Lymphocyte subset markers as predictors of survival after concordant cardiac xenotransplantation.
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Animals↗
Biomedical subjects
M Kawauchi
Publications and source records attributed to M Kawauchi.
Which is the target vessel of lung rejection? A primate heart-lung transplantation study.
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Analysis of Variance↗
Transplantation and reanimation of hearts removed from donors 30 minutes after warm, asystolic 'death'.
OBJECTIVE: To test whether hearts from "dead," pulseless, asystolic donors could be transplanted and reanimated successfully using reperfusion manipulations. DESIGN AND INTERVENTIONS: Ten infant lambs (mean [+/- SD] weight, 4 +/- 1 kg) were anesthetized and pretreated with 50% dextrose, methylprednisolone, prostaglandin E1, and sublingual nifedipine. Five of these lambs were paralyzed; hypoxic asystolic arrest occurred 10 +/- 2 minutes later. Thirty minutes following asystole (mean, 40 +/- 2 minutes after paralysis) sternotomy was performed and the hearts were excised. Aortic blood gases were as follows: pH, 6.6 +/- 0.1; PCO2, 180 +/- 20 mm Hg; and PO2, 8 +/- 2 mm Hg. Donor hearts were given 30 mL/kg of Cardiosol (Water's Instrument Co, Danburg, Conn), a new cardioplegic agent, at 4 degrees C, and explanted into iced saline. The remaining five lambs then underwent cardiopulmonary bypass, were cooled to 20 degrees C, and hypothermic arrest was instituted. After excision of the recipient's heart, the donor heart was implanted in an orthotopic position. Total cold ischemic time was 1 hour 40 minutes +/- 10 minutes. The donor heart was retroperfused for 10 minutes with low-hematocrit, low-calcium blood via a coronary sinus catheter, then normal aortic inflow reperfusion was continued for 50 minutes. MAIN OUTCOME MEASURES: Removal of the cardiopulmonary bypass and measurement of hemodynamic parameters. RESULTS: One half hour after the bypass, mean systolic aortic pressure was 71 +/- 6 mm Hg; mean right atrial pressure was 6 +/- 2 mm Hg; mean left atrial pressure was 7 +/- 2 mm Hg; and mean pulmonary arterial pressure was 20 +/- 8 mm Hg. No inotropic drugs were given for postbypass blood pressure support. CONCLUSION: It is possible to transplant and reanimate hearts that have been dead for 30 minutes. When further developed, the use of donors who were not brain dead but allowed to die naturally could greatly increase the donor pool.
Animals↗
Thyroid nodules in female uremic patients on maintenance hemodialysis.
We investigated the incidence of thyroid nodules in female uremic patients on maintenance hemodialysis using a high-frequency sonographic scanner. In 47 (21.0%) of the 224 female normal controls and 33 (55.0%) of the 60 female patients, thyroid nodules were detected. The difference in these incidences between controls and patients was significant. There were no differences in age, duration of hemodialysis, the level of blood urea nitrogen, parathyroid hormone or thyroid stimulating hormone between the patients with thyroid nodules and those without nodules. Although there is a correlation between uremia and the development of thyroid nodules, the details of the underlying mechanism of their association remain unclear.
Adult↗
Male donor into female recipient increases the risk of pediatric heart allograft rejection.
Sixty-one infants and children, 12 years old or younger, who received an orthotopic cardiac allograft between November 1985 and December 1989 were analyzed for the incidence of rejection. Rejection was diagnosed non-invasively within the first 3 months and during the first year. Rejection episodes were diagnosed by signs and symptoms according to previously reported criteria. Multiple regression analysis with recipient age, donor age, donor-recipient weight ratio, number of HLA mismatches, sex of the recipient, sex-encoded minor tissue antigen incompatibility (H-Y: female recipients receiving male donor organ), graft ischemic time, lowest cyclosporine level during the first 2 postoperative weeks, and prophylactic use of OKT3 showed that H-Y was the only significant contributing factor for rejection at 3 months and 1 year (r = 0.308, p < 0.02; r = 0.308, p < 0.02; respectively). Patients were divided into two groups: group 1, 45 patients who were H-Y compatible (male and female recipients receiving female donor hearts); and group 2, 16 patients who were H-Y incompatible (female recipients with male hearts). Patients in group 2 had significantly more episodes of graft rejection than did patients in group 1 by 3 months and by 12 months after heart transplantation (3 months: 2.75 +/- 1.48 versus 1.67 +/- 1.41, p < 0.05; 1 year: 4.80 +/- 1.87 versus 2.59 +/- 1.93, p < 0.01; respectively). There were six grafts lost due to rejection in group 2 (6/15, 37.5%) and 7 grafts lost (7/45, 15.5%) in Group 1 (not significant). Heart transplantation with H-Y incompatibility resulted in a significantly greater incidence of rejection episodes.
