Improved lung microvascular permeability by heparin infusion in rabbit lungs from non-heart-beating donors.
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Animals↗
Biomedical subjects
H Date
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Tracheal allotransplantation after varying terms of cryopreservation.
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Animals↗
Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.
To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.
Animals↗
Angiographic evaluation of culprit lesions in acute coronary syndrome: relation to the original site on previous coronary angiography.
Culprit lesions in acute coronary syndrome [acute myocardial infarction (AMI) and unstable angina pectoris (UAP)] were examined angiographically in 222 patients who had previously undergone coronary angiography (CAG). The observation period lasted 5 years after primary CAG in medically treated patients (group M, 127 cases) and after final follow-up CAG in patients treated by percutaneous transluminal coronary angioplasty (PTCA) (group B, 95 cases). There were 33 AMIs, including 5 deaths (22/127, 17.3%, in group M vs 11/95, 11.6%, in group B; p<0.01) and 189 UAPs (105/127, 82.7%, in group M vs 84/95, 88.4%, in group B; NS). High-grade stenoses (>75%) were found in 76 (59.8%) patients in group M, of which 41 lesions (54%) resulted in acute coronary syndromes (ACSs). In group M, ACSs resulted from insignificant stenosis (< or =50%) in 67 (53%) patients and from significant stenosis (>50%) in 60 (47%) patients. In group B, ACSs resulted from insignificant stenosis in 78 (82%) patients and from significant stenosis in 17 (18%) patients. Out of 95 PTCA sites, high-grade restenosis occurred in 3 lesions and ACSs (2 AMI, 14 UAP) in 16 (16.8%). We conclude that ACSs are more likely to develop from insignificant lesions than from significant lesions. High-grade stenoses are prone to become occlusive lesions and PTCA reduces this potential risk. Most target sites of PTCA that escaped restenosis were stable in the long term.
Aged↗
Expression of endothelin-1 and effects of an endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model.
BACKGROUND: Rapid increase of pulmonary vascular resistance (PVR) early after reperfusion remains a major issue in clinical lung transplantation. A potent vasoconstrictor peptide, endothelin- plays an important role in various pulmonary pathophysiologic conditions and might induce increased PVR. We investigated the expression and influence of endothelin-1, and the effects of an ETA and ETB nonselective endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model. METHODS: Left single lung allotransplantation procedures were performed in three groups of animals. In group I (n=5) lungs were preserved for 12 hours; in group II (n=5) lungs were preserved for 18 hours; and in group III (n=6) lungs were also preserved for 18 hours, and TAK-044 (5 mg/kg) was administered just before reperfusion. All donor lungs were flushed and preserved with low-potassium dextran glucose solution at 4 degrees C. RESULTS: Six hours after reperfusion, arterial oxygen tension (mm Hg, inspired oxygen fraction=1.0) was 512.9+/-34.7 in group I, 152.4+/-46.7 in group II, and 509.6+/-29.0 in group III; PVR index (dyne x sec x cm(-5) x m2) was 1130+/-142 in group I, 1820+/-142 in group II, and 1287+/-191 in group III. Plasma endothelin-1 level was elevated significantly, and endothelin-1-like immunoreactivity was found in a variety of pulmonary vascular tissue and was seen less with immunohistochemical evaluation in group II in bronchial tissue. CONCLUSIONS: These results suggest that endothelin-1 is expressed as a result of ischemia-reperfusion injury and may worsen early graft function. TAK-044 is beneficial in protecting the graft from high pulmonary vascular resistance and pulmonary edema during the early posttransplantation stage.
Animals↗
[A case report of dumbbell neurogenic tumor of the superior mediastinum].
A 15-year-old female was admitted because of the superior mediastinum mass on chest X-rays and sensory loss of ulnar side of the left arm. Computed tomographic scanning and magnetic resonance imaging revealed that the tumor was dumbbell-shaped and invaded the vertebral canal through the intervertebral foramen between C 7 and Th 1. At first laminectomy of vertebrae (C 6-Th 1) was made in a prone position and intra-spinal portion of the tumor was resected. Then the patient was placed in a supine position and the chest was opened by left hemicollar incision and sternotomy to the 2nd intercostal space. The tumor was divided into two parts at the level of 1st rib and completely removed. The pathological diagnosis was schwannoma. This procedure is safe and useful for dumbbell type tumor located in superior mediastinum, especially in case of large tumor from neck to the thoracic cavity.
