Free-floating ball thrombus in the left ventricle with dilated cardiomyopathy.
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Biomedical subjects
Publications and source records attributed to Jun-ichi Hayashi.
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We have used HeLa cells without mitochondrial DNA (rho0-cells) and transient rho0-phenocopies, obtained from wild-type cells by short-term treatment with ethidium bromide, to analyze how the absence of a functional mitochondrial respiratory chain slows down proliferation. We ruled out an energetic problem (ATP/ADP content) as well as defective synthesis of pyrimidine, iron-sulfur clusters or heme as important causes for the proliferative defect. Flow cytometric analysis revealed that reactive oxygen species were reduced in rho0-cells and in rho0-phenocopies, and that, quite unusually, all stages of the cell cycle were slowed down. Specific quenching of mitochondrial ROS with the ubiquinone analog MitoQ also resulted in slower growth. Some important cell-cycle regulators were reduced in rho0-cells: cyclin D3, cdk6, p18INK4C, p27KIP1, and p21CIP1/WAF1. In the rho0-phenocopies, the expression pattern did not fully duplicate the complex response observed in rho0-cells, and mainly p21CIP1/WAF1 was downregulated. Activities of the growth regulatory PKB/Akt and MAPK/ERK-signaling pathways did not correlate with proliferation rates of rho0-cells and rho0-phenocopies. Our study demonstrates that loss of a functional mitochondrial electron transport chain inhibits cell-cycle progression, and we postulate that this occurs through the decreased concentration of reactive oxygen species, leading to downregulation of p21CIP1/WAF1.
OBJECTIVE: The purpose of this study was to investigate the effects of cardiopulmonary bypass and ultrafiltration on graft function in a canine single-lung transplantation model. METHODS: Fifteen left single-lung transplantations were done in weight-mismatched canine pairs. The animals were divided into 3 groups: group 1, in which transplantation was done without cardiopulmonary bypass; group 2, in which transplantation was done with cardiopulmonary bypass and in which the cardiopulmonary bypass flow was decreased slowly with controlled pulmonary artery pressure; and group 3, in which transplantation was done with cardiopulmonary bypass and ultrafiltration. Hemodynamic parameters and lung function were monitored for 6 hours after reperfusion. The grafts were harvested for histologic studies, myeloperoxidase assay, and real-time quantitative reverse transcription-polymerase chain reaction of mRNA encoding interleukin 6. RESULTS: The hemodynamic parameters were similar among the 3 groups. In group 1 PaO2 and alveolar to arterial gradient for O2 levels were excellent throughout the 6-hour observation period, but in group 2 they progressively deteriorated. However, ultrafiltration significantly (P = .02) improved the PaO2 level in group 3. On histology, interstitial edema and polynuclear cell infiltration were most marked in group 2 and significantly worse than in groups 1 and 3. Myeloperoxidase assay and real-time quantitative reverse transcription-polymerase chain reaction showed increased myeloperoxidase activity and interleukin 6 gene expression in group 2 grafts compared with group 1 grafts. Myeloperoxidase activity and interleukin 6 gene expression were suppressed with ultrafiltration. CONCLUSIONS: Cardiopulmonary bypass had negative effects on the graft, but ultrafiltration attenuated acute lung dysfunction by reducing the inflammatory response.
BACKGROUND: In experimental reports, blood flow redistribution occurred during cardiopulmonary bypass (CPB) and perfusion pressure was restored by vasoconstrictor administration without improving splanchnic perfusion. The influence of vasoconstrictor administration during CPB was clinically examined. MATERIALS AND METHODS: Twenty-two consecutive pediatric CPB cases of ventricular septal defect without blood transfusion were divided into two groups, depending upon whether a vasoconstrictor was administered during CPB or not (n = 7 vs. 15). Bypass flow and systemic perfusion pressure during CPB were maintained at 2.5 L/m(2)/min and not lower than 30 mm Hg by vasoconstrictor administration, respectively. RESULTS: Although preoperative state and CPB conditions were comparable between the two groups, more sodium bicarbonate was administered (P < 0.05); duration from the operation to extubation was longer (P < 0.05); and bowel movement occurred later in the vasoconstrictor-administered group than in the control group. CONCLUSIONS: Vasoconstrictor administration during CPB may deteriorate the acid-base balance and the postoperative state in infants and children.
