A model for preservation of thymocyte-depleted thymus.

DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.

A model for preservation of thymocyte-depleted thymus

DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.

Left ventricle to coronary sinus fistula complicating the outcome of transposition of the great arteries.

We report a case in which a neonate with transposition of the great arteries and intact ventricular septum with unrestricted atrial communication had persistent hypoxemia probably due to a congenital left ventricle to coronary sinus fistula.

Influence of hypoxia on nitric oxide synthase activity and gene expression in children with congenital heart disease: a novel pathophysiological adaptive mechanism.

BACKGROUND: Chronic hypoxia has been shown to modulate nitric oxide (NO) responses in different cell models, but the relationship between hypoxia and NO synthase (NOS) regulation in humans was not studied. We studied the relationship between endothelial and inducible NOS (eNOS and iNOS) activities and expression and chronic hypoxia in children with cyanotic and acyanotic congenital heart defects. METHODS AND RESULTS: Right atrial tissue was excised from 18 patients during cardiac surgery. eNOS and iNOS activities were measured by conversion of L-[H(3)]arginine to L-[H(3)]citrulline. Gene expression of eNOS and iNOS was quantified by competitive reverse transcription-polymerase chain reaction. The eNOS activity and expression were significantly reduced in cyanotic hearts compared with acyanotic hearts: 0.38+/-0.14 versus 1.06+/-0.11 pmol. mg(-1). min(-1) (P<0.0001) and 0.54+/-0.08 versus 0.80+/-0.10 relative optical density (ROD) of cDNA (P<0.0001), respectively. In contrast, iNOS activity and expression were significantly higher in cyanotic than in acyanotic children: 7.04+/-1.20 versus 4.17+/-1.10 pmol. mg(-1). min(-1) (P<0.0001) and 2.55+/-0.11 versus 1.91+/-0.18 ROD of cDNA (P<0.0001), respectively. CONCLUSIONS: Hypoxia downregulates eNOS activity and gene expression in cardiac tissue from patients with cyanotic congenital heart defects. By contrast, iNOS activity and expression are increased in cyanotic children and may represent an alternative mechanism to counteract the effects of hypoxia in the cardiovascular system. Therefore, a novel adaptive mechanism during hypoxia is suggested.

Influence of the maze procedure on the treatment of rheumatic atrial fibrillation - evaluation of rhythm control and clinical outcome in a comparative study.

OBJECTIVE: The aim of this study was to evaluate the influence of the maze procedure on the treatment of rheumatic atrial fibrillation in patients with mitral valve disease. METHODS: Fifty-five patients (mean age 51 years; 47 females) with rheumatic mitral valve disease and associated atrial fibrillation in New York Heart Association functional class III or IV, preoperatively, were operated upon. Thirty-five had double dysfunction, 19 had stenosis, and one had mitral regurgitation. None had other associated heart diseases or previous operations. The patients were divided into two groups: GI, 20 patients were treated for mitral valve disease with associated maze procedure; GII, 35 patients were treated for mitral valve disease without the maze procedure. The preoperative echocardiogram showed a left atrial diameter in GI of 5.35 mm and in GII of 5.57 mm (P=0.779). The groups were considered clinically similar (P=0.759). Cardiopulmonary bypass was used in all patients. The mitral valve was replaced with a biological prosthesis in 24 patients and repaired in 31 patients. RESULTS: Three hospital deaths occurred, one in GI, two in GII. After cardiopulmonary bypass, 37.1% of patients in GII remained in atrial fibrillation. All patients in GI recovered regular rhythm (P<0.0001). In the ICU, atrial fibrillation was detected in 80% of patients in GII and maintained in 76.4% in a mean follow-up period of 38.5 months. In GI, atrial fibrillation occurred in 20% of patients in the ICU and maintained in 5.3% in 41 months of mean follow-up (P=0.0001). None of the patients in GI and 20.6% of patients in GII had a thromboembolic episode 1-63 months after the operation (P=0.041). Four late deaths occurred (two in each group), two being due to progression of valvular disease, one after an episode of pulmonary infection and one with no cardiac cause. CONCLUSION: The maze procedure is effective in treating atrial fibrillation in patients with rheumatic mitral valve disease. The results are sustained in the mid-term follow-up period, preventing postoperative thromboembolic episodes, and with acceptable morbidity and mortality.

