Evidence of altered dihydropyridine receptor binding capacity following cardiac transplantation.
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Biomedical subjects
Publications and source records attributed to C Chartrand.
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Between 1977 and 1988, 20 patients underwent the Fontan operation. Their age ranged from 4 to 24 years (mean 11 years). The basic disease was tricuspid atresia with ventriculo arterial concordance and right ventricular hypoplasia. Pulmonary stenosis was present in 16 patients. Twenty-eight palliative procedures had been performed previously in the group of patients presenting some forms of pulmonary stenosis. In 2 cases a non-valved conduit has been used for correction, in a third case a valve conduit was utilised, and in a fourth case a right atrioventricular connection was carried out. In the remaining 16 patients, a wide posterior connection between the right atrium and the pulmonary arteries was performed. There were 2 early deaths (10%), and 2 late deaths (10%). After a follow-up ranging from 6 months to 11 years, all survivors are in a satisfying functional condition. We think that a wide unrestricting atriopulmonary anastomosis is mainly responsible for those good functional results. Age at operation has not influenced the results. Previous and long standing shunts may be responsible for immediate and late postoperate cardiac failure. Consequently, we now prefer an earlier corrective procedure, particularly when the patient has a patent systemic pulmonary shunt.
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The phenotypic analysis of human thymic dentritic cells (DC) in culture and in purified suspensions has been studied with light and electron microscopic (EM) immunolabelling techniques. Using a series of monoclonal antibodies (mAb) and a protein A-gold technique, we demonstrated that DR- and T6-positive cultured DC strongly bind the 9.3F10 mAb, an anti-DR-related antibody produced against human blood DC, and weakly express the T4 antigen, a membrane marker shared by Langerhan's cells (LC). On the other hand, thymic-cultured DC are negative for the other T-cell and monocyte-macrophage antigens. These results support the hypothesis that human thymic DC may be related to blood DC and epidermal LC. Moreover DC, unlike thymic macrophages, do not phagocytose latex particles, opsonized sheep red blood cells (SRBC) or Candida albicans. An efficient two-step technique of isolation, using a Percoll density gradient followed by an indirect panning technique, yields a purified (70-80%) thymic DC population, OKIa1-, 9.3F10- and OKT6-positive and esterase-negative. Immunolabelling and electron microscopy confirm that these isolated DC present similar phenotypic and ultrastructural features to human thymic DC in situ and in culture. Purified DC, used as stimulator cells in mixed leucocyte reaction (MLR), induce stronger proliferative responses than peripheral blood monocytes used as a control; blocking assays with OKIa1 mAb plus complement greatly reduced this stimulatory potency. These functional assays demonstrate that we obtained a purified typical DC population that can be used in immunological functional studies to elucidate the specific role of DC in human thymus.
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Between 1971 and 1986, 85 pacemakers were implanted at the St Justine Hospital, Montreal, in 57 young patients (25 girls, 32 boys) then aged from one day to 23 years (mean 10.3 years). The patients were followed up for periods ranging from 15 days to 13.5 years (mean 4.5 years); 119 epicardial electrodes were positioned by thoracotomy in 52 patients and by sternotomy in 5 patients; the 85 pacemaker cases were placed in the left retroperitoneal cavity. The pacemakers were programmed in modes VVI (28), AAI (1) and DDD (28). The indications for pacemaker implantation were: complete atrioventricular block in 39 cases (postoperative 16, congenital 22, acquired 1), sinus node disease in 17 cases (postoperative 13, cardiomyopathy 3, normal heart 1) and Romano-Ward syndrome in 1 case. Operated heart diseases which required pacemaker implantation were: D-transposition of the great arteries in 17 cases (complete atrioventricular block 7, sinus node disease 10), tricuspid valve atresia in 3 cases (sinus node disease 3) and tetralogy of Fallot in 3 cases (complete atrioventricular block 3). Twenty-four patients underwent a total of 33 reoperations: 21 changes of battery, 12 changes of electrodes (6 for fibrosis, 6 for breakage). Only one patient developed infection of the pacemaker case. Altogether, the incidence of complications (infection and/or breakage) was low in this series, regardless of the pacing mode. Pacing in children is now an acceptable treatment with low risk provided the indications are well selected.
In cardiac allografts acute rejection produces deleterious effects on blood flow adjustments. In order to differentiate the role of rejection over that of denervation cardiac denervated and cardiac transplanted dogs were compared. A canine model of orthotopic cardiac transplantation was utilized. Electronic devices were implanted for chronic hemodynamic studies. Regional myocardial blood flow distribution was assessed by radioactive microspheres (15 micron in diameter). Studies were carried out when animals had fully recovered (two to three days postoperatively), then in the 'early rejection' stage (five to six days post transplant) and in the 'severe rejection' stage (24 h before death). No significant difference in hemodynamic data or blood flow values were observed between groups in the recovery stage. In the denervated group, adequate cardiac function and myocardial blood perfusion was maintained throughout the study. In the transplanted group, significant loss of function was observed at the severe rejection stage. This was combined with significant decrement in blood flow to all areas of the myocardium. No selective area of underperfusion nor an early reduction in total blood flow could be observed. This study indicates that within cardiac rejection there is a parallel impairment in function and transmural myocardial blood flow which is unrelated to denervation or interruption of lymphatics.
