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Biomedical subjects

M Otaki

Publications and source records attributed to M Otaki.

At least 37 records · Page 2Linked to original sources

Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation.

The inhibitor of apoptosis (IAP) proteins form a highly conserved gene family that prevents cell death in response to a variety of stimuli. Herein we describe a newly defined murine IAP, designated Tiap, that proved to be a murine homologue of human survivin based on sequence comparison. TIAP has one baculovirus IAP repeat and lacks a C-terminal RING finger motif. TIAP interacted with the processed form of caspase 3 and inhibited caspase-induced cell death. Histological examinations revealed that TIAP is expressed in growing tissues such as thymus, testis, and intestine of adult mice and many tissues of embryos. In in vitro studies, TIAP was induced in splenic T cells activated with anti-CD3 antibody or Con A, and the expression of TIAP was up-regulated in synchronized NIH 3T3 cells at S to G2/M phase of the cell cycle. We propose that during cell proliferation, cellular protective activity may be augmented with inducible IAPs such as TIAP.

Amino Acid Sequence↗

Experimental orthotopic heart and bilateral lung transplantation completed without cardiopulmonary bypass.

INTRODUCTION: Most experimental studies of orthotopic heart and lung graft failure are complicated by an inability to eliminate the rejection-specific inflammatory mediator from the cardiopulmonary bypass. METHODS: The following model was developed in our laboratory to investigate the feasibility of performing an orthotopic heart and bilateral lung transplantation without performing a cardiopulmonary bypass. Nineteen transplants were attempted using 19 pairs of mongrel dogs. The recipient dog (mean weight, 23 kg) was anesthetized, and the ascending aorta, the superior vena cava (SVC), the inferior vena cava (IVC), and the main bronchus were dissected. Then, the donor dog (mean weight, 20 kg) was anesthetized, and the heart and lung block was prepared and explanted from the chest under cardioplegic arrest. A Gore-tex shunt (W. L. Gore; Flagstaff, AZ) was placed side-to-side between the recipient IVC and SVC, and then the donor right atrium was anastomosed to the Gore-tex shunt. The donor ascending aorta was anastomosed to the recipient ascending aorta with a partial clamp. On completion of these anastomoses, the donor heart was reperfused by the recipient heart and allowed to beat. When hemodynamic conditions were stable with double hearts, the recipient SVC and IVC were ligated just proximal to the venous anastomosis and the recipient aorta was ligated proximal to the anastomotic site. The recipient trachea was anastomosed to the donor trachea with an end-to-end anastomosis. Finally, the recipient heart and lungs were removed from the chest and the sternum was closed. RESULTS: Four of the 19 transplants failed. Three died due to left ventricular dysfunction, and one died due to bleeding. Mean (+/- SD) ischemic time was 67 +/- 11 min with a mean (+/- SD) anastomotic time of 54 +/- 12 min. The 15 survivors were hemodynamically stable with or without the minimal use of inotropic support (dopamine, 2 to 3 microg/kg/min) 6 h after grafting, with normal cardiac output, satisfactory oxygenation, and normal wall motion. The sternotomy was repaired without loss of cardiopulmonary function. CONCLUSIONS: On the basis of our experiences, the experimental model of orthotopic heart and bilateral lung transplantation completed "off pump" can be technically feasible without the loss of cardiac and pulmonary functions.

Anastomosis, Surgical↗

Two-directional aortic annular enlargement for aortic valve replacement in the small aortic annulus.

We have encountered 3 patients with a small aortic annulus for whom the conventional posterior enlargement alone was not extensive enough to implant an artificial valve of acceptable size. Therefore, we performed two-directional enlargement, which is a combination of posterior and anterior enlargement. First, the posterior enlargement was done, and then an additional aortotomy was made anteriorly and extended to the ventricular septum. The aortic annulus was enlarged by 68% after the two-directional enlargement. At a follow-up of 31 months, the patients' functional status was New York Heart Association class I.

Adult↗

Reconstruction of right ventricular outflow tract by pedicled pericardial valved conduit.

