先天性心脏病婴幼儿外科治疗对策分析(附115例报告)

目的 探讨婴幼儿先天性心脏病外科围术期处理对策.方法我院于2008年6月至2011年12月对115例患先天性心脏病的婴幼儿实施外科手术治疗,男性73例,女性42例,年龄3个月至3岁,体重3.5～20.0 kg;其中室间隔缺损(VSD)54例,法洛四联症(TOF)14例,室间隔缺损合并房间隔缺损(VSD+ASD)10例,房间隔缺损(ASD)9例,动脉导管未闭(PDA)8例,肺动脉瓣狭窄(PS)7例,室间隔缺损合并动脉导管未闭(VSD+PDA)5例,完全型肺静脉异位引流(TAPVC)4例,右室双出口(DORV)3例,主动脉缩窄合并室间隔缺损(CoA+VSD)1例.结果全组死亡5例,死亡率为4.3%.死亡原因:低心排出量综合征1例,肺高压危象2例,呼吸道梗阻2例.结论先天性心脏病患儿在婴幼儿期外科治疗可以取得满意疗效,根据婴幼儿生理、病理特点采取个体化治疗对策是成功的关键.     

Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group.     

Surgical management of congenital cardiac defects in neonates and young infants born with extremely low weight

Surgical treatment of cardiac defects in infants born with extremely low weight is sometimes required during the neonatal period. Optimal timing of these operations has yet to be clarified. With this in mind, we reviewed our experience of surgical treatment for 29 infants born with extremely low weight between 1994 and 2001. The main surgical procedures were ligation of a patent arterial duct in 26, a Brock procedure in 2, and ligation of an aorto-pulmonary window in 1 infant. The age at operation ranged from 5 to 57 days, with a median of 30 days, and weighed from 506 to 902 g, with a median of 710 g. There were no deaths. For the 2 infants undergoing the Brock procedure, the reduced systemic blood flow also necessitated closure of the arterial duct. For almost all the 26 infants with a patent arterial duct, indomethacin was given as the initial therapy, but the duct had not closed completely. Increased symptomatology just before the operation due to reduced systemic blood flow, such as decreased cerebral blood flow, decreased urine output, and intestinal ischemia, mandated the earlier surgical ligation (r = -0.576, p = 0.004). The youngest infant needed an infusion of catecholamines perioperatively to maintain stable hemodynamic conditions (r = 0.554, p = 0.003). In 4 infants, including the youngest 2, steroids were administered intravenously just after the ligation. Our results suggest that reduced systemic blood flow is the main indication of surgical repair in infants born with extremely low weight. Even for one in whom the supply of pulmonary blood is dependent on the arterial duct, early reconstruction of the pulmonary arterial pathways, using the Brock procedure, followed by ligation of the duct, is required. Acute adrenal insufficiency should not be overlooked just after the surgery, particularly in the youngest patients.     

Alfentanil in infants and children with congenital heart defects

The use of an alfentanil infusion as a supplement to a nitrous oxide-halothane anesthetic and the pharmacokinetics of alfentanil were evaluated in infants and children undergoing surgery for correction of congenital heart defects. Eleven patients, six infants and five children, were studied. Anesthesia was induced with nitrous oxide-halothane and pancuronium, 0.15 mg/kg. After intubation, anesthesia was maintained with nitrous oxide-oxygen and halothane to a maximum inspired concentration of 0.6%. After administration of atropine, 20 tag/kg, alfentanil, 20 μg/kg, was given, followed by a continuous infusion of 1 μgkg/min, which was stopped after closure of the sternum. Supplemental boluses of alfentanil, 5 μ/kg, were given when, during surgery, blood pressure and/or heart rate increased more than 20% above control values. At the end of surgery, after antagonism of residual neuromuscular blockade, the patients were extubated. Arterial blood samples were collected at regular intervals during surgery and for six hours thereafter for determination of alfentanil plasma concentrations by gas chromatography. Pharmacokinetic data were calculated using the method of residuals and noncompartments moment analysis. Although atropine was administered, heart rate decreased significantly (2.5% to 15%) in all infants after administration of alfentanil. In the older children, blood pressure decreased 10% to 35%. In the period before bypass, three infants and four children needed supplemental boluses of alfentanil. During and after bypass, anesthesia was adequate. All patients could be extubed within 34 minutes of stopping the alfentanil infusion. Naloxone was not required in any patient, and postoperative respiratory depression did not occur. In the infants and children, total plasma clearance was 8.2 ± 2. mL/kg/min and 6.3 ± 0.8 mL/kg/min, respectively. Distribution volume was 0.48 ± 0.12 L/kg and 0.31 ± 0.08 L/kg, and elimination half-life was 69 ± 25 min and 62 ± 9 min, respectively. It is concluded that a continuous infusion of alfentanil as a supplement to nitrous oxide-halothane anesthetic is a feasibly method of anesthesia in infants and children undergoing surgery for correction of congenital heart defects.     

