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Asians have a higher carrier rate of pulmonary arterial hypertension (PAH)-related genetic variants than Caucasians do. This study aimed to identify PAH-related genetic variants using whole exome sequencing (WES) in Asian idiopathic and heritable PAH cohorts. A WES library was constructed, and candidate variants were further validated by polymerase chain reaction and Sanger sequencing in the PAH cohort. In a total of 69 patients, the highest incidence of variants was found in the BMPR2, ATP13A3, and GDF2 genes. Regarding the BMPR2 gene variants, there were two nonsense variants (c.994C>T, p. Arg332*; c.1750C>T, p. Arg584*), one missense variant (c.1478C>T, p. Thr493Ile), and one novel in-frame deletion variant (c.877_888del, p. Leu293_Ser296del). Regarding the GDF2 variants, there was one likely pathogenic nonsense variant (c.259C>T, p. Gln87*) and two missense variants (c.1207G>A, p. Val403Ile; c.38T>C, p. Leu13Pro). The BMPR2 and GDF2 variant subgroups had worse hemodynamics. Moreover, the GDF2 variant patients were younger and had a significantly lower GDF2 value (135.6 ± 36.2 pg/mL, p = 0.002) in comparison to the value in the non-BMPR2/non-GDF2 mutant group (267.8 ± 185.8 pg/mL). The BMPR2 variant carriers had worse hemodynamics compared to the patients with the non-BMPR2/non-GDF2 mutant group. Moreover, there was a significantly lower GDF2 value in the GDF2 variant carriers compared to the control group. GDF2 may be a protective or corrected modifier in certain genetic backgrounds.
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Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/genética , Hipertensão Pulmonar Primária Familiar/genética , Mutação de Sentido Incorreto , Hemodinâmica , Deleção de Sequência , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Mutação , Adenosina Trifosfatases/genética , Proteínas de Membrana Transportadoras/genética , Fator 2 de Diferenciação de Crescimento/genéticaRESUMO
In patients with repaired tetralogy of Fallot (rTOF), the regurgitant fraction (RF) in left pulmonary artery (LPA) and right pulmonary artery (RPA) is usually unequal. The morphometrics may play a crucial role in this RF discrepancy. Cardiovascular MR of 79 rTOF patients and 20 healthy controls were retrospectively enrolled. Forty-four from the 79 patients were matched in age, sex and body surface area to the 20 controls and were investigated for: (1) phase-contrast flow of main pulmonary artery (MPA), LPA, and RPA; (2) vascular angles: the angles between the thoracic anterior-posterior line (TAPL) with MPA (θM-AP), MPA with RPA (θM-R), and MPA with LPA (θM-L); (3) cardiac angle, the angle between TAPL and the interventricular septum; (4) area ratio of bilateral lung and hemithorax regions. Compared with the 20 controls, the 44 rTOF patients exhibited wider θM-AP, sharper θM-L angle, and a smaller θM-L/θM-R ratio. In the 79 rTOF patients, LPA showed lower forward, backward, and net flow, and greater RF as compared with RPA. Multivariate analysis showed that the RF of LPA was negatively associated with the θM-L/θM-R ratio and the age at surgery (R2 = 0.255). Conversely, the RF of RPA was negatively associated with the left lung/left hemithorax area ratio and cross-sectional area (CSA) of LPA, and positively associated with CSA of RPA and MPA (R2 = 0.366). In rTOF patients, the RF of LPA is more severe than that of RPA, which may be related to the vascular morphometrics. Different morphometric parameters are independently associated with the RF of LPA or RPA, which may offer potential insights for surgical strategies.