Aortic valve assessment. Anatomical study of 100 healthy human hearts.

PURPOSE: To assess anatomical characteristics of the aortic valve, so that they may be useful in diagnostic situations and surgical treatment. METHODS: The study analyzed 100 healthy fixed human hearts; 84% of them obtained from males, 61% of them from Caucasian individuals. The ages of the individuals ranged from 9 to 86 years (mean 30 +/- 15.5 years). The characteristics assessed related to age, sex, and race were the following: number and height of the cusps, size of the lunulae, internal and external intercommissural distance, position of the coronary ostium in relation to the aortic valve, position of the ventricular septum in relation to the aortic valve, thickness of the cusps. RESULTS: All hearts assessed had a tricuspidal aortic valve. In regard to the height of the cusps and size of the lunula, the left coronary cusp was larger, followed by the right coronary cusp and the noncoronary cusp. The internal and external intercommissural distances had mean values of 24.6 +/- 5.7 mm and 19.7 +/- 7 mm, respectively. In regard to the position of the coronary ostia, in one heart two ostia emerged from the left coronary sinus, and in another, the ostium was supracommissural. The mean diameter of the aorta was 21.8 +/- 3.6 mm, and there were no significant sexual or racial differences, but the diameter increased progressively with the increase in age. The thickness of the cusps did not show any significant difference in the 3 points assessed. CONCLUSION: The aortic valve annulus did not show a perfect circumference, with some variations in the measurements of the annulus, in the cusps and in the relation with the ventricular septum.

Transxiphoid approach without median sternotomy for the repair of atrial septal defects.

BACKGROUND: Interest in minimally invasive procedures has recently increased because it results in less surgical trauma, decreased patient discomfort, short hospital stay, reduced costs, and better cosmetic appearance. Based on these facts, we have been using the transxiphoid process approach without sternotomy for the correction of atrial septal defects. METHODS: From July 1996 to January 1997, the xiphoid process window approach was performed in 10 patients with ostium secundum atrial septal defect. Ages ranged from 6 months to 14 years (mean, 5.3 years). In all patients, extracorporeal circulation was carried out by means of cannulation of the femoral artery and both caval veins and of aortic cross-clamping. Videothoracoscopy was used to improve visualization of the aorta. RESULTS: There were no intraoperative or postoperative complications, and in all but 1 patient, extubation was possible while in the operating room. CONCLUSIONS: The xiphoid process window, with no median sternotomy, permitted closure of the atrial septal defects with good results and could be used as a less invasive technique for their correction.

Double-outlet right ventricle with nonrelated ventricular septal defect: surgical results using the multiple patches technique.

OBJECTIVE: Introduce a new surgical technique for biventricular correction of double-outlet right ventricle with noncommitted ventricular septal defect. METHODS: From April 1987 to February 1996, 15 patients with double-outlet right ventricle with noncommitted ventricular septal defect were operated on using a new technique for biventricular repair with multiple bovine pericardial patches to create a tunnel between the left ventricle and the aorta. Ages ranged from two months to 13 years (mean age 4.8 years). Thirteen patients had situs solitus and levocardia, one patient had situs inversus and dextrocardia, and one patient had situs solitus and dextrocardia. Construction of the tunnel began at the right atrium. The ventricular septal defect (VSD) was enlarged anteriorly, if restrictive or small, and the first patch was sutured in the infero-posterior edge of the VSD. The second, third and sometimes the fourth patches were sutured in sequence, through the right ventriculotomy, directing the tunnel to the aortic annulus. RESULTS: Overall mortality was 20%, with two early and one late death. The surviving patients were followed-up for a period ranging from ten months to nine years (mean 33 months), and all were in functional class I (NYHA). Minimal residual ventricular septal defect was observed in one patient, stenosis in two patients and moderate pulmonary insufficiency in one. There was no obstruction of the intraventricular tunnel between the LV and the aorta. CONCLUSION: Based on these data, we conclude that this technical modification for the biventricular repair of the double-outlet right ventricle with noncommitted VSD allows for the construction of a tunnel with adequate internal diameter, respecting the spatial changes between the VSD and aorta. In addition, the intraventricular bovine pericardial tunnel takes up less space, thus reducing the incidence of right ventricle outlet obstruction.