Child↗
Retrograde gastric varices in a patient with total cavopulmonary shunt.
Gastric varices formed in a patient who had undergone a total cavopulmonary shunt operation 7 years previously. The varices were found to be due to development of collaterals from high-pressure systemic vein to low-pressure portal vein. Bleeding gastric varix can be a late complication of total cavopulmonary shunt.
Arteriovenous Shunt, Surgical↗
Neuromas of the facial nerve: a report of 12 cases.
Twelve patients with facial nerve neurinoma have been treated at The National Hospital, Queen Square, London, during the last 20 years. Nine tumours lay in the middle fossa arising from the area of the geniculate ganglion, two lay in the posterior fossa arising from the segment of the facial nerve in the internal auditory canal, and one tumour arose from the vertical segment of the facial nerve with extracranial extension through the stylomastoid foramen. Two patients had neurofibromatosis. The clinical and radiographic features of those tumours, the operative approaches employed, and the postoperative outcome are described. Complete tumour excision was achieved in all patients; all 12 remain free of recurrence 3-80 months after surgery. Facial nerve function was restored at least in part in all cases by transposition with end-to-end anastomosis, placement of a cable graft from the sural nerve or hypoglosso-facial anastomosis. The major determinant of the outcome of facial nerve function was the duration of preoperative facial paralysis, the results being invariably poor when this was of long duration.
Adolescent↗
Prolonged survival of orthotopically transplanted heart xenograft in infant baboons.
Orthotopic concordant xenotransplantation in a juvenile primate model was examined. Eighteen donor rhesus monkeys weighing 2.4 to 3.8 kg (mean 2.9 kg) were matched with juvenile baboons, aged 9 to 19 months (mean 12.7 months) and weighing 3.2 to 4.8 kg (mean 3.9 kg), using ABH blood type and mixed lymphocyte culture. Rhesus monkey hearts were orthotopically transplanted without immunosuppression into six control baboons (group I). In five baboons (group II), 4 mg/kg per day of antilymphocyte globulin was administered for 3 days before the operation and 5 days after the operation. Splenectomy was also performed, and 18 mg/kg per day of FK 506 was administered orally. Intravenous methotrexate, methylprednisolone, or both were used as rescue therapy. Seven baboons (group III) received the same immunosuppression as those in group II, but an intravenous dose of methotrexate (0.1 to 5 mg) was given twice weekly to suppress the proliferative response as monitored by in vitro immunologic assays. Baboons in group I had a mean survival of 8 days; all died as a result of classic cellular rejection. Baboons in group II had a mean survival of 48.4 days (p < 0.05 versus group I). Two died during rescue therapy for rejection, and three died of cytomegalovirus infection. Two group II baboons showed mild rejection at autopsy. Baboons in group III had a mean survival of 127 days, and one baboon was still alive after 286 days. Two died of cytomegalovirus infection, one of toxoplasmosis, one of Klebsiella pneumoniae, one of massive micropulmonary embolism, one of renal failure aggravated by ganciclovir. Only two of the baboons that died showed rejection (estimated as mild) at autopsy. The baboon still alive at 286 days had no rejection on myocardial biopsy on the two hundred forty-fourth postoperative day. FK 506 coupled with low-dose maintenance methotrexate and splenectomy has produced prolonged host survival in this xenotransplantation model. Results suggest that concordant xenotransplantation would be a suitable biologic bridge to allotransplantation.
Animals↗
Transplantation of hearts after arrest and resuscitation. Early and long-term results.