BACKGROUND: Tricuspid valve regurgitation occurs with other congenital heart defects, especially the right-sided obstructive lesions. We applied the selective annuloplasty technique for the treatment of tricuspid regurgitation in children. METHODS: Between 2001 and 2003, 15 patients whose ages averaged 7.6 +/- 3.1 years (range 4 to 17 years old) underwent selective annuloplasty during correction of other heart defects. The patients had repair of pulmonary stenosis (5 patients), pulmonary stenosis and ventricular septal defect (7 patients), and tetralogy of Fallot (3 patients). Eight patients preoperatively had moderate tricuspid regurgitation, and 7 patients had severe tricuspid regurgitation. RESULTS: No deaths nor heart block occurred after the operation. The length of the tricuspid regutgitation flow was significantly decreased from 2.9 +/- 0.7 cm before the operation to 0.9 +/- 0.6 cm after the operation (p < 0.01), and the tricuspid annular diameter decreased from 3.9 +/- 0.3 cm to 3.3 +/- 0.3 cm (p < 0.01). Annular circumference was reduced by 1.9 +/- 0.2 cm. No tricuspid regurgitation was detected in 3 patients (20%), mild tricuspid regurgitation was seen in 10 (67%), moderate tricuspid regurgitation in 2 (13%). The right atrial mean pressure was significantly decreased from 7.5 +/- 0.5 mm Hg before the operation to 3.1 +/- 0.2 mm Hg after the operation (p < 0.01), right ventricular systolic pressure from 55.5 +/- 2.3 mm Hg to 29.8 +/- 1.9 mm Hg (p < 0.01), and right ventricular end-diastolic pressure from 8.4 +/- 0.7 mm Hg to 4.9 +/- 0.9 mm Hg (p < 0.01). Preoperatively, the degree of tricuspid regurgitation flow correlated significantly with the right ventricular systolic pressure (r = 0.89; p < 0.001). There was no correlation between tricuspid regurgitation flow and right ventricular systolic pressure postoperatively (p = 0.88). No child has symptomatic or significant tricuspid stenosis. CONCLUSIONS: Selective annuloplasty presents a useful procedure for young patients with moderate or severe tricuspid regurgitation and right-sided obstructive lesions resulting from functional reconstruction of the tricuspid valve.
The coexistence of abdominal aortic aneurysm (AAA) and colorectal carcinoma needs special operative consideration. A single-stage operation for concomitant AAA and colorectal carcinoma has been thought to increase the risk of vascular prosthetic graft infection. We report two patients who received a single-stage operation for AAA and colorectal carcinoma. The first patient had a fusiform aneurysm of the infrarenal aorta. The second patient had a saccular aneurysm of the infrarenal aorta and a fusiform aneurysm of the left internal iliac artery. Both patients had left-sided colorectal carcinoma classified as Dukes' stage B. The two patients underwent a single-stage operation with Hartmann's procedure to avoid graft infection caused by anastomotic leakage. They tolerated the operation and had no postoperative complications including graft infection. A single-stage operation for concomitant AAA and left-sided colorectal carcinoma could be safely performed with Hartmann's procedure in two cases.
To determine zygosity in transgenic (Tg) mice, a new technology, real-time quantitative PCR, has recently been introduced in transgenic research to overcome several drawbacks (time-consuming, specialized techniques and/or ambiguity in the results) of previously established methods, for example, Southern blot hybridization, dot blot hybridization, fluorescence in situ hybridization (FISH), etc. However, the previous real-time quantitative PCR method still possesses several drawbacks, for example, it needs two sets of primers/probes and the complicated setting up of appropriate conditions, both of which are expensive and remain time-consuming. We therefore developed an improved real-time quantitative PCR system for determination of zygosity, which is easy, rapid and less expensive, because the technique needs only two experimental processes: estimation of DNA concentration and CYBR Green PCR. We found that homozygous, hemizygous and non-Tg animals could easily be distinguished among F1 littermates in crosses of hemizygous EGFP- and DsRed2-Tg mice. Our improved method will be applicable to any Tg mouse strains, when a primer set is matched to the corresponding transgene.
Left ventricular unloading and energy charge as effects of transaortic catheter venting (TACV) during venoarterial bypass (VAB) in normal and failing hearts has been reported previously. The aim of this study was to assess the effectiveness and safety of a special multipurpose catheter for TACV during percutaneous cardiopulmonary support (PCPS) in a preclinical setting. Six adult pigs underwent PCPS with or without the TACV. With standard hemodynamic monitoring, LV volume and function were assessed by direct ultrasonic cardiography (UCG) in each condition. PCPS was smoothly established and the TACV catheter was safely introduced in all cases. As compared with isolated PCPS, the TACV combined with PCPS maintained significant blood flow with LV venting and systemic perfusion: the heart rate of the native heart, systemic arterial pressure, and central venous pressure were stable. Also the additional TACV led to a significant reduction of LV preload during PCPS, and the reduction was 25-30% of LVDd and 20-35% of LVAd. The results of this investigation suggest that clinical application of the TACV technique with a clinical PCPS circuit would be feasible and additional TACV might be use-ful for LV recovery during PCPS in patients with severe heart failure.