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Insuficiência da Valva Pulmonar , Tetralogia de Fallot , Septo Interventricular , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia , Estudos Retrospectivos , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/cirurgia , Valor Preditivo dos TestesRESUMO
Pulmonary stenosis (PS) affects cardiopulmonary function and exercise performance. Cardiopulmonary exercise testing (CPET) together with transthoracic echocardiography (TTE) can measure exercise performance, PS progression, and treatment effects. We assessed exercise capacity in PS patients using these methods. We enrolled 28 PS patients aged 6-35 years who received surgery, balloon pulmonary valvuloplasty, and follow-up care. The control population was selected by a 1:1 matching on age, sex, and body mass index. Baseline and follow-up peak pulmonary artery pulse wave velocity (PAV) were compared using TTE. Initial CPET revealed no significant differences in anaerobic metabolic equivalent (MET), peak oxygen consumption (VO2), and heart rate recovery between the two groups, nor were significant differences in pulmonary function identified. Within the PS group, there were no significant differences in MET, peak VO2, and heart rate recovery between the baseline and final CPET. Similarly, no significant differences were observed between the baseline and final PAV. The exercise capacity of patients with properly managed PS was comparable to that of healthy individuals. However, during the follow-up, declining trends in pulmonary function, aerobic metabolism, and peak exercise load capacity were observed among adolescents with PS. This study provides long-term data suggesting that PS patients should be encouraged to perform physical activity. Regular reevaluation should also be encouraged to limit performance deterioration.
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OBJECTIVE: To analyze the aerobic fitness and evolution of exercise tolerance in patients with single-ventricle physiology after total cavopulmonary connection (TCPC) with an extracardiac conduit (ECC). STUDY DESIGN: This retrospective cohort study included patients with previous ECC-TCPC who underwent cardiopulmonary exercise testing (CPET) between September 2010 and September 2019. Patients who completed at least 2 tests (≥6 months apart) with adequate levels of effort were recruited for the serial CPET evaluation. RESULTS: We identified 70 patients (50% male) with a mean age of 6.45 ± 5.14 years at ECC-TCPC and 15.67 ± 5.03 years at the initial CPET. The peak oxygen consumption (peak VO2) to predicted value (peak PD) was 55.90 ± 16.81%. Twenty of the 70 identified patients (50% male) were recruited for serial analysis. The average number of CPETs was 2.6 per patient. The average duration from the first CPET to the last CPET was 3.64 years. The peak VO2 and PD increased slowly, with mean rates of 38.77 ± 129.01 mL/min and 1.66 ± 6.40%, respectively, during the study period. CONCLUSIONS: Although the patients had lower exercise tolerance after ECC-TCPC compared with their normal peers, exercise tolerance appears to have been preserved over the adolescent period in those who underwent serial testing after ECC-TCPC.
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Limiar Anaeróbio/fisiologia , Teste de Esforço/métodos , Técnica de Fontan/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Masculino , Estudos Retrospectivos , TaiwanRESUMO
BACKGROUND: The relationship between adenovirus infection and Kawasaki disease (KD) is unclear. The purpose of this study was to determine the relationship between adenovirus infection and KD using a cohort study in Taiwan. METHODS: We used Taiwan National Health Insurance data (from 2000 to 2008) to conduct a population-based cohort study, analyzing children that was under 18 years of age. In total, 5280 children had adenovirus infection, and 5280 children without adenovirus infection were matched and followed up. Subsequent KD was the major outcome event. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence intervals (CIs) of developing KD associated with adenovirus infection. RESULTS: There was a significantly higher cumulative incidence of KD in the adenovirus-infected cohort than that in the control cohort (log-rank test, p < 0.001). In the adenovirus-infected cohort, overall incidence of KD was 5.29 times higher than that of the control cohort (adjusted HR 5.29, 95% CI: 2.48-11.3). Increased KD risk was associated with previous adenovirus infection in children aged 3-5 years, in female patients, in those with a low urbanization level, and in those with allergies. CONCLUSION: An association between previous adenovirus infection and KD was identified in Taiwanese children, but other potential risk factors were not fully analyzed. The relationship between infection and KD requires further study.
