Técnica de cultivo de mioblastos autólogos humanos para transplante clínico / Technique of culture of human autologous mioblasts for clinic transplant

Introducción: El trasplante celular para reparar o regenerar el miocardio dañado es un nuevo objetivo en la enfermedad cardiovascular. Los mioblastos esqueléticos autólogos son las células más estudiadas y constituyen la primera elección para la reparación cardíaca. Objetivos: Puesta a punto de la técnica de cardiomioplastia celular en muestras obtenidas de donantes multiorgánicos y llevar a cabo esta técnica junto con la revascularización en dos pacientes. Material y métodos: Se han obtenido 15 biopsias de músculo vasto lateral de donantes multiorgánicos y de dos pacientes con infarto de miocardio no reciente. Después de tres semanas de cultivo, se evaluó en todas las muestras el porcentaje de mioblastos con los anticuerpos CD56, desmin y miogenin. Los dos pacientes fueron sometidos a cirugía de revascularización e inyección intramiocárdica de mioblastos esqueléticos autólogos obtenidos tras cultivo con suero autólogo. Resultados: Se demostró la presencia de un gran número de células positivas con los marcadores desmina y miogenin. El implante de mioblastos esqueléticos autólogos no se asoció con el desarrollo de efectos adversos. Conclusiones: En pacientes con un infarto de miocardio no reciente, el tratamiento con mioblastos en conjunción con bypass arteria coronaria es seguro y fácil y es relativamente fácil obtener mioblastos de tejido muscular para trasplantar (AU)

Introduction: Cellular transplant to repair or regenerate damaged myocardium is a new objective in cardiovascular disease. The autologous skeletal myoblasts are the most studied cells and constitute the first election for cardiac repair. Objectives: fine adjustment of the cellular cardiomyoplasty technique with revascularization in two patients. Material and methods: 15 biopsies were obtained from multiorganic donors and from two patients with no recent infarct. After three weeks of culture, the percentage of myoblasts were evaluated using monoclonal antibodies CD56, desmin and myogenin. The two patients were subjected to revascularization surgery and intramyocardic injection of autologous skeletic myoblasts obtained after culture with autologous serum. Results: The presence of a great number of positive cells with desmin and myogenin markers was shown. The implantation of autologous skeletal myoblasts was not associated with the development of adverse effects. Conclusions: In patients without a recent myocardium infarct, the treatment with myoblasts together with coronary artery bypass is sure and easy and it is straightforward to obtain myoblasts from muscle tissue for transplant (AU)

Late noncardiac surgery in heart transplant patients.

OBJECTIVE: Because of improved long-term survival of heart transplants (HT), patients often need noncardiac surgery (NCS). Immunosuppression may increase the infection rate. Inadequate management may increase the risk of dysfunction or acute rejection episodes (ARE). Long-term outcomes of NCS and optimal immunosuppressive management in the perioperative period are not well known. The objective of this study was to analyze the incidence, morbidity, and mortality of late NCS after HT. METHODS: We retrospectively evaluated the incidence and type of late NCS as well as the risk factors for complications and the mortality among 207 HT patients. Immunosuppression and ARE rates were also analyzed. RESULTS: One hundred and sixteen late NCS (84.5% elective) were performed in 72 HT patients (34.8%). Interventions were: 35 urologic (30.2%), 29 abdominal (25%), 14 vascular (12.1%), 13 ENT (11.2%), 11 skin and soft tissue (9.5%), and 7 orthopedic (6%). Malignancy was the main indication for NCS (33.6%). Only 4 patients (5.6%) died preoperatively. Mortality was higher among emergent vs elective procedures (16.6% vs 1%; P = .012) and among patients with preoperative high vs middle/low risk (26.6% vs 0%). Postsurgical infection was the most frequent complication (6.9%). However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was <15 days in two thirds of patients. Immunosuppression was modified in 33 patients (28.4%), especially when the surgical indication was neoplasia (P < .001). None of the patients with NCS displayed allograft dysfunction or an ARE. CONCLUSIONS: More than one-third of HT patients needed a late NCS. In our experience, elective surgical procedures with middle/low preoperative cardiovascular risk are safe. In this context, the risk of rejection was low when immunosuppression was carefully monitored to reduce the risk of infection.

