RESUMO
BACKGROUND: The reported incidence of necrotising enterocolitis in neonates with complex CHD with ductus-dependent systemic circulation ranges from 6.8 to 13% despite surgical treatment; the overall mortality is between 25 and 97%. The incidence of gastrointestinal complications after hybrid palliation for neonates with ductus-dependent systemic circulation still has to be defined, but seems comparable with that following the Norwood procedure. METHODS: We reviewed the incidence of gastrointestinal complications in a series of 42 consecutive neonates with ductus-dependent systemic circulation, who received early hybrid palliation associated with a standardised feeding protocol. RESULTS: The median age and birth weight at the time of surgery were 3 days (with a range from 1 to 10 days) and 3.07 kg (with a range from 1.5 to 4.5 kg), respectively. The median ICU length of stay was 7 days (1-70 days), and the median hospital length of stay was 16 days (6-70 days). The median duration of mechanical ventilation was 3 days. Hospital mortality was 16% (7/42). In the postoperative period, 26% of patients were subjected to early extubation, and all of them received treatment with systemic vasodilatory agents. Feeding was started 6 hours after extubation according to a dedicated feeding protocol. After treatment, none of our patients experienced any grade of necrotising enterocolitis or major gastrointestinal adverse events. CONCLUSIONS: Our experience indicates that the combination of an "early hybrid approach", systemic vasodilator therapy, and dedicated feeding protocol adherence could reduce the incidence of gastrointestinal complications in this group of neonates. Fast weaning from ventilatory support, which represents a part of our treatment strategy, could be associated with low incidence of necrotising enterocolitis.
Assuntos
Algoritmos , Nutrição Enteral/métodos , Enterocolite Necrosante/prevenção & controle , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Procedimentos de Norwood , Complicações Pós-Operatórias/prevenção & controle , Enterocolite Necrosante/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Recém-Nascido , Itália/epidemiologia , Masculino , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
A relevant number of patients undergoing total cavopulmonary connection (TCPC) experience heart failure (HF). Heart transplant is then the final option when all other treatments fail. The axial flow blood pumps are now the state of the art; however, there is little experience in low-pressure circuits, such as support of the right ventricle or even a TCPC circulation. A new T-shaped model of mechanically assisted TCPC using the "Jarvik Child 2000" axial pump, (flow rates between 1 and 3 L/m in a range of 5000-9000 rpm) was designed, simulated numerically, and then tested in animals. Eight sheep (42-45 kg) were studied: two pilot studies, four pump-supported (PS) TCPC for 3 h, and two not pump-supported (NPS) TCPC. In the PS, the axial pump was set to maintain the baseline cardiac output (CO). Pressures, CO, systemic and pulmonary vascular resistance, lactate levels, and blood gases were recorded for 3 h. Computational fluid dynamics (CFD) study allows us to set the feasible operating condition and the safety margins to minimize the venous collapse risk. In the NPS animals, a circulatory deterioration, with increasing lactate level, occurred rapidly. In the PS animals, there was a stable cardiac index of 2.7 ± 1.4 L/min/m(2), central venous pressure of 12.3 ± 1 mm Hg, and a mean pulmonary artery pressure (PAP) of 18.1 ± 6 after 3 h of support up to 9000 rpm. systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), blood gasses, and arterial lactate levels remained stable to baseline values. No caval collapse occurred. A new pediatric axial flow pump provides normal CO and physiologic stability in a new T-shaped model of TCPC in sheep, in vivo. CFD and in vivo data showed that this experimental arrangement will allow us to evaluate the potential for mechanical support in patients with Fontan failure avoiding major adverse events.
Assuntos
Simulação por Computador , Técnica de Fontan/efeitos adversos , Insuficiência Cardíaca/terapia , Coração Auxiliar , Hemodinâmica , Modelos Cardiovasculares , Animais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Modelos Animais , Análise Numérica Assistida por Computador , Desenho de Prótese , Ovinos , Fatores de TempoRESUMO
Hypoplastic left heart syndrome is a spectrum of complex congenital cardiac defects. Although in borderline cases, biventricular repair is a viable option, in the majority of cases, univentricular palliation is the treatment of choice. Hybrid palliation can be a valid alternative to classic Norwood operation in the neonatal period, especially in selected cases such as high-risk patients or borderline left ventricles. Echocardiography is the main diagnostic modality in this pediatric population, from the fetal diagnosis to the subsequent surgical steps of palliative treatment. Hybrid palliation is performed after birth and is characterized by surgical banding of the pulmonary arteries along with transcatheter stenting of the ductus arteriosus. There are some peculiar aspects of cardiac imaging that characterize this type of palliation, and that should be considered in the different phases before and after the procedure. We aimed to review the current literature about the role of echocardiography in the management of patients with hypoplastic left heart undergoing hybrid palliation.