Adolescent↗
The impact of cytolytic therapy on bronchiolitis obliterans syndrome.
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of morbidity and death after lung transplantation. Therapy has focused on augmented immunosuppression with a variety of agents. Although transient responses are often achieved, sustained remission has been unusual. The outcome of cytolytic therapy for BOS at our center has been analyzed and is reported. METHODS: Between July 1988 and July 1994, 233 patients underwent lung transplantation at Barnes-Jewish Hospital. Among 207 recipients (88.8%) who survived more than 3 months, 81 recipients (39%) had development of BOS; 48 of these patients underwent 64 courses of treatment with a cytolytic agent (antilymphocyte globulin, antithymocyte globulin, or OKT3 monoclonal antibody). The cases of BOS were retrospectively analyzed to determine the impact of cytolytic therapy. RESULTS: The 4-year survival rate was significantly greater in recipients without BOS than in those with BOS (82.8% vs 46.0%; p < .05). Various clinical factors, including diagnosis, forced expiratory volume in 1 second at onset of BOS, presence or absence of pathologically proven bronchiolitis obliterans, type of transplant operation, cytomegalovirus serologic status, and cytomegalovirus pneumonia, were examined, but no significant predictor of survival after the development of BOS was discerned. The mean decrement in forced expiratory volume in 1 second was significantly reduced by cytolytic therapy (-23.5% +/- 2.3% in the 3 months before therapy vs -9.9% +/- 3.5% in the 3 months after the therapy; p < .002). Nevertheless, the stage of BOS progressed over time in spite of therapy in most cases, and only 4 recipients (4.9%) with BOS remained in a lower BOS stage 2 years after treatment. CONCLUSIONS: Recipients with BOS had a significantly lower survival rate than recipients without BOS. No predictor of survival after the onset of BOS was identified. Although cytolytic therapy decreased the rate of decline in pulmonary function in the 3 months after treatment, the stage of BOS ultimately progressed in most patients.
Antilymphocyte Serum↗
EPC-K1 is effective in lung preservation in an ex vivo rabbit lung perfusion model.
BACKGROUND: L-Ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1) is a phosphate diester of alpha-tocopherol and ascorbic acid. It has been reported that EPC-K1 inhibits lipid peroxidation and phospholipase A2. We hypothesized that EPC-K1 might enhance lung preservation and reduce the degree of posttransplantation lung dysfunction. METHODS: Eighteen rabbits were divided into three groups, as follows: group 1, no preservation (n = 6); groups 2 (n = 6) and 3 (n = 6), 24 hours of preservation at 8 degrees C. Low-potassium dextran-1% glucose solution was used for flushing and immersion in all groups, but EPC-K1 (0.5 mg/L) was added to the solution used in group 3. After storage the left lung was reperfused with autologous blood and ventilated using a membrane oxygenator in an isolated rabbit lung reperfusion model. The grafts used in the group 1 rabbits were perfused for 5 hours to confirm the reliability of this model, and the grafts used in the group 2 and 3 rabbits were perfused for 2 hours. Pulmonary arterial pressure, airway pressure, blood gas analysis, and the lipid peroxide level of the perfusate were assessed. The lipid peroxide levels of the lung tissue before and after storage and the wet-dry weight ratio of the perfused lung were determined in groups 2 and 3. RESULTS: Superior graft function was noted in group 3 in terms of all indices. The lipid peroxide level in the perfusate and the wet-dry weight ratio were also suppressed in group 3. The lipid peroxide level in the lung tissue did not change during storage in either group. CONCLUSIONS: The administration of EPC-K1 in the flush and preservation solution helps enhance lung graft function and suppresses lipid peroxidation after reperfusion.
Animals↗
Diagnostic Brachial Coronary Arteriography Using a Power-Assisted Injector and 4 French Catheters with New Shapes.