Inhaled nitric oxide through a noninvasive ventilation device to assess reversibility of pulmonary hypertension in selecting recipients for heart transplant.

INTRODUCTION: Pulmonary hypertension (PHT) is an independent risk factor for right ventricular failure and death after heart transplant. Nitric oxide (NO) is a powerful and selective vasodilator, indicated in this scenario, but its response is unpredictable. Thus, it should be assessed prior to the intervention. However, preoperative assessment has not been widespread due to its difficulties and risks. OBJECTIVE: We describe herein a pulmonary vasodilatory test with NO administered through a noninvasive ventilation (NIMV) device. We also assessed the effect of NO in patients with severe PHT owing to cardiac disease. Assessment of the utility of the test to select patients for heart transplant. METHODS: We enrolled 19 patients with severe PHT for a preoperative assessment for heart transplant. Thresholds used were as follows: systolic pulmonary arterial pressure (SPAP) > or =65 mm Hg, transpulmonary gradient (TPG) > or =15 mm Hg, and pulmonary vascular resistance (PVR) > or =4.5 Wood units (WU). NO was administered through a modified noninvasive ventilation device. Cardiac output and pulmonary pressures were measured simultaneously by right heart catheterization. RESULTS: All patients agreed to be enrolled in the test. No difficulties, interruptions, or severe complications happened in any case. Basal and NO average measured values were SPAP (74.16 and 57.95 mm Hg), PVR (7.5 and 3.7 WU), and TPG (23.25 and 12.58 mm Hg). The differences were significant (P < .05) for all three tests. We consider acceptable for heart transplant a response that reduces PHT to a moderate grade. Using these criteria 14 patients were accepted and 11 underwent heart transplant. Two deaths in the postoperative period were both secondary to mediastinal bleeding and not related to right ventricular failure. CONCLUSIONS: A pulmonary vasodilatory test with NO administered through a NIMV device was feasible and useful to select suitable heart transplant recipients with severe pulmonary hypertension.

Long-term results of heart transplant in recipients older and younger than 65 years: a comparative study of mortality, rejections, and neoplasia in a cohort of 445 patients.

BACKGROUND: Whether being older than 65 years should be considered an absolute counterindication to heart transplant (HT), as it is in some centers, is controversial. In our centre, patients older than 65 years are accepted for HT if they satisfy stringent conditions. The aim of this study was to examine whether heart recipients older than 65 years have a greater risk of rejection, neoplasia, or mortality than younger ones. METHODS: We studied 445 patients who underwent HT between April 1991 and December 2003, 42 of whom were older than 65 years and 403 who were 65 years or younger. The parameters evaluated were the cumulative incidences of neoplasias and rejections (ISHLT grade > or = 3A), and the survival rates 1 month, 1 year, and 5 years post-HT. RESULTS: The two groups had similar percentages of patients with at least one rejection episode (< or =65 years 56.9%, >65 years 51.3%; P > .05), and although there were proportionally almost twice as many tumors in the older group (14.2%) as in the younger (7.9%), this difference was not statistically significant either. Nor were there any significant differences in survival, the 1-month, 1-year, and 5-year rates being 87.8%, 82.1%, and 68.8%, respectively, in the younger group and 85.7%, 78.6%, and 73.4%, respectively, in the older. CONCLUSIONS: Among carefully selected patients aged more than 65 years, HT can be performed without incurring greater risk of rejection, malignancy, or death than is found among recipients younger than 65 years.

Hypotension, acidosis and vasodilation syndrome after heart transplant: incidence, risk factors, and prognosis.

