Comparative proteomic analysis of plasma of children with congenital heart disease.

Congenital heart disease is one of the largest class of birth defects. Eight subjects with ventricular septal defect (VSD, a kind of congenital heart disease) and 11 health children were enrolled in tandem mass tags label-based quantitative proteomic analysis to compare plasma proteins differentially abundance. A total of 66 proteins were significantly upregulated or downregulated in VSD patients compared with healthy children. These proteins were involved in pathways linked to platelet activation, fructose and mannose metabolism, complement and coagulation cascades, glycolysis/gluconeogenesis, regulation of actin cytoskeleton, and carbon metabolism. The amount of ten proteins changed significantly (p < 0.05) in newly recruited 30 VSD compared with 15 control children, which were validated by ELISA. The areas under the receiver operating characteristic curve values of fructose-bisphosphate aldolase B (ALDOB) and thymosin beta-4 (Tß4) were higher than those of other candidate proteins. ALDOB and Tß4 might be potential biomarkers applied for identifying VSD in the further works.

Determination of dynamic thiol/disulphide homeostasis in children with tetralogy of Fallot and ventricular septal defect.

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p < 0.001, p < 0.001, and p < 0.01, respectively). While native thiol levels were decreased (p < 0.01), disulphide levels were elevated in the TOF group (p < 0.05). We observed marked augmentation of disulphide/native thiol (p < 0.001) and disulphide/total thiol ratios (p < 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p < 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.

Changes in the levels of inflammatory markers after transthoracic device closure of ventricular septal defects in pediatric patients.

BACKGROUND: Transthoracic device closure of ventricular septal defect (VSD) is widely used in the clinic, especially in China. Changes in inflammatory marker levels after transthoracic device closure of VSD in pediatric patients have not been reported. METHODS: We retrospectively collected clinical data for 85 pediatric patients in our hospital from September 2017 to January 2018. The patients were divided into two groups according to treatment (device group vs. surgical group). The clinical and experimental data from the two groups were statistically analyzed. RESULTS: Clinical outcomes were good in all patients without any fatal complications. Similar increasing trends in inflammatory markers (white blood cell (WBC) count, procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6)) were found in the two groups, both of which showed noticeable systemic inflammatory responses. In addition, no significant difference in the postoperative levels of inflammatory markers was observed between these two groups. CONCLUSIONS: Although transthoracic device closure of VSD seems to be less traumatic and involves a quicker recovery, it also induces a systemic inflammatory response as measured by WBC count and PCT, CRP and IL-6 levels, and the altered trends in inflammatory markers were similar to those of conventional surgery under CPB.

Associations of trace elements in blood with the risk of isolated ventricular septum defects and abnormal cardiac structure in children.

This study sought to determine correlations between the presence of isolated ventricular septum defects (VSDs) and blood levels of trace elements. A total of 144 patients with VSDs and 144 controls were recruited for cross-sectional assessment of trace elements and examination of cardiac structures in the Jiangsu and Anhui provinces between 2016 and 2018. Logistic regression was performed to explore the relationships between VSDs and trace elements. Additionally, general linear regression models were used to investigate relationships between trace elements and echocardiography indicators. Relative to the lowest zinc (Zn) concentrations, the highest Zn concentrations may be associated with lower odds of VSD development (OR = 0.03, 95% confidence interval [CI] = 0.01-0.29, P < 0.001). However, no significant relationships between the concentrations of other trace elements and the risk of VSD were identified. Aorta (AO) diameters were markedly smaller in the VSD group, whereas no significant between-group differences were observed for other echocardiography indicators. After adjusting for age and gender, linear regression indicated a significant association between Zn level and mean AO diameter (beta coefficient = 0.247, 95% CI = 0.126-0.367). Zn deficiency was observed in patients with isolated VSDs. Further work to explore the mechanisms by which Zn deficiency leads to VSDs is warranted.

Levels of Circulating mRNA for the Tenascin-X (TNXB) Gene in Maternal Plasma at the Second Trimester in Pregnancies with Isolated Congenital Ventricular Septal Defects.