Distribution of ABO phenotypes in patients with congenital cardiac defects

BACKGROUND: Cardiac anomalies are among the most frequent congenital malformations, but the basic underlying causes for most cardiac defects remains undetermined. Some 40 years ago, a higher incidence of blood group B was reported in a small number of African-American children with congenital cardiac defects. In this study, we sought to re-evaluate this association using a larger population.Methods and RESULTS: We collected data from 1985 patients undergoing cardiac surgery from July, 2000, through December, 2004. We divided the patients into 6 subgroups according to their diagnosis. We then compared the prevalence of ABO phenotypes between the patients and the general population of the United States of America by chi-square analysis. There were no significant differences in the distribution of the ABO phenotypes amongst the subgroups of those with congenital cardiac disease, or any for subgroup compared to the general population.CONCLUSION: While statistical significance is influenced by the size of the population within the United States of America and the small numbers within each of our subgroups of patients with congenital cardiac disease, we have been unable to show any relationship between the distribution of ABO phenotypes and the existence of congenital cardiac disease.     

Catheter closure of congenital cardiac defects

In summary, the role of the pediatric cardiac catheterization laboratory has changed from that of a primary diagnostic facility to a major therapeutic arena. We have reviewed our experiences with various occlusion devices to successfully treat patients with various congenital cardiac malformations, particularly the PDA. The future for interventional therapeutic procedures appears bright with the possibility of closure of certain defects in an outpatient setting now a reality, thereby lowering hospitalization costs and lessening post-therapeutic morbidity while preserving a high level of successful outcomes.     

Electrocardiographic signs of autonomic imbalance in infants with congenital heart defects

Infants with congenital heart disease (CHD) and heart failure have elevated plasma norepinephrine levels (NE) as a sign for sympathetic activation. We analysed ECGs of 64 infants with CHD and found normal heart rates on average in four groups split up according to their NE. Mean heart rate in Holter ECGs was significantly reduced in infants with low NE (below 350 ng/l) but normal in the other groups (NE < 350 ng/l: 121 +/- 10/min; NE = 350-700 ng/l: 139 +/- 11/min; NE = 700-1300 ng/l: 142 +/- 13/min; NE > 1300 ng/l: 135 +/- 12/min). An analysis of heart rate variability in a subgroup of 25 infants showed significantly reduced values in patients with elevated NE in comparison to 70 healthy infants. Significantly reduced frequency domain measures in infants with elevated NE but also normal NE are evidence for a high diagnostic sensitivity of an analysis of heart rate variability for autonomic imbalance with sympathetic activation and parasympathetic withdrawal in infants with CHD.     

Variants of the CFC1 gene in patients with laterality defects associated with congenital cardiac disease