Cardiac transplantation is followed by the interruption of afferent nerves to the heart. Knowing that some of the afferent nerves are responsible for the homeostasis of the blood volume, we undertook a serial and long-term study of the blood volume in 25 dogs with denervated hearts. The animals were autotransplanted in order to eliminate repercussions linked to rejection and to its treatment. To discern the effects of surgery and of extracorporeal circulation from those of denervation, a group of 11 control dogs was operated upon and subjected to a period of extracorporeal circulation. In both groups, serial and long-term studies of blood volume were carried out daily with 131I-labeled albumin. Analysis of the results demonstrated that in the hours following surgery, blood volume is significantly decreased by 11% in the control group and by 22% in group 2. By the 5th postoperative day, the blood volume had increased gradually to attain normal values in both groups. At the 2nd postoperative week, the total blood volume remained normal in the control group, whereas blood volume had increased by 5.7% in the autotransplanted dogs, this being due to a 38% increase of the plasmatic phase. This increment persisted from the 14th to the 42nd postoperative day and attained 7.4%. Our conclusion is that the variations in blood volume during the 1st postoperative week in the autotransplanted heart are inherent in surgery and in extracorporeal circulation. Afterwards, the hypervolemia shown in the transplanted dogs is secondary to cardiac denervation.
In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [131I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [131I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [131I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [123I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.
The variations of blood volume after autotransplantation have been documented recently by our group. Since, in the homotransplanted heart, acute rejection affects cardiac function we felt that the blood volume variations might be different than that of the autotransplants. In thirty-one immunosuppressed dogs with an orthotopic homotransplanted heart, daily assessments of blood volume with iodine 131 tagged albumin was carried out from preoperative period (control) until death from acute rejection. In the immediate postoperative period there was a significant fall of 21% of the blood volume caused by a 20% fall of plasmatic volume and of a 23% fall in erythrocyte volume. From the second to the fifth postoperative day in spite of persistence of a low erythrocyte volume the blood volume progressed to normal due to a compensatory increase of the plasmatic volume. In the terminal phase of rejection there was a 32% increase of the plasmatic volume leading to an 8% increase of the total blood volume.
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Congenital absence of a pulmonary artery is a rare entity often followed by complications. Up to now only two patients have done well after revascularization of the affected lung. We have had the opportunity to operate upon the two youngest patients suffering from an absence of a right or left pulmonary artery. In both cases revascularization of the lung was achieved with the use of a PTFE graft. In the second case, a non previously described technique has been applied successfully. Both children have been doing well up to now. This experience has led us to believe that revascularization of the affected lung should be done even in very young patients and that pulmonary hypertension may regress.
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Cardiac autotransplantation (excision and reimplantation) is a unique model that isolates totally the cardiac afferent and efferent neural pathways and results in hemodynamic misadaptability to many provocative tests. Since the cardiovascular response to acute hypercalcemia is modulated by numerous factors among which the autonomic innervation plays a major role, the hemodynamic response to bolus administration of calcium gluconate was compared in normal and cardiac autotransplanted dogs. Twenty-two animals underwent an autotransplantation while a sham procedure was performed in 18 animals. Each dog was equipped with an electromagnetic flow probe positioned around the ascending aorta and with central venous and aortic catheters. Hemodynamic data were collected daily during 1 month, before and during rapid intravenous administration of calcium gluconate (0.90 mEq). Baseline hemodynamic studies indicate that for both groups myocardial failure is evident in the immediate postoperative period; despite progressive recovery, the autotransplants always show lower cardiovascular performance. Calcium administration elicits transient positive inotropism, which is more important in presence of myocardial failure; this is true for both control and autotransplanted dogs. In the early postoperative period, hemodynamic adaptability to this stress is impaired in the autotransplants. However, long-term results indicate that minimal differences subsist over time in response to calcium administration, and when they are observed, they result from interferences in baroreceptor regulation and reflexes.
Cells with dendritic shape, the so-called dendritic cells (DCs), have been described in many tissues. In order to characterize one DCs population, normal human thymus specimens were obtained from children undergoing cardiovascular surgery. These specimens were either put in culture or fixed for in situ ultrastructural, immunocytochemical and cytochemical studies. In culture, DCs could be differentiated from other non-lymphoid cell populations. They presented long, fine processes and an irregular nucleus. Like interdigitating cells (IDCs) in situ, their cytoplasm contained many free ribosomes and mitochondria, and a well-developed endoplasmic reticulum and Golgi complex. They showed a variable number of tubulovesicular structures and membrane-bound dark homogeneous granules. They never displayed phagolysosomes, tonofilaments or desmosomes. They were Ia+, ATPase+, S-100 protein+, vimentin+, esterase-, lysozyme-, and cytokeratin- cells. Macrophages were easily identified by their numerous lysosomes and large phagolysosomes. They were esterase+, lysozyme+, vimentin+, ATPase +/-, S-100 protein- and cytokeratin-. Although they were Ia+, membrane labelling was not as important as on DC's membrane. In situ, S-100 protein-positive cells had a dendritic shape and were located mainly in medullary regions and at the cortico-medullary border. The staining was diffused both in the nucleus and in the cytoplasm. Lysozyme-positive cells were randomly distributed in the cortex, the medulla and the connective septa. They were round cells and the staining was intracytoplasmic. These observations demonstrate that DCs can be isolated in human thymic cultures, and they suggest that these cells correspond to IDCs in situ. They also provide evidence to suggest that DCs and macrophages are two distinct cellular populations.
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