OBJECTIVE: Maternal plasma is a source of circulating placental nucleic acids. In this study, we validated previous observations on abnormal levels of circulating messenger RNA (mRNA) for the tenascin-X gene in pregnancies with ventricular septal defects in the second trimester of pregnancy. METHODS: This was a bicentric retrospective study conducted from March 2016 to July 2017. Real-time polymerase chain reaction was used to identify abnormally expressed genes, comparing ten women carrying a euploid fetus with ventricular septal defects to 30 controls at 19-24 weeks of gestation. The univariable analysis was used to determine whether the mean mRNA for the tenascin-X gene values would differ from the expected values for the controls. RESULTS: mRNA for tenascin-X gene values was higher in ventricular septal defects, 4.38 ± 3.01 versus 1.00 ± 0.80. The result was still significant even after adjustment for gestational age. CONCLUSIONS: These data confirm previous studies on the specific association of mRNA species and type of congenital heart defect and confirm that ventricular septal defects are associated with abnormal mRNA for the tenascin-X gene. The positive predictive value of this molecular marker in the general population should be assessed through prospective studies.

Influence of high-flow modified ultrafiltration on brain oxygenation and perfusion during surgery for children with ventricular septal defects: a pilot study.

BACKGROUND: Modified ultrafiltration (MUF) can be performed in infants with ventricular septal defects (VSDs) after cardiopulmonary bypass (CPB) to reduce haemodilution and its potential adverse effects. High-flow MUF might reduce ultrafiltration duration and hasten the necessary correction of haemodilution during CPB. However, its influence on brain oxygenation remains controversial. OBJECTIVE: This non-randomized, prospective, pilot study aimed to investigate the influence of high-flow MUF on brain oxygenation in infants with VSDs. METHODS: High-flow MUF (≥20 mL/kg/min) was performed in twenty infants. Brain oxygen saturation (rSO2) and tissue haemoglobin index (tHI) were non-invasively and continuously measured intraoperatively using near-infrared spectroscopy (NIRS). Transcranial Doppler non-invasively detected the mean flow velocity of the middle cerebral artery (Vmean). RESULTS: rSO2 increased significantly during MUF, as did tHI, Vmean, mean arterial pressure and haematocrit (all p<0.05). No correlation was found between changes in rSO2 and changes in other parameters (all p≥0.05). CONCLUSION: In infants with ventricular septal defects managed with CPB during VSDs repair, high-flow MUF did not reduce brain oxygenation.

Perioperative plasma mitochondrial DNA dynamics and correlation with inflammation during infantile cardiopulmonary bypass.

OBJECTIVE: Numerous studies in animals and humans have demonstrated that inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 play a role in cardiopulmonary bypass (CPB), which might affect surgical outcomes. Plasma mitochondrial DNA (mtDNA), a recently discovered pro-inflammatory agent, is released by cells upon insult. This study aimed to detect changes in plasma mtDNA levels at different time points after infantile CPB and explore its potential association with inflammatory mediators. METHODS: In the present study, we analyzed the perioperative plasma mtDNA and inflammatory cytokine levels of 48 infants undergoing ventricular septal defect closure. Blood samples were collected before aortic cross-clamping (T1), at the end of CPB (T2), and 6h (T3), 12h (T4), and 24h (T5) post-CPB. Reverse transcription-polymerase chain reaction and specific enzyme-linked immunosorbent assay were used to quantify the plasma mtDNA and inflammatory cytokines, respectively. Bivariate correlation analysis was used to determine the correlations between plasma mtDNA and inflammatory cytokines. RESULTS: Plasma mtDNA levels increased at T2 and peaked at T3. Significant positive correlations were found between peak plasma mtDNA (at T3) and several inflammatory biomarkers, including IL-6 (at T3) (r=0.62, P<0.001), IL-8 (at T2) (r=0.53, P<0.001), and TNF-α (at T3) (r=0.61, P<0.001). CONCLUSION: Here we report that mtDNA may participate in a systemic inflammatory response to CPB.