A modification of the Rastelli technique using a pedicled autologous pericardial valved conduit was performed on 3 patients aged 10 months to 3 years. Two patients in whom a prosthetic gusset was not used or was partially used showed good recovery during the follow-up period (3 months to 3 years). The pedicled autologous pericardial conduit may be expected to increase its diameter with physical growth.

Child, Preschool↗

Single lead atrial synchronous ventricular pacing in Japanese patients with complete atrioventricular block.

The purpose of this study was to review our experience with atrial synchronous ventricular pacing devices (THERA VDD pacing systems, Medtronic, Inc., U.S.A.) using single atrioventricular leads in Japanese patients with complete atrioventricular block and normal sinus function. Twenty patients with a mean age of 55 +/- 13 years underwent implantation of VDD pacemakers. At implantation the amplitude of atrial signals in the supine position during normal breathing, which was measured directly using an external pacing system analyzer, ranged from 1.8 to 5.8 mV with a mean amplitude of 3.4 +/- 1.4 mV. Atrial amplitudes did not change during deep breathing (3.3 +/- 1.1 mV) or in the semi-Fowler position (3.4 +/- 1.6 mV). Atrial oversensing or undersensing was not observed in any of the patients. During a follow-up period, the percentage of atrial synchronization was >95% in 19 patients, and none of the patients had pacemaker related tachycardia or pacemaker related complications. These results were promising enough to warrant the extension of the clinical use of the VDD pacemaker.

Adult↗

[Acute pulmonary thromboembolism treated with E6010].

A 22-year-old man was admitted to our hospital because of sudden dyspnea and dizziness. Hypoxemia was found. Lung perfusion scintigraphy and pulmonary angiography showed massive pulmonary thromboembolism. The patient received E6010, a derivative of tissue plasminogen activator by intravenous injection for about 2 minutes. One hour after this treatment, pulmonary angiography showed lysis of the ciot, the pulmonary arterial pressure had decreased, and the cardiac index and PaO2 had increased. Despite anticoagulant therapy, pulmonary embolism recurred so we implanted a Greenfield filter in the inferior vena cava. This was the first case of pulmonary thromboembolism in which E6010 had a beneficial effect. We were also able to document hemodynamic and radiologic changes after intravenous infusion of this drug. Recurrent pulmonary embolism is an indication for filter placement, and this patient will need a long period of follow-up.

Acute Disease↗

Extracardiac adjustment of mitral chordae replacement.

This study was designed to determine the feasibility of completing mitral chord repair externally when the heart was weaned from bypass. Ten anesthetized dogs (22.9 +/- 4.6 kg) were placed on cardiopulmonary bypass through a left thoracotomy. The left atrium was opened and one or two marginal chords of the anterior mitral leaflet were divided. A double-armed 2-O polypropylene suture was placed in the margin of the mitral leaflet, and both suture ends were brought outside of the ventricle through the anterior papillary muscle, but were not anchored. Production of mitral incompetence was verified when the animals were weaned from bypass. Mean left atrial pressure (LAPm), the v wave of the left atrial pressure (LAPv), systolic billowing of the anterior leaflet into the left atrium above the mitral closure line (two-dimensional echocardiography, long axis), and function curves (left atrial-aortic systolic pressure, LAPv-AoSP) were used to determine valve competence and functionality of the repair. All values are expressed as means +/- SE. Acute mitral incompetence in this model was associated with severe left atrial bulging, left atrial billowing of the anterior leaflet (7-12 mm, 9.6 +/- 1.6 mm), significantly increased left atrial pressure [LAPv, 30.5 +/- 5.8; LAPm, 23.6 +/- 4.3 mm Hg; both P < 0.01 vs control (10.5 +/- 2.5 and 7.5 +/- 2.7 mm Hg, respectively)], and decreased systemic pressure development (AoSP, 84 +/- 8.8 vs 108 +/- 12.3 mm Hg; P < 0.01). The slope of the atrial-systemic pressure curve was decreased significantly, shifted to the right and reduced by more than half (2.1069 vs 0.9190; P < 0.05). External adjustment of the pledgeted suture ends returned all values to within control limits (LAPv, 12.7 +/- 4.1; LAPm, 9.8 +/- 4.3; AoSP, 104 +/- 10.5; LAP-AoSP slope, 2.0909; all P = n.s.), atrial bulging was not evident, and atrial displacement of the valve leaflet could no longer be visualized. These data suggest that mitral chord repair is feasible through a thoracotomy and, more importantly, final adjustments to obtain optimal chord length can be completed externally, guided by changes in dynamic, physiologic parameters.