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Infecções por Adenoviridae/complicações , Síndrome de Linfonodos Mucocutâneos/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
BACKGROUND: Hepatic dysfunction is an important long-term complication in Fontan patients. The purpose of this study was to evaluate the hepatic computed tomography (CT) findings after Fontan surgery and identify their association with clinical parameters. METHODS: This study recruited 43 patients (23 male and 20 female patients aged 15.3 ± 6.8 years), who underwent Fontan surgery. Medical records were reviewed to collect their age, sex, congenital heart disease type, date of Fontan surgery, laboratory data, and hepatic CT findings. The relationship between hepatic findings and clinical parameters was analyzed. RESULTS: The follow-up duration was 6.8 ± 4.1 years. Abnormal hepatic parenchymal enhancement was observed in 77% of the patients, with mild degree in 18, moderate degree in 10, and severe degree in 5 patients. According to the univariate analysis, risk factors for hepatic parenchymal enhancement were follow-up duration (odds ratio [OR]: 1.354 [95% confidence interval (CI): 1.024-2.078]; p = 0.042), hypoplastic left heart syndrome (HLHS) (OR: 3.262 [95% CI: 1.145-5.628]; p = 0.002), mean pulmonary artery pressure (OR: 1.598 [95% CI: 1.089-2.132]; p = 0.026), pulmonary vascular resistance index (OR: 1.263 [95% CI: 1.068-1.245]; p = 0.032), and brain natriuretic peptide (OR: 1.956 [95% CI: 1.085-2.673]; p = 0.045). According to the multivariate analysis, only HLHS (OR: 3.856 [95% CI: 1.389-5.863]; p = 0.001), mean pulmonary artery pressure (OR: 1.846 [95% CI: 1.362-2.549]; p = 0.015), and pulmonary vascular resistance index (OR: 1.185 [95% CI: 1.042-1.736]; p = 0.047) were significant risk factors for abnormal parenchymal enhancement. CONCLUSION: Abnormal hepatic parenchymal enhancement detected through CT is common in Fontan patients. Regular liver function test in conjunction with imaging studies may be considered when following up Fontan patients.
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Técnica de Fontan/efeitos adversos , Fígado/patologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Criança , Feminino , Hemodinâmica , Humanos , Fígado/diagnóstico por imagem , Masculino , Peptídeo Natriurético Encefálico/sangue , Adulto JovemRESUMO
MicroRNA (miRNA/miR) dysfunction is a hallmark of lung cancer, and results in the dysregulation of tumor suppressors and oncogenes during lung cancer progression. Selection of the 5p and 3p arms of miRNA is a mechanism that improves the modulation of miRNA biological functions and complicates the regulatory network in human types of cancer. However, the involvement of arm selection preference of miRNA in lung cancer remains unclear. In the present study, changes in miRNA arm selection preference were comprehensively identified in lung cancer and corresponding adjacent normal tissues by analyzing The Cancer Genome Atlas. Arm selection was revealed to be consistent in the majority of miRNAs in lung cancer. Only a few miRNAs had significantly altered arm selection preference in lung cancer. Among these, the biological functions of the individual arms of miR-324 were investigated further. The data revealed that miR-324-5p and -3p were significantly overexpressed in lung cancer cells. Ectopic expression of miR-324-5p significantly promoted cell proliferation and invasion in lung cancer cells, while miR-324-3p overexpression significantly increased cell proliferation but did not alter the invasion of lung cancer cells. In conclusion, the arm selection preference of miRNA may be an additional mechanism through which biological functions are modulated. The results of the present study provide a novel insight into the underlying mechanisms of lung cancer and may direct research into future therapies.
