sarcoma development, the biological functions of SYT, SSX and SYT-SSX genes are unclear. Transfections of Gal4 DNA binding domain fusion protein constructs demonstrate that SYT protein acts as a transcriptional co-activator at the C-terminal domain and that the activity is repressed through the N-terminus. The N-terminal 70 amino acids of SYT bind not only to BRM, but also to Brg1, both of which are subunits of SWI/SNF chromatin remodelling complexes. Here, we have investigated the functions of BRM and Brg1 on the repression of SYT activity. The negative regulation of SYT transcriptional co-activator activity is dependent on the ATP-hydrolysis of BRM and Brg1 in the protein complexes. This indicates that the SWI/SNF protein complexes regulate SYT activity using the chromatin remodelling activity.

Adenosine Triphosphate↗

G-CSF promotes bone marrow cells to migrate into infarcted mice heart, and differentiate into cardiomyocytes.

A recent study showed that granulocyte-colony stimulating factor (G-CSF) treatment improved the infarcted cardiac function. Although mobilized stem cells may affect it, the mechanism is unclear. In this study, we investigated the origins of stem cells and phenotypic changes of the migrated cells, and evaluated the efficacy of G-CSF. Eighteen C57BL/6 mice were irradiated (900 cGy) and GFP mouse-derived bone marrow cells (GFP-BMC: 10(6) cells) were injected via a tail vein followed by splenectomy 4 weeks later. Ligation of the left descending coronary artery was performed 2 weeks later. Recombinant human G-CSF (200 microg/kg/day) was injected for 3 days before and 5 days after ligation (group 1, n = 10). Saline was injected in group 2 (n = 8). Four weeks after infarction, hearts and other organs were fixed for histology. The survival rate after postoperative day 3 in group 1 was 100%, while that in group 2 was 50% (p = 0.03). Bone marrow-derived GFP cells (BMD-GFP) in group 1 (103.3+/-71.9/mm2) were located at the infarcted border area significantly more than those in group 2 (43.6+/-23.7/mm2) (p < 0.0001). BMD-GFP cells were positive for troponin I (16.6%), myosin heavy chain-slow (16.7%), and nestin (8.8%) in group 1. Ki-67-positive BMD-GFP in group 1 (10.0+/-7.0/mm2) were significantly more than those in group 2 (4.8+/-6.1/mm2) (p = 0.01). G-CSF increased the survival rate after infarction. G-CSF promoted BMC to migrate into the infarcted border area. Bone marrow was one of the origins of regenerated cardiomyocytes.

Animals↗

Early results of complete off-pump coronary revascularization using left internal thoracic artery with composite radial artery.

OBJECTIVE: Off-pump coronary artery bypass (OPCAB) using the left internal thoracic artery (LITA) with a composite radial artery (RA) was employed for arterial revascularization in order to minimize neurological complication. METHODS: Sixty-one patients underwent OPCAB using the LITA with a composite RA. Angiography was performed in all patients at two weeks postoperatively. RESULTS: The mean number of distal anastomoses was 3.2 +/- 0.4. A Y-composite graft was used in 55 patients, and K-composite graft was used in the other 6 patients. There was no hospital death, no neurological complication nor deep sternal infection. Furthermore, there was no episode of perioperative myocardial infarction nor hypoperfusion syndrome. Patients have been angina-free during a mean follow-up period of 1 year. The graft patency of the LITA to the left anterior descending artery (LAD) was 100% (61/61 anastomoses). The RA became occluded in 4 patients, and the patency rate was 95.6% (130/136 anastomoses). String or coronary-coronary bypass resulting from flow competition was observed in the LITA of 6 patients and in the RA of 13 patients. The string of the LITA occurred in the segment distal from the anastomosis with the composite RA. The string or coronary-coronary bypass was observed more often in cases in which the recipient coronary artery had less than 75% stenosis. CONCLUSION: OPCAB using only the LITA with a composite RA can be successfully and safely performed in patients with multivessel disease. Late postoperative follow-up of the flow competition is necessary to delineate the significance of flow competition.

Aged↗

Early adaptation of the left internal thoracic artery as a blood source of y-composite radial artery grafts in off-pump coronary artery bypass grafting.