Transplant surgeons are reluctant to use hearts that have undergone cardiopulmonary resuscitation for cardiac arrest because of the fear of poor early and late cardiac function. A policy of minimizing contraindications to use of donor hearts has led to the unique opportunity of assessing the effects of donor arrest and successful cardiopulmonary resuscitation on early and late cardiac function in pediatric heart transplantation. A number of 140 infants and children undergoing transplantation from birth to 17 years of age were studied retrospectively and divided into two groups on the basis of cardiopulmonary resuscitation status. Group 1 (72 patients) received donor hearts that were not subjected to cardiopulmonary resuscitation; group 2 (68 patients) received donor hearts that had cardiopulmonary resuscitation for a mean of 18.8 +/- 14.6 minutes, the longest period of time being 60 minutes. Mean ischemic times were almost identical in the two groups: 4.43 +/- 2.0 hours (cardiopulmonary resuscitation) versus 4.5 +/- 2.1 hours (no cardiopulmonary resuscitation). Early cardiac function was assessed on the basis of the number of days the recipient was supported by the ventilator, days receiving dopamine, days receiving isoproterenol, and the amount of inotropic agents required after the operation. The groups did not differ. Parameters of systolic function included fractional shortening, posterior wall thickening, and maximum velocity of change in left ventricular posterior wall dimension during systole. Diastolic function was measured on the basis of left ventricular end-diastolic volume, left ventricular mass, and maximum velocity of change in left ventricular posterior wall dimension during diastole. Both systolic and diastolic function were measured and analyzed from M-mode echocardiography at 1 week, 1 month, 6 months, 1 year, and 2 years after the operation. There were no statistically significant differences in graft function between the two groups in any of the echocardiographic parameters studied, even at 2 years. No group differed from ranges of normal. Our results suggest that hearts undergoing cardiopulmonary resuscitation for periods of up to 60 minutes can be used safely without evidence of deterioration of early or late cardiac function.
Adolescent↗
[Surgical treatment of patients with congestive heart failure].
Surgical intervention is a treatment of choice in chronic congestive heart failure from long standing myocardial ischemia or old myocardial infarction. Right sided heart failure is a higher risk factor for surgery than a left sided one. Hemodynamic instability following acute myocardial ischemia in spite of medical treatment is an indication for urgent surgery. Hemodynamic deterioration from acute valvular lesions, such as infectious endocarditis, malfunction of the prosthetic valve, and trauma, are also indications for urgent surgery. Although surgical results are correlated with NYHA classification, chronic right sided heart failure increases the morbidity. Dynamic cardiomyoplasty is a new treatment for otherwise uncorrectable congestive heart failure. Multicenter trial reported 40% of mortality and an average improvement of NYHA class from 3.5 to 2.1.
Cardiomyopathies↗
Myosin light chain efflux after heart transplantation in infants and children and its correlation with ischemic preservation time.
Serum levels of cardiac myosin light chain 1 after heart transplantation were studied in 24 infants and children who underwent heart transplantation between June 1990 and April 1991. The ages of the patients ranged from 4 days to 6 years 7 months (mean, 9.9 months), and their body weights ranged from 2.2 to 20 kg (mean, 5.6 kg). The ages of the donors ranged from 2 days to 8 years, 7 months (mean, 26.6 months), and their body weights ranged from 2.5 to 26 kg (mean, 11.4 kg). The donor heart ischemic time ranged from 90 minutes to 482 minutes (mean, 279 minutes). Peak myosin levels after heart transplantation showed significant correlation with the duration of graft ischemia (p < 0.01) and with diastolic cardiac function in the first posttransplant week (p < 0.05). Peak myosin levels did not correlate with systolic cardiac function, age of the donor, or age of the recipient. Myosin levels of the 15 patients with graft ischemic times exceeding 4 hours averaged 6.30 +/- 3.50 ng/ml. These levels were significantly higher than those of patients with graft ischemia lasting less than 4 hours (2.60 +/- 1.20 ng/ml; p < 0.01). Both of the values are higher than previously reported values of normal controls but lower than previously reported values of patients with myocardial infarction. Preservation techniques used for this series of transplant operations provided good clinical protection of the donor heart for up to 8 hours, although release of the cardiac myosin light chain fragment correlated with duration of graft ischemia. Cardiac myosin levels appeared to be a good indicator of heart graft damage during ischemic preservation. It remains to be determined at what level of myosin release (and, hence, at what duration of graft ischemia) irreversible myocardial damage, which might result in permanent functional compromise, occurs.
Child↗
Successful transplantation of hearts harvested 30 minutes after death from exsanguination.