Cryosurgical ablation of fetal atrioventricular node: new model to treat fetal malignant tachyarrhythmias.

BACKGROUND: Sustained tachyarrhythmia resulting in fetal hydrops is often refractory to medical therapy. Fetal atrioventricular node ablation associated with epicardial fetal pacing has the potential to be an effective procedure for this morbid association. METHODS: To assess the feasibility of therapeutic fetal heart block, we developed a technique of intrauterine cryosurgical ablation of fetal atrioventricular node without the need for cardiac bypass in 8 fetal lambs. Complete heart block was obtained by applying the cryoprobe over the coronary sinus. Fetal pacing was then performed to allow fetal survival. RESULTS: Complete heart block was achieved in 100% of the fetal lambs. Postoperative evaluation revealed persistent atrioventricular block. The hearts were studied at different postoperative times. Morphologic evaluation of the area containing the cryosurgical lesion revealed varied extension of necrosis of the atrioventricular node and hemorrhage, with involvement of the His bundle and proximal right bundle branch. CONCLUSIONS: This procedure is technically feasible and offers an alternative approach to the treatment of drug-resistant, life-threatening fetal supraventricular tachyarrhythmias associated with hydrops fetalis.

[Surgical treatment of congenital fistulas of the coronary artery]. / Tratamento cirúrgico de fístulas congênitas da artéria coronária.

PURPOSE: To evaluate the surgical result of the cases of congenital fistulae of the coronary artery. METHODS: Seven patients were surgically treated since January 80 until February 94. The ages ranged from 3 days to 52 years old. The diagnosis was suspected by echocardiogram and established by cardiac catheterization. RESULTS: Regarding the clinical status, 3 (42.85%) patients were asymptomatic, 3 (42.85%) presented congestive heart failure and 1 (14.28%) precordial pain and palpitation. The fistulae, located in inferior wall of the right ventricle in 1 (14.28%) patient, apex of the right ventricle in 1 (14.28%), right atrium in 3 (42.85%), and coronary sinus in 1 (14.28%), were isolated in 4 (57.17%), 1 (14.28%) also had fixed subaortic stenosis, 1 (14.28%) had previously undergone the ligate of the ductus arteriosus and 1 (14.28%) also had aortic coarctation and ductus arteriosus. After surgical treatment, 5 (85.72%) had follow up abnormalities, showing good clinical outcome; 1 (14.28%), that also had aortic and subaortic stenosis, followed with minimal aortic regurgitation and poor left ventricular performance; 1 (14.28%), that had aortic coarctation and ductus arteriosus, who had been operated on in unfavourable hemodynamic conditions, died 5 days after surgery. CONCLUSION: Surgical correction should be proposed as a treatment of the congenital fistulae of the coronary artery, since it is technically feasible, and has low in-hospital mortality and morbidity.

[Video-assisted surgery for closure of persistent ductus arteriosus. Study in sheep and initial clinical experience]. / Cirurgia vídeo-assistida para fechamento de canal arterial persistente. Estudo em carneiros e experiência clínica inicial.