OBJECTIVE: Y-composite grafting with the radial artery (RA) is often used in off-pump coronary artery bypass grafting (OPCAB). However, the early flow reserve of the left internal thoracic artery (LITA) as a blood source of the Y-composite RA graft has not been delineated. METHODS: The size of the LITA was examined angiographically in 42 patients who underwent OPCAB using LITA and Y-composite RA grafting between June 2000 and February 2002. In these patients, the LITA was used as a blood source of the Y-composite RA graft. The mean patient age +/- SD was 67 +/- 8 years. The average number of d i stal anastomoses was 3.2 +/- 0.7. Total coronary revascularization was carried out in 34 patients with only LITA and Y-composite RA grafting. RA grafting was used for revascularization of the circumflex artery alone in 5 patients, for the right coronary artery system (RCS) alone in 6 patients, and for both the circumflex and the RCS in 23 patients. The average number of distal anastomoses using the RA was 1.9 +/- 0.7. Flow measurements of the proximal LITA were achieved intraoperatively with a transit-time flowmeter. The diameters of the LITA before and after the operation were measured angiographically. Intraoperative flow volume was correlated with the ratio of the LITA diameters before and after the operation. RESULTS: The mean flow rate of the LITA was 61 +/- 35 mL/min (range, 9-196 mL/min). The mean diameters of the LITA before and after the operation were 1.97 +/- 0.36 mm and 2.74 +/- 0.60 mm, respectively. The mean ratio of the LITA diameter after the opera t ion to that before the operation was 1.43 +/- 0.27. The intraoperative flow volume was positively correlated with the ratio of LITA diameters (r = 0.414; P =.006). CONCLUSION: These results demonstrate the early adaptation of the LITA as a blood source of the Y-composite RA graft in OPCAB and the rationale for using the LITA as a single blood source for total coronary artery revascularization.

Aged↗

Perioperative advantages of off-pump coronary artery bypass grafting.

For the first time in Japan, off-pump coronary artery bypass grafting (OPCAB) was compared with the conventional on-pump technique, retrospectively examining the morbidity associated with coronary artery bypass grafting (CABG) and assessing the efficacy of OPCAB. In 2000, 158 patients underwent CABG: 95 patients (60%) had OPCAB (Group I) and 63 patients (40%) had conventional CABG (Group II). The operating time, length of intensive care unit (ICU) stay, ventilation time, postoperative bleeding, transfusion, postoperative renal function, occurrence of stroke, and early graft patency were examined in both groups. There were no hospital deaths in either group. The operating time, ICU stay, and ventilation time were significantly (p < 0.0001, p = 0.013, and p < 0.0001, respectively) shorter in Group I (351 +/- 85 min, 3.0 +/- 1.4 days, and 5.1 +/- 2.8h) than in Group II (449 +/- 112 min, 3.6 +/- 1.8 days, and 13.7 +/- 18.0 h). The postoperative blood loss within 12h and the transfusion volume were significantly (p = 0.0004 and p < 0.0001, respectively) smaller in Group I (480 +/- 210 ml and 300 +/- 490ml) than in Group II (720 +/- 430ml and 1,230 +/- 1,180 ml). Peak serum blood urea nitrogen and creatinine concentrations (excluding patients with preoperative chronic renal failure, ie a preoperative serum creatinine > 1.5 mg/dl) were significantly (p < 0.0001 and p < 0.0001, respectively) lower in Group I (16.2 +/- 15.2mg/dl and 0.81 +/- 0.72 mg/dl) than in Group II (19.2 +/- 7.6 mg/dl and 0.92 +/- 0.28 mg/dl). There were no perioperative strokes in Group I, but 6.4% of Group II patients suffered a stroke. There was no significant difference in graft patency between the groups (95.6% vs 94.9%). OPCAB reduced the mortality and morbidity of coronary revascularization, with a shorter operating time and more rapid recovery from surgery.

Aged↗

Total arterial off-pump coronary revascularization with only internal thoracic artery and composite radial artery grafts.

OBJECTIVE: Total arterial off-pump coronary artery bypass (OPCAB) grafting with only internal thoracic artery (ITA) and composite radial artery (RA) grafts has been applied extensively to avoid cerebral complications and late vein graft failure. We evaluated the initial experience with this method by clinical and angiographic study. METHODS: Between April 2000 and May 2002, 257 patients underwent OPCAB grafting with this technique. The range of ages at operation was 42 to 86 years (mean, 66.1 +/- 8.6 years). On average, 3.28 +/- 0.86 grafts per patient were completed. More than 4 distal anastomoses were performed in 88 patients (34%). For coronary revascularization, 289 ITA and 555 RA grafts were used. The RA was used as a Y graft in 211 patients, as an I graft (for ITA extension) in 52 patients, and as a K graft (the side of the RA attached to the side of the left ITA) in 28 patients. Sequential bypass grafting was performed with 190 RA and 7 ITA grafts. The sites of distal anastomoses were 256 left anterior descending arteries (30%), 236 posterolateral branches (28%), 144 posterior descending arteries (17%), 106 diagonal branches (13%), 82 obtuse marginal branches (10%), and 19 right coronary arteries (2%). RESULTS: There were 1 operative death (0.4%) due to cerebral hemorrhage and 2 episodes of stroke (0.8%) during postoperative angiography. There were no clinical underperfusion syndromes or new intra-aortic balloon pump insertions. Perioperative myocardial infarction occurred in 12 patients (4.7%), sternal dehiscence in 5 (1.9%), and early coronary intervention in 4 (1.6%). There was no deep wound infection, reexploration for bleeding, or hand ischemia. The actuarial survival rate and the cardiac event-free rate at 2 years were 98.6% +/- 2.4% and 94.2% +/- 0.8%, respectively. Early postoperative angiography revealed a 97.8% (264/270) graft patency of ITAs and 97.9% (512/523) graft patency of RAs in 238 patients. Flow competition of the RA graft was recognized in 22 patients and, as indicated by follow-up angiographic study, did not cause late graft occlusion. CONCLUSIONS: OPCAB grafting with ITAs and composite RAs provides excellent early and intermediate clinical results and graft patency.