OBJECTIVES: This study was designed to assess the frequency and types of genetic variants in CFC1 in children with laterality disorders associated with cardiovascular involvement. BACKGROUND: Laterality syndromes are estimated to comprise 3% of neonates with congenital cardiac disease. Genetic predisposition in some cases of laterality defects has been suggested by associated chromosomal anomalies and familial aggregation, often within consanguineous families, suggesting autosomal recessive inheritance. Mice with induced homozygous mutations in cfc1, and heterozygous CFC1 mutations in humans, have been associated with laterality defects. METHODS: Direct sequence analysis of the coding sequence of CFC1 was performed in 42 subjects with laterality defects and congenital cardiac disease. RESULTS: We identified 3 synonymous coding variants, 3 non-synonymous coding variants (N21H, R47Q, and R78W), and 2 intronic variants in CFC1. The N21H variant was observed in 3 of 19 affected Caucasians, and the R47Q variant in another 2. Neither polymorphism was observed in Caucasian controls. Furthermore, all subjects with the N21H polymorphism had double outlet right ventricle. Transmission of both the N21H and R47Q polymorphisms from unaffected parents was demonstrated, and all three non-synonymous variants had significant allele frequencies in unaffected African-American subjects, suggesting that other factors must also contribute to laterality defects. CONCLUSIONS: Three non-synonymous variants in CFC1 were identified, the N21H variant being associated with laterality defects in Caucasians, but not fully penetrant. One or more of these non-synonymous missense variants may act as a susceptibility allele in conjunction with other genes, and/or environmental factors, to cause laterality defects.     

Oxygen consumption in infants and children with congenital heart defects]

Resting oxygen uptake was determined by a diaferometer in 90 children with congenital heart disease and in 39 children without cardiac defects, both groups ranging in age from 1 month to 15 years. The children with cardiac defects were classified according to the kind of the defect. The values of all children were related to body surface area and in every case compared with standards of basal metabolic rate of Karlberg and Fleisch. Although there was a tendency to higher values of resting oxygen uptake in children with cardiac defects, a statistically definite difference to the standard values could not be established. The possibly influencing factors of oxygen uptake in children with cardiac defects, as weight reduction, sedation, heart dynamics and oxygen cost of breathing are discussed regarding the literature.     

Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects

We identified a consecutive series of 12 children with noncyanotic congenital cardiac lesions with loss of the largest plasma von Willebrand factor (vWF) multimers determined by SDS-agarose electrophoresis. Seven had previous histories of mucocutaneous hemorrhage; ten had a prolonged bleeding time. Analysis of the factor VIII molecular complex revealed that six patients had reduced vWF measured both immunologically (vW:Ag) and by ristocetin cofactor assay (vW:rist). All had normal or borderline normal factor VIII procoagulant (F VIII) concentrations. Three children had prolonged partial thromboplastin times due to concurrent factor XII deficiency; none had laboratory evidence of intravascular coagulation. Five of the children were restudied after surgical correction of their cardiac lesions. Four had normalization of vWF multimers; the fifth, whose vWF was abnormal postoperatively, had a residual pressure gradient across a previous pulmonary artery banding site. Multimeric abnormalities were not found in the parents of three patients. Thus some patients with noncyanotic congenital heart disease may have an acquired abnormality of vWF that is normalized with correction of the abnormal hemodynamic state.     

Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair

We postulated that combining cell based hVEGF165 gene delivery with cytokine-induced mobilization of bone marrow cells (BMC) may give better prognosis in an infarcted heart. Forty-eight myoabalated female C57BL/6J mice (20-25 g) received 1 x 10(6) BMC from transgenic GFP+ male mice. One month later, acute myocardial infarction (MI) model was developed by coronary artery ligation. Animals were grouped (N = 12) to receive intramyocardial injections of 10 microl DMEM without cells (group 1; group 2) or with 1x10(5) mesenchymal stem cells (MSC) over-expressing hVEGF165 (group 3; group 4). The animals received either cytokine therapy (group 2 and 4) or saline solution (group 1 and 3) for 7 days after MI. Hemodynamic data were obtained 4 weeks after MI using Millar's P-V system and cardiac tissue was harvested for immunohistological studies. We observed regeneration and extensive survival of BMC in and around the infarcted myocardium in groups 3 and 4. Blood vessel density was markedly enhanced in group 4 as compared with groups 1 and 2 in peri-infarct area. Fibrotic area was significantly reduced with improved LV-contractile function in group 2 and 4. LV-systolic and diastolic functions were well-preserved in group 4 as indicated by +dP/dt, -dP/dt and Tau (glantz). We therefore conclude that transplantation of MSC overexpressing VEGF combined with cytokine induced BMC mobilization is superior to either of the monotherapy approach for angiomyogenesis and LV-function recovery.