Animals↗

Distal flow determinants in canine myocardium perfused through internal thoracic artery bypass grafts.

The dynamic reactivity and the acute, recruitable flow capacity of an internal thoracic artery (ITA) graft remains unclear. These experiments were conducted in 20 anesthetized dogs with the left ITA grafted to the circumflex artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle, including anterior descending artery and circumflex regions, totally dependent on the ITA graft. When the left main coronary artery was occluded, the ITA flow immediately increased more than fivefold (93.4 +/- 9.6 mL/min; mean +/- standard deviation), representing an absolute flow value three times higher than ITA flow measured in situ on the chest wall (27.5 +/- 9.6 mL/min; p < 0.05 versus control), and the ITA graft provided total resting flow requirements (93.4 +/- 9.6 mL/min) for both left anterior descending and circumflex coronary artery perfusion territories at levels comparable with measured native flow values (y = (0.9555)x + 21.9272; r = 0.976; p < 0.05). Pharmacologic challenge with adenosine (0.2 mg.kg-1.min-1 intravenously) significantly increased the graft flow (120.3 +/- 18.7 mL/min; p < 0.05 versus control), but also significantly decreased the mean arterial pressure (85.4 +/- 5.0 versus 74.6 +/- 6.1 mm Hg; p < 0.05). Phenylephrine (0.003 mg.kg-1.min-1 intravenously) significantly decreased ITA graft flow (81.2 +/- 9.0 mL/min; p < 0.05 versus control) despite significantly increased perfusion pressure (84.8 +/- 6.3 versus 108.2 +/- 8.6 mm Hg; p < 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Experimental supplemental vein grafting and hypoperfusion syndrome.

An additional saphenous vein graft (SVG) sometimes is required to the same coronary system if acute internal thoracic artery (ITA) graft flow is inadequate. These experiments were conducted to determine the consequences produced by ITA-SVG dual grafting. Fourteen dogs each received two coronary grafts (without bypass, using local occlusion) to the proximal circumflex coronary artery, using the ITA and an SVG, and then the circumflex artery was ligated proximally. Simultaneous flow in both grafts was determined at rest and after pharmacologic (adenosine, phenylephrine) or physiologic (cardiac pacing) stimulation. Serial angiography was performed during the first 4 weeks after grafting to determine patency patterns of the ITAs and SVGs. In the resting heart, flow was 7.5 +/- 1.6 mL/min (17.5%) in the ITA graft and 35.3 +/- 5.2 mL/min (82.5%) in the SVG (mean +/- standard deviation [% total distal perfusion]), and the combined flow was not significantly different from the original native flow. Intravenous adenosine (0.2 mg.kg-1.min-1) preferentially increased both the total ITA flow and its fractional contribution to total distal perfusion (18.4 +/- 3.2 [31.1%]; p < 0.05 versus rest). Saphenous vein graft flow was not changed significantly (40.3 +/- 6.0 mL/min), in part due to a modest decrease in arterial pressure. In contrast, intravenous phenylephrine (0.003 mg.kg-1.min-1) decreased both absolute ITA flow and its relative contribution to distal perfusion (6.1 +/- 1.1 [10.9%]; p < 0.05 versus rest), despite an increased systemic perfusion pressure, which increased SVG flow significantly (50.1 +/- 4.8 [89.1%]; p < 0.05 versus rest).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free model.