BACKGROUND: There have been a number of recent reports on the use of autologous bone marrow implantation (BMI) in the treatment of peripheral arterial disease, with a clinical response rate of approximately 70%. However, the factors that influence efficacy have not yet been clarified. We have analyzed the relationship between the number of implanted bone marrow cells and the clinical efficacy of BMI. METHODS AND RESULTS: Eight patients with arteriosclerosis obliterans were treated with BMI. Bone marrow was aspirated from the ilium (500-1,000 ml), the mononuclear cells were separated and then were implanted. The clinical effectiveness of BMI was evaluated by assessing changes in the ankle-brachial pressure index (ABI) and the transcutaneous oxygen pressure (TcO2) between the pre-treatment baseline, with follow-up testing at 4 weeks. These changes were defined as DeltaABI and DeltaTcO2. The mean number of CD34-positive cells was 1.04+/-0.60 x10(6) /kg body weight. There was a strong correlation between the number of CD34-positive cells and DeltaABI (r=0.754, p=0.028). CONCLUSIONS: It is likely that the number of implanted CD34-positive cells is one of the primary factors that influence the clinical efficacy of BMI.
Our clinical experiences of treatment for definite or probable thrombosed mechanical valve prostheses was presented and discussed concerning with surgical indication, several operative approaches to a target valve and detail surgical techniques. Preoperative diagnosis includes loss of metallic click sound, abnormal restricted disc movement and echocardiographic evidences of annular, occluder or housing thrombus. Valve re-replacement or thrombus removal was performed with re-do sternotomy or thoracotomy in urgent or elective cardiopulmonary bypass. Careful preparation of right atrium, superior and inferior vena cava and ascending aorta, and establishment of moderate hypothermic cardiopulmonary bypass were essential for re-replacement of the thrombosed valve. Among 15 patients, mitral re-replacement was performed in 10, aortic re-replacement in 3, tricuspid re-replacement in 2 and thrombus removal in 1. Hospital mortality rate was 6.7%, and late recurrence of thrombosed valve was observed in a patient. Pathophysiology of thrombotic process and bioactivity on the prosthetic valves are yet unsolved. Further refinement of clinical strategy would be necessary in relation to the effect of antithrombotic and antiinflammatory treatment.
OBJECTIVE: The purpose of this study was to determine whether lobectomy without radical systematic mediastinal lymphadenectomy (LA) is a satisfactory alternative surgical treatment for octogenarians with clinical stage I non-small cell lung cancer (NSCLC). METHODS: From April 1985 through December 2001, 49 patients aged 80 years and older who underwent surgical treatment for clinical stage I NSCLC were reviewed. Lobectomy without radical systematic mediastinal LA was performed for 27 patients (LA0 group) and lobectomy with radical systematic mediastinal LA was performed for 22 patients (LA group). RESULTS: The mortality rate was 0% in the LA0 group and 4.5% in the LA group. Five-year survival rate according to the type of surgery was 44.8% in the LA0 group and 55.5% in the LA group, a difference that was not significant (P=0.88). Although there was no significant statistical difference, postoperative pulmonary complication was more frequent in the LA group than in the LA0 group (32% in the LA group versus 11% in the LA0 group P=0.07). Five-year survival rates according to serum carcinoembryonic antigen (CEA) levels were 0% for patients with elevated CEA levels (n=9) and 56.5% for patients with normal CEA levels (n=40) (P<0.01). CONCLUSION: Lobectomy without radical systematic mediastinal LA appears to be a satisfactory surgical procedure for octogenarians with clinical stage I NSCLC. However, mediastinoscopy is necessary in such octogenarians if their serum CEA level is elevated so that the precise clinical stage can be determined and an accurate prognosis can be given.
Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a potentially life-threatening side effect of heparin therapy, triggered by an immune response, and has been reported to be related not only to the therapeutic use of heparin but also to heparin-coated catheters. A 45-year-old woman with intrapelvic malignancy developed an acute pulmonary thromboembolism (PE) after hysterectomy despite prophylactic heparin use. Subsequent large doses of heparin for treatment of the PE exacerbated the thrombocytopenia and, moreover, a large thrombus formed around the heparin-coated central venous catheter. Anti-heparin-platelet factor 4 complex antibody and heparin-induced platelet aggregation assay were positive, so the diagnosis was HITTS, and heparin was replaced by argatroban after carrying out thrombectomy. This therapy was successful, and the patient made favorable progress.
A 23-year-old man with Marfan syndrome, who had undergone surgery for pectus excavatum and scoliosis and who had severe respiratory dysfunction, was referred for surgical repair of annuloaortic ectasia. The preoperative pulmonary function test revealed severe obstructive and restrictive respiratory dysfunction, with forced expiratory volume in one second of 650 ml and vital capacity of 1,220 ml. These parameters improved after 4 months respiratory physiotherapy. A modified Bentall's procedure was performed after respiratory physiotherapy. A tracheostomy made on the 7th postoperative day (POD) appeared to improve respiratory condition and he was weaned off mechanical ventilation on the 14th POD. The lower limits of pulmonary function for open heart surgery have not been established clearly; however, our case will help elucidate these limits of respiratory function for open heart surgery. Preoperative respiratory physiotherapy improved parameters of pulmonary function test and may decrease the morbidity of postoperative pulmonary complications in a patient with severe respiratory dysfunction.