PURPOSE: The aim of this study was to analyse the effectiveness of patent ductus arteriosus (PDA) closure by the video-assisted thoracic surgery (VATS). METHODS: The technique was utilized in 6 newborn lambs firstly. Three to four small incisions (3 to 10mm) were used in each animal to permit the introduction of lung retractors, video equipment, dissectors and clip appliers. The procedure was accompanied by video monitoring and after the dissection, the PDA was closed by 2 titanium clips. Seven days after, the animals were sacrificed and submitted to pathological study. Based on this initial experience seven patients (ages between 17 and 108 months) were operated on with this technique. RESULTS: In lambs, we have some difficulty to retract the lung. Despite this fact the closure of PDA was successful and proved by pathologic study. In children the dissection of PDA was easier due to manual ventilation. The interruption of PDA using the proposed method was obtained in 4 patients, those with good relation between ductus diameter and clip size and defined by echocardiography and angiographic studies. CONCLUSION: The use of VATS for interruption of PDA in both, experimental and initial clinical experiences, has showed to be an effective method.

Fetal heart block: a new experimental model to assess fetal pacing.

Epicardial fetal pacing via thoracotomy has the potential of being a safer and more reliable procedure to treat congenital complete heart block (CHB) associated with fetal hydrops refractory to medical therapy. To assess the acute electrophysiological characteristics of two ventricular epicardial leads, a new experimental model of fetal heart block induced by cryosurgical ablation of the AV node without the need for fetal cardiac bypass was performed in 12 pregnant ewes at 110-115 days gestation. A modified screw-in lead (1 1/2 turns) was used in six fetal lambs and a stitch-on lead in the other six lambs. CHB was achieved in 100% of the fetal lambs, with no ventricular escape rate noticed in any of the lambs. The acute stimulation thresholds were consistently low for both leads, with lower values for the screw-in lead at pulse duration below 0.9 msec (P < 0.03). Current measured at voltage threshold with pulse width below 0.5 msec was lower for the screw-in lead (P < 0.048). Stimulation resistance, measured during constant-voltage pacing, was not statistically different between the two leads (441.8 +/- 13.7 omega for the screw-in lead vs 480.2 +/- 59.2 omega for the stitch-on lead). No significant differences (P > 0.20) were found in R wave amplitude between the two electrodes. Slew rates were significantly higher in the screw-in group than in the stitch-on group (1.40 +/- 0.2 vs 0.62 +/- 0.2 V/sec, P = 0.04). This model of CHB is a simple and reproducible method to assess fetal pacing. We find the screw-in electrode to be a better option when fetal pacing is indicated.

[Ischemic mitral valve insufficiency. Incidence, diagnosis and surgical treatment]. / Insuficiência valvar mitral isquêmica. Incidência, diagnóstico e tratamento cirúrgico.

PURPOSE: To study the incidence of ischemic mitral regurgitation (MR) and the mortality. METHODS: One-hundred-five cases of acute myocardial infarction (AMI) with MR were reviewed. Patients were divided in two groups: group A-59 (56.2%) necropsied patients without previous surgical procedures to correlate clinical pictures with the aim to determine the cause of death; group B-46 (43.8%) patients were submitted to surgical treatment. This group was subdivided in mild, moderate and severe forms of MR, and studied comparatively the type of surgical treatment and its evolution. RESULTS: Group A-23 (39%) patients with mild forms and predominant ischemic heart disease, responsible for death; 18 (30.5%) patients without previous diagnosis, masked by myocardial failure and 18 (30.5%) with severe MR and coronary heart disease; group B-14 (30.4%) patients died at the immediate post-operatory period. Higher mortality associated to ejection fraction (EF) below 35% (47.6%; p = 0.022), severe MR (41.7%; p = 0.044) and cardiogenic shock (52.9%; p = 0.14). In 41 (89.1%), the mitral valve repair was combined to coronary artery bypass grafting operation (CABG), in 4 (8.7%) this last procedure was made without mitral repair and in the remaining patients the surgery was limited to the valve. Mitral valvuloplasty was performed in 23 (50%) patients with 3 (13%) deaths, and in 19 (42.3%) the mitral valve was replaced with 9 (47.4%) deaths. CONCLUSION: The prognosis is related to the grade of EF and to the severity of MR. In mild to moderate forms, the surgical indication is due to the associated coronary heart disease and the valvuloplasty is preferred, in this instance. In severe forms, surgical intervention must be performed as soon as possible, before cardiogenic shock appears.