The ability of allopurinol to protect against reperfusion injury in the heart has usually been attributed to its xanthine oxidase (XO)-inhibiting properties. Human myocardium however, has exhibited low levels of XO activity. To investigate the effects of allopurinol in an XO-free model and determine whether pretreatment is necessary, 12 domestic pigs (15 kg to 20 kg) underwent occlusion of the left circumflex for 8 minutes followed by reperfusion for 4 hours. One group received allopurinol infusion (5 mg/kg IV) at occlusion over 45 minutes and a control group (n = 6) received a saline infusion (same volume). Left ventricular and aortic pressure, electrocardiograms, and regional wall motion (sonomicrometry) were monitored throughout the process. Regional blood flow (microspheres) were obtained before, during, and 5, 10, and 30 minutes after ischemia. Occlusion decreased transmural flow at the midpapillary level by 75% (0.28 versus 1.10 mL/minute/g). The allopurinol-treated group exhibited a mild, generalized hyperemia at 5 minutes (ischemic zone: 1.44 versus 1.10 mL/min/g, which returned to control levels at 10 and 30 minutes. In contrast, the control group was associated with only 80% restoration of resting blood flow at 5 minutes (0.84 versus 1.10 mL/min/g), which stabilized at 63% of control levels at 10 and 30 minutes. When evaluated for the propensity of arrhythmias using an arbitrary arrhythmia score, the allopurinol group demonstrated no myocardial ectopy when compared with the focal ectopy routinely encountered in the control group at all time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗

Effect of chronic native flow competition on internal thoracic artery grafts.

Residual competitive flow from the native coronary artery has been proposed as a mechanism that reduces flow in an internal thoracic artery graft (ITA), resulting in narrowing and ultimately failure of the graft. Results from acute experiments have indicated that competitive flow from a fully patent native artery did not abolish ITA graft flow. The present study was designed to examine the consequences of dynamic flow competition between the native vessel and the ITA graft in a chronic model. Fifteen mongrel dogs underwent coronary artery bypass grafting using the pedicled left ITA anastomosed to the normal, fully patent circumflex (CFX) coronary artery. The procedure was performed through a sterile thoracotomy, without systemic cardiopulmonary bypass, using a brief local occlusion to construct the anastomosis. Intraoperatively, ITA flow was measured in situ on the chest wall, before the pedicle was mobilized. Internal thoracic artery graft and distal CFX flow were measured after the anastomosis was completed, with and without brief occlusion of the proximal CFX. Angiography was performed 72 hours, 4 weeks, and 8 weeks later; graft patency and diameter were evaluated. After 8 weeks, open-chest direct flow measurements comparable with the intraoperative assessment were obtained. Two grafts (13%) occluded early, the technical result of poor anastomotic construction. In the 13 remaining animals, all grafts were widely patent at all time points. Internal thoracic artery flow in situ averaged 10.9 +/- 7.8 mL/min (mean +/- standard deviation), and was maintained after grafting (11.5 +/- 4.4 mL/min; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A new modification of debridement valvuloplasty for acquired aortic valve disease.

A high speed electric rasp was used to remove fibrous thickening from the aortic valve in conjunction with aortic valve commissurotomy in ten patients. All patients had moderate rheumatic aortic valve disease combined with severe mitral valve disease, and were treated by mitral valve replacement and aortic valve repair. All patients survived the operative procedure. There were no deaths or complications during hospitalization related to the valve repair process. The transaortic valve gradient was relieved from an average of 21.0 +/- 8.6 mmHg to 5.6 +/- 4.0 mmHg (catheterization), and from moderate to less-than-mild stenosis (echocardiography). Aortic valve regurgitation was reduced from an average of 2.2+ to 0.7+ on a scale of 0 to 4+ (aortography), and from an average of 2.5+ to 1.1+ on a scale of 0 to 4+ (echocardiography). During the follow-up period, no patients were reoperated on because of aortic valve dysfunction. Follow-up echocardiographic study demonstrated that the transaortic pressure gradient and valvular regurgitation had not progressed, and immediate postoperative conditions were maintained. There were two late deaths not related to the aortic valve. One patient died of prosthetic valve endocarditis in the mitral prosthesis 14 months postoperatively, and the other of a cerebrovascular accident 21 months postoperatively. Based on these data, we believe that aortic valve repair with a high speed electric rasp can effectively relieve aortic stenosis, reduce valvular regurgitation, and provide an excellent hemodynamic result at early and mid-term follow-up.