BACKGROUND: Right brachial access in diagnostic coronary arteriography (CAG) has demonstrated advantages over femoral approaches, including earlier ambulation and more predictable hemostasis, particularly when small diameter catheters were used. Poor results from some earlier reports of brachial CAG have been due partially to the need to use large diameter catheters for positional control. Technical advances in catheters and contrast injection may increase the utility of brachial access CAG. PURPOSE AND STUDY DESIGN: We evaluated three 4 French (Fr) catheters with new shapes and with a large internal to external diameter ratio that were designed to overcome previous limitations to brachial CAG. Contrast agent was delivered with a novel power injector (CAG-20) intended for arteriography using small catheters. Routine right brachial access CAG and left ventriculography (LVG) were evaluated in 2663 (69%) of 3880 consecutive patients admitted for examination from 1991 to 1995. The study population included 128 patients (5%) with left main trunk disease, 819 (21%) with old myocardial infarctions and 1747 (66%) with more than one vessel disease. For this trial, 1217 patients with valvular disease, ischemia associated with aortic or peripheral vascular disease, congenital cardiac disease and post-surgical and emergency catheterization were excluded because femoral access or a larger catheter (> 4 Fr) were required in those cases. RESULTS: A total of 2573 (97%) diagnostic quality CAG (> grade 3/5) were obtained solely with 4 Fr catheters placed via the right brachial artery. Of the other 66 examinations, 50 were completed through the brachial route but with alternate size or shape catheters and 16 cases required the femoral JudkinÕs technique. Useful LVG (> grade 2/4) were obtained from 2604 patients (98%). Overall, 2536 (95%) of cases provided clinically valuable images for both CAG and LVG from brachial access. We experienced one semi-emergency bypass operation and one emergency stent implantation caused by coronary dissection. There were no deaths, acute myocardial infarctions, loss of pulse or nerve injuries. CONCLUSION: Power-injector assisted, brachial 4 Fr CAG and LVG proved to be safe and cost-effective. Brachial access has the potential to become a routine method for out-patient cardiac opacification.
Journal Article↗
[Four cases of thymoma associated with pure red cell aplasia].
Thymomas associated with pure red cell aplasia (PRCA) constituted only 3.3% of 122 thymomas treated in our department from 1963 to March, 1995. Four patients with this disease (2 men and 2 women, mean age: 58 years, range: 41 to 66 years old) are reported. Auto-antibodies were found in all 4 cases, increase of T cell in two, suppression of erythropoietin production in one, and antibody to EB virus in one. Operation was performed in all cases (two thymothymectomies, one extended thymothymectomy, and one thymomectomy), and 3 of 4 patients were in the progressive stage of Masaoka's classification (I, III, IVa, and IVb each). As for the pathological findings, mixed type was found in three cases and lymphocyte predominant type in one. Two patients died from radiation pneumonia. As for PRCA, postoperative therapy was effective (100%) in all patients.
Adult↗
[PCR-RFLP analysis of epithelium in canine cryopreserved tracheal allograft].
In this study, we investigated whether the regenerated epithelia were recipient phenotype or donor phenotype using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. Preoperatively 24 mongrel dogs were classified to 14 types by PCR-RFLP result from peripheral blood. The PCR-RFLP result of peripheral blood agreed to that of recipient epithelia. The cryopreserved tracheal allotransplantation was performed among the five pairs in which we could distinguish donor from recipient by PCR-RFLP. The epithelia of graft at 10 days after transplantation showed donor phenotype, but the epithelia at postoperative 20 days or more showed recipient phenotype. These results showed that allogenic epithelium remained in early post-transplant time and was gradually omitted. The epithelia migrated gradually from the anastomotic site, and the graft was covered with regenerated epithelia showing recipient phenotype within about 50 post-transplant days.
Animals↗
[Preoperative evaluation for volume reduction surgery of pulmonary emphysema using MRI: usefulness of HASTE (half-Fourier single-shot turbo SE) sequence during deep respiration].
Volume reduction surgery has recently been an important surgical procedure for patients with severe pulmonary emphysema. We compared the sagittal and coronal images taken by the HASTE sequence with those obtained by turbo FLASH during deep breathing and with CT images obtained under deep inspiration. Clear images were obtained from both sequences, without cardiac or respiratory motion artifacts. The emphysematous areas were demonstrated as low signal intensity areas, as in CT images. The ratio of signal intensity in the expiratory phase to that in the inspiratory phase was lower than that of volunteers in the HASTE sequence. The HASTE sequence provides useful information about respiratory movement as well as about changes in the pulmonary parenchyma when used for preoperative examination.