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BACKGROUND: The aim of this prospective study was to assess biventricular performance in asymptomatic adolescents with repaired tetralogy of Fallot (TOF) using 2D speckle tracking and real time 3D echocardiography simultaneously. METHODS: We studied 31 patients with repaired TOF (M/F: 22/9, age: 16.1 ± 6.1 yrs) who had history of cardiac surgery with mean follow-up duration of 12.8 years, and 32 age- and sex-matched normal individuals (M/F: 23/9, age: 16.6 ± 5.1 yrs). All subjects underwent speckle tracking and 3D echocardiography, electrocardiogram, treadmill, and blood sampling for measurement of brain natriuretic peptide (BNP). RESULTS: Compared to the control group, the TOF group had higher BNP level (31.8 ± 21.4 vs 14.1 ± 12.4 pg/ml, p < 0.01), lower peak oxygen consumption (8.4 ± 1.7 vs 9.9 ± 1.6 ml/kg/min, p < 0.05), and longer QRS duration (126 ± 30 vs 82 ± 9 ms, p < 0.01). Patients with repaired TOF had significantly impaired right ventricle (RV) global and all six regional longitudinal strain and strain rate than normal controls. Left ventricle (LV) global and mainly apical regional longitudinal strain and strain rate were reduced in patients with repaired TOF. There was a significant correlation of global longitudinal strain (r = 0.456, p = 0.01) and global time to peak longitudinal strain (r = 0.484, p < 0.01) between LV and RV in patients with repaired TOF. In terms of 3D echo cardiographic volume data, patients with repaired TOF had lower LV stroke volume index (p < 0.05), but higher RV end diastolic volume index (p < 0.01), RV end systolic volume index (p < 0.01), RV stroke volume index (p < 0.01), and pulmonary regurgitation fraction (p < 0.01) than normal controls. CONCLUSION: Our results suggest asymptomatic adolescents with repaired TOF had abnormal biventricular myocardial performance, as demonstrated by combined 2D speckle-tracking and 3D echocardiography. The implications of these findings for management of adolescents late after repaired TOF remain to be determined.
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Ecocardiografia Tridimensional/métodos , Ecocardiografia/métodos , Tetralogia de Fallot/cirurgia , Disfunção Ventricular/diagnóstico por imagem , Adolescente , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: The purpose of this article was to evaluate the effect of maternal smoking exposure during pregnancy on postnatal outcomes. METHODS: This prospective study enrolled 278 pregnant women in the third trimester, who were asked to complete a questionnaire which included inquires about the nature and extent of smoking exposure during their pregnancy. In addition to the questionnaire, each study subject provided urine sample for the measurement of cotinine. Using data generated from this inquiry, we analyzed the association between maternal smoking exposure and birth outcomes. RESULTS: From the 278 enrollees in this study, a minority of subjects (7.2%) smoked, while 40.6% of the study subjects were exposed to environmental tobacco smoke during pregnancy. There was significantly higher birth weight (3205.2 ± 373.1 vs 3089.7 ± 363.0 vs 2959.0 ± 403.7 g, p = 0.004), larger chest size (33.1 ± 1.7 cm vs 32.7 ± 1.5 cm vs 32.0 ± 1.7 cm, p = 0.009), higher bilirubin on postnatal day 3 (8.9 ± 1.6 vs 8.6 ± 1.5 vs 7.8 ± 1.4 mg/dL, p = 0.015), but lower maternal urinary cotinine level (83.7 ± 132.4 vs 153.2 ± 96.0 vs 800.5 ± 1027.8 µg/g creatinine, p < 0.001) in smoking-free status than in passive or active smoking status. Significant risks of birth weight < 2500 g (AOR 3.93 (95% CI 1.61-9.59), p = 0.003) and maternal urinary cotinine ≥ 143 µg/g creatinine (AOR 3.38 (95% CI 2.02-5.66), p < 0.001) were observed as smoking exposure increased. There was significantly higher birth weight (p = 0.048), larger chest size (p = 0.045), and higher bilirubin level on postnatal day 3 (p < 0.001) in the group with cotinine <143 µg/g creatinine than in the group with cotinine ≥ 143 µg/g creatinine. CONCLUSION: Our results demonstrated that maternal smoking exposure during pregnancy is associated with low birth weight and small chest circumference. Although the incidence of active smoking in Taiwanese pregnant women is low, most of them are exposed to passive smoking environment. Further studies are required to evaluate useful interventions to enhance a smoking-free environment during pregnancy.