Adult↗

Eight-year experience of combined valve repair for mitral regurgitation and maze procedure.

BACKGROUND AND AIMS OF THE STUDY: Although atrial fibrillation (AF) is often associated with severe mitral regurgitation (MR), a simultaneous maze procedure for AF associated with repair of MR remains controversial. In this study, mid-term results of combined mitral valve repair and the maze procedure were examined. METHODS: Between May 1992 and April 2001, 85 patients (61 males, 24 females) underwent valve repair for MR and the maze procedure. Mean age at surgery was 61.8+/-9.1 years; mean follow up was 4.7+/-2.3 years. Valve lesions were anterior in 26 patients (31%), posterior in 31 (36%), anterior + posterior in 23 (27%), and simple dilated annulus in five (6%). Chordal replacement with expanded PTFE sutures was performed in 40 patients (47%), and leaflet resection in 41 (48%). Ring annuloplasty was also applied in 61 patients (72%). Associated procedures were tricuspid valve annuloplasty in 33 (36%), coronary artery bypass grafting in four, atrial septal defect closure in two, aortic valve repair in one, and resection of abnormal septum in the left atrium in one. RESULTS: There was one hospital death (1%), and one late death (1%). Reopening the chest for bleeding was necessary in six cases (7%). One thromboembolic episode was detected during follow up (0.25%/patient-year). Reoperation for MR was performed in three patients (4%). Actuarial event-free survival rate was 90.0+/-6.4% at eight years. Sinus rhythm was regained in 68 patients (81%), and atrial A-wave was detected in 57 (68%) by pulsed Doppler study. Postoperative left ventricular diastolic and systolic dimensions were significantly (p = 0.001 and p = 0.017) smaller in patients who restored sinus rhythm than in those who did not (48.6+/-4.6 versus 54.6+/-4.7 mm, and 33.0+/-6.0 versus 38.1+/-6.9 mm). CONCLUSION: Combined mitral valve repair for MR and the maze procedure showed satisfactory midterm results. Postoperative sinus rhythm conversion by the maze procedure may reduce left ventricular size, and the incidence of thromboembolic episodes in mitral valve repair.

Adult↗

Multiple off-pump coronary revascularization with "aorta no-touch " technique using composite and sequential methods.

BACKGROUND: Although off-pump coronary artery bypass grafting (OPCAB) has been widely applied in patients who are considered high risk for cardiopulmonary bypass (CPB), there is still a risk of stroke during the operation because of the ascending aortic partial clamp for proximal anastomosis. In the present study, we report the initial results of an "aorta no-touch " technique using an in-situ graft and composite and sequential grafting methods. METHODS: Between March 2000 and April 2001, 120 patients underwent OPCAB with this technique. The age of patients ranged from 47 to 86 years, with a mean age of 65.7 +/- 8.7 years. On average, 3.12 +/- 0.77 grafts per patient were completed. More than 4 distal anastomoses were performed in 32 patients (27%). As in-situ grafts, 140 internal thoracic arteries (ITAs) and 9 gastroepiploic arteries were used. The radial artery (RA) was used as a Y composite graft in 91 patients, as an I composite graft in 25, and as a K composite graft in 2. Sequential bypass grafting was performed using the RA in 60 patients, the saphenous vein (SV) in 6, the ITA in 4, and the gastroepiploic artery (GEA) in 3. Arterial grafts were used in 92% (345/374) of total bypass grafts. Distal anastomosed sites were 119 left anterior descending arteries (LADs) (32%), 90 posterolateral branches (24%), 64 posterior descending arteries (17%), 49 diagonal branches (13%), 39 obtuse marginal branches (10%), and 13 right coronary arteries (3.5%). RESULTS: There was no operative death or stroke. Early postoperative angiography revealed 95.5% (321/336) graft patency with 100% patency (119/119) of ITA to LAD grafts. Graft patency of the ITAs and RAs (98.5% and 95.9%) were significantly better than that of the GEA (79.0%, p = 0.0064 and p = 0.030) and saphenous vein (82.3%, p = 0.011 and p = 0.048). CONCLUSION: OPCAB performed with the aorta no-touch technique using an in-situ graft and composite and sequential grafting methods provides excellent early clinical results and graft patency.

Aged↗