RESUMO
OBJECTIVES: We sought to investigate the effectiveness of glucocorticoid administration or continuous venovenous hemodiafiltration on endothelin and corticotropin-releasing factor release or clearance during prolonged fetal cardiac bypass and on the overall performance of fetuses. METHODS: Circulating endothelin 1, 2, and 3 and corticotropin-releasing factor levels were measured in fetal ewes during a 60-minute cardiac bypass period performed with an inline axial flow pump. Blood samples were collected before, during, and 90 minutes after cardiac bypass. Animals were divided into 4 groups. The betamethasone group (n = 6) received maternal treatment with 12 mg of betamethasone 1 and 2 days before the experiment. The methylprednisolone group (n = 5) received fetal treatment with 40 mg/kg intravenous methylprednisolone at the beginning of cardiac bypass. The continuous venovenous hemodiafiltration group (n = 4) underwent continuous venovenous hemodiafiltration with a 0.3-m(2) polysulfone filter during cardiac bypass. The final group was the control group (n = 4). RESULTS: Maternal steroid pretreatment failed to decrease endothelin or corticotropin-releasing factor production when compared with levels in the control animals. Fetal treatment with methylprednisolone produced a significant decrease in endothelin 2 production during cardiac bypass (P <.02) and endothelin 1 production at the end of the experiment (P <.02). Continuous venovenous hemodiafiltration blocked completely the increase of endothelin and corticotropin-releasing factor levels during cardiac bypass (P <.02), which was maintained 90 minutes after cardiac bypass. Acid-base balance was preserved during cardiac bypass by the continuous venovenous hemodiafiltration but worsened after disconnection of the extracorporeal circuit, whereas animals treated with methylprednisolone had better pH, Paco(2), and bicarbonate levels by the end of the experiment. The overall tolerance of the procedure was better in the continuous venovenous hemodiafiltration group during cardiac bypass and in the methylprednisolone group at the end of the experiment. CONCLUSIONS: Continuous venovenous hemodiafiltration provides sustained stability of endothelin levels during fetal cardiac bypass. This technique might help, in association with fetal steroid treatment, to contain the inflammatory response leading to postbypass placental dysfunction.
Assuntos
Hormônio Liberador da Corticotropina/sangue , Endotelinas/sangue , Circulação Extracorpórea , Feto/cirurgia , Glucocorticoides/administração & dosagem , Hemodiafiltração , Equilíbrio Ácido-Base , Animais , Betametasona/administração & dosagem , Feminino , Metilprednisolona/administração & dosagem , Gravidez , OvinosRESUMO
The high toll of death among first-week infants is due to infections occurring at the end of pregnancy, during birth or by breastfeeding. This problem significantly concerns industrialized countries also. To prevent the typical "first-week infections", a vaccine would be protective as early as at the birth. In utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. We have already published results of a 2-year follow-up showing long-term safety, protective antibody titers at birth and long-term immune memory, following intramuscular in utero anti-HBV DNA immunization in 90-days pig fetuses. We have now analyzed further parameters of short-term safety. Two different reporter genes were injected in the thigh muscles of 90-days fetuses. At 8 days following DNA injection, we found high-level of transgenes expression in all injected fetuses. A step gradient of expression from the area of injection was observed with both reporter genes. CMV promoter/enhancer produced higher levels of expression compared to SV40 promoter/enhancer. Moreover, no evidence of local or systemic flogistic alterations or fetal malformations, mortality or haemorrhage following intramuscular injection were observed. A single anti-HBV s-antigen DNA immunization in 90-days fetuses supported protective antibody levels in all immunized newborns, lasting at least up to 4 months after birth. Our report further sustains safety and efficacy of intramuscular in utero naked gene transfer and immunization. This approach may support therapeutic or prophylactic procedure in many early life-threatening pathologic conditions.