Adult↗

Modification of De Vega's tricuspid annuloplasty for experimental tricuspid regurgitation.

We propose a new experimental model of tricuspid annular dilatation and provide some modifications to De Vega's tricuspid annuloplasty to treat this condition. Tricuspid annular dilatation was done by creating ten 1.5-mm incisions around the circumference of the tricuspid annulus. The annulus became significantly dilated from 7.6 cm to 9.4 cm (p < 0.01). After dilatation, 2-0 polypropylene stitches were placed circumferentially around the tricuspid annulus and the suture ends were brought outside the heart through the right atrial wall. After cardiac resuscitation, the following hemodynamic variables were measured as preload was increased incrementally: mean right atrial pressure, v wave of atrial pressure, right ventricular end-diastolic pressure, and cardiac output. Measurements were obtained and preload-output curves were constructed for three time periods: before annular dilatation (Control); after dilatation, but before external adjustment (Before); and after external modification of the annulus (After). Following cardiac resuscitation, right atrial and ventricular pressures were significantly higher after annular dilatation, compared to control values. The preload-output curve was shifted to the right, and cardiac output could not be increased above 0.9 L/min. Once the extracardiac adjustment was accomplished, these pressures were returned to control values, and the preload-output relationship was returned to normal curve.

Animals↗

Surgical treatment of patients with cardiac cachexia. An analysis of factors affecting operative mortality.

During the period from 1982 to 1990, we operated on 25 patients with cardiac cachexia associated with a long history of combined mitral and tricuspid diseases. The age distribution was 44 to 68 years, with an average of 58 years. The overall operative mortality was 28 percent (7/25). However, the operative mortality differed according to various factors. Patients with preoperative nutritional support had a mortality rate of 17 percent, as compared with 57 percent for those without nutritional support (p < 0.05). The operative mortality was higher in patients with giant left atrium (39 percent vs 0 percent, p < 0.01). The postoperative cardiothoracic ratio in chest radiographs was significantly decreased by left atrial plication (91.6 percent vs 74.1 percent, p < 0.05). However, the operative mortality in patients with plication was still higher than in patients whose left atrium was left intact (67 percent vs 16 percent, p < 0.025). Advanced age, female sex, advanced tricuspid regurgitation, preoperative renal failure (serum urea nitrogen > 30 mg/dl), and hepatic failure (ascites or serum total bilirubin > 2.5 mg/dl) had no significant effects on operative mortality. The results demonstrated that preoperative nutritional support resulted in significant decreases in the incidence of postoperative respiratory failure and operative mortality. In contrast, postoperative respiratory failure occurred in a high percentage of patients without nutritional support even though left atrial plication was successfully performed.

Adult↗

Bilateral vs single internal thoracic artery grafting for left main coronary artery occlusion.

This study was conducted to compare the coronary flow distributed by single and bilateral internal thoracic artery (ITA) grafts in the setting of the left main coronary occlusion. Ten dogs underwent coronary artery bypass grafting through a left thoracotomy, off pump, using a brief local occlusion to perform the anastomosis. Dogs were randomly assigned to receive either a single left ITA (LITA) graft to the circumflex coronary artery (CFX), or bilateral ITA grafts, with additional placement of the right ITA (RITA) to the left anterior descending artery (LAD). After the grafts were placed, the left main coronary artery was ligated. Electromagnetic flows were obtained in the LAD and the CFX proximally and distally to ITA grafts in both groups before grafting and after grafting. ITA flow in situ was also measured before rotation from the chest wall. Total left ventricular flow requirements were satisfied equally well by either a single LITA graft (116.7 +/- 11.6 mL/min) or bilateral ITA grafts (total, 116.8 +/- 9.6 mL/min divided as LITA, 55.9 +/- 7.4 mL/min; RITA, 60.9 +/- 12.0 mL/min). When two grafts were replaced, competitive flow in the proximal regions of both native vessels was noted, although basal flow requirements were maintained. When an individual graft was occluded in the bilaterally grafted system, the remaining graft immediately recruited the additional flow, demonstrating that either right or left ITA can support flow demands five to six times higher than in situ chest wall flow (RITA, 21.9 +/- 3.1 mL/min; LITA, 22.3 +/- 4.9 mL/min). These data suggest that in this canine model, a single ITA graft can support the entire flow requirements of the left ventricle. Assuming no intervening stenosis is present in native coronary systems, bilateral ITA grafting may provide a margin of safety, but under resting conditions, provides no perfusion advantages over a single ITA graft.