The donor pool for heart transplants is severely limited. Unfortunately, many trauma patients who might be donors die of exsanguination before their organs can be used. We tested whether hearts "dead" for one half hour after exsanguination could be used as heart transplants in 8 lambs (mean weight, 8 kg). Four lambs were exsanguinated by severing the subclavian artery while simultaneously infusing intravenous saline solution to mimic resuscitation attempts. All animals died. Thirty minutes after hypotensive arrest and death, simulating the time needed to secure donation permission, the heart was harvested, perfused with 250 mL of cold cardioplegia containing 200,000 units of streptokinase to dissolve intravascular clots, and stored in iced saline solution for a mean of 1.5 hours while 4 recipient lambs were prepared for operation. After bypass and recipient heart excision, the "dead" donor heart was transplanted orthotopically. The heart was reperfused with low flow (25 mL/min), low pressure (30 mm Hg), low hematocrit (hematocrit, 0.08 to 0.12) blood supplemented with prostaglandin E1 and nifedipine for 15 minutes, followed by full flow rewarming for 45 minutes. All hearts resumed normal contractions. All animals were weaned from bypass without inotropes. Pressures a half hour after bypass were (in mm Hg): aorta, 80 +/- 10; pulmonary artery, 20 +/- 5; right atrium, 9 +/- 5; and left atrium, 9 +/- 2. We conclude that hearts "dead" for one half hour after exsanguination are capable of being reanimated and used successfully as donor organs. With further development, this method could potentially greatly expand the donor heart pool.
Animals↗
The Dynamic Dento-palatography System: a new approach for evaluating speech.
The assessment of speech in patients with craniofacial anomalies is important to develop appropriate treatment strategies to optimize this aspect of oropharyngeal function. The Dynamic Dento-palatography System which uses multi-electrode array sensors to detect tongue position during articulation is described. Three levels of the speech chain, articulatory, auditory and acoustic, may be analysed in an integrated fashion using this instrument; preliminary results are described. These studies suggest that the quality of speech sounds such as 's' and 't' improve post-operatively.
Dental Arch↗
Electrical stimulation of motor cortex in experimental cortical ischaemia: pyramidal responses at C5 and the surface EMG.
In 7 baboons maintained under propofol anaesthesia, pyramidal tract responses were related to the corresponding peripheral EMG evoked by electrical stimulation of the motor cortex under conditions of focal cortical ischaemia. Pyramidal responses were recorded epidurally at the C5 level and the EMG was recorded from the contralateral hand or foot muscle using subdermal needle electrodes. Cortical ischaemia was produced by transorbital occlusion of the common anterior cerebral artery, and regional cortical blood flow was measured by the hydrogen clearance method. In the normally perfused brain, the later I waves of the C5 response required a lower stimulus strength to elicit them than the earlier I1 wave. It was more difficult to record the EMG from the hand than from the foot following stimulation of the corresponding cortex even though the C5 responses were always obtained in both cases. With moderate ischaemia, the later I waves were selectively abolished, leaving the D and I1 waves. EMG amplitude was significantly correlated with cortical blood flow (r = 0.88, P less than 0.005), and the threshold of cortical flow for the EMG was 10-13 ml/100 g/min. Our results indicate that changes in amplitude of the late I waves and particularly of the EMG are sensitive indicators of cortical ischaemia.
Animals↗
A model of acute focal ischemia in the territory of the anterior cerebral artery in baboons.
BACKGROUND AND PURPOSE: We developed a model of acute focal ischemia in the territory of the anterior cerebral artery in baboons to study the ischemic pattern following occlusion and changes in regional cerebral blood flow. METHODS: In nine anesthetized animals, a Scoville clip was placed on the proximal segment of the common anterior cerebral artery via a unilateral transorbital approach. Regional cerebral blood flow was measured by hydrogen clearance in the cortex and corpus callosum. Postexperimentally, arteries were selectively injected. RESULTS: The resulting ischemia involved both hemispheres symmetrically and the corpus callosum. Cortical flows were significantly reduced within a region 15 mm from the midline on each side (p less than 0.01). A gradient of cortical flow reduction was produced between 10 and 25 mm from the midline. This area defines the boundary region between the territories of the anterior and middle cerebral arteries, and is identified as the "penumbra" of the ischemic core, which itself lies within 10 mm of the midline. Blood flows in the corpus callosum decreased from an average of 21.0 to 6.7 ml/100 g/min in the body (p less than 0.01) and from 22.5 to 10.7 ml/100 g/min in the genu (p less than 0.05). CONCLUSIONS: This ischemic model has close physiological and morphological relevance to stroke-related clinical circumstances, in particular the acute conditions of focal cerebral ischemia associated with vascular surgery. It also provides a new framework for experimental investigation of the ischemic penumbra.