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Exposição Materna/efeitos adversos , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Bilirrubina/sangue , Estudos Transversais , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: The effect of maternal exposure to essential minerals and heavy metals on fetus is an important issue, which affects women around the world. Few data are available on the concentration of both essential minerals and heavy metals in maternal/fetal medicine. The aims of this study were to (1) assess the correlation of mercury (Hg), manganese (Mn), iron (Fe), and copper (Cu) in paired maternal/fetal blood samples, and (2) study potential confounding factors during pregnancy. METHODS: Our study recruited 145 healthy pregnant women with a mean age of 28.06 years, gathering information by collecting interviewer-administered questionnaires. Paired maternal/fetal blood samples were collected by delivery. RESULTS: There was a positive correlation of Hg (r = 0.78, p<0.001), Mn (r = 0.31, p<0.001), Fe (r = 0.17, p = 0.038), and Cu (r = 0.21, p = 0.010) in paired maternal/fetal samples. Prenatal vitamin use (>3 times/wk) was significantly associated with lower maternal Hg (adjusted odds ratio 0.272, p = 0.005) and lower maternal Cu (adjusted odds ratio 0.267, p = 0.004) levels. Median fetal Hg, Mn, and Fe levels were higher than corresponding maternal levels, while median fetal Cu level was lower than maternal Cu level. CONCLUSION: There was a positive correlation of Hg, Fe, Cu, and Mn in paired maternal/fetal samples in this series. Our findings have raised the possibility of reducing maternal Hg and Cu by way of prenatal vitamin supplementation.
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Sangue Fetal/química , Metais Pesados/sangue , Adulto , Cobre/sangue , Estudos Transversais , Suplementos Nutricionais , Feminino , Humanos , Recém-Nascido , Ferro/sangue , Manganês/sangue , Mercúrio/sangue , Gravidez , Vitaminas/administração & dosagemRESUMO
UNLABELLED: Renovascular hypertension due to fibromuscular dysplasia is an uncommon but important cause of pediatric hypertension. It is usually ignored and diagnosed after a long delay because blood pressure is infrequently measured in children. We report a case of previously undiagnosed renovascular hypertension complicated with right renal infarction in a 2-year-10-month-old child, who initially presented as a case of conscious disturbance. The patient's brain CT displayed brain stem hemorrhage, and a brain MRI showed acute hemorrhage and multiple old intracerebral hemorrhage. Therefore, intimal fibromuscular dysplasia of the right renal artery was diagnosed by computed tomography and confirmed after renal angiography. Her blood pressure was gradually normalized after medical therapy, including use of Losartan. She is presently asymptomatic on OPD follow-up. The importance of BP measurement can not be overemphasized in pediatric patients less than three years of age with underlying diseases. KEY WORDS: Conscious disturbance; Fibromuscular dysplasia; Renovascular hypertension.
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BACKGROUND: The relationship between cytokine gene polymorphisms and susceptibility to Kawasaki diseases (KD) is still controversial, so the aim of the present study was to investigate the association of 14 various polymorphisms of 9 cytokine genes (interleukin (IL)-1A, IL-1B, IL-1RN, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-A and transforming growth factor-B) with KD risk. METHODS AND RESULTS: A total of 211 KD children and 221 adult controls were recruited. All controls were frequency matched to KD patients on sex and ethnicity. PCR and TaqMan assays were used for genotyping. There were no significant differences between KD children and adult controls in the genotype or allelic type frequencies of the 14 polymorphisms. No significant associations were found between haplotypes, constructed by IL-1B, IL-4, IL-8, and IL-10 cytokine genes, and risk of KD. Additionally, a linear trend was observed when these single nucleotide polymorphisms were combined, as evidenced by an increasing risk of KD as the number of at-risk genotypes increased (P(linear trend)=0.002). In the stratification analysis of age and sex, there was a linear trend of KD risk as the number of at-risk genotypes increased among those aged >12 months (P=0.014) or female (P=0.001), respectively. CONCLUSIONS: No associations between individual cytokine genetic polymorphisms and susceptibility of KD were observed, but a gene-dosage effect on the risk of KD was found, especially for older or female subjects.