Animals↗

Total composite graft replacement of the ascending aorta and aortic valve.

Ten patients (nine male and one female), ranging in age from 21 to 68 years, were operated on for total composite replacement of the ascending aorta and the aortic valve. Among them annulo-aortic ectasia was the most common indication (five patients), followed by annulo-aortic ectasia with aortic dissection (three patients), the aneurysm and aortic valve regurgitation associated with aortitis syndrome (one patient), and the syphilitic aneurysm and aortic valve regurgitation (one patient). In the first four patients, composite replacement was conducted according to the original procedure described by Bentall and DeBono (1986). The next six patients were treated according to the procedure modified by Cabrol et al. (1981). There were no operative deaths or complications during hospitalization. However, late complications occurred in two patients at 46 months and 15 months after surgery, respectively. Despite the repair on an urgent basis, one died of hepatic failure and the other died on the table with massive disruption. Eight late survivors remain in the New York Heart Association (NYHA) class 1 on an average of 4.3 years postoperatively. It is concluded that total replacement with a composite graft is feasible in all patients with low operative mortality, but this procedure needs a close follow-up because of the potential for anastomotic dehiscences.

Adult↗

Prosthetic valve endocarditis: surgical procedures and clinical outcome.

Over a period of 10 years, 25 patients underwent reoperation for prosthetic valve endocarditis. The basic procedure for surgical treatment differed depending on the presence or absence of annular ring abscess. Standard valve replacement was employed in 15 patients without annular ring abscess (three aortic, eleven mitral and one tricuspid). The ten other patients who had had partial destruction of the annulus underwent complex surgical treatment (six aortic, three mitral and one aortic and mitral). Complex operative techniques consisted of three different procedures, depending on the anatomical lesion in each patient. Aortic valve replacement was performed by subannular implantation with horizontal Dacron felt-supported mattress sutures through the ventricular septum, ventricular outflow wall muscles and base of the anterior mitral leaflet. A prosthesis with a polytetrafluoroethylene flange was used for mitral valve replacement to permit double suturing of the prosthesis and firm anchoring. Double valve replacement (mitral, aortic) with destruction of the fibrous skeleton was carried out using a composite graft consisting of a triangular-shaped Dacron patch and two Björk-Shiley valves. There were four operative deaths (16%; three who underwent standard valve replacement and one who had complex surgical treatment). In no case could the cause of death be related to the surgical procedure. These patients had had haemodynamic decompensation before operation and required urgent reoperation. Preoperative New York Heart Association functional class IV (P < 0.05) and operative urgency (P < 0.05) had a significant correlation with mortality. On the basis of these results, operative mortality can be improved if conditions leading to myocardial damage are prevented and proper reconstruction conducted.

Adult↗

[A case of endobronchial tuberculosis complicated with atelectasis of right upper lobe].

A case of endobronchial tuberculosis complicated with atelectasis of upper lobe of the right lung is reported. A 79-years old female was admitted to our hospital for rehabilitation of her Parkinsonisms. On admission, her chest X-ray photo showed atelectasis of right upper lobe. A nodule of a broad-bean size was observed at the orifice of the right upper bronchus by a bronchofiberscopic examination and it was considered as the cause of the atelectasis. Histological examination of a specimen obtained by transbronchial biopsy of this nodule showed epithelioid granuloma. Mycobacterium tuberculosis was isolated from a bronchial washing after 4-weeks cultivation. Anti-tuberculous treatment with INH, RFP and EB was started on January 1992 and, consequently, her chest X-ray findings showed remarkable improvement. Bronchofiberscopic examination in January 1993 showed a marked reduction in the size of the nodule, and the atelectactic shadow had disappeared and just a residual scar was observed on her chest X-ray photo in June 1993.

Aged↗