BACKGROUND: HAV syndrome, the combination of hypotension, acidosis and vasodilation (HAV), is a serious postoperative complication after heart transplantation (HT). Its etiology and prognosis are poorly understood. AIM: To determine the incidence and prognosis of post-HT HAV syndrome and examine possible risk factors. METHODS: Retrospective examination of the records of 85 consecutive patients who underwent HT between December 1999 and June 2002 sought the HAV criteria: systolic BP <85 mm Hg plus HCO3 <19 mEq/l whole excluding cardiogenic, hypovolemic and septic shock. Donor variables included sex, age, weight, height, cause of death, time in ICU, and ischemic time; while recipient variables, sex, age, weight, height, etiology of cardiopathy, previous cardiopulmonary bypass surgery, preoperative amiodarone, beta-blockers, catecholamines, mechanical ventilation or intra aortic balloon pump (IABP), RVP, time on waiting list, pump time, reoperations, polytransfusion, preoperative creatinine, GOT, GPT and GGT, induction with OKT3 or anti-CD25, bypass-to-HAV time, duration of catecholamine treatment, and 1 month survival after HT. RESULTS: The 11 HAV cases (13%) appeared between 1 and 72 h after HT (75% in the first hour). Catecholamines were used for 1 to 6 days; control was achieved within 48 h in 58% of cases. Two HAV patients (18%) died within the first month versus six non-HAV patients (8.1%) (P=.275). Only polytransfusion showed more than a borderline value to predict HAV syndrome. CONCLUSIONS: HAV syndrome has an incidence of 13% and a mortality of 18% within 1 month post-HT. The only likely risk factor is polytransfusion.

CT and MR findings in a calcified myocardial tuberculoma of the left ventricle.

Tuberculosis can involve a multitude of organ tissues but generally affects the respiratory tract. Heart tuberculosis is rare, and the pericardium is the most common location reported in the literature, accounting for 0.5% of extrapulmonary tuberculosis. Isolated myocardial tuberculosis is a very unusual occurrence, with only a few case reports in the literature, usually diagnosed at necropsy. Findings of myocardial tuberculoma on cross-sectional images previously have not been reported. We present computed tomography and magnetic resonance imaging findings of an isolated calcified myocardial tuberculoma.

[Total arterial myocardial revascularization with both mammary arteries without extracorporeal circulation]. / Revascularización miocárdica arterial completa con ambas arterias mamarias sin circulación extracorpórea.

INTRODUCTION: Tector has described the off-pump total arterial revascularization technique, using multiple anastomosis with both internal thoracic arteries. To reduce surgical morbid-mortality, we have proposed the use of this technique without extracorporeal circulation. PATIENTS AND METHODS: From April, 1998 the off-pump <> technique was performed in 92 patients, 74 male (80%) and 18 female (20%), with a mean age of 64.9+/-8.1 years (42-78). Preoperative angiography demonstrated triple-vessel disease in 58 (63%) patients, and left main disease was present in 19 (20.5%) patients. Forty patients (43.5%) showed unstable angina, 24 patients (26%) significant peripheral vascular disease, and 26 (28%) diabetes mellitus. Both internal thoracic arteries were harvested using the skeletonization technique and were used like a <> graft. The flow in the graft was measured using a flowmeter, and in 24 (26%) patients by angiographic study. RESULTS: A total of 274 distal anastomoses were performed, 122 (44.6%) in the lateral or inferior wall, and 69 (25.2%) were sequential, with an average of 2.98 bypass/patient. In 59.8% of the patients a triple bypass was performed, 22% double bypass, 17% cuadruple bypass and 1 patient a quintuple bypass. During the initial six hours 64.9% of patients were extubated. Only one patient (1.1%) needed intraaortic ballon pumping and 3 (3.2%) inotropics during the postoperative course. Hospital mortality was 3 (3.2%) patients. Reoperation for bleeding was needed in just one patient (1.1%), and 78.3% of patients were not transfused. Mediastinitis occurred in 3 patients (3.2%). Postoperative stroke was not observed. At 7.7+/-2.8 months of mean follow-up all patients were free of symptoms and the global patency rate of 94%. CONCLUSIONS: Off-pump Tector technique appears to be safe, offering a complete arterial revascularization and showing a reduction of surgical morbidity.

[Practice guidelines of the Spanish Society of Cardiology. Cardiac and heart-lung transplants]. / Guías de actuación clínica de la Sociedad Española de Cardiología. Trasplante cardíaco y de corazón-pulmones.