Adult↗
The effect of combination therapy with EPC-K1 and low-dose cyclosporine to pulmonary allograft after rat lung transplantation.
BACKGROUND: EPC-K1, a diester of alpha-tocopherol and ascorbic acid, has a hydroxyl radical scavenging effect and also has antiinflammatory properties through its phospholipase A2 inhibitory effect. With a view to decreasing the total dose of cyclosporine, the effect of a combination of EPC-K1 and cyclosporine on rejection was investigated by use of a rat orthotopic left lung transplantation model. METHODS: Orthotopic left lung transplantation was performed with brown Norway rats as donors and Lewis rats as recipients. Recipients were assigned to one of four experimental groups. Control group animals were given no immunosuppression. The EPC-K1 group received continuous intraperitoneal infusion of EPC-K1 (5 mg/kg/day) by osmotic pump on postoperative days (POD) 0 through 6. The cyclosporine group received cyclosporine (1.25 mg/kg/day) intramuscularly on POD 1 through 6. The EPC-K1 + cyclosporine group received both EPC-K1 and cyclosporine in the same manner as the EPC-K1 and cyclosporine groups. Recipients were killed on POD 7, and the transplanted lungs were examined histologically and graded in a blinded fashion (grade 0 to 4). The effect of EPC-K1 and cyclosporine treatment on the primary immune response was examined by mixed lymphocyte reaction (MLR) between brown Norway rat stimulator cells (treated with mitomycin) added to Lewis rat responder lymphocytes. RESULTS: Control group animals exhibited the severe destructive changes of grade 4 lung rejection. The EPC-K1 + cyclosporine group showed significantly less graft rejection compared with the EPC-K1 group and the cyclosporine group (p < 0.01). In MLR assay, the EPC-K1 + cyclosporine group (793 +/- 210 cpm) showed significantly suppressed lymphocyte proliferation compared with the control group (2188 +/- 360 cpm), EPC-K1 group (1869 +/- 541 cpm), and cyclosporine group (1873 +/- 326 cpm) (p < 0.01). CONCLUSION: EPC-K1 significantly improves effects of cyclosporine at lower doses both in preventing pulmonary allograft rejection and in suppressing lymphocyte proliferation in MLR.
Animals↗
Efficacy of combining donor-specific presensitization with a simultaneous single injection of tacrolimus on pulmonary allografts.
BACKGROUND: We investigated the effects of combining donor-specific presensitization with a simultaneous injection of tacrolimus by use of a fully allogeneic rat lung allograft model. METHODS: Lungs from Brown Norway donor rats were orthotopically transplanted into Lewis recipient rats. Seven days before transplantation, allograft recipients received a transfusion of donor splenocytes (1 x 10(8) cells, intravenously), tacrolimus (3 or 1.5 mg/kg, intramuscularly), or a combination. No posttransplantation immunosuppression was given. In the transplantation study, graft survival was evaluated, and histologic characteristics of acute rejection were graded. In the in vitro studies, mixed lymphocyte reaction assays were used to investigate the effects of pretreatment on immune response. RESULTS: The graft survival evaluation disclosed that untreated rats rejected the allografts at 4.6 +/- 0.2 days. Donor splenocyte transfusion alone accelerated the graft rejection (3.3 +/- 0.2 days). Tacrolimus (3 mg/kg) alone moderately improved the graft survival (8.7 +/- 0.6 days). When donor splenocyte transfusion was combined with tacrolimus, graft survival was significantly increased to 29.6 +/- 12.0 days. In a mixed lymphocyte reaction assay, peripheral blood lymphocytes obtained from animals pretreated with donor splenocyte transfusion alone seemed to be hyperresponsive against the donor lymphocytes. In contrast, donor splenocyte transfusion with tacrolimus significantly suppressed the proliferative response against the donor lymphocytes but not against third-party lymphocytes obtained from naive Wistar King A rats. CONCLUSION: These data demonstrate that donor-specific presensitization with a simultaneous single injection of tacrolimus prevented both sensitization and graft rejection and induced donor-specific unresponsiveness.