[Posttraumatic chylothorax. Experience in the postoperative period following cardiothoracic surgery]. / Quilotórax pós-traumático. Experiência no pós-operatório de cirurgia cardiotorácica.

PURPOSE: To report the accumulated experience in the treatment of patients with postoperative chylothorax (CHT) recovery utilizing pleural drainage associated to alipoidic diet and/or intravenous nutrition. METHODS: The aim of this work is to analyse the management of 11 patients (8 males; 11 months to 70 years old) with post-operative CHT. The previous pathologies were: congenital heart disease in 7; coronary insufficiency in 2; pulmonary tumor in 1 and mediastinal tumor in 1. The diagnosis was made up to 2nd postoperative week in 6, up to 4th week in 3 and later in 2 patients. The volume through the drain ranged from 200 to 3200ml/24h (median 636ml/24h). The laboratory diagnosis was made by lipidic presence in pleural effusion. In all patients the clinical management was made by hipo or alipoidic diet. RESULTS: In 7 the response was good with a decrease of drainage progressively. In 4, it was necessary the introduction of intravenous nutrition by the insufficient response and maintenance of drainage. The reoperation was not used and lymph fistula closed in a period until 10 days in 1 patient; until 20 days in 6 and after this in 4. CONCLUSION: In conclusion, the post-operative CHT may be treated by thoracic drainage and alipoidic diet and/or intravenous nutrition with fistula closure in all patients and without need of reoperation.

Late results (50 to 182 months) of the Jatene operation.

Between May 1975 and August 1991, 184 patients with transposition of the great arteries (TGA) were operated upon by Jatene operation. One hundred and sixteen underwent corrective surgery prior to June 1987 with a follow-up period of between 50 and 182 months. The ages of these 116 patients ranged from 1 day to 84 months (11.53 +/- 15.98). Eleven percent were less than 1 month old, 38% were between 1 and 6 months, 29% between 7 and 12 months and 22% were older than this. Eighty-eight patients (76%) were boys and the weight ranged from 2.4 to 17.0 kg (6.39 +/- 3.38). Thirty-eight patients (20.7%) died in the immediate postoperative period. Of the survivors, 5 died in the late follow-up between 9 and 66 months (endocarditis at 9 and 66 months; gastroenteritis at 20 months; sudden death at 48 months; and during reoperation for relief of pulmonary stenosis (PS) at 60 months). Of the surviving 73 patients, 24 (32.9%) are anatomically normal at a mean period of 92.5 months postoperatively. Twenty-two (30.1%) have dysfunctions without clinical repercussion. Nineteen (26%) have had no recent evaluation and 8 (11%) were submitted to reoperation or angioplasty for relief of PS. Ninety-eight percent of the patients have normal left ventricular function. The majority of the patients surviving 50 to 182 months are in good clinical condition and if dysfunctions are present these show no progression or severe hemodynamic alterations.

[Myocardial revascularization after reperfusion in the acute phase of myocardial infarction]. / Revascularização miocárdica após reperfusão na fase aguda do infarto do miocárdio.

PURPOSE: To evaluate the coronary artery bypass grafting (CABG) after successful coronary reperfusion (CR) by streptokinase and/or percutaneous transluminal coronary angioplasty in acute myocardial infarction (AMI). PATIENTS AND METHODS: During 65-months period, 245 patients underwent CR during AMI. In 47 (19.2%) CABG were performed in the acute period due to multi-vessel disease (31%), residual lesion (20%) and post-reperfusion angina (17%). There were two distinct periods: in the first, between Jun/81 and Jun/83, 34 patients underwent CABG, 47 hours average after reperfusion; in the second, between Jul/83 and Nov/86, 13 patients underwent CABG, 7 days average after reperfusion. RESULTS: There were 7 deaths (21%) in the first period and 1 (8%) in the second one. CONCLUSION: After a multifactorial analysis the authors concluded that better results with inferior mortality (p less than 0.05) were obtained when CABG was performed later (mean 7 days) than in the immediate post-reperfusion period (mean 47 hours).