Assuntos
Técnicas de Transferência de Genes , Músculos/embriologia , Suínos/embriologia , Transgenes , Vacinas de DNA/administração & dosagem , Animais , Estudos de Viabilidade , Feminino , Plasmídeos , Gravidez , Vacinas de DNA/genética , Vacinas de DNA/imunologiaRESUMO
Cardiac surgery with cardiopulmonary bypass (CPB) elicits an inflammatory response and has a multitude of biological consequences, ranging from subclinical organ dysfunction to severe multiorgan failure. Pediatric patients are more prone to have a reaction that can jeopardize their outcome. Cytokines are supposed to be important mediators in this response: limiting their circulating levels is, therefore, appealing. We investigated the pattern of cytokine release during pediatric operation for congenital heart anomalies in 20 patients, and the effect of hemofiltration. Tumor necrosis factor alpha (TNF-alpha) was elevated after anesthesia induction and showed significant decrease during CPB. Hemofiltration reduced its concentration, but the effect disappeared on the following day. Interleukin-1 (IL-1) increased slowly at the end of CPB and hemofiltration had no effect. Interleukin-6 (IL-6) showed a tendency toward augmentation during rewarming and hemofiltration did not significantly affect the course. Soluble interleukin-6 receptor (sIL-6r) had a pattern similar to TNF-alpha, but hemofiltration had no effect. On the other hand, interleukin-8 (IL-8) behaved like IL-6. Our findings suggest that baseline clinical status, anesthetic drugs, and maneuvers before incision may elicit a cytokine response, whereas rewarming is a critical phase of CPB. Hemofiltration is effective in removal of TNF-alpha, but its role is debatable for the control of IL-1, IL-6, sIL-6r and IL-8 levels.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Citocinas/sangue , Hemofiltração/normas , Inflamação/sangue , Adolescente , Procedimentos Cirúrgicos Cardíacos/métodos , Criança , Pré-Escolar , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Citocinas/isolamento & purificação , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Inflamação/etiologia , Interleucinas/sangue , Interleucinas/isolamento & purificação , Masculino , Reaquecimento , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/isolamento & purificaçãoRESUMO
The intracoelomic route for in utero hematopoietic stem cell transplantation has been evaluated in pre-immune fetal sheep and the engraftment characteristics defined. Twelve ovine fetuses (gestational ages: 40-45 days) received intracoelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34-selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspension of the liver, spleen, bone marrow and thymus by flow cytometry, cloning assays and polymerase chain reaction (PCR) analysis for human beta(2)-microglobulin gene. The engraftment of liver samples was also evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescent in situ hybridization (FISH) and immunohistochemistry. Four fetuses (33%) aborted shortly after intracoelomic transplantation and were not evaluable for engraftment. Engraftment was detected in 4 fetuses obtained from cesarean delivery on day 70 after transplantation of CD3-depleted cord blood cells. The degree of engraftment in these 4 fetuses ranged from 6 to 22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (No. 435184) and 105 (Nos 915293, 037568) days and 1 fetus delivered at term, which received CD34-selected cord blood cells, had human engraftment with 10, 32, 20 and 10% CD45+ cells in bone marrow, respectively. A further check of human chimerism was done at 1 year after birth of the fetus delivered at term and 7.6% of bone marrow chimerism was detected. In 6 out of 8 fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human beta(2)-microglobulin which also identified human cells in brain, spinal cord, heart, lung and skeletal muscle. On liver samples, FISH and RT-PCR confirmed the xenograft of human cells and the immunohistochemical analysis detected human markers of hematopoietic and hepatic lineage of differentiation. This preliminary study indicates that intracoelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feto/cirurgia , Animais , Antígenos CD34/análise , Coleta de Amostras Sanguíneas , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas/imunologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígenos Comuns de Leucócito/análise , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ovinos/embriologia , Transplante HeterólogoRESUMO
The intracelomic route for in utero hematopoietic stem cell transplantation was evaluated in preimmune fetal sheep and the engraftment characteristics were defined. Twelve twin ovine fetuses (gestational age: 40-45 days) received intracelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34-selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspensions of the liver, spleen, bone marrow, and thymus by flow cytometry, cloning assays, and polymerase chain reaction (PCR) analyses of human beta2-microglobulin. Four fetuses (33%) aborted shortly after intracelomic transplantation and were not evaluable for engraftment. Engraftment was detected in four fetuses obtained from cesarean delivery on day 70 after transplantation of CD3-depleted cord blood cells. The degrees of engraftment in these four fetuses ranged from 6%-22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (no. 435184) and 105 (no. 915293, no. 037568) days and one fetus delivered at term that received CD34-selected cord blood cells had human engraftment with 10%, 32%, 20%, and 10% CD45(+) cells in bone marrow, respectively. In six of eight fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human beta2-microglobulin, which also identified human cells in brain, spinal cord, heart, lung, and skeletal muscle. This preliminary study indicates that intracelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.