Cardiac transplantation is the only therapy that is able to substantially modify the natural evolution of patients with severe heart failure, along with angiotensin converting enzyme inhibitors. Nevertheless, because of the limited number of donors, its impact is scarce compared to the magnitude of the problem. Up to the end of 1998, 48,541 orthotopic cardiac transplantations and about 2,510 heart and both lung transplantations have been registered throughout the world. In Spain 2,780 procedures have been performed in the last 15 years. The survival expectations for a transplanted patient is 75% after the first year and 60% the following 5 years. The average duration of the graft is 8 years and 6 months. Cardiac transplantation is indicated for young and middle-age patients with irreversible cardiac process in bad clinical condition, with no other possibility of medical or surgical management and with a limited life expectancy. The major debate when choosing this therapy appears with the critical patients, patients older than 65 years, and some patients with systemic diseases. The great demand of transplantation obliges the teams to enlarge the criteria for donors' acceptance. At the same time, the increase of the knowledge about the transmission of some infections, mainly viral, forces to review those criteria day-to-day. The use of different immunosuppressive strategies pursues the control of rejection. The most commonly used is the so-called triple therapy (cyclosporine-azathioprine and steroids). The use of antilymphocytic antibodies such as cytolytic induction treatment is not unanimously accepted. Some of the new immunosuppressive agents such as myphenolate-mofetil and tacrolimus seem to offer advantages mainly due to their greater potency. Since transplantation is a limited procedure, of which its practise has an effect on the whole health system of a country, a perfect planning and adequacy of the Centers is compulsory, as well as the setting-up of clear rules for the use of donors and priority of transplantation. Finally, the patient must be informed clearly and comprehensively at length of the risks, limitations and expectations of these complex procedures.

[Combined perioperative ultrafiltration in pediatric cardiac surgery. The preliminary results]. / Ultrafiltración combinada perioperatoria en cirugía cardíaca pediátrica. Resultados preliminares.

INTRODUCTION AND OBJECTIVES: Recently, ultrafiltration techniques are used more and more as a treatment for the inflammatory response of cardiopulmonary bypass. It also provides fine control of fluids. The purpose of this study is to present a technique which combines conventional and modified ultrafiltration and to analyze the obtained results. PATIENTS AND METHODS: 22 patients (mean weight 13.1 +/- 8.4 kg) operated on cardiopulmonary bypass. Combined ultrafiltration was performed during cardiopulmonary bypass (conventional) and after pump (modified ultrafiltration). We analyzed cardiopulmonary bypass variables, the first 24-hour hemodynamics, biological variables (arterial blood gases, cell counts, IL-6, adhesion molecules ICAM-1 and VCAM-1, and coagulation profiles). RESULTS: A total amount of 1,399 +/- 680 ml/m2 of mean combined ultrafiltrate volume was obtained (657 +/- 386 ml/m2 during cardiopulmonary bypass and 845 +/- 358 ml/m2 post-cardiopulmonary bypass). After modified ultrafiltration, hematocrit rose from 23 +/- 2.3 to 32 +/- 4.1, arterial systolic blood pressure rose from 74 +/- 13 to 98 +/- 20 mmHg, heart rate decreased from 133 +/- 22 to 126 +/- 23 bpm, and central versus pressure did not change. A statistically significant relationship (multivariable), was shown between modified ultrafiltration time and VCAM-1 post-ultrafiltration levels. Platelet count was lower and diuresis rose related to cardiopulmonary bypass ultrafiltration volume and diuresis increased. CONCLUSIONS: Perioperative combined ultrafiltration is feasible without undue morbidity and provides adequate hemoconcentration and excellent postoperative hemodynamic results. More studies with control groups are necessary to better define the therapeutic influence in antiinflammatory properties of this technique.

Cytomegalovirus colitis mimicking a colonic neoplasm or ischemic colitis 4 years after heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) colitis is a polymorphous disease presenting in immunodepressed patients in a variety of clinical forms that can delay diagnosis and therapy. We report the case of a patient who presented with abdominal pain 4 years after heart transplantation; clinical and x-ray findings were suggestive of a neoplastic or ischemic stenosis, and histopathological examination likewise initially suggested an ischemic etiology. METHODS: Tissue samples were fixed in 10% formaldehyde, embedded in paraffin, cut, and stained with hematoxylin/eosin and periodic acid-Schiff-Alcian Blue. Immunohistochemistry with monoclonal antibodies was performed using an indirect immunoperoxidase method. RESULTS: CMV colitis was eventually diagnosed and resolved with surgery and specific anti-CMV therapy. CONCLUSIONS: CMV colitis should be suspected in any heart transplant patient with signs or symptoms of abdominal pathology, even without classical signs or symptoms of CMV infection. If stenotic lesions are present, surgery may be required not only to remove the obstruction but also to rule out malignancy.