Animals↗
Subfrontal schwannoma--case report.
A rare case of subfrontal schwannoma occurred in a 33-year-old male with the chief complaint of headache. Computed tomography demonstrated a low-density mass in the subfrontal region. Magnetic resonance imaging indicated the mass extension into the ethmoidal sinus. The tumor was totally removed via a subfrontal approach. The histological diagnosis was schwannoma. The most likely origin of the tumor is the meningeal branches or anterior ethmoidal nerve.
Adult↗
The Mustard procedure for correction of simple transposition of the great arteries before 1 month of age.
Since April 1976, 34 infants (25 male and 9 female) less than 1 month of age underwent a Mustard intraatrial baffle procedure for repair of simple transposition of the great arteries. Thirty patients were less than 2 weeks old and 19 patients less than 1 week (mean 7.8 +/- 6 days). The weights ranged from 2.6 to 4.4 kg (mean 3.4 +/- 0.4 kg). Rashkind balloon atrial septostomy was performed in the first hours or days of life in 29 patients. The average interval from balloon atrial septostomy to baffle repair was 3.9 days (range 2 hours to 14 days). Mechanical ventilation was required in eight patients preoperatively and prostaglandin E1 was infused in 17 patients to maintain ductal patency. In all patients, the Mustard procedure was performed with the use of deep hypothermic circulatory arrest, averaging 53 minutes (range 37 to 82 minutes). The duration of postoperative intubation and ventilatory support averaged 1.7 +/- 1.0 days (range 1 to 5 days). Inotropic drugs were used in 24 patients during a period of 1.4 +/- 1.3 days (range 1 to 6 days) postoperatively. There were no hospital deaths. Follow-up evaluation has extended from 1 month to 14 years (mean 3 +/- 3 years). One infant died 2 months postoperatively as a result of milk aspiration; no cardiac defects were found at the autopsy. A second infant died at 1 year with right ventricular and tricuspid valve dysfunction. Baffle complications occurred in 6 of the 32 survivors, including superior vena caval stenosis in 4, inferior vena caval stenosis in 1, and pulmonary venous obstruction in 3. Reoperations for baffle obstructions were performed in three patients (8.8%) and balloon angioplasties in two. One patient required permanent pacemaker implantation. Results with the Mustard procedure before 1 month of age show that it can be performed with negligible mortality and a low incidence of late complications at an age comparable to when arterial switching would be performed. Until long-term studies demonstrate superiority of arterial operations, the low operative mortality favors continued evaluation of the neonatal Mustard repair as a valid alternative to the arterial switch.
Cardiac Surgical Procedures↗
The effects of donor-recipient size disparity in infant and pediatric heart transplantation.
To determine the effect of heart donor and recipient size mismatches in infant and pediatric heart transplantation, we studied all 69 patients (age 1 day to 11 years) having 71 orthotopic heart transplants from 1985 to 1989. Patients were divided into three groups based on donor to recipient weight ratios. Group I comprised 13 heart transplants with a donor to recipient weight ratio less than 0.95 (mean 0.81, range 0.48 to 0.94); group II comprised 29 heart transplants with a weight ratio between 0.95 and 1.60 (mean 1.28); and group III had 27 heart transplants with weight ratios greater than 1.60 (mean 2.2, range 1.61 to 3.09). All chests were closed primarily. The cardiothoracic ratio by chest radiography was significantly larger in group III (p = 0.0002); 75% of group III patients had periods of lobar or complete lung collapse by chest radiography compared with 28% of group II and 19% of group I patients (p < 0.05). Despite this, there was no difference in the number of days of ventilator support for any group (p = 0.92). There was no difference in graft ischemic time or inotropic drug use among groups, nor were differences found in the cardiac systolic function parameters of left ventricular preejection time (p = 0.975), left ventricular ejection time (p = 0.975), left ventricular fiber shortening (p = 0.97), and left ventricular fractional shortening (p = 0.596). Thus despite a high incidence of transient lobar or complete lung collapse in high donor to recipient weight ratio transplants, large donor heart size produces very little clinical impairment in recipient lung function. Size mismatches do not influence cardiac systolic function. Overall, large size mismatches appear to be very well tolerated in infant and pediatric heart transplantation.
Body Weight↗