Altered Carnitine Homeostasis in Children With Increased Pulmonary Blood Flow Due to Ventricular Septal Defects.

OBJECTIVES: Congenital heart disease with increased pulmonary blood flow results in progressive pulmonary vascular endothelial dysfunction and associated increased perioperative morbidity. Using our ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated progressive endothelial dysfunction associated with disruption in carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide signaling, and enhanced reactive oxygen species generation. However, potential alterations in these parameters in patients with congenital heart disease have not been investigated. The objective of this study was to test the hypothesis that children with increased pulmonary blood flow will have evidence of altered carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide levels, and increased reactive oxygen species generation. DESIGN: A prospective single-center cohort study. SETTING: A tertiary care cardiac ICU/PICU. PATIENTS: Arterial blood samples from 18 patients with congenital heart disease associated with increased pulmonary blood flow (ventricular septal defect), 20 with congenital heart disease without increased pulmonary blood flow (tetralogy of Fallot), and 10 without heart disease (controls) were obtained. INTERVENTIONS: Plasma levels of total carnitine, free carnitine, acylcarnitine, and lactate-to-pyruvate ratios, an indicator of mitochondrial function, were determined and compared. In addition, levels of superoxide and hydrogen peroxide were determined and compared in patients with ventricular septal defect and controls. Statistical analysis was performed using an unpaired t test and analysis of variance. MEASUREMENTS AND MAIN RESULTS: Baseline acylcarnitine levels (25.7 ± 13 vs 12.7 ± 8.3; p < 0.05), the acylcarnitine-to-free carnitine ratio (0.8 ± 0.1 vs 0.3 ± 0.05; p < 0.05), and the lactate-to-pyruvate ratio were higher in ventricular septal defect (27.5 ± 3.8 vs 11.1 ± 4.1, p < 0.05) than tetralogy of Fallot; there were no differences between tetralogy of Fallot and control. Superoxide and H2O2 levels were also higher in ventricular septal defect compared with controls, and NOx levels were lower in ventricular septal defect patients compared with tetralogy of Fallot and controls (p < 0.05). CONCLUSIONS: These data suggest that increased pulmonary blood flow from ventricular septal defect results in altered carnitine and mitochondrial homeostasis, decreased nitric oxide signaling, and increased reactive oxygen species production. These data are consistent with our animal data demonstrating that altered carnitine homeostasis results in mitochondrial dysfunction, increased reactive oxygen species production, and decreased bioavailable nitric oxide. Since disruption of carnitine metabolism may contribute to endothelial dysfunction, carnitine supplementation may attenuate endothelial dysfunction associated with increased pulmonary blood flow and warrants further investigation.

Population Study Confirms Serum Proteins' Change and Reveals Diagnostic Values in Congenital Ventricular Septal Defect.

This study was designed to validate thrombospondin 1 (TSP-1), vascular endothelial-cadherin complex (VE-cad), insulin-like growth factor 2 (IGF-2), and amyloid precursor protein (APP) and assess their diagnostic value in ventricular septal defect (VSD). We investigated the serum levels of TSP-1, VE-cad, IGF-2, and APP by enzyme-linked immunosorbent assay in a hospital-based case-control study that included 40 VSD children and 40 healthy controls. Logistic regression analysis was applied to evaluate the relationship of the proteins and VSD, and receiver operating characteristic (ROC) curve was used to assess the diagnostic value of the significant proteins. The serum levels of TSP-1, VE-cad, and IGF-2 were significantly higher in VSD patients than those in healthy controls (p < 0.05). Multivariate logistic regression analysis demonstrated that high levels of TSP-1, VE-cad, and IGF-2 were significantly associated with an increased risk of VSD [TSP-1 (OR 26.91, 95% CI 6.60-72.66, p < 0.001), VE-cad (OR 11.91, 95% CI 3.90-36.36, p < 0.001), IGF-2 (OR 3.25, 95% CI 1.25-8.43, p = 0.015)]. Areas under the ROC curve for TSP-1, VE-cad, and IGF-2 were 0.985, 0.838, and 0.658, respectively. These data demonstrated that TSP-1, VE-cad, and IGF-2 were significantly associated with risk of VSD and manifested diagnostic values, which may provide new evidence for understanding the etiology and promote the early diagnosis and prevention of VSD.

[Suspended Ventricular Septal Defect Closure Due to Heparin Resistance;Report of a Case].

We present a case of heparin resistance whereby open heart surgery was discontinued. A 53-year-old woman who was diagnosed with ventricular septal defect and atrial septal defect was scheduled for intracardiac repair. However, after intravenous heparin (400 U kg-1) supplementation, the activated clotting time (ACT) increased only to seconds. The operation was discontinued because the addition of heparin( 200 U kg-1) did not show sufficient prolongation of ACT, fully indicative of heparin resistance. Additional antithrombin III concentrate was also ineffective. Postoperative study of the administration of heparin in vitro to the patient's serum showed the probability of transient heparin resistance arising from the stress of surgery.

Hypothermia During Cardiopulmonary Bypass Increases Need for Inotropic Support but Does Not Impact Inflammation in Children Undergoing Surgical Ventricular Septal Defect Closure.

Minimizing the systemic inflammatory response caused by cardiopulmonary bypass is a major concern. It has been suggested that the perfusion temperature affects the inflammatory response. The aim of this prospective study was to compare the effects of moderate hypothermia (32°C) and normothermia (36°C) during cardiopulmonary bypass on markers of the inflammatory response and clinical outcomes (time on ventilator) after surgical closure of ventricular septal defects. During surgical closure of ventricular septal defects under cardiopulmonary bypass, 20 children (median age 4.9 months, range 2.3-38 months; median weight 7.2 kg, range 5.2-11.7 kg) were randomized to a perfusion temperature of either 32°C (Group 1, n = 10) or 36°C (Group 2, n = 10). The clinical data and blood samples were collected before cardiopulmonary bypass, directly after aortic cross-clamp release, and 4 and 24 h after weaning from cardiopulmonary bypass. Time on ventilation as primary outcome did not differ between the two groups. Other clinical outcome parameters like fluid balance or length of stay in the intensive care were also similar in the two groups. Compared with Group 2, Group 1 needed significantly higher and longer inotropic support (P < 0.001). In Group 1, two infants had junctional ectopic tachycardia, and another had a pulmonary hypertensive crisis. Perfusion temperature did not influence cytokine release, organ injury, or coagulation. Cardiopulmonary bypass temperature does not influence time on ventilation or inflammatory marker release. However, in the present study, with a small patient cohort, patients operated under hypothermic bypass needed higher and longer inotropic support. The use of hypothermic cardiopulmonary bypass in infants and children should be approached with care.

Altered Cisatracurium Pharmacokinetics and Pharmacodynamics in Patients with Congenital Heart Defects.

The neuromuscular blocking agent cisatracurium is frequently used adjunctively in anesthesia to facilitate endotracheal intubation and to provide muscle relaxation during surgery. We aimed to determine the pharmacokinetics (PK)/pharmacodynamics (PD) of cisatracurium in patients with congenital heart defects (CHDs), such as ventricular septal defects and atrial septal defects, and to assess the effects of CHDs on the PK/PD profiles of cisatracurium. A modified two-compartment model with drug clearance from both compartments was best fitted to the PK data to determine the PK parameters. The model suggested that septal defects significantly lowered the rate of cisatracurium distribution from the central to peripheral compartment. The intercompartment rate constants k12 and k21 were significantly reduced (35%-60%, P < 0.05) in patients with ventricular septal defects and in patients with atrial septal defects compared with control patients. Consistently, septal defects caused a marked increase (160%-175%, P < 0.001) in the distribution half-life. Furthermore, significantly delayed pharmacodynamic responses to cisatracurium were observed in patients with septal defects. The onset time (i.e., the time to maximal neuromuscular block) was prolonged from 2.2 minutes to 5.0 minutes. PK/PD modeling suggested that reduced concentrations of cisatracurium in the effect compartment due to poorer distribution were the main cause of lagged pharmacodynamic responses. In conclusion, cisatracurium PK/PD were significantly altered in patients with septal defects. Our study should be of use in clinical practice for the administration of cisatracurium to patients with CHDs.

Acute phase proteins altered in the plasma of patients with congenital ventricular septal defect.

PURPOSE: Ventricular septal defect (VSD) has intracardiac left-to-right shunt and increased pulmonary flow that may affect the acute phase response (APR). We examined the hypothesis that plasma proteins of VSD patients may be altered. EXPERIMENTAL DESIGN: 2DE and MS were used to detect differential plasma proteins in VSD patients (n = 55) and controls (n = 70). Candidate APR proteins were confirmed by ELISA in new samples. RESULTS: Among three differentially expressed APR proteins from 322 protein spots detected, haptoglobin (0.4 ± 0.04 versus 0.6 ± 0.07 mg/mL; p = 0.016) and serum amyloid P-component (SAP) (3.8 ± 0.2 versus 6.3 ± 0.8 ng/mL; p = 0.003) were significantly lower and orosomucoid 2 (3.1 ± 0.1 mg/mL versus 2.3 ± 0.1 mg/mL; p < 0.001) was significantly higher in VSD patients than in normal controls. CONCLUSIONS AND CLINICAL RELEVANCE: The plasma concentration of three acute phase proteins, haptoglobin, SAP, and orosomucoid 2 are altered that may reflect inflammation, be associated with decreased innate immune system function, and predispose the VSD patients to vulnerability to infections and pulmonary disease. These three proteins in plasma may also be developed as biomarkers for the function of innate immune system in patients with congenital heart disease.

Inflammatory response to hyperoxemic and normoxemic cardiopulmonary bypass in acyanotic pediatric patients.

BACKGROUND: Hyperoxemic management during cardiopulmonary bypass (CPB) is still common, and there is no consensus about physiologic oxygen tension strategy (normoxemic management) during pediatric CPB. In this study, we compared the postoperative conditions and measures of inflammatory response among patients with acyanotic congenital heart disease subjected to either hyperoxemic or normoxemic management strategy during CPB. METHODS: We studied 22 patients with a ventricular septal defect and pulmonary artery hypertension. The patients were divided into two groups. Group I (n=9) received normoxemic management (PaO2=100-150 mm Hg) and group II (n=13) received hyperoxemic management (PaO2=200-300 mm Hg) during CPB. There was no difference between groups with regard to age, body weight, duration of CPB, and aorta clamping time or preoperative pulmonary hypertension (pulmonary pressure/systemic pressure [Pp/Ps]). In each group, the blood samples to measure the cytokine levels were collected before and after the CPB. RESULTS: Although we observed no statistically significant differences in postoperative intubation time, alveolar-arterial oxygen difference, creatine kinase MB level, and pulmonary hypertension (Pp/Ps) between group I (10.7±13.4 hours, 197±132 mm Hg, 148±58.6 IU/L, 42.8%±22.1%, respectively) and group II (27.8±36.5 hours, 227±150 mm Hg, 151±72.6 IU/L, 50.4%±16.0%, respectively), levels of median interleukin 6 and tumor necrosis factor α were lower in group I (129.8 and 17.0 pg/mL, respectively) than that in group II (487.8 and 22.5 pg/mL, respectively). CONCLUSION: During the CPB in acyanotic pediatric patients, normoxemic management can minimize the systemic inflammatory response syndrome associated with CPB. We can apply this physiologic oxygen tension strategy to surgical advantage during heart surgeries in acyanotic pediatric patients.

Platelet activation through the efficacy of aspirin in congenital heart disease patients undergoing transcatheter closure of atrial septal defects or ventricular septal defects.

OBJECTIVES: The aim of this study is to compare preoperative and postoperative conditions of GMP-140 concentration, the aggregation and activation of platelets in congenital heart disease patients undergoing transcatheter closure of atrial septal defects (ASDs) or ventricular septal defects (VSDs), and the appropriate dose of aspirin of patients after transcatheter closure. MATERIALS AND METHODS: Thirty-two consecutive patients with ASD (n=16) and VSD (n=16), as shown on transthoracic echocardiography and right heart catheter examination, were treated with a percutaneous catheter occlusion. The patients comprised 13 males and 19 females with a mean age of 25.6±9.15. Patients were randomly assigned into two groups within half an hour after ASD or VSD occlusion. Group A cases were treated with 3 mg/kg/day enteric-coated aspirin tablets for 6 months, while patients in group B received 5 mg/kg/day enteric-coated aspirin tablets for 6 months. RESULTS: The rates of platelet aggregation (PAG) in the immediate postoperative ASD/VSD occlusion were significantly higher than those in the preoperative ASD/VSD occlusion (adenosine diphosphate [ADP]-induced PAG: 64.98%±7.65% vs. 86.33%±6.54%, p<0.05; arachidonic acid [AA]-induced PAG: 62.92%±9.11% vs. 86.96%±6.90%, p<0.05, respectively). After treatment with aspirin, the GMP-140 levels presented a clearly defined downward trend in the immediate postoperative period (3 mg/kg/day aspirin: 18.30±3.42 vs. 13.37±1.80, p<0.05; 5 mg/kg/day aspirin: 18.30±3.42 vs. 13.41±1.60, p<0.05), but no obvious difference was observed considering the GMP-140 levels in the 4 days after occlusion (all p>0.05). CONCLUSION: Our study showed that the GMP-140 serum level and PAG were increased after ASD and VSD occlusion, and patients may have a trend of decreased GMP-140 serum levels after the ASD or VSD occlusion surgeries after the treatment with aspirin. Daily oral administration of 3 and 5 mg/kg/day aspirin can induce a significant decrease in PAG of patients after VSD/ASD occlusion.

Characterization of circulating microRNA expression in patients with a ventricular septal defect.

OBJECTIVES: Ventricular septal defect (VSD), one of the most common types of congenital heart disease (CHD), results from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in development of CHD. This study was to characterize the expression of miRNAs that might be involved in the development or reflect the consequences of VSD. METHODS: MiRNA microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR) were employed to determine the miRNA expression profile from 3 patients with VSD and 3 VSD-free controls. 3 target gene databases were employed to predict the target genes of differentially expressed miRNAs. miRNAs that were generally consensus across the three databases were selected and then independently validated using real time PCR in plasma samples from 20 VSD patients and 15 VSD-free controls. Target genes of validated 8 miRNAs were predicted using bioinformatic methods. RESULTS: 36 differentially expressed miRNAs were found in the patients with VSD and the VSD-free controls. Compared with VSD-free controls, expression of 15 miRNAs were up-regulated and 21 miRNAs were downregulated in the VSD group. 15 miRNAs were selected based on database analysis results and expression levels of 8 miRNAs were validated. The results of the real time PCR were consistent with those of the microarray analysis. Gene ontology analysis indicated that the top target genes were mainly related to cardiac right ventricle morphogenesis. NOTCH1, HAND1, ZFPM2, and GATA3 were predicted as targets of hsa-let-7e-5p, hsa-miR-222-3p and hsa-miR-433. CONCLUSION: We report for the first time the circulating miRNA profile for patients with VSD and showed that 7 miRNAs were downregulated and 1 upregulated when matched to VSD-free controls. Analysis revealed target genes involved in cardiac development were probably regulated by these miRNAs.

Importance of plasma endothelin-1 level in the evaluation of heart failure severity in infants with ventricular septal defect.

BACKGROUND: Haemodynamic disturbances due to ventricular septal defect (VSD) can lead to heart failure (HF) and cause neurohormonal activation. Endothelin-1 (ET-1) clearance takes place mainly in the pulmonary circulation. We hypothesized that increased pulmonary blood flow in children with VSD could influence ET-1 level and reflect haemodynamic disturbances in these patients. AIM: To analyse usefulness of plasma ET-1 level in the evaluation of HF severity in infants with VSD without pulmonary hypertension. METHODS: The study group included 34 children (aged 38-338 days, mean 130 ± 81 days) with VSD. Evaluation included history, physical examination, ET-1 level measurement, standard 12-lead electrocardiogram, chest X-ray, and transthoracic echocardiography in all children. The control group consisted of 31 healthy children. RESULTS: Mean plasma ET-1 level was significantly (p < 0.01) higher in the study group compared to the control group. We found no significant difference (p > 0.05) in mean plasma ET-1 level between children with or without HF. No significant correlation was found between plasma ET-1 level and the severity of HF. CONCLUSIONS: Infants with VSD show higher ET-1 level compared to healthy children. Plasma ET-1 level does not reflect the severity of HF in infants with VSD.

Circulating matrix metalloproteinase-2 and -9 enzyme activities in the children with ventricular septal defect.

Ventricular septal defect (VSD) is the most common form of congenital heart diseases. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in causal cardiac tissue remodeling. We studied the changes of circulating MMP-2 and MMP-9 activities in the patients with VSD severity and closure. There were 96 children with perimembranous VSD enrolled in this study. We assigned the patients into three groups according to the ratio of VSD diameter/diameter of aortic root (Ao). They were classified as below: Trivial (VSD/Ao ratio ≤ 0.2), Small (0.2 < VSD/Ao ≤ 0.3) and Median (0.3 < VSD/Ao) group. Plasma MMP-2 and MMP-9 activities were assayed by gelatin zymography. There was a significant higher MMP-2 activity in the VSD (Trivial, Small and Median) groups compared with that in Control group. The plasma MMP-9 activity showed a similar trend as the findings in MMP-2 activity. After one year follow-up, a significant difference in the MMP-9 activity was found between VSD spontaneous closure and non-closure groups. In conclusion, a positive trend between the severity of VSD and activities of MMP-2 and MMP-9 was found. Our data imply that MMP-2 and MMP-9 activities may play a role in the pathogenesis of VSD.

Comparison of cardioprotective effects of volatile anesthetics in children undergoing ventricular septal defect closure.

BACKGROUND: Volatile anesthetic agents may precondition the myocardium and protect against ischemia and infarction. Preconditioning by volatile anesthetic agents is well documented in adults but is underinvestigated in children. The present study compares the effect of preconditioning in children by three volatile anesthetic agents along with several other variables associated with cardioprotection. METHOD: Eighty children scheduled for ventricular septal defect closure under cardioplegic arrest were assigned to preconditioning for five minutes after commencement of cardiopulmonary bypass (CPB) with one minimum alveolar concentration (MAC) of one of the following agents: isoflurane, sevoflurane, desflurane, or placebo (oxygen-air mixture). The plasma concentration of creatine kinase MB (CK-MB) was determined after initiation of CPB, and again 6 and 24 hours after admission to the intensive care unit (ICU) after surgery. Duration of inotropic support, mechanical ventilation, and length of ICU stay in all the groups were also recorded. RESULTS: Preconditioning with isoflurane, sevoflurane, and desflurane was associated with significantly decreased postoperative release of CK-MB as compared to placebo group at 6 (group 1: 237.2 ± 189, group 2: 69.8 ± 15.8, group 3: 64.7 ± 37.8, and group 4: 70.4 ± 26.7) and 24 hours (group 1: 192.4 ± 158.2, group 2: 67.7 ± 25.0, group 3: 85.7 ± 66.8, and group 4: 50.4 ± 31.6) after admission to ICU. No significant differences were observed in the CK-MB levels among the three volatile anesthetic agents. Duration of inotropic support, mechanical ventilation, and length of ICU stay were greater in placebo group as compared to other groups without reaching statistical significance. CONCLUSION: Volatile anesthetic appear to provide definite cardioprotection to pediatric myocardium. No conclusion can be drawn regarding the best preconditioning agent among isoflurane, sevoflurane, and desflurane.