Animals↗
Effect of a single injection of high-dose FK506 on lung transplantation in rats.
Orthotopic left lung grafts from Brown Norway (BN) donors were transplanted to Lewis (LEW) rat recipients which had been treated with a single dose of FK506 10mg/kg body weight intramuscularly on postoperative day 3. Although the lungs were rejected with a median survival time of 7 days, with a range of 6-8 days in the untreated controls, maximum survival was prolonged to 60 days. The major adverse effects of this therapy were reduction of feeding, loss of body weight, and diarrhea. One of the 7 rats died on the 21st postoperative day due to anorexia. The effects of this therapy were investigated by histopathological examination and flow cytometric analysis using monoclonal antibodies against rat lymphocytes: OX-39 (anti-interleukin 2 receptor (IL-2R)) and OX-6 (anti-class II MHC). Histopathologically, the lung allografts showed mild perivascular and peribronchiolar cuffs of mononuclear cells, while marked reduction of the thymic medulla with FK506 treatment was also observed. Flow cytometric analysis of the transplanted lung showed no significant changes. Regarding the thymus, the percentages of positive cells labeled with OX-39 and OX-6 were significantly suppressed after this treatment. In the spleen, the number of OX-6-positive cells significantly decreased. The results using this therapy thus suggest that the suppression of IL-2R and MHC class II expression was systemically maintained for a long time.
Animals↗
T2 shortening in childhood moyamoya disease.
We examined T2 shortening in six children with infarcts due to moyamoya disease to clarify whether there are characteristic patterns of T2 shortening in the deep grey and white matter. Profound T2 shortening in the deep grey and white matter was observed in the acute stage of infarct in two cases, which changed to high intensity in the chronic stage; in this stage no T2 shortening was demonstrated in any case. Neither haemorrhagic infarction nor calcification was seen on CT or MRI. There could be longitudinally different T2 shortening patterns between infarcts due to moyamoya disease and other disorders.
Cerebral Cortex↗
Increased plasma adrenomedullin in acute myocardial infarction.
Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects (p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study (p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.
Adrenomedullin↗
Inhaled nitric oxide reduces human lung allograft dysfunction.
OBJECTIVE: Early severe graft dysfunction, as manifested by hypoxia and pulmonary hypertension, occurs in 10% to 20% of lung transplant recipients. We retrospectively investigated whether inhaled nitric oxide would reduce human lung allograft dysfunction by comparing postoperative hemodynamic data, gas exchange, and outcome in lung transplant recipients with early graft dysfunction treated with or without nitric oxide. METHOD: Among 243 adult lung transplant procedures, there were 32 patients (13.2%) in whom immediate severe allograft dysfunction developed (arterial oxygen tension/inspired oxygen concentration ratio <150). Group 1 (n = 17) included patients who underwent transplantation before nitric oxide became available in our center and were treated conventionally. Group 2 (n = 15) included those treated with nitric oxide as soon as severe allograft dysfunction was diagnosed. Duration of nitric oxide therapy (20 to 60 ppm) was 15 to 217 hours (average 84 hours). RESULTS: In group 2, nitric oxide lowered mean pulmonary artery pressure from 30 +/- 2 to 26 +/- 2 mm Hg (p < 0.05), improved the ratio of arterial oxygen tension to inspired oxygen fraction from 88 +/- 10 to 153 +/- 30 (p < 0.05) within 1 hour, and caused a sustained improvement in these parameters during extended therapy. Mean arterial pressure and cardiac index were unchanged during nitric oxide therapy. Transient methemoglobinemia (>6%) developed in two patients. However, no complications were associated with nitric oxide use. Duration of mechanical ventilation was 17 +/- 5 days in group 1 and 12 +/- 3 days in group 2. Four patients had airway complications in group 1, whereas no airway complication was encountered in group 2. Mortality was 24% (4/17) in group 1 and 7% (1/15) in group 2. CONCLUSION: Nitric oxide improves oxygenation and decreases pulmonary artery pressure without systemic circulatory effects in patients with severe allograft dysfunction. Furthermore, in these patients, nitric oxide may shorten postoperative mechanical ventilation time and reduce airway complications and mortality.
Administration, Inhalation↗