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Citocinas/genética , Dosagem de Genes , Predisposição Genética para Doença , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo Genético , Adulto , Fatores Etários , Povo Asiático , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , TaiwanRESUMO
The purpose of this study was to evaluate the feasibility, clinical outcome, and resource utilization of transcatheter closure of large, symptomatic patent ductus arteriosus (PDA) in young infants, and compare the results with those of surgery. From January 2003 to December 2006, successful transcatheter implantation of the Amplatzer duct occluder was performed in 20 young infants (< or = 3 months of age) with large PDA who suffered from severe congestive heart failure despite medical treatment. The data was compared with a historical control of 18 young infants who underwent surgical ligation of PDA. Patient ages ranged from 18 to 89 days (mean 51.8) in the study group and 13 to 82 days (mean 39.9) in the control group. Patient weight ranged from 2.7 to 7.1 kg (mean 4.24) in study group and 2.5 to 5.7 kg (mean 3.79) in the control group. Between the 2 groups, there was no significant difference in the rate of complications. Patients who underwent transcatheter closure utilized significantly fewer resources (length of hospital stay and total cost) than those who underwent surgery. In conclusion, percutaneous device occlusion with Amplatzer duct occluder in small, symptomatic infants is feasible and more cost-effective compared with surgery. In experienced hands with careful preprocedural evaluation and delicate manipulation, the safety of transcatheter closure with Amplatzer ductus occluder in this age group can be assured and major complication avoided. Revision of the delivery sheath, making it kink-resistant, and PDA shape-tailored devices should further optimize the procedure.
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Cateterismo Cardíaco , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/cirurgia , Aortografia , Feminino , Humanos , Lactente , Recém-Nascido , Ligadura , MasculinoRESUMO
A healthy 15-year-old male patient presented with a 6-month history of recurrent attacks of palpitations. On multiple emergency room visits, a sustained wide QRS complex tachycardia with a right bundle branch block and northwest axis deviation was documented. The tachycardia was not terminated by intravenous adenosine, but was suppressed with intravenous verapamil. There was no evidence of structural heart disease, myocarditis, long QT syndrome, or electrolyte imbalance after a series of standard examinations. Idiopathic left ventricular tachycardia (ILVT) was suspected. Electrophysiologic studies revealed 2 inducible tachycardias, which were shown to represent atrioventricular nodal reentrant tachycardia (AVNRT) and ILVT. Transformation from AVNRT to ILVT occurred spontaneously following atrial pacing. Successful ablation of ILVT and the slow atrioventricular nodal pathway resulted in cure of the double tachycardia.
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Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Taquicardia Ventricular/cirurgia , Adolescente , Humanos , MasculinoRESUMO
The aim of this study was to investigate the effect of peritoneal dialysis (PD) on fluid balance and renal function in 17 infants with low cardiac output syndrome after open heart surgery. Peritoneal catheters were inserted prophylactically at the end of the cardiac operation. An effective negative fluid balance was achieved in all infants (P<0.01). They had significantly increased diuresis (P<0.01), increased mean arterial blood pressure (P<0.05), decreased central venous pressure (P<0.05), and decreased dopamine medication (P<0.05) after PD compared to before PD. Complications of PD, present in 7 patients, were transient and of minor significance. No patients died during PD or required discontinuation of PD due to severe cardiorespiratory distress. Thirteen patients recovered and had normal function upon discharge from our ward. Four died due to severe congestive heart failure. The overall mortality rate among all 17 patients was 24%. We conclude that PD is helpful in promoting fluid removal and may be used prophylactically for those infants who are at high risk for low cardiac output after cardiac surgery.