A 48-year-old woman with Wolff-Parkinson-White syndrome underwent surgical division of the accessory pathway in the left lateral wall. At 6 months after the procedure, she developed dyspnea and chest oppression. Coronary angiography revealed total occlusion in the left circumflex coronary artery (segment 13) at the exact site where cryoablation had been performed. The coronary occlusion was treated with an intracoronary bolus injection of urokinase (960,000 U) and subsequent percutaneous transluminal balloon angioplasty. No significant residual stenosis remained after the balloon angioplasty, and no further evidence of myocardial ischemia was noted for 13 years to date after the procedure.
To clarify special imaging assessment that is useful for minimally invasive cardiac surgery (MICS), we examined 141 cases of MICS operations with ministernotomy or minithoracotomy. In the 141 patients, 62 valve, 42 coronary, 37 congenital heart, and 2 other procedures were successfully completed without conversion to full sternotomy. Preoperative chest x-ray, computed tomography, and/or magnetic resonance imaging were necessary for determining the level of ministernotomy, especially in aortic valve operations. Transthoracic echocardiography was useful for selecting procedures of mitral valve or intracardiac repair through the MICS approach. Intraoperative transesophageal echocardiography was essential for continuous monitoring of cardiac function, intracardiac flow, air bubbles, and so forth. The above results suggest that intensive imaging assessment might be very important for successful MICS operations with ministernotomy or minithoracotomy and that extensive indications for this technique exist for various cardiovascular diseases.
Aortic pressure declines during cardiopulmonary bypass (CPB), particularly at normothermia. It has been reported that administering vasoconstrictors during normothermic CPB (NCPB) to restore perfusion pressure might induce hypoperfusion of splanchnic organs. We have reported that prostaglandin (PG), metabolized in the lung but increased during CPB, might have played a substantial role in hypotension, and that a PG synthesis inhibitor (PGSI) could improve hypotension during CPB. This study was designed to examine whether regional perfusion of splanchnic organs was reduced when PGSI restored systemic perfusion pressure during NCPB. NCPB was performed in eight adult goats for 60 minutes (body weight 57.0 +/- 5.9 kg). PGSI was administered in group P (n = 4), while norepinephrine was administered in group C (n = 4), to keep aortic pressure in the range of 50 to 80 mm Hg. The total systemic flow was maintained at approximately 70 ml/kg/min. Tissue blood flow was measured by means of the colored microsphere method before and 30 and 60 minutes after the start of CPB. In group P, gut blood flows after the start of CPB were higher than those before CPB, significantly in the stomach and jejunum at 30 minutes (p < 0.05), whereas gut blood flows in group C were decreased or not changed. In conclusion, PGSI prevents hypotension without impairing gut perfusion during NCPB.
During cardiopulmonary bypass (CPB), tissue perfusion injury occurs even if perfusion pressure is maintained. Although a vasodilator and a vasoconstrictor are clinically administered if bypass flow is maintained, they may restore perfusion pressure without improving tissue perfusion. We evaluated the influence of vasodilators and vasoconstrictors on the whole body during CPB. Fifty-six patients with valvular disease who received moderately hypothermic CPB without blood transfusion were divided into four groups, depending upon whether a vasodilator and/or a vasoconstrictor was administered, and postoperative data were compared. Bypass flow and aortic pressure were maintained at 2.4 l/min/m and 5090 mm Hg. Body weight, dilution, hematocrit level, CPB, and aortic clamp duration, blood temperature, bypass flow, perfusion pressure, base excess levels during CPB, cardiac index, arterial and mixed venous oxygen pressure, and alveolar-arterial oxygen distribution after CPB were comparable among the four groups. However, the time to extubation was significantly longer. Blood lactate levels, measured for patients returned to the ward, were significantly higher in the agent-administered groups than in the no-agent group, whereas blood lactate levels on extubation and blood creatinine levels on postoperative day 1 were comparable among the groups. Vasodilator and/or vasoconstrictor administration during CPB may deteriorate the body oxygen metabolism, which might imply tissue perfusion and worsen the complications induced by hypoperfusion during CPB.
We use aortic root endoscopy for assessment of the aortic valve in pediatric patients. A flexible fiberscope inserted through the ascending aorta provides clear and precise visualization of the aortic valve. This technique of endoscopic assessment will help to judge the cusp prolapse and malcoaptation of the aortic valve in